Large Animal Neurology

Large Animal Neurology

Third edition

I. G. Joe Mayhew
Massey University
Palmerston North, NZ

Robert J. MacKay
University of Florida
Gainesville, Florida, USA
This edition first published 2022
© 2022 John Wiley & Sons Ltd

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Table of contents

Preface to third edition vii

About the companion website ix

PART I Evaluation of Large Animal Neurologic Patients

1 Practical neuroanatomy 3
2 Neurologic evaluation 11
3 Ancillary diagnostic aids 52
4 Pathologic responses of the nervous system 75

PART II Clinical Problems in Large Animal Neurology

5 Disorders of behavior 91
6 Seizures and epilepsy 97
7 Sleep and acute collapse disorders 103
8 Coma and other altered states of consciousness 107
9 Blindness 111
10 Miosis, mydriasis, anisocoria, and Horner syndrome 114
11 Strabismus 121
12 Dropped mandible and masticatory muscle atrophy 125
13 Decreased and increased facial sensation 129
14 Facial paralysis and facial spasm 133
15 Pharyngeal dysphagia 137
16 Dilated esophagus 142
17 Laryngeal paresis and paralysis: roaring 144
vi Table of contents

18 Tongue paralysis 147

19 Head tilt, circling, nystagmus, and other signs of vestibular dysfunction 150
20 Deafness 156
21 Disorders of posture and movement 159
22 Incoordination of the head, neck, trunk and limbs: cerebellar diseases 171
23 Tetraparesis, paraparesis, and ataxia of the limbs: spinal cord diseases 175
24 Diffuse weakness 181
25 Paresis and paralysis of one limb: monoparesis 185
26 Bilateral brachial paresis to paralysis 191
27 Urinary bladder distention, dilated rectum and anus, and atonic tail:
cauda equina syndrome 194
28 Pruritus, self-­mutilation, headshaking, complex regional pain syndrome,
and miscellaneous distressing disorders 198
29 Autonomic nervous system dysfunction 206
30 Vertebral and paravertebral problems:
stiff neck and sore back 210

PART III Mechanisms and Specific Diseases

31 Congenital, familial, and genetic disorders 217

32 Infectious, inflammatory, and immune diseases 292
33 Physical, chemical, and thermal causes 373
34 Toxic diseases 412
35 Nutritional diseases 481
36 Metabolic diseases 503
37 Neoplasms and other tumors 521
38 Multifactorial and idiopathic disorders 532

Index588
Preface to third edition

For this third edition of Large Animal Neurology, Therefore, as with all diagnostic ancillary aids we use,
we have enlisted Rob MacKay as coauthor to help the results must be taken in conjunction with the
us keep up with current trends and to maintain a results of repeated examinations to help formulate the
­reason­ablyworldwide—­albeitsomewhatAnglosphere— most appropriate diagnostic and therapeutic plans. It
perspective. also must be considered before undertaking any test,
As with previous editions, the general structure whether the results, considering their ­margin of error,
of the book consists of three parts. Part I will inform clinical management to a degree that ben-
(Chapters 1–4) covers the background disciplines efit outweighs risk and cost. Otherwise, we might be
required for the evaluation of neurologic cases; Part better off not undertaking them.
II (Chapters 5–30) provides concise overviews of Another ongoing revolution of tools is in mod-
the commonly encountered, major clinical present- ern IT equipment and apps, not least, in a specialty
ing scenarios; and Part III (Chapters 31–38) offers so dependent on visual observation and pattern
an extensively resourced discourse of most neuro- recognition, as a means of instantly sharing images
logic diseases of domestic large animals following and videos of cases to better indicate clinical find-
an etiologic category. Readers thus can approach ings. Thus, it made sense to develop a library of
the text with a view to updating their evaluation of still and motion images of clinical material to share
suspected clinical neurologic patients (Part I), with with readers in this edition of Large Animal
a specific clinical syndrome in mind (Part II), or to Neurology. The video library is not only a compila-
delve into details on most of the specific neurologic tion of a wide variety of cases we have been fortu-
diseases of large domestic animals (Part III). nate enough to see but, more importantly, provides
Since the second edition of 2008, genetics and examples of actions, movements, postures and
modern imaging techniques, in particular, have had a syndromes, and particularly visual examples to
major impact on large animal neurology. Despite assist in the definition of clinical signs and syn-
their profound utility, these diagnostic tests are not dromes such as bizarre behavior, the ataxias, sleep
perfect. Thus, even dramatic and clearly defined attacks, tetany, and tremor.
changes seen on an MR or a CT image of a patient As with most clinicians and neurologists, we have
with a neurologic syndrome does not always indicate likely reviewed thousands of videos and images of clin-
cause and effect. Likewise, as our genetic modeling of ical cases over the years. Very often, new aspects of a
many diseases unravels, particularly of those with case come to light after multiple viewings at both nor-
complex genetic characteristics, identifying a genetic mal and slow speeds. Similarly, and particularly with
association with a particular disorder does not cases that are enigmatic or show fluctuating signs, by
mean that the patient’s signs are due solely to that returning to study the patient or the video, subtle and
inborn—­ or even acquired—­ genetic fingerprint. interesting—­and sometimes profound—­signs that had
viii Preface to third edition

not previously been noted become apparent. Typical Following on from the influence of our learned
examples of this include a change in eyelash angle seen mentors, we have tended to remain critical of misuse
in Horner syndrome; brief, repeated, minor facial gri- of terminology, particularly regarding anatomic
maces of a foal with focal epilepsy; movement of lice terms. We thus continue to strive to follow both the
toward areas of skin with sympathetic denervation; and Oxford English Dictionary (OED, 2009), and particu-
reversion from pacing gait at birth, then four-­beat walk larly the Nomina Anatomica Veterinaria (NAV, 2017).
at 2 weeks of age, back to a pacing gait before the onset We humbly acknowledge the instruction, friend-
of overt ataxia in a young foal with progressive signs of ship, and encouragement that we have been fortunate
spinal and other forms of ataxia. One can then approach to receive and share with colleagues at Massey
new cases with this information so that when such University (NZ), Guelph University (Canada), the
“new” signs are present, one will look for them and thus University of California at Davis (USA), the University
see them. It is worth iterating: of Florida (USA), Cornell University (USA),
Cambridge University (UK), and the University of
More mistakes are made from not looking than Edinburgh (UK). It’s been fun. Quentin Roper again
not knowing, and further mistakes are made from deserves special thanks for his painstaking electronic
not seeing rather than not looking draftsmanship in preparing many of the drawings in
(Radostits et al., 2000). the second edition and again in this edition. Most
especially, we are indebted to the many patients that,
Simply informing a student, at whichever stage of through their misfortune, taught us neurology.
their career, of one’s expert opinion on a case is rarely Our families remain as our sustainers for which we
helpful. As a clinical teacher, one should be prepared to are eternally grateful.
“think aloud” and share the thought processes as to
how one is synthesizing the facts of a case to arrive at a Joe Mayhew Rob MacKay
particular differential diagnosis and course of action, Massey University University of Florida
namely, the diagnostic reasoning used. We have also New Zealand USA
found two other maxims useful in teaching over the
years. First, we should not take ourselves too seriously, NAV. Nomina Anatomica Veterinaria, International Committee
we all make mistakes. Second, we need to remember on Veterinary Gross Anatomical Nomenclature (ICVGAN). 2017
that the next generation in our profession will be better OED. Oxford English Dictionary. Oxford University Press, Oxford.
2009
equipped than us; if we can be fortunate enough to con- Radostits OM, Mayhew IG, and Houston DM. Veterinary Clinical
tribute to that advancement then so much the better. Examination and Diagnosis. WB Saunders, London. 2000
About the companion website

Don’t forget to visit the companion website for this book:

www.wiley.com/go/mayhew/neurology

There you will find valuable materials, including:

• Video clips presenting a wide variety of diseases that show actions, movements, postures, and syndrome
characteristics of the disorders
• Figures from the book as downloadable PowerPoint slides

Scan this QR code to visit the companion website

 Part I
Evaluation of Large Animal
Neurologic Patients

Chapter 1 Practical neuroanatomy 3 Chapter 3 Ancillary diagnostic aids 52

Chapter 2 Neurologic evaluation 11 Chapter 4 Pathologic responses of the

nervous system 75
 1
Practical neuroanatomy

Disease  Page References10

Basic descriptive terminology 4

Functional neuroanatomy 5

Some of the most rewarding aspects of clinical neurology syndrome of ataxia in a purebred patient and associating
involve being able to associate observed signs and it with a familial cerebellar disorder for a client.
syndromes with neuroanatomic sites of the lesions. This Alternatively, one may be able to explain to a producer
may, for example, be experienced when recognizing a how a certain lesion, detected by an astute neurologic

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
4 Large animal neurology

examination of one representative animal and con- their fatty, myelin (myelino) coats. In tall, large animals,
firmed at postmortem examination is the cause of the some of these neuronal fibers extend 2–3 m, and many
clinical syndrome observed in the herd. The basic exit and enter the CNS via the cranial and spinal nerves
requirement for achieving this degree of diagnostic of the peripheral nervous system (PNS).
acumen is an understanding of applied neuroanatomy. Structurally, the forebrain (prosencephalon) is
This chapter provides the basic information neces- composed of the cerebral hemispheres (most of the
sary to allow the clinician to appreciate the fundamen- telencephalon), thalamus and hypothalamus (dien-
tals of a neurologic examination and to interpret, cephalon), hippocampus, basal nuclei, and the limbic
accurately, the results of such an examination. As the system, all situated in the rostral fossa of the neuro-
clinician becomes adept at these tasks, further anatomic cranium. The middle fossa contains the midbrain
details may be sought. These can be found in the texts (mesencephalon). Caudally, the hindbrain (rhom-
listed in the references. bencephalon) is composed of the cerebellum and
At this point, a plea is made for a clear use of ana- pons (together with the metencephalon) and the
tomic terms, based on Nomina Anatomica Veterinaria, medulla oblongata (myelencephalon) that all reside
Nomina Embryologica Veterinaria and Nomina in the caudal fossa. Both the cerebrum (cerebro) and
Histologica,1 along with the clinically applied terms used cerebellum (cerebello) have their own outer (cortical)
in functional neuroanatomy,2–4 clinical neurology,5–7 and inner (medullary) portions, composed particu-
and veterinary neuropathology.8–10 larly of gray matter (neuronal cell bodies) and white
matter (neuronal fibers), respectively. The remainder
of the brain comprising the midbrain, pons, and
Basic descriptive terminology
medulla oblongata makes up the brainstem. This
The following is a review of basic descriptive terminol- contains white matter pathways passing to and from
ogy; note that the derivation, abbreviation, combining brain and spinal cord regions, and gray matter, mostly
form, synonym, or explanation is given parenthetically. contained in nuclei as relay centers and sensory and
The central nervous system (CNS) consists of the motor nuclear areas for the body, including the cranial
brain (encephalo) (Figure 1.1) and spinal cord (myelo). nerve nuclei.
It contains collections of neuronal cell bodies or somata
in layers (laminae), nuclei, and columns of gray matter To avoid some confusion, vertebral levels are labeled
(polio). Tracts, sheets, and pathways of dendritic (affer- as C7, T3, L4, S5, Ca6 (caudalis as opposed to coc-
ent) and particularly axonal (efferent) processes of cygeal), etc., and spinal cord segments are labeled
these cell bodies make up the white matter (leuko). as C8, T3, L4, S5, Ca6, etc.
These processes make up most of the CNS along with

The spinal cord is the conduit between the brain

and the peripheral spinal (non-cranial) nerves and
their innervated structures of the body. Thus, it con-
tains all the afferent and efferent neuronal fibers con-
CEREBRUM CEREBELLUM necting to and from the brain as superficial white
us
o c amp matter tracts. It has a cervicothoracic (brachial)
Hipp
us Medulla enlargement (intumescence) and a lumbosacral (pel-
lam Midbrain
Tha Pons oblongata
lam
us vic) enlargement at the levels of the thoracic and the
otha
Hyp pelvic limbs, respectively. These swellings are the
result of a higher density of neuronal cell bodies at
these sites, collected in the butterfly-­shaped, central
FOREBRAIN Brainstem
gray matter and supplying the sensory and motor
Figure 1.1 Basic areas of the brain can be readily recognized on this spinal nerves for the limbs.
diagram of a median section of a horse brain. The terminology used in this Clinically, the autonomic nervous system functions
book is shown. Wherever possible the authors use the terminology of independently and involuntarily from the rest of the
Nomona Anatomica Veterinaria; however, some license is taken nervous system, receiving afferent input from the
with respect to forebrain, which here refers to the prosencephalon plus
diencephalon, as clinically, lesions in these collective regions generally environment via the basic and special senses to main-
present the same syndromes. It is important to recognize these various tain the body’s internal milieu. The parasympathetic
areas when sending brain sections for histopathologic examination. component has a brainstem and sacral outflow to the
 Practical neuroanatomy 5

head and body, whereas the sympathetic component down collagen in response to injury to the CNS.
has a thoracolumbar outflow. Originally, the processes of other small glial cell types
The entire CNS is protected within the bony neu- were thought to be few (oligo); these cells being
rocranium of the head and in the vertebral canal named oligodendrocytes. We now know that their
within the vertebral column. It is covered by meninges processes are extensive and extend to and maintain
consisting of the thick (pachy) dura mater and thin all the myelin sheaths covering CNS axons. The small
(lepto) arachnoid and pia mater. Between the latter microglial cells appear to be the tissue macrophages
two membranes, is cerebrospinal fluid (CSF), pro- of the mononuclear phagocytic system within the
duced by the choroid plexuses of the lateral and CNS, responding along with migrating inflammatory
fourth ventricles. This fluid also fills the cavities cells from the circulation when there are inflamma-
within the brain (ventricles) and spinal cord (spinal tory processes occurring in CNS tissues.
canal), which are lined by ciliated ependymal cells. The neuronal processes in the peripheral nervous
system (PNS) with their myelin sheaths are called nerve
fibers and make up the nerve roots, nerve plexuses, and
Because we refer to vertebral structures very often, it peripheral nerves. Some neurons, particularly those in
is worth reviewing the recommended correct nomen- the autonomic nervous system and the sensory neu-
clature as in Nomina Anatomica Veterinaria rons, have their cell bodies in aggregations known as
http://www.wava-­a mav.org/wava-­d ocuments.html ganglia. Also, several networks of interwoven nerves
(plexuses) occur in the PNS, the largest of which are the
Columna Vertebralis brachial plexus supplying the thoracic limbs and the
Corpus vertebrae lumbosacral plexus for the pelvic limbs.
Extremitas cranialis (Caput vertebrae) The cells that ensheathe PNS nerve fibers are
Extremitas caudalis (Fossa vertebrae) Schwann cells. These assist in maintaining a frame-
Crista ventralis work for nerves, as well as producing the abutting lay-
Arcus vertebrae ers of myelin that surround all the larger fibers, allowing
Pediculus arcus vertebrae quite rapid saltatory (leaping, jumping) conduction of
Lamina arcus vertebrae electrical impulses. The PNS has a fibrous connective
Foramen vertebrale tissue cytoskeleton that consists of the epineurium
Canalis vertebralis that wraps around a whole nerve, the perineurium that
Spatium interarcuale surrounds a bundle or fascicle of fibers, and the endo­
Foramen intervertebrale neurium that separates the individual nerve fibers.
Incisura vertebralis cranialis
Incisura vertebralis caudalis
Foramen vertebrale laterale Functional neuroanatomy
Sulcus n. spinalis Probably the most important structural and func-
Processus spinosus tional unit of the nervous system is the simple reflex
Processus transversus pathway (Figure 1.2). A neurologic examination
Processus costalis basically involves testing simple and complex reflex
Processus articularis cranialis pathways and interpreting the effected reflex activity
Processus articularis caudalis and complex responses (see Chapter 2, Neurologic
Processus accessorius Evaluation).
A simple spinal reflex pathway, depicted as a patel-
lar tendon reflex in Figure 1.2, is composed of two
As well as meningeal cells, ependymal cells, neu- neurons. Stimulation of a sensory stretch receptor in
rons (somata and their axons and dendrites), and a tendon with its sensory neuronal cell body in the
blood vessels, several other types of supporting, pro- dorsal root ganglion stimulates an efferent motor
tective, and nutritive glial (glue) cells (neuroglia) neuron. These motor neurons are usually alpha
make up a large part of the volume of the CNS. The motor neurons and are collectively referred to as
largest of these glial cells are the astrocytes with their final motor neurons, having their cell bodies in the
star-­shaped processes. These cells basically act to ventral gray matter of the spinal cord (and in cranial
support the CNS, which has little cytoskeletal frame- nerve nuclei in the brainstem). Reflex motor
work. They also act as pseudofibroblasts and can lay responses to sensory stimuli will occur without any
6 Large animal neurology

SENSORY
NEURON

FINAL
MOTOR
NEURON

Figure 1.2 Basic monosynaptic spinal reflex

pathway (patellar reflex) showing the sensory
neuron synapsing on the final motor neuron.
In many other reflex pathways, there is at
least one internuncial neuron within the CNS
allowing further modulation of the reflex.

other afferent or efferent connections within the subtle deficits in motor functions such as jumping
CNS; so long as these two (or more) neurons com- fences and hopping on the thoracic limb opposite the
prising the reflex arc, as well as the sensory nerve side of the lesion. In contrast, quite small lesions in the
ending, the neuromuscular junction, and the effector midbrain and medulla oblongata usually result in hemi-
muscle, all are intact. In contrast, lesions, due to any paresis or tetraparesis because of damage to central
cause, that damage parts of the reflex pathway will motor centers and tracts such as the rubrospinal
suppress those reflexes. Indeed, if the damage is to (Figure 1.3B), reticulospinal (Figure 1.3C), and vestibu-
the alpha motor neurons in the ventral gray matter of lospinal (Figure 1.3D) pathways. These central motor
the spinal cord or the cranial nerve motor nuclei, or neuronal pathways tend to have a calming effect on
to their peripheral axons, there will be loss of reflexes reflexes, particularly those involved with supporting the
and severe weakness and ultimate muscle atrophy, body against gravity such as the patella reflex. Because
i.e., signs of a final motor neuron lesion. of this, central motor pathway lesions do not suppress
The various reflex pathways with their respective reflexes and can indeed result in hyperactive reflexes
final motor neurons throughout the brainstem and spi- and responses. The major role of these central motor
nal cord are controlled for voluntary movement by neu- pathways however is to direct the various final motor
rons in motor centers in the brain which are collectively neurons in (voluntary) movement such that central
referred to as central motor neurons. Figure 1.3 depicts motor pathway lesions will result in poor or absent vol-
generic central motor pathways. Corticospinal motor untary effort (paresis or paralysis) in the face of very
pathways with neuronal cell bodies in the cerebral cor- active spinal (and cranial) reflexes.
tex (A) are very important in primates but do not appear Just as brain motor centers help control the final
to be very important in initiating voluntary limb and motor neurons within the reflex arcs, the sensory
body movement in domestic animals. Quite massive inputs to these arcs are relayed to brain centers to
lesions destroying the cerebrocortical motor centers give feedback on position sense (proprioception)
that would be devastating in higher species do not cause touch, and pain perception (nociception) (Figure 1.4).
permanent demonstrable abnormality in the gait of Sensory pathways travel to the thalamus, and proba-
large animals. After the acute effects of such large lesions bly to the somatosensory cerebral cortex, for the per-
in our veterinary species have resolved, there can be ception of pain. These pathways are multisynaptic
 Practical neuroanatomy 7

CENTRAL
MOTOR
NEURONS
A
B C D

SENSORY
NEURON

FINAL
MOTOR
NEURON

Figure 1.3 Central motor neuronal pathways

predominantly originate in the brainstem and
synapse on final motor neurons to effect motor
activity. Depicted here are A the cortico (rubro)
spinal, B the rubrospinal, C the reticulospinal,
and D the vestibulospinal neurons and tracts.

A
B
SENSORY NEURONAL PATHWAY
C B
B
C
E A
C
SENSORY
NEURON

FINAL
MOTOR
NEURON

Figure 1.4 Sensory pathways convey somatic,

proprioceptive, and visceral input to brain centers.
Subconscious proprioceptive neurons A project
to the cerebellum, whereas conscious propriocep-
tive neurons B and somatic and visceral afferent
neurons C project to the thalamus and ultimately
project to forebrain centers.

and contain small fibers, both characteristics making ment sense) is contained in spinocerebellar tracts
them resistant to interruption. Proprioceptive path- that pass directly to the cerebellum.
ways that are presumed to be consciously perceived In summary, damage to the spinal cord at the level
(position sense at rest) travel to thalamic and thence of a reflex arc at its final motor neuron will denervate
to cerebral conscious proprioceptive centers. Other the effector muscle, resulting in flaccid (loss of tone)
subconscious proprioceptive information (move- paralysis with degrees of hypotonia and hyporeflexia
8 Large animal neurology

at the level of the lesion. In contrast, a similar severe oblongata. Finally, there is a generator at the spinal level
lesion cranial or rostral to a reflex arc will result in that can initiate reflex actions and indeed probably is
hypertonic (spastic) paralysis. The latter is character- responsible for primitive gait patterns (viz. “spinal walk-
ized by loss of voluntary motor function as with a final ing”); the interested reader may find further reading on
motor neuron lesion, but the reflex is not diminished. this concept quite intriguing.12–15 For several reasons,
Indeed, the reflex may be released from the calming therefore, there is a strong argument in veterinary
influence of its controlling central motor pathways anatomy and neurology to dispense with upper motor
and be hyperactive with concomitant hypertonia neuron (UMN) and lower motor neuron (LMN) termi-
(spasticity—­sic.) or stiffness in body parts such as nologies: a strategy we have accepted for this text. The
limbs. When a central motor pathway lesion causes a CNS pathways involved with initiating motor function
degree of spastic paralysis, the involvement of adjacent and maintaining appropriate muscle tone and hence
proprioceptive and nociceptive sensory pathways also body posture are referred to as central motor pathways
results in ataxia and possibly hypalgesia, respectively. that directly influence the final motor neurons inner-
Certainly, the concept of considering motor activity vating muscle to effect all motor functions. Many final
on the basis of “upper” and “lower” motor neuron func- motor neuron somata reside in the brainstem and spinal
tion and lesions, even for quadrupeds, is entrenched in cord of the CNS with axons in the PNS, the exceptions
veterinary neurology, although not without some com- being the presynaptic final motor neurons of the
ment.3,5 Anatomically, upper and lower are not accept- autonomic nervous system (ANS) which are wholly
able (with the exception of some cranial structures such in the periphery.
as eyelids) as terms of direction in veterinary anatomy The cerebellum is the major coordinating center
(Nomina Anatomica Veterinaria, 6th Edition),1 making for voluntary movement (Figure 1.5). It synthesizes
the use of these descriptors confusing to say the least. impulses received from the cerebral cortex, the brain-
Also, in contrast to “upper” and “lower” motor function stem motor centers, and spinocerebellar and vestibu-
generators and pathways, the concept of central pattern lar (special) proprioceptive pathways. It then provides
generators has its merits when considering gait and pos- feedback impulses to the motor centers to coordinate
ture in humans and animals.11 In this model, there is a all motor functions.
generator of highly developed skilled motor activity Cranial nerves (CNs), numbering I through XII,
initiated, in primates, in the cerebrum. A further gen- leave the forebrain and brainstem (Figure 1.6). Some
erator of motor function, most prominent in our large are involved with specialized modalities such as smell
animals, resides in the midbrain and rostral medulla (CN I), sight (CN II), and balance and hearing (CN

C D
B

Figure 1.5 Important cerebellar connections

include subconscious general proprioceptive
input from the body such as via spinocerebel-
lar pathways shown as D (same as A in
Figure 1.4). Other input is received from cere-
brocortical A and brainstem B motor areas and
vestibular centers C. All cerebellar efferent
output is from cerebellar cortical (Purkinje)
neurons connecting to brainstem B and cere-
brocortical A motor areas.
 Practical neuroanatomy 9

IV
B
III VI XII
IX X
I
II V
VIII
FACIAL
VII
REFLEX Figure 1.7 A state of alertness or consciousness is maintained by the
forebrain A and particularly the reticular activating center B. These
ARC regions receive input from many other regions of the nervous system and
are interconnected.
Figure 1.6 Some cranial nerves are involved with specialized modalities
such as smell CN-I, vision CN-II, and balance and hearing CN-VIII. Others
innervate extraocular muscles CNs-III, IV, and VI, pharynx and larynx C
B
CNs-IX and X, and tongue CN-XII, while some are involved with reflex
function such as facial reflexes CNs V-VII, similar to spinal reflex arcs.

D
VIII). Some innervate eyeball muscles (CNs III, IV,
A
and VI), muscles of facial expression (CN VII), phar- F
ynx and larynx (CNs IX and X), and tongue (CN
XII). Others are involved with reflex functions such G
as facial reflexes (CNs V and VII) and the gag reflex
(CNs IX and X). These cranial final motor neurons E
have central motor pathways controlling them. A
final motor neuron lesion at the level of a CN or its
Figure 1.8 Functional regions of the forebrain include the frontal
nucleus can paralyze the motor function of the CN.
cortex A involved with mentation, behavior, and motor activity; the
Alternatively, a lesion affecting the efferent central parietal cortex B involved with pain perception particularly from the
motor pathways that influence the final motor neuron head and conscious proprioception; the occipital cortex C involved
can curtail such CN motor function. As with spinal with vision; the temporal cortex D involved with behavior and hearing;
reflexes, in the latter case the structure (e.g., face) the hypothalamus and pituitary E involved with autonomic and endo-
crine functions; and the deep-­seated limbic system F involved with
shows variable hypertonic, spastic paralysis (e.g.,
innate behavior.
grimacing), with intact or hyperactive reflexes.
Consciousness or mental awareness must be main-
tained within the forebrain (Figure 1.7A) for neuro- lobes (A) are involved with mentation and behavior,
logic functions to occur. Numerous sensory inputs, and with fine motor activity at least in primates. As in
including light, sound, touch, gravity, and metabolic humans, the parietal lobes (B) integrate conscious pro-
and endocrine factors, interact, usually on an area of prioceptive and nociceptive input in the large animal
the brainstem known as the reticular activating sys- species. Certainly, vision appears to require an intact
tem (Figure 1.7B). This system, by relaying impulses occipital cortex (C). Control of normal learned behav-
to the forebrain and brainstem, maintains the state of ior and perception of sound may be functions of the
awareness and activity. temporal lobes (D). The hypothalamus and its pituitary
The final concept of clinical neuroanatomy impor- gland (E) help control autonomic and endocrine func-
tant in interpreting large animal neurologic examina- tions of the body, whereas the deeper, old part of the
tions is that of the specialized areas of relatively brain known as the limbic system (F) may be involved
well-­developed functional centers that exist in the fore- with innate behavioral patterns. Finally, the basal nuclei
brain, but having brainstem connections, as introduced (G) do appear to have some motor control at least for
in Figure 1.8. The frontal and prefrontal cerebral cranial nerve function in horses. Irrespective of the
10 Large animal neurology

regions of the cerebral cortex, large lesions can occur 5 Thomson C and Hahn C. Veterinary Neuroanatomy: A
Clinical Approach. 1st ed. Saunders Elsevier. 2012; 208.
which in their stable state do not result in permanent 6 Peele TL. The Neuroanatomic Basis for Clinical Neurology.
disability; ­so-­called silent areas (e.g. Figure 2.5). 3rd ed. McGraw-­Hill Book Company, New York. 1977; 144.
With this understanding of functional neuroanatomy 7 de Lahunta A, Glass E, and Kent M. Veterinary Neuroanatomy
and Clinical Neurology. 4th ed. Saunders, Elsevier, St. Louis,
and a little practice, a neurologic examination can be MO. 2015.
readily performed and interpreted. An outline of such a 8 Innes JRM and Saunders LZ. Comparative Neuropathology.
neurologic examination is given in the next chapter. Academic Press, London. 1962.
9 Vandevelde M, Higgins RJ, and Overmann A. Veterinary
Neuropathology: Essentials of Theory and Practice. Wiley-­
Blackwell, Hoboken, NJ. 2012; 216.
References 10 Summers BA, Cummings JF, and de Lahunta A. Veterinary
Neuropathology. Mosby, St. Louis, M.O. 1995; 527.
1 WAVA. Nomina anatomica veterinaria, Nomina histologica 11 Rossignol S, Dubuc R, and Gossard JP. Dynamic sensorimotor
­veterinaria and Nomina embryologica veterinaria. World Asso­ interactions in locomotion. Physiol Rev 2006; 86(1): 89–154.
ciation of Veterinary Anatomists. 2017. Available from: http:// 12 Clayton HM. Horse Species Symposium: biomechanics of the
www.wava-amav.org/wava-documents.html . exercising horse. J Anim Sci 2016; 94(10): 4076–4086.
2 Jenkins TW. Functional Mammalian Neuroanatomy. Lea & 13 Dietz V. Spinal cord pattern generators for locomotion. Clin
Febiger, Philadelphia, PA. 1972; 410. Neurophysiol 2003; 114(8): 1379–1389.
3 King AS. Physiological and Clinical Anatomy of the Domestic 14 Duysens J and Van de Crommert HW. Neural control of loco-
Mammals, Volume 1: Central Nervous System. Oxford Science motion: the central pattern generator from cats to humans.
Publications, Oxford. 1987; 325. Gait Posture 1998; 7(2): 131–141.
4 Waxman SJ. Clinical Neuroanatomy. 25th ed. McGraw-­ Hill 15 Yuste R, MacLean JN, Smith J and Lansner A. The cortex as a
Medical, 2002; 400. central pattern generator. Nat Rev Neurosci 2005; 6(6): 477–483.
 2
Neurologic evaluation

Disease  Page Brain and cranial nerve disease 19

Overview12 Spinal cord disease 33

Signalment12 Peripheral nerve disease 47

History12 Where and what is the lesion? 49

Procedure for the neurologic examination 13 Initial plan 50

Interpretation of findings 19 References50

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
12 Large animal neurology

Overview reflex testing in smaller patients. Additionally, one

may decide to return to observe the patient for facial
Traditionally, a detailed neurologic examination expression and head posture when totally undisturbed,
follows the collection of information on a patient’s when blindfolded, during rising from recumbency or
signalment and history, an evaluation of the environ­ supported in a sling, and observed while performing
ment, and a complete physical examination.1–13 How­ its intended use, while maneuvering in a maze, after
ever, during the evaluation of a large animal suspected standing still for many minutes, after strenuous exer­
of having a neurologic disorder, most busy practi­ cise, when frightened, after short acting sedatives and/
tioners include several components of a neurologic or analgesic drugs, and when the patient is returned to
examination during variations of the general physical its natural environment and herd/flock mates.
examination as listed in Table 2.1.

Signalment
To distinguish between vertebral bodies and spinal
cord segments, vertebral bodies and regions will be The age, breed, sex, use, and value of a patient all are
defined by site and standard numerals, whereas spinal important considerations in the diagnosis and prog­
cord segments will be defined by site with subscripted nosis of many neurologic conditions. Several diseases
numerals. Thus, the last three cervical vertebrae are are age-­dependent. Certain diseases are associated
C5–7 and the last three cervical spinal cord segments with breed (see Chapter 31). Only a few neurologic
are C6–8. diseases depend upon sex. The uses to which animals
are put can be associated with certain diseases, and
this impacts considerably on the prognosis that
Sometimes enough evidence is available from this accom­panies the diagnosis. Because many large ani­
examination to proceed with a tentative diagnosis and mals are kept for economic purposes, the value of the
therapy. However, if this initial general evaluation is patient must always be kept in mind with respect to
not enough to make an accurate anatomic diagnosis, time spent on evaluation, cost of therapy, and future
especially if a thorough case workup is warranted or productivity; the survival and productivity of any
requested, then a complete neurologic examination herd mates must also be considered.
should be undertaken that will often uncover further
neurologic findings helpful to case workup. In fact,
even with second opinion cases, we usually go quite History
rapidly through a neurologic examination in say In addition to taking a general history of the patient,
5 min, then return to scrutinize major components of questioning of the client should focus on the primary
the examination dependent on clues from the history, complaint. Information concerning the precise cir­
physical examination, contributory test results, and cumstances of the environment, other animal con­
initial examination. Even then, it can be useful to tacts, and the nature of the first signs observed ought
develop a mental list of further procedures to under­ to be sought first. Further questioning is aimed at
take to assist with this diagnostic process. These may defining a relationship between the severity of the
include testing eye responses in dim and bright light, syndrome and the passage of time—­the sign:time
testing nasal and temporal field vision, and spinal graph.
Most congenital and familial diseases begin early in
Table 2.1 The following tests and criteria can be evaluated in a
physical examination to assist in the detection of a neurologic disorder life, and signs usually progress relentlessly. Even struc­
tural neuraxial malformations, such as myelo­dysplasia,
Mental attitude/awareness Symmetry of neck, trunk, and limbs will frequently show progressive signs as the patient
Normal behavior patterns Tail and anal tone matures and ages. Syndromes resulting from physical
Menace tests Anal reflex
causes, particularly external injury, have a sudden onset
Pupillary light reflexes Rectal examination
Fundoscopic examination Postures adopted at rest and after days then often stabilize or improve. Signs
Symmetry of parts of the head Proximal limb muscle bulk caused by infectious agents can be acute or chronic,
Tongue position and tone Gait at walk and trot and frequently fluctuate in severity. Immune-­mediated
Absence of nasal discharge Gait while turning diseases often result in fulminant signs that can improve
External thoracolaryngeal Faster gaits
dramatically, particularly with therapy. Progression of
(slap) reflex
metabolic, toxic, and ­nutritional ­disorders, which are
 Neurologic evaluation 13

usually symmetric, is very variable. Perhaps surpris­ An outline of the recommended format for the
ingly, signs due to neoplastic involvement of the nerv­ neurologic examination of large animals, based on
ous system may begin abruptly and even wax and wane, the evaluation of the adult horse, is given in Table 2.2,
but most often are progressive. along with a summative description of the evaluation
Historical data can give clues as to how wide­ of cranial nerve function in Table 2.3 and of the gait
spread, focal, or multifocal the disease process is, evaluation in Table 2.4. A format for recording results
whether there was evidence of asymmetry, and how of the neurologic examination can be very useful,
severe the signs have been. These aspects of the and the format of this can be adapted to the ­examiner’s
pathogenesis of diseases are obviously helpful in preference. Some prefer a detailed checklist for most
determining the cause. of the observations and tests carried out, others uti­
lize an anatomic breakdown of most of the testing
and observations, while some prefer a blank sheet to
Procedure for the neurologic examination simply record abnormal findings. An example of a
The primary aim of a neurologic examination is to neurologic examination recording form, based on
confirm whether a neurologic abnormality exists. both anatomic sites and many of the tests and obser­
Because omission of parts is the most common mis­ vations to record results of, is provided in Figure 2.1.
take made during the neurologic examination, the Some comments as to differences important to recall
order in which the examination is performed when evaluating neonates also are indicated. Such a
becomes important. Here, we provide a precise prac­ format is very applicable to other large animal spe­
tical format that is logical in sequence, easy to cies, modified according to practical circumstances
remember with practice, and emphasizes the need such as size, containment and behavior of the patient,
for an anatomic diagnosis (Where is the lesion?) to be monetary value, and the disease processes possibly
made before an etiologic diagnosis (What is the cause involved such as zoonoses and trauma.
of the condition?) is made. The rationale for the We encourage those readers who are not reasonably
sequence of the examination presented here is as fol­ well practiced in performing and recording neuro­
lows: first, it starts at the head and proceeds caudally logic examinations and in both normal and diseased
to the tail; second, it is used for patients of all sizes patients, to practice on a friendly, neighborhood,
and species, whether the patient is ambulatory or mid-­sized dog. The approach for such an examina­
recumbent; third, it considers the anatomic location tion will be as for a calf, foal, lamb, kid, or (bless their
of lesions as the examination proceeds. Even if parts little larynges) piglets. Should the practice dog or
of the examination must be omitted because of the such patient be small enough, the close aspects of the
nature of the patient, suspicion of fracture, or finan­ procedure used are readily performed by sitting with
cial constraints, the sequence ought to be followed the patient on one’s knees or having the patient on a
mentally. Frequently, the presence of a neurologic table. Mid-sized patients of these types can be exam­
lesion(s) cannot be deduced until the end of a thor­ ined by standing straddled above the dorsum of the
ough neurologic examination. patient while supporting the head, both for restraint
and comfort.
Below is given an overview of the practicalities of
In practice, some experienced neurologists will under-
performing an efficient neurologic examination fol­
take a preliminary examination along these lines and
lowed by assistance in interpreting some of the
then perform a more detailed and focused study of the
findings.
patient to help rule in and rule out involvement of
the various parts of the nervous system. The nature of
the latter will be based upon findings from the primary We make no excuse for the rather excessive detail
examination, from aspects of the examination that included in this chapter. Although one can always go to
were overlooked or were uncertain, and from the his- E-­references for factual information on disease processes,
tory. During this focused assessment, it is just as above all else it is the specific findings from an accurate
important to rule out involvement of certain regions of and repeated neurologic examination, with only then
the nervous system — ­e.g., forebrain, cervical spinal careful reflection on the significance of the findings, that
cord — ­as it is to define those components that are successful and accurate diagnoses are made.
likely affected. If all else fails, examine the patient again!
14 Large animal neurology

Table 2.2 Outline of basic format for the neurologic examination, based on that for the horse

Region Evaluation Sites evaluated Points to emphasize

Adult Neonate <2 weeks

Head Behavior Forebrain History and owner’s understanding Quick adjustment ~2–7 days
Seizures, especially mild and focal. VIDEO Paralytic state with cradling
Subtle asymmetry in menace and nasal Partial seizures—­just face,
sensation jaw
Mentation/sensorium Forebrain Response to environment Adjustment ~24 h
Midbrain Sleep attacks more common than
epilepsy
Cardiovascular syncope very rare
Head posture and Neck Stiff/twisted neck Flexed head posture and
movement Forebrain—­head and neck Head tilt (VIII) verses head turn ataxic movements normal
turn (forebrain)
Vestibular—­head tilt Head tremor—­cerebellar
Tremor—­check eyeballs Head/neck ataxia—­cerebellar/spinal
Head shaking—­trigeminal
Cranial innervation CN II – XII Evaluate regions of head Menace deficit <7 days
Brainstem Fundic examination Eye rotation dorsomedial
Cervical sympathetic supply Repeat test for subtle asymmetries
Reevaluate when totally relaxed
Body Neck and forelimbs C1–T2 Particularly asymmetry All reflexes
Only flexor reflex useful Hyperreflexia normal
Hopping Crossed extension normal
Trunk and hindlimbs T3–S2 Particularly asymmetry All reflexes
L4—­femoral n. Patellar reflexes useful Hyperreflexia
L5—­cranial gluteal n. Crossed extensor reflex
L6–S1—­sciatic n. Flexor reflex useful Extensor thrust response
Tail Ca1+ Extension and flexion
Perineum, anus, S1–5 S1–2 is common fracture site
rectum, and bladder
Gait ORTHOPEDIC PROBLEMS! Neuromusculoskeletal VIDEO! SEPSIS!
and Shoulder and hip atrophy common
posture Possible analgesic trial
Positional CP deficits Brainstem, spinal cord, and Manual placement of feet/limbs Prematurity
sensory nerves noncontributory
Extensor weakness Brainstem, spinal cord, and Especially final motor neuron lesion Extensor strength dominant
PNS
Flexor weakness Brainstem, spinal cord, and
PNS
Ataxia Spinal ataxia Irregular position and placement
Cerebellar ataxia Hypermetria characteristic; F > H Normal to degree
Vestibular gait Crouched posture Normal to degree
Deliberate (predictable) stepping
Wide-­based, staggering gait

CP, conscious proprioception; CN, cranial nerve.

Head
midline to determine what neck and head asymme­
For the routine large animal patient examination, try may be present. Allow the patient to smell an
evaluate what one can from a distance, preferably (often peppermint-­ tainted) hand for introduction
before the patient is disturbed, for the first observa­ and observe the face, particularly eyes and associated
tions of behavior, mentation and head, neck, trunk, structures, for an expressional response. Then,
and limbs. Head and neck deviations need to be ­examine the parts of the head and neck for the evalu­
assessed closely by straightening the neck along the ation of cranial nerve function (Table 2.3).
 Neurologic evaluation 15

Table 2.3 Assessment of cranial nerve function

Cranial nerve Major function Normal reflex/response/assessment

I Olfactory Sense of smell Challenging—­most odors also stimulate CNV

II Optic Afferent pathway for vision and light Menace response. Pupillary light reflex. Swinging light test
Dazzle response
III Oculomotor Pupillary constriction Pupillary light reflex
Upper eyelid levator muscle Induced eyeball movement
Extraocular muscles Medial movement of globe
Ptosis rarely apparent
IV Trochlear Extraocular muscle (dorsal oblique) Ventrolateral rotation of globe
V Trigeminal Sensory Sensory to head, face, and tongue Ear, eyelid, and lip (facial) reflexes
Pain perception: head, nasal septum, and rostral tongue
     Motor Motor to muscles of mastication Chewing, jaw tone, and muscle mass (temporalis, masseter, and
pterygoid)
VI Abducens Extraocular muscle (retractor oculi) Induced eyeball retraction
Extraocular muscle (lateral rectus) Eyeball retraction (corneal reflex)
Lateral movement of globe
VII Facial Motor to muscles of facial expression Ear, eyelid and lip (facial) tone, reflexes, and movement
Facial expression and symmetry
VIII Vestibular Afferent branch of vestibular system Head posture. Induced eyeball movement. Normal vestibular
nystagmus. Normal gait. Blindfold test
Cochlear Hearing Ear movement in response to noise (Preyer reflex)
IX Glossopharyngeal Sensory/motor to pharynx Swallowing (observation and palpation)
X Vagus Sensory/motor to pharynx and larynx Gag reflex (nasopharyngeal tube)
XI Accessory Endoscopy
XII Hypoglossal Motor to tongue Tongue size and symmetry

Table 2.4 Prominent gait and postural abnormalities present with neurologic lesion at different locations

Lesion Gait and postural abnormalities

location
Postural deficits Paresis Ataxia Hypometria Hypermetria

Forebrain +++ 0 0 0 0
Brainstem ++ ++ ++ ++ ++
Vestibular +++ 0 ++ ++ 0
Cerebellum ++ 0 +++ + +++
Spinal cord central sensory ++ ++ ++ ++ ++
and motor pathways
Final motor neuron ++ +++ + (++)# (+++)#
(peripheral nerve)
Musculoskeletal + ++ 0 + 0

0 = not usually expected; + = mild if present; ++ = usually present; +++ = quite characteristically present
#
= usually only with selective sensory fiber involvement

At this stage, while standing in front of the

Abnormal behavior may be blatantly obvious (e.g.,
patient and holding the head collar with one hand
head-­ pressing), very subtle (e.g., repeated yawning),
for some degree of safety, make sure you have
may be difficult to distinguish from physiologic activity
the patient’s attention by tapping lightly once or
(e.g., an aggressive, diestrus mare), may require com-
twice above the eye with your fingertips on a
ment from keeper (e.g., failure to respond to commands),
cupped hand to induce a combined visual and
and can even occur with non-­neurologic problems (e.g.,
facial response of palpebral closure, proceeding to
myotonia). We include seizure activity as abnormal
a menace response (Figure 2.2) from nasal and
behavior as well, partly because it reflects forebrain dys-
temporal fields. This is followed by observation of
function and very often it is seen as such by an owner.
eye position and pupil size and symmetry using a
16 Large animal neurology

Neurological Evaluation Form

HISTORY:
PATIENT DETAILS
Case No.: .....................................................
Owner’s Name: ............................................
Tel./E-Mail: ...................................................
Animal’s Name: ............................................
Species: ....................................................... PHYSICAL EXAMINATION:
Breed: ..........................................................
Ref. Vet.: ......................................................
Clinician: ......................................................
NEUROLOGICAL EXAMINATION: VIDEO?
HEAD Behavior, seizures Head Posture [tilt, turn]

Mental Status Head, Neck and Trunk Movement, and Co-ordination

CRANIAL NERVES
EYES Left Right VESTIBULAR/EAR Left Right
Ophthalmic Exam Eye drop, normal/abnormal
Vision; II Nystagmus; normal vestibular
Menace; II–VII, cerebellum Abnormal
Pupils, PLR; II–III, Symp. Blindfold
Horner; Symp. TONGUE
Strabismus; III, IV, VI, and VIII Mass and use; XII, cerebrum
FACE PHARYNX, LARYNX
Sensation; Vs, cerebrum Voice; IX, X
Muscle mass/jaw tone; Vm Swallow; IX, X, cerebrum
Ear, eye, nose, and lip reflex; V–VII Endoscopy
Expression; VII, cerebrum T-L reflex
Sweating; Symp.
GAIT and POSTURE Left Right
Thoracic Limb/Neck Pelvic Limb/Trunk Thoracic Limb/Neck Pelvic Limb/Trunk
Paresis
Ataxia
Hypometria
Hypermetria
Posture
Postural responses [hop, hemi, knuckle]
Lameness

LOCALISING SIGNS [reflexes, sensation etc.] Left Right

Thoracic Limb/Neck
Pelvic Limb/Trunk
Tail, Anus, Bladder, and Rectum
ASSESSMENT General [circle]: cerebrum brainstem peripheral CNs cerebellum
spinal cord peripheral nerve muscle skeleton
Site of lesion[s] Specific:

Cause of lesion[s]

PLAN Diagnostic

Therapeutic

Prognostic

KEY: 0 = absent; 1+ = hyporeflexic; 2+ = normal; 3+ = hypereflexic; 4+ = hypereflexic and clonus

Figure 2.1 Example of a neurological examination form of large (and small) animal patients.
 Neurologic evaluation 17

should be used. Evidence of optic nerve atrophy,

peripapillary retinal lesions, globe position, trem­
bling and ataxic eye movements, and nystagmus all
can be detected.
Again, while directly in front of the patient, eyeball
position in the bony orbit along with the size of the
palpebral aperture and the angle of the dorsal eye­
lashes can then be determined. Both ventral move­
ment and induced, normal, horizontal nystagmus of
the globe can then be evaluated by first slowly raising
the mandible to horizontal and then swinging the
head and neck to both sides through a horizontal arc
of 60–90°. Facial symmetry, reflexes, movement, and
especially muscle tone all can then be observed as
well as the bulk and symmetry of the temporalis
(Figure 2.3), masseter, and pterygoid muscles being
compared. The symmetric bulk of all these muscles,
plus other retrobulbar soft tissues, can be determined
by the symmetry of depth of the supraorbital fossae.
During facial reflex testing with blunt needle holders,
Figure 2.2 A positive menace response is the observation that the
sensation in the form of cerebral perception and
patient blinks its eyelids in response to a minimally threatening hand
gesture as shown. This is assumed to equate to the presence of vis- resentment is evaluated from the nasal septum on
ual perception. The opposite is not true as there are several reasons each side. During this stage, any increased tempera­
why a patient that appears to see perfectly well and does not bump ture and presence of sweat at the base of an ear will
into strange, nonodiferous objects in its visual field may not have be evident. Nasal, oral, laryngeal, pharyngeal, and
this positive menace response. Attracting the patient’s attention
hyoid region inspection, and particularly palpation,
using a light tap to the side of the face is useful to precede the test.
If the visual threat is too strong, the patient will often pull the head is performed, and the external, palpable thoraco­
away in a startle response without blinking. Whether or not the laryngeal responses are tested.
patient can see, this startle response, akin to the dazzle (blink-­to-­
bright-­light) response, likely is subcortical, involving the midbrain
and other brainstem structures without necessarily involving the
forebrain visual cortex. Temporal and nasal visual fields of each eye
in turn (the contralateral eye being kept covered) can be tested to
evaluate uncrossed (at the optic chiasm) and crossed visual pathway
fibers, respectively. This does however take a cooperative patient and
some experience to be repeatable and reliable.

bright penlight from 20 to 40 cm. Swinging the

light quickly from illuminating one eye to the other
and pausing for say 5 s in front of each pupillary
aperture as the light source is brought closer in
front of each eye, allows the immediate pupillary
response to be observed, unencumbered by blink­ Figure 2.3 Many normal adult horses have slightly to moderately asym-
ing. Any asymmetry or suspected deficit means metric temporalis musculature covering the temporal fossae (arrows). It
that a dazzle response must be performed, and appears the origins of the paired muscles on the temporal crest can arise
these tests need to be performed in dim and bright asymmetrically even with there being no measurable asymmetry in
light, but not direct sunlight. With practice, the ­muscle bulk. If there is asymmetry in such bulk of retrobulbar tissue
­(muscle), there will usually be asymmetry in eyelash angle, being more
central fundus and optic disc can be directly upright over the eyeball with less retrobulbar muscle bulk, as for the left
inspected by looking along the shaft of light from a eye here. Certainly, asymmetric dental disease most often will result in
penlight; otherwise, an angle-­poise ophthalmoscope such findings.
18 Large animal neurology

Body Gait and posture

Neck and thoracic limbs The evaluation of posture and gait comprises the fol­
Attention is immediately moved to the neck where lowing minimal components:
bone and muscle symmetry is assessed by close
palpation, and the local cutaneous coli and cervico­ • Observing the patient walking in a straight line
facial responses are seen and felt. A solid blunt viewed from the side as well as from behind and in
instrument, such as 15–25 cm artery forceps or nee­ front.
dle holders, is best for performing this and other • Firmly but not abruptly pulling laterally on the tail
cutaneous testing. On occasion, with a very fright­ with the patient standing still and while the patient
ened patient, the tip of a rigid index finger may have is being walked forward.
to suffice as being better tolerated. A firm thrust • Assessing stride length and trajectory and place­
needs to be applied over sites at the level of and ment of all four limbs both while walking freely
10–15 cm dorsal to the articular processes of cervi­ and while the tail is pulled to each side in turn.
cal vertebrae to consistently induce these cervical • Trotting the patient away from and back toward
responses. The two-­pinch technique is used to test the examiner.
cervical dermatomes and to test limb autonomous • Watching the patient being walked in circles and
zones for areas of hypalgesia if a reflex suppression turning very tightly in circles in both directions.
or a final motor neuron lesion are suspected. • Taking the patient oneself and, by walking back­
Regional muscle atrophy, bony asymmetry, and ward, leading the patient forward in a serpentine
areas of sweating are to be noted. path to observe limb placement. In this maneuver,
one leads in a manner such that the direction of
each forefoot in turn is required to change direc­
Trunk and pelvic limbs tion during its swing phases.
Testing can continue caudally to transfer to the tho­ • Leading the patient oneself to walk in circles and to
rax testing the cutaneous trunci reflex over the mid-­ turn tightly in circles in both directions.
third of the lateral thorax, again with forceful stimuli. • Continuing these maneuvers while pulling on the
There is a variable region over the point of the shoul­ lead rope and the tail simultaneously, assessing
der, about the C7–T3 dermatomal region, where nei­ limb placement and strength of resistance.
ther responses are well obtained, and the cutaneous • Releasing the tail abruptly after stopping from
trunci reflex usually fades in the caudal thoracic turning tightly to observe for adoption of and
region. Flexion, extension, and lateral bending of the standing with abnormal limb positions.
thoracolumbosacral vertebral column is then con­ • Hopping the patient on at least the thoracic limbs
veniently tested with the instrument used to firmly (Figure 2.4).
stroke the lateral dorsum from the withers to the cau­
dal gluteal region. Again, the two-­pinch technique is
used to test lateral thoracic dermatomes and to test Manually placing the limbs in abnormal posi­
limb autonomous zones for areas of hypalgesia if tions and placing them with the dorsum of the hoof
there is any evidence whatsoever of a reflex or final resting on the ground are not useful in detecting
motor neuron lesion. Regional loss of muscle bulk, neurologic motor or proprioceptive abnormalities
bony asymmetry, and areas of sweating also should in our hands. Likewise, the use of a sliding sack under
invoke detailed scrutiny. one weight-­bearing foot in turn never alone appears
to add information regarding the assessment of
conscious proprioception.
Rectum, bladder, anus, and tail A patient that is or can be placed in lateral recum­
Tail extension and flexion is evaluated during anal bency can be tested for classical limb reflexes. In
reflex and perineal sensory testing. A strong, blunt-­ practical terms, these simply consist of the flexor
probe stimulus applied to the anal ring results in a reflexes in thoracic and pelvic limbs and the extensor
brisk anal contraction and flexion (clamping) of the or patellar reflex in the pelvic limbs; other described
tail, whereas a light stimulus results in an anal reflex reflexes (responses) are very unrepeatable and
alone, and a soft, tactile stroking stimulus results in ­unreliable in adult patients while trying to define an
tail extension. anatomic neurologic lesion site. A reflex is reported
 Neurologic evaluation 19

At the conclusion of the gait evaluation, any issue

that is unclear can be returned to for further evalua­
tion and confirmation, and further testing can be
considered as appropriate. As suggested above, this
will frequently include observations while blind­
folded, hemiwalking, hopping on pelvic limbs, wheel
barrowing on thoracic limbs with head and neck held
extended, after exercise, up and down slopes, and
when performing any expected tasks.
For documentation, further study, and possible
consultation purposes, taking a video of any possi­
ble neurologic signs displayed by a patient is worth
considering. It must be recalled however that a
badly produced video clip is likely to be worse than
a clear verbal or written description—­the descrip­
tion, not its interpretation. At best, video sequences
of neurologic movement abnormalities, particularly
involving the gait, are less precise and less accurate
than in real life.

Interpretation of findings
Figure 2.4 Performing postural reactions such as hopping on one
­thoracic limb as shown can express underlying neurologic deficits. These
Interpretation of signs of brain and cranial
include a slow onset of response on a limb with flexor weakness, a hyper- nerve disease
metric response with spinocerebellar disease, and collapsing on a limb
with extensor weakness. In larger patients where these testing proce-
Sometimes, quite large chronic forebrain lesions will
dures are difficult or impossible, such observations may depend on be present but clinically silent (Figure 2.5), whereas
­performing complex gait maneuvers such as turning tightly on a slope smaller but acute lesions can often have clinical
and walking the patient in a serpentine path and changing direction expression.
while one forelimb is protracting in its stride.

as present or hyperactive in a limb if such a normal or

very strong response is detected in the recumbent
patient while the limb is uppermost or is dependent.
A clonic response is when there are multiple muscle
contractions occurring in response to a single stimu­
lus. A crossed extensor reflex occurs when there is
limb extension into the untested limb in response to
a graded, increasing stimulus to a distal limb.
Hyperactive, clonic, and crossed extensor reflexes all
reflect central motor pathway lesions with sparing of
the final motor pathway.
All other limb reflex testing in adult patients really
does not usefully contribute to a neuroanatomic
diagnosis and results of such additional limb reflex Figure 2.5 Large regions of the forebrain of large domestic animals can
testing should not be used to alter a neuroanatomic be regarded as “clinically silent” because when affected by disease pro-
diagnosis achieved by the interpretation of results of cesses there may be minimal or no associated clinical signs. Such was the
the remainder of the examination. Finally, poor or case with a yearling horse whose brain is shown here in section with a
defect in the right parietal cerebral cortex that likely resulted from a vas-
absent reflexes can be found in a heavy patient very cular infarct. At the acute stage of disease, this patient, as a neonate, did
soon after the onset of ­recumbency, presumably due demonstrate mild obtundation and wandering in wide circles to the right
to mechanical and decubital effects. but made a full clinical recovery within a few days.
20 Large animal neurology

Behavior Mental status

The owner or handler will frequently be the best An assessment of mental status is made based on the
source of information regarding the patient’s behav­ patient’s level of awareness or consciousness that is
ior, and age, breed, and sex will influence expected evidenced by bodily activity seen as a state of arousal.
response patterns. Occasionally, auditory and tactile This may well require considerable forebrain func­
stimulation can elicit seizure activity. Focal and mild tions to be active but requires input from the ascend­
generalized seizures in neonatal animals may be seen ing reticular activating system (ARAS) in the rostral
as episodes of repetitive jaw champing, facial twitch­ brainstem and thalamus for the state of arousal to be
ing, or periods of tachypnea. Bizarre and inappropri­ maintained (see Figure 1.7). The level of activity in the
ate behavior, such as head pressing, compulsive ARAS is affected by inputs received by all components
wandering, circling, changes in voice and appetite, of the sensory nervous system, particularly from the
and licking objects and aggressiveness, is usually easy special senses of smell, sight and sound, and from
to recognize. Other more subtle behavioral abnor­ noxious inputs. Coma is a state of complete unrespon­
malities, such as continual yawning, can be regarded siveness to noxious stimuli and the deepest comas are
as signs of cerebral disease. An animal with a fore­ usually related to rostral brainstem or particularly
brain lesion that compulsively circles tends to do so thalamic lesions within the ARAS. Semicoma is a state
toward the side of the lesion. of partial or inappropriate responsiveness to stimuli.
It is often difficult for a clinician to distinguish Other, less profound, levels of loss of awareness are
between behavioral aberrations associated with variously described as stupor, obtundation, somno­
organic forebrain disease and compulsive or stereo­ lence, delirium, lethargy, and inactivity. The term
typic disorders in which no morbid neurologic depression is to be avoided in describing suppressed
lesion can usually be identified (see Figure 2.5). activity in animals because of the subjective connota­
Characteristics of behavioral disorders defined as tions it includes in human medicine. Large animals
seizures can be mistaken for altered mentation alone that are recumbent because of spinal cord disease are
such as sleep disorders (see below) and syncope of usually bright and alert unless they are anorectic,
cardiac origin, and these need to be identified and dehydrated, exhausted, or unduly frightened.
differentiated. The former two are far more fre­ Prominent changes in behavior and a markedly
quently encountered than syncope, although the dampened mental attitude are seen with many forms
separation of those two syndromes can be difficult. of forebrain disease, especially those of traumatic,
Other signs of forebrain disease such as an asymmet­ inflammatory, toxic, and metabolic origin. The signs
ric menace response, asymmetric sensation per­ can often fluctuate considerably over minutes to
ceived from the nasal septum, and asymmetric days, and such cases may quickly alternate between a
forelimb hopping all can add to the confidence of a somnolent, unresponsive state to one of hyperexcita­
diagnosis of asymmetric forebrain disease resulting bility and violent behavior.
in multiple seizures (epilepsy) as opposed to a diag­ Disordered sleep patterns, particularly paroxysmal
nosis of a sleep disorder. With true narcolepsy in episodes of sleep as seen with narcolepsy, may require
large animals, a prominent degree of cataplexy or loss CCTV video monitoring to be seen and to help dis­
of all muscle tone is usually seen, and thus recum­ tinguish from seizures.
bency and recovery are most frequently quiet events
as opposed to the tonic and clonic situation with epi­ Head posture and movement
lepsy. Seizures and sleep attacks both tend to occur All normal animals maintain the head in a certain
more often during quiet times, although both may be posture and maneuver it quickly and smoothly to per­
associated with precipitating factors such as being form acts such as prehension of food. Unilateral and
released into a paddock, feeding, grooming, and asymmetric lesions involving the vestibular system
other forms of presumably pleasant manipulation. consistently result in a head tilt that is characterized
Indeed, strong evidence for focal seizures that do not by the poll rotating laterally while the caudal neck and
fully generalize (i.e., do not cause recumbency) has the muzzle remain, or are placed back to, the median
been encountered in racehorses during preparation plane. In comparison, a horse with a forebrain lesion
for and after racing. These have tended to involve that tends to turn to one side and to circle, usually,
facial grimacing, followed by head, neck, and even though not always (see Fig 33.1), to the side of the
forelimb jerky movements. lesion, often has the head and neck d ­ eviated toward
 Neurologic evaluation 21

the direction of the turn. The presence of a head tilt Animals with neck pain may hold their neck in an
should be evaluated for only when the muzzle and abnormal fixed position and be reluctant to move the
neck are held by the examiner as close to the median head and neck. Also, diseases causing neck weakness
plane as possible and rotation of the poll and muzzle may result in an animal carrying its head lower to the
can be viewed relative to the median plane. In com­ ground. Examples of this include diffuse neuromus­
parison, with a head turn as seen with forebrain cular weakness seen with botulism and with equine
disorders, the long axis of the head usually aligns on motor neuron disease. This is also but rarely seen
the median plane when the muzzle is gently brought with extensive cervical spinal cord, final motor
back to a median position. A severe vestibular lesion neuron lesions involving ventral gray matter, and for
can result in a significant head tilt and head and neck example with extensive cervical myeloencephalitis.
turn, usually both toward the side of the lesion. Finally, an extended head and neck posture, referred
Animals with bilateral central or peripheral vestibu­ to as a star-­gazing attitude, may indicate a severe
lar (and cerebellar) disease frequently show swinging forebrain disorder such as polioencephalomalacia of
movements of the head and neck, i.e., head and neck ruminants and basilar empyema, and is also present
ataxia. with diseases causing increased extensor muscle
A musculoskeletal disorder, especially involving tone, such as equine tetanus and bovine myotonia.
the neck, must be considered if there is any asymme­
try or deviated head and neck posture. Additionally, Cranial nerves
congenitally blind horses may have abnormal head In practice, it is convenient to evaluate separate parts
posture, including a true head tilt, along with jerky of the head and face as described in the neurologic
head movements, and corresponding eyeball devia­ examination outline and forms (Tables 2.2 and 2.3;
tions and movements. Such a syndrome may be equiv­ Figure 2.1). Thus, the evaluation moves from the
alent to amblyopia in children. In addition, congenital, eyes, face, jaws, and mouth to the pharynx and lar­
asymmetric strabismus in horses has been associated ynx. When the examination is completed, deficien­
with a head tilt with no other evidence of vestibular cies ultimately need to be related to specific cranial
involvement, and abnormal head posture can be seen nerves. Thus, the following section covers the inter­
in Appaloosa horses with night blindness. Particularly pretation of neurologic examination findings relative
at the onset of a fast gait, many normal horses will to individual cranial nerves.
hold the head and neck deviated from the median
plane: perhaps more related to a reaction to a mouth Olfactory nerve—­CN I
bit than to speed. Painful conditions such as dental Normal function is usually equated with the patient’s
disease, forelimb and hindlimb14 lameness, and caudal ability to smell the hand of the examiner or its feed.
cervical arthritis, and asymmetric visual acuity, can However, because such stimuli almost certainly irritate
also result in abnormal head, neck and trunk posi­ the nasal mucosa, this test evaluates the sensory branch
tioning during exercise or at rest. of the trigeminal nerve, probably as much as CN I.
The cerebellum modulates movement of the head
and limbs so that cerebellar lesions usually result in Optic nerve—­CN II
alterations in the force, speed, and range of move­ An owner may report that a patient appears to be act­
ment of body parts including the head and neck.15 ing blind. However, a moribund, somnolent or inat­
With cerebellar disease, fine control of head posi­ tentive patient, or one with marked weakness or with
tioning is often lost, resulting in awkward, jerky loss of balance due to vestibular disease, may stumble
movements. Even at rest, the lack of control is often over objects without being blind.
seen as bobbing movements of the head, which can The visual pathway is tested by the menace response,
be exaggerated by increased voluntary effort. The whereby a mildly-threatening gesture of the hand
resulting fine jerky movements of the head are called toward the eye elicits immediate closure of the eye­
intention tremor. Such animals will overshoot when lids (Figure 2.2). In large animals, 80–90% crossing of
positioning their head, when moving to eat, for optic nerve fibers occurs at the chiasm (Figure 2.6).16
example. Newborn foals normally hold their head However, for initial, practical purposes, vision in one
flexed slightly on the neck and move it in a jerky eye can be regarded as being perceived in the visual
manner, especially in response to visual or tactile cortex of the opposite or contralateral cerebral
stimuli, rather resembling cerebellar dysfunction. hemisphere. The incoming, afferent pathway for the
22 Large animal neurology

Figure 2.6 Visual pathway.

­ enace response is the ipsilateral eye and optic

m present menace response, and the above assessments
nerve, the optic chiasm, the contralateral optic tract, are very useful to detect such lesions.
lateral geniculate nucleus in the thalamus, optic As indicated, the true menace response is a blink
radiation, and visual cortex that is mostly in the that immediately follows a visually threatening ges­
occipital lobe (Figures 2.6 and 2.9). The outgoing, ture, without necessarily being accompanied by with­
efferent pathway of the menace response is from drawal of the head (Figure 2.2). The latter visual
this contralateral visual cortex to the ipsilateral avoidance response may well not require an intact
facial nucleus effecting closure of the eyelids. With visual (occipital) cortex but most probably involves
an intact efferent pathway resulting in blinking, it is central pathways just within the brainstem and cer­
assumed that the visual input reached the visual tainly without input from the ipsilateral cerebellar
cortex. Some stoic, moribund, somnolent, and even cortex as is the case with the menace response. If
excited animals may not respond to a hand menace there is an absent menace response, then we use a
with closure of the eyelids, or they may keep the eye­ more powerful threat, after tapping the forehead sev­
lids closed. A true visual deficiency may be detected eral more times, to try to detect eyeball retraction or
while the animal moves about its environment, head withdrawal that will at least confirm a partial
when objects are placed in front of it—­a visual maze afferent visual pathway input to the brainstem but
test—­ or when nonaromatic objects are dropped not necessarily to the visual cortex. However, this
noiselessly in its visual field. Partial, unilateral blind­ can be somewhat problematic except in the most
ness can be difficult to detect and it may take repeated obliging patients. With little or no menace response
efforts, such as blindfolding each eye in turn, to but some visual avoidance response obviously pre­
determine this. Total unilateral blindness with absence sent, then facial musculature and cerebellar function
of a menace response in only one eye is usually quite requires further evaluation. Should these be without
easy to detect. However, repeated testing is usually problems, then a visual maze test may be required
necessary to confirm an asymmetric but bilaterally to ­better scrutinize visual acuity. Interpretation of
 Neurologic evaluation 23

a­ rtificial maze tests can be rather uncertain, and a ­ enacing gesture, thus demonstrating degrees of
m
decision on visual acuity often concludes with gen­ amblyopia. It has been assumed that in large animals
eral observations of the patient’s response in its envi­ the pathway for the menace response passes from the
ronment to nonauditory, nonaromatic, visual clues, occipital cortex contralateral to the visual threat, back
such as a brightly lit open doorway or gate. across the midline and through the ipsilateral cerebel­
When a visual deficit is suspected, a visual field lum, before targeting the facial nucleus ipsilateral to
deficit may be determined in large animals having the visual stimulus. It is perhaps as likely that the cer­
unilateral or prominently asymmetric cerebral or tha­ ebellum exerts both stimulatory and inhibitory influ­
lamic lesions. In describing these subtle field deficits, ences on many cerebral functions, including visual
it is necessary to be clear about two things. First, the responses.17 Cerebellar disease may well thus interfere
eye not being tested should be covered to avoid non­ with such modulating influences, thereby effecting an
specific crossover from visual stimuli. Second, the left altered, suppressed, menace response. Foals and
visual field is detected predominantly via the nasal calves appear to be able to see by a few hours of age
(medial) retina of the left eye and partly (~10–20%) but do not blink in response to a menacing gesture
via the temporal (lateral) retina of the right eye; the until several days to 2 weeks of age.18 They do blink in
latter region of the retina containing most of the neu­ response to a dazzling bright light and pull their heads
rons whose axons do not cross at the optic chiasm away from a strong menacing gesture, often in a jerky
(Figure 2.6). Likewise, the right visual field is per­ manner. These normal findings in the neonatal period
ceived predominantly via the nasal retina of the right are reminiscent of those found with cerebellar disease
eye and partly via the temporal retina of the left eye. in more mature animals.
Thus, with a prominent lesion in the right dorsal thal­
amus, right occipital radiation, or right occipital cor­ Oculomotor nerve—­CN III (parasympathetic)
tex, a patient will appear to be blind in the left eye The diameter of the pupillary aperture is controlled by
with normal pupillary responses bilaterally. The left the constrictor muscles of the pupil, which are inner­
visual field deficit may be detected as a poor or absent vated by the parasympathetic fibers in the oculomotor
menace response in the nasal retina of the left eye nerve (Figure 2.7), and by the dilator muscles of the
when using the threatening stimulus directed from pupil, which are innervated by the sympathetic fibers
the lateral aspect of the left eye and by a poor response from the cranial cervical ganglion (Figure 2.8). These
to a visual threat directed to the temporal retina of the autonomic innervations originate from centers in the
right eye with the stimulus directed from the medial brainstem, and change pupil diameter in response to
aspect of the right eye. The nontested eye should light via the oculomotor nerve, and from fear and
always be covered during these visual field tests. excitement via the sympathetic innervation (Figure 2.9).
Lesions of the eye and optic nerve result in ipsilateral The first observation of CN III function to be made
blindness. Lesions of the optic tracts and lateral genic­ is the size and symmetry of the pupillary apertures,
ulate nucleus cause contralateral central blindness with considering the amount of ambient light and the
normal pupillary function. Space occupying lesions of emotional status of the patient. The response of the
the brain frequently produce such central blindness pupils to light directed into each eye, the pupillary
(amblyopia) by interfering with the optic radiations or light responses, can be noted after observing the
visual cortex. However, with a large forebrain mass eyeballs for any lesions that may interfere with the
on one side, possibly resulting in contralateral central response of the pupil such as iritis, iris atrophy, or
blindness with normal pupils, the optic nerve may sec­ adhesions. The normal response to light directed into
ondarily become compressed on the ipsilateral (to the one eye is constriction of both pupils. This is referred
lesion) side resulting in ipsilateral peripheral blindness. to as a direct response in the same or ipsilateral eye in
Similarly, secondary compression of the oculomotor which the light is shone and a slightly less pronounced
nerve under the midbrain can cause additional mydri­ consensual (indirect) response in the other, contralat­
asis ipsilateral to such a mass lesion. eral eye. The incoming or afferent pathway for this
Animals with various diffuse cerebellar diseases reflex is similar to that for the menace response to the
have been observed to have bilaterally deficient men­ level of the brainstem. The pathway goes via the optic
ace responses. These animals are not blind, do not nerve with most axons crossing within the optic chi­
have facial paralysis that would explain the menace asm, then through the optic tracts lateral and dorsal
deficit, and they pull their head away from the to the thalamus, and finally passing ventrally into the
 Figure 2.7 Pupillary light pathway.

Figure 2.8 Ocular sympathetic pathway.

 Neurologic evaluation 25

Figure 2.9 Visual and light pathways.

midbrain. Interconnections between left and right test in dim light, and in performing the test in this
sides occur via the caudal commissure so that manner the patient becomes accustomed to the
impulses arrive at each parasympathetic oculomotor swinging bright light so that it does not blink with a
nucleus in the midbrain on both sides. The motor, dazzle response when the light reaches the retina,
efferent pathway is from these nuclei, via the oculo­ which often obscures the initial fast pupillary
motor nerves to the ciliary ganglia behind the eyeball response. If the pupil dilates when the light reaches
and to the constrictor muscles of the pupils. the second eye in this test, there must be an afferent
Because the observation of pupillary light optic lesion involving that second eye.
responses in both eyes simultaneously is awkward to The reason for further pupillary constriction
perform alone in large animals, the swinging light occurring when the light reaches the second, nor­
test is a useful alternative. The use of this test essen­ mal eye is that the direct pupillary light reflex is
tially removes the need to do consensual pupillary stronger in its effect than the indirect or consensual
light reflex testing. The swinging light test is per­ pupillary light reflex. This fact should be recalled
formed as follows. A bright focused source of light is when interpreting some complex results of testing
shone into one eye, and after pupillary constriction is vision and pupillary responses, and two other issues
completed, the light is quickly transferred to the are also worthy of iteration. First, the mydriatic
opposite eye in which further pupillary constriction effect of atropine can last for days if not weeks, pro­
is expected to occur if the eye is normal. This test is ducing confusion in evaluation and interpretation
then performed in reverse and repeated with swing­ of pupillary responses to light. Second, it appears to
ing movements of the light source, starting at say take a more complete optic nerve or chiasmal lesion
30 cm from the eyes and moving step-­wise closer to to cause observable mydriasis even with poor vision
say 5 cm from the eyeball. It is best to perform this and a poor or even absent menace response, most
26 Large animal neurology

particularly with bilateral lesions. Consider for following injury. Progressive, bilateral, pupillary dilation
example a yearling colt with obvious bilateral blind­ following cranial injury warrants a grave prognosis.
ness when in its environment, that followed head
trauma occurring after rearing and falling over Sympathetic innervation to the eyes and head
backward onto the poll and suffering from bilateral, Although not classical cranial nerves, these neu­
focal, traumatic optic neuropathy. The colt may still ronal fibers are involved in pupillary function and
have essentially appropriate, mid-­sized pupils that can be conveniently considered here. Nuclei within
even respond somewhat to a bright light. Evaluation the brain that control sympathetic motor function
of partial, especially asymmetric lesions such as are in the hypothalamus, midbrain, pons, and
this can be problematic unless this factor is medulla oblongata. First-­ order neuronal fibers
appreciated. descend through the midbrain, medulla, and cervi­
These pupillary light reflexes are within the brain­ cal spinal cord to synapse on cell bodies in the lat­
stem and thus are not affected by lesions involving the eral intermediate gray columns in the thoracolumbar
cerebral visual cortex (Figure 2.9). A widely dilated, spinal cord. The preganglionic, second-­order, sym­
mydriatic pupil in an eye that has normal vision sug­ pathetic cell bodies supplying the head and neck are
gests an oculomotor nerve lesion; the pupil being situated in this position in the cranial thoracic seg­
unresponsive to light directed into either eye. The ments, T1–T3. Axons leave these segments of the
pupil in the contralateral eye, with normal oculomotor spinal cord, traverse the cranial thorax,19 ascend the
function, responds to light directed into both the ipsi­ neck in the cervical sympathetic trunk adjacent to
lateral eye (direct response) and the contralateral eye the vagus nerve, and pass to the cranial cervical
(consensual response). The oculomotor nerves are ganglion that lies under the cranial part of the atlas.
subject to damage following diffuse brain swelling and In the horse, this ganglion is on the caudodorsal
from space-­occupying lesions in the forebrain. Both wall of the medial compartment of the guttural
processes can cause pressure to be exerted ventrally pouch. Postganglionic, third-­ order, sympathetic
onto the brainstem and these nerves can be damaged fibers leave the cranial cervical ganglion to inner­
as they lay between the midbrain and the basilar bones. vate the glands, smooth muscles and blood vessels
With asymmetric swelling of cerebral tissue, greater of the eyeball, and the head and cranial cervical area
pressure may be applied to one oculomotor nerve at the level of C1 and C2 (Figure 2.10). Sympathetic
resulting in unequal pupils or anisocoria, which is usu­ fibers supplying the skin of the neck from C2–C8
ally evident as ipsilateral pupillary dilation. A severe leave the parent bundles in the thorax and pass cra­
brainstem contusion can produce various pupillary nially as the vertebral nerve with the vertebral ves­
abnormalities in association with coma or semicoma, sels all running within the lateral vertebral foramina
and these can change rapidly in the first few hours to join the segmental vertebral nerves supplying
each cervical dermatome.
Damage to the sympathetic supply to the eye and
its associated structures results in slight ptosis of the
When reporting results of pupillary function and light
upper lid, a miosis or constriction of the pupil, slight
responses, it removes considerable confusion to
enophthalmos, and a slight protrusion of the nictitat­
describe what happens to each pupil when light is
ing membrane. Vision and the pupillary light
shone in each eye in turn and not to use the terms
responses are unaffected. In most species, this is
direct and consensual or indirect responses. Thus, with
referred to as the Horner syndrome. Prominent in
a left-­sided retrobulbar abscess involving left CN III
horses is a resulting change in eyelash angle that
parasympathetic fibers or ciliary ganglion or nerve, as
occurs due to loss of innervation of eyelid muscles
well as the left optic nerve, the unambiguous descrip-
under sympathetic control, especially the m. arec-
tion would be as follows. The patient is blind in the left
tores cilliorum, all of which help maintain a relatively
eye only and has no menace response in the left eye
horizontal eyelash angle.
with normal facial nerve function and normal palpebral
In the horse at least, lesions involving the sympa­
reflexes. The left pupil is widely dilated, and light
thetic supply to the head result in these ophthalmic
directed into the left eye causes no response in either
signs, as well as additional signs consisting of dila­
pupil. Light directed into the right eye causes the right
tion of facial blood vessels, hyperemia of nasal and
pupil to constrict but the left pupil remains dilated.
conjunctival mucous membranes, and increased
 Neurologic evaluation 27

e­xtending down to the level of the shoulder with

involvement of other thoracic sympathetic nerves in
addition to the cranial cervical sympathetic trunk.
Selective lesions in the neck involving segmental
branches from the paravertebral nerve that passes up
the vertebral lateral foramina can result in linear
saddles of sweating over the neck between C3 and C8
dermatomal segments. Although extremely rare,
lesions of the spinal cord involving the descending
sympathetic pathway can result in eye involvement
and sweating of the whole side of the body ipsilateral
to the lesion. This is because all the sympathetic fib­
ers leaving the spinal cord have lost their central
motor neuron connections and are thus decentral­
ized and nonfunctional.
The reason for sweating with cutaneous sympa­
thetic denervation in horses is not entirely clear as
equine skin probably has predominantly cholinergic,
not adrenergic neural supply, and although nerve
endings are close to sweat glands and their accompa­
nying prominent small blood vessels, they may not
actually innervate the glandular secretory cells.20 An
explanation is that loss of sympathetic supply results
in cutaneous vasodilation that brings more circulat­
Figure 2.10 Sympathetic pathways showing outflow from CNS to face,
ing adrenalin to the sweat glands, and this hormone
neck, and trunk. has a powerful sudomotor effect in that species.
Cattle that have lost the sympathetic supply to the
temperature and sweating of the face. Sweating is head show the same signs involving the eye and peri­
most prominent at the base of the ear—­due to a high orbit, dilated blood vessels over the pinna, and a lack
sweat gland population there—­and can extend a of sweat production on the muzzle. Only eye signs
variable distance down the neck dependent upon the have been detected with sympathetic denervation of
exact lesion site. Ptosis is the eye sign most consist­ the head and neck in sheep and goats, although this
ently observed in large animals, and this may be the could be studied with greater diligence.
only sign with retrobulbar sympathetic involvement
but usually accompanied by periorbital sweating in Sympathetic innervation to the trunk
horses. However, with more proximal lesions of the Other first-­order neuronal fibers descend through
sympathetic supply to the head in horses, there is the midbrain, medulla, and cervical spinal cord to
usually prominent sweating and vasodilation of the synapse on second-­order cell bodies in the lateral
sympathetically denervated skin.20, 21 Lesions in the intermediate gray columns in the thoracolumbar spi­
region of the guttural pouch and cranial cervical nal cord to leave the T-­L spinal cord segmentally,
ganglion will result in sweating of the face and the supplying the sympathetic trunk that supplies third-­
cranial neck down to the level of C2.22 Most likely order neurons to glands (including the adrenal) and
the postganglionic fibers follow branches of the blood vessels over the trunk and remainder of the
trigeminal nerve, thus some lesions of these branches body. Damage anywhere along this pathway can
have resulted in localized sweating of the rostral face result in diffuse (proximal lesions) or selective (more
only with infraorbital involvement of the maxillary distal lesions) sweating over the caudal body.
branches in the absence of signs of eye involvement.
Lesions further down the neck involving the sympa­
Is it not interesting to ponder the systemic effects of
thetic trunk may result in sweating of the face and
decentralizing the adrenal medulla on one or both
the neck extending down to the level of C3. Lesions
sides?
in the thoracic inlet can result in this sweating
28 Large animal neurology

Oculomotor nerve—­CN III; trochlear nerve—­CN e­ yeballs resulting from a disturbance of the vestibular
IV; abducens nerve—­CN VI system that alters the normal tonic mechanism con­
In addition to parasympathetic innervation of the trolling eye position. This strabismus is usually ipsi­
pupillary constrictor smooth muscles, the oculomo­ lateral to the vestibular lesion and most often is
tor nerve also innervates the somatic extraocular ventral, but may be medial. The important difference
muscles, along with the trochlear and abducens is that the eyeballs can be moved out of this position.
nerves. The function of these muscles and nerves is Periorbital lesions, particularly those of trauma and
tested by observing the normal position of the eyes neoplasia, often result in mechanical eye deviations.
within the bony orbits and by observing eye move­ The eyeball position of newborn foals often is rotated
ment. An abnormal eye position or strabismus results ventromedially relative to that of adult horses.18 Also,
when these nerves or muscles are damaged. Physical animals that are congenitally blind may have abnor­
deformity of the bony orbit and prominent, particu­ mal eyeball positioning and movement.
larly congenital, blindness all can result in degrees of By observing the corneal reflex, one can assess
abnormal eye position. sensation from the cornea in the ophthalmic branch
When evaluating eye position and movement, of the trigeminal nerve (see below) and the ability to
consideration must be given to the normal response retract the eyeball. The latter is purportedly mediated
of the eyes to head posture and movement. When the by just the retractor oculi muscle innervated by the
nose of a large animal is elevated to extend the head, abducens nerve CN VI. However, full eyeball retrac­
the eyes tend to maintain a horizontal axis and thus tion in large animals may require full function of all
move ventrally in the bony orbits. As the head is extraocular muscles innervated by CNs III, IV and
moved to one side, the eyes move in a rhythmical VI to be effective. This reflex can be usefully tested by
manner until head movement stops. There is slow pressing on the closed eyelids while palpating for
phase movement in the direction opposite to the reflex eyeball retraction, thereby avoiding potential
direction of head movement, followed by a fast (catch- corneal damage.
up) phase in the direction of head movement. These
eye movements are regarded as physiologic vestibular Trigeminal nerve—­CN V
nystagmus and result from the connection from the This large, well-­ protected cranial nerve contains
vestibular apparatus in the inner ear and the medul­ motor nerve fibers that innervate the muscles of mas­
lary vestibular nuclei to the nuclei of the cranial tication in the mandibular branch, as well as sensory
nerves controlling eye movement, CNs III, IV and VI. nerve fibers from most parts of the head in mandibu­
Normal inducible vestibular nystagmus thus requires lar, maxillary, and ophthalmic branches.
an intact vestibular system, intact cranial nerves III, The total loss of motor function of the mandibular
IV, and VI, and the connections between all of these nerve bilaterally results in a relaxed, flaccid, and low­
in the medial longitudinal fasciculus. ered jaw and an inability to chew; it is quite rarely
The forms of strabismus described for paralysis of seen, but occurs in large animals. The tongue pro­
each of these cranial nerves should be present in all trudes because it drops forward in the mouth.
positions of the head. Such examples of true strabis­ Drooling results because of the lack of jaw move­
mus are not often encountered in large animals. ment. After 1–2 weeks, atrophy of the temporal, mas­
Mydriasis is seen with oculomotor nerve disease, and seter, and pterygoid muscles results. Asymmetric
a tendency for lateral eyeball deviation has been lesions cause asymmetric muscle atrophy and a
observed in horses with midbrain lesions presumably slightly deviated lower jaw without dysphagia that
involving the oculomotor nuclei. The dorsomedial, can become prominent with major dental problems
rotational positioning of the eyeball seen in many dif­ due to irregular dental ware.
fuse brain diseases in ruminants such as polioenceph­ Normal horses frequently have visible asymmetry
alomalacia and meningitis has been ascribed to the of the temporalis musculature (Figure 2.3). Most
involvement of the trochlear cranial nerve IV. This often this would appear to be a difference in the
may not however be due to a true trochlear paralysis attachment of the origin of the muscle at the dorsal
as the eyeballs can be moved from this position by crests of the temporal fossae of the parietal bones
moving the head, suggesting that the dorsal oblique and is often associated with marked, asymmetric
muscle and CN IV are functional. What is most fre­ dental problems with some asymmetry in muscle
quently seen in large animals is a deviation of the bulk. Any loss or gain in ­tissue bulk in, around, or
 Neurologic evaluation 29

behind one orbit results in asymmetric supraorbital Facial nerve—­CN VII

fossae, and this can be used as a barometer for such This is predominantly a motor nerve innervating the
abnormalities, including modest atrophy of chew­ muscles of facial expression, as well as the lachrymal
ing muscles resulting from a trigeminal lesion. and certain salivary glands. It contains the final
Marked, asymmetric dental disease does cause motor neurons for movement of the ears, eyelids,
asymmetry to the depth of the supraorbital fossae lips, and nostrils, including the motor pathways of
Function of the sensory branches of this cranial the menace, palpebral and corneal reflexes. Unilateral
nerve is tested reflexly and directly by assessing facial paralysis is generally seen as drooping of an ear,
­sensation to the head. Movement of the ear, eyelids, ptosis of an upper eyelid, drooping of the upper lip,
and lower lips, in response to blunt stimulation of the and pulling of the affected nostril toward the unaf­
face, is mediated via the sensory branches of the fected side. General inspection of the symmetry of
trigeminal nerve and the motor branches of the facial facial expression is useful. Some normal horses have
nerve. Thus, these reflexes require an intact brain­ an asymmetric contour of the external nares and
stem and trigeminal CN V sensory and facial CN VII slight deviation of the nostrils to one side. Very close
motor nuclei and nerves, but do not require the ani­ inspection is required in production animals to
mal to feel the stimuli. Perception of sensation from detect a partial facial paresis because of the presence
the head should be assessed in the distribution of of collagenous facial structures compared to horses.
each of the major branches of the trigeminal nerve by Comparison of tone in the ears, eyelids, and lips on
observing a behavioral response such as head shak­ each side helps to detect facial weakness, especially
ing in response to mild noxious stimuli applied to when the patient is relaxed. Occasionally, a small
the facial regions innervated by the mandibular, amount of food may remain in the cheeks on an
maxillary, and ophthalmic branches of CN V. The affected side. This must not be confused with diffi­
mandibular branch certainly supplies sensory inner­ culties with swallowing that result from sensory and/
vation for the major part of the rostral tongue in or motor trigeminal paralysis and from pharyngeal
horses. In most patients, especially stoic or obtunded dysfunction. Because of a lack of muscle tone in
animals, general cerebral perception of such stimuli cheek and lips, saliva may drool from the commis­
may be best assessed from lightly probing the inter­ sure of the lips with facial paralysis. If only weakness
nal nares and particularly the nasal septum. Lesions of the lips and a deviated nasal philtrum without a
of the sensory nucleus of the trigeminal nerve in the drooped ear and ptosis occur, probably only the buc­
lateral medulla oblongata can cause hypalgesia and cal branches along the side of the face are involved.
hyporeflexia of the face, without weakness of the Mild weakness of facial muscles can often be felt
muscles of mastication. This may result in feed rather than seen and will also become more evident
impacting in the rostral cheek pouch. In distinction when the patient is resting quietly or has been tran­
to this, and especially in horses, prominent cerebral quilized. Involvement of one or two, but not all three
and thalamic lesions can produce contralateral facial branches of the facial nerve more commonly occurs
hypalgesia without facial hyporeflexia, being most with peripheral facial nerve diseases such as poly­
evident in the nasal septum. This is due to the neuritis or head trauma. However, central lesions can
involvement of the sensory pathways in the rostral selectively involve individual regions of the facial
brainstem and thalamus or to the parietal, sensory nucleus thus mimicking peripheral nerve disease, at
cerebral cortex, while sparing the trigeminal nuclei least in diseases such as equine protozoal myeloen­
and reflex pathways in the brainstem. cephalitis and listeriosis.
Detection of nasal hypalgesia in the form of slight As with other cranial nerves, a diagnosis of CNS
asymmetry in the behavioral or avoidance response disease, compared to peripheral nerve involvement,
to a stimulus applied to the nasal septum can take can be made by identifying involvement of adjacent
considerable patience and should be confirmed by structures in the medulla oblongata when signs such
repeated testing. However, confirmation of this clue, as lethargy, limb weakness and ataxia, and a head tilt
along with the presence of asymmetric menace will often result. With lesions of the inner ear, which
responses and an asymmetric hopping response in cause vestibular signs, there is often accompanying
the thoracic limbs, may be the only subtle evidence facial nerve paralysis because of concurrent middle
needed to help confirm the presence of asymmetric ear involvement, and the facial nerve is only sepa­
forebrain disease. rated from the tympanic cavity by a thin membrane.
30 Large animal neurology

Lack of any involvement of other central pathways is intact and may be hyperactive. Irritative lesions, such
used to differentiate signs of such peripheral facial as viral encephalitis, meningitis, and facial neuritis,
and vestibular nerve disease from involvement of can also cause spontaneous and reflexly induced
their nuclei and their pathways in the medulla oblon­ facial grimacing.
gata. Exquisitely focal lesions resulting from agents
such as Sarcosystis neurona and Listeria monocytogenes Vestibulocochlear nerve—­CN VIII
can exceptionally destroy single and multiple central The cochlear or auditory division of this nerve trans­
nuclear regions causing signs of selective cranial nerve mits impulses involved with hearing. Bilateral middle
dysfunction without producing clinical evidence of ear disease causes deafness, but unilateral hearing
adjacent brainstem involvement, thereby mimicking loss would be difficult or impossible to detect clini­
peripheral cranial nerve disease. cally in large animals without the use of auditory
Of some note here is involvement of the parasym­ evoked potential recordings.
pathetic greater petrosal branch of the facial nerve The vestibular division of CN VIII supplies the
innervating the lacrimal gland. Lesions affecting this major input to the vestibular system (Figure 2.11),
component of the facial nerve anywhere from the thereby controlling balance. Fibers from the inner
medulla oblongata to the back of the eye often result ear pass through the internal acoustic meatus in the
in a dry eye. Subsequent development of keratocon- petrosal bone and penetrate the lateral medulla
junctivitis sicca can mean the loss of an eye, making oblongata to terminate in the vestibular nuclei. A few
early detection of such a sign most important. fibers pass to small areas in the ventral cerebellum
With various thalamic and cerebral lesions in that are part of the vestibular system. The vestibular
horses, the facial muscles may be hypertonic and system receives input from the inner ear and func­
facial reflexes may be hyperactive, resulting in tions by controlling orientation of the head, body,
spontaneous and reflexive grimacing of the face. limbs, and eyes in space and with respect to gravity.
This is due to the involvement of the central motor Signs of vestibular disease can be seen with lesions
pathway controlling facial movement that normally involving any part of the vestibular system. The eye­
influences the facial nucleus and facial reflexes. balls are checked for normal vestibular nystagmus
Importantly, even in the presence of poor facial when the head is moved from side to side. The pres­
expression and control, the facial reflexes are still ence of spontaneous nystagmus seen with the head in

Figure 2.11 Vestibular system.

 Neurologic evaluation 31

a normal position, and positional nystagmus seen Glossopharyngeal nerve—­CN IX; vagus nerve—­CN
with the head held still in various abnormal positions, X; accessory nerve—­CN XI
indicate a disorder of the vestibular system. In uni­ A major function of these cranial nerves is achieved
lateral peripheral vestibular system disorders, the fast through innervation of the pharynx and larynx with
phase of any nystagmus is quite consistently directed both sensory and motor fibers. This is tested by lis­
away from the side of the lesion and away from the tening for normal laryngeal sounds, observing nor­
direction of the head tilt. It is usually horizontal, mal swallowing of food and water, assessing the
although it may be rotary or arc-­shaped. Only in a few swallowing reflex by passage of an esophageal tube,
horses with peracute signs of bilateral vestibular and finally by inspection of the larynx and pharynx
neuritis, histologically consistent with polyneuritis manually and preferably with the aid of an endo­
equi, transient, dorsally directed nystagmus has been scope. The major centers for control of the pharynx
observed with a peripheral—­in this case bilateral—­ and larynx via these three cranial nerves are the
vestibular disorder. With lesions involving the nucleus ambiguus and nucleus solitarius in the cau­
­central components of the vestibular system in the dal medulla oblongata. The most important clinical
medulla oblongata, spontaneous and positional signs of dysfunction are related to paralysis of the
nystagmus may be horizontal, vertical or rotary, and pharynx and larynx, and the severity of signs depends
may change direction with changes in head posture. on whether there is unilateral or bilateral involve­
Such lesions frequently affect adjacent structures, ment. In pharyngeal paralysis, usually food, water,
such as the proprioceptive and motor pathways for and saliva can be seen at the nostrils in horses, and at
voluntary limb movement, and the reticular forma­ the nostrils and mouth in ruminants, and spilling
tion, resulting in ataxia and tetraparesis, and somno­ onto the floor. During exercise, unilateral paralysis of
lence, respectively. Particularly with acute peripheral the larynx results in an abnormal respiratory noise—­
vestibular disease, signs often improve within several so-­called roaring in physically active horses, but is
days because of accommodation, mediated by other usually subclinical in sedentary animals. Stertorous
inputs to the vestibular system including propriocep­ breathing may be detected with diseases that cause
tive modalities and especially vision. By blindfolding bilateral pharyngeal or laryngeal paralysis.
a patient that has accommodated to its vestibular In the horse at least, the thoraco-­laryngeal adduc­
disease, signs frequently become exacerbated imme­ tor response, or slap test (Figure 2.12), should be
diately. Additionally, blindness interferes with recovery performed.26 The skin just caudal to the dorsal aspect
from vestibular disease. of the scapula is slapped firmly with a hand while the
On rare occasions, central unilateral or asymmet­ horse is exhaling, and while the larynx is observed
ric CNS lesions, particularly if in the region of the with an endoscope, the normal response being brief
caudal cerebellar peduncle, may result in paradoxical adduction of the contralateral arytenoid cartilage.
vestibular signs. This is seen as any head tilt and cir­ Contraction of the contralateral dorsal and lateral
cling being away from, and the fast phase of nystag­ laryngeal musculature over the muscular process of
mus being toward, the side of the lesion. Defining the the arytenoid cartilage can also be palpated with the
side of such a lesion will depend on identifying other fingers while the withers are slapped. This has been
signs of cerebellar and/or medullary disease. detected in cooperative foals as early as 2 weeks of
A rather forgotten component to the vestibular age. Usually, this response can be felt externally as a
system is proprioceptive input from the cranial cervi­ slight tap or muscular contractions under the fingers.
cal vertebrae, ligaments, and muscles.23,24 From this The afferent pathway is through the segmental dorsal
region, afferent fibers pass via at least the C1–3 dorsal thoracic nerves to the spinal cord, cranially in the
spinal nerve roots to ascend the spinal cord to the contralateral cervical spinal cord white matter, and
caudal part of the medial vestibular nuclei that thus to the contralateral vagal motor nucleus in the
receive no other afferent inputs (Figure 2.11).25 Like medulla oblongata. From there, the efferent path­
damage to the vestibular nerve, lesions involving way is through the contralateral vagus nerve to the
these cervical nerves or the cervical spinal input to cranial thorax and then back up the neck in the
the vestibular apparatus can result in signs of vestibu­ recurrent laryngeal nerve to the larynx. The reflex
lar disease. This certainly can be seen with asymmet­ can be interrupted at any of these sites.
ric lesions of the dorsal nerve roots of C1–3 when loss Lesions in the nucleus ambiguus and in the swal­
of balance, eye deviation, and a head tilt can be seen. lowing center of the medulla oblongata usually
32 Large animal neurology

Figure 2.12 Pathway for the thoracolaryngeal

response test.

affect adjacent structures causing degrees of som­ Hypoglossal nerve—­CN XII

nolence, ataxia, weakness, and signs of involvement This last cranial nerve has its cell bodies in the hypo­
of other cranial nerve nuclei. Many severe, diffuse glossal nucleus of the caudal medulla oblongata. It is
brain diseases can result in dysphagia without the motor nerve to muscle of the tongue. Thus, the
lesions in the medulla oblongata, which is the result tongue must be inspected for symmetry, normal
of interference with the voluntary central motor movement, and evidence of atrophy. Normally, there
neuronal control of swallowing. Because of their is a strong resistance to withdrawing the tongue from
close association with the guttural pouch, CNs IX, the mouth in all species. A unilateral lesion of the
X and XI can be involved with guttural pouch dis­ nucleus or nerve results in unilateral atrophy of the
eases. Finally, dysphagia is seen with diseases tongue, with weak retraction; however, the tongue
affecting pharyngeal muscles as well as the diffuse usually will not remain protruding from the mouth
neuromuscular paralysis of botulism and the hyper­ and cause minimal interference with eating and
tonicity of tetanus. drinking. Bilateral involvement interferes with pre­
Most tall horses over 1.6 m (16 hands) have a pal­ hension and swallowing, the tongue usually pro­
pable asymmetry to the laryngeal musculature, irre­ trudes, and the animal is not able to withdraw it back
spective of whether they have an asymmetric into the mouth. Horses that habitually play with their
thoracolaryngeal reflex or make abnormal respira­ tongue using their lips and jaws are referred to as
tory noises during exercise. This finding, along with tongue chewers or tongue suckers and appear to have
results of testing the thoracolaryngeal reflex, there­ poor tone in this organ although it functions per­
fore needs to be interpreted cautiously; a negative fectly normally (Figure 2.13).
right-­to-­left test result being of no real additional In adult large animals with a lowered mandible
clinical value in such patients. (dropped jaw), from say mandibular fractures or
bilateral motor trigeminal lesions, the tongue can be
Accessory nerve—­CN XI seen to rest rostrally between the separated jaws.
This nerve is motor to at least the trapezius and cra­ Also, with severe forebrain lesions that result in som­
nial part of the sternocephalicus muscles. Loss of nolence, but without focal brainstem involvement,
function is difficult to detect, in horses at least, the tongue may remain protruded and be slow to
­without an electromyographic study. Some cases of return to its normal position when pulled out of the
cervical scoliosis, associated with lesions such as mouth. This is the result of a lesion in the central
those with listeriosis and equine protozoal myeloen­ motor centers in the forebrain or thalamus control­
cephalitis, may involve the accessory nuclei. ling hypoglossal function. The voluntary control
 Neurologic evaluation 33

pathways for function of the tongue are interfered

with, without involving the hypoglossal nuclei or In other words, non-­n eurologic problems should
nerves, causing weakness without atrophy, be always considered as being a component of
any gait abnormality, and these often confound
Interpretation of signs of spinal cord disease interpretation of gait and posture evaluation.

Gait and postural abnormalities The essential components of neurologic gait and
Musculoskeletal and painful disorders causing gait and postural abnormalities are paresis and ataxia, and
postural disorders are far more commonly encountered considerable effort needs to be made to define the
in large animals than are those involving just the presence, characteristics, and severity of these find­
nervous system (Figure 2.13). Thus, two questions to be ings when evaluating patients suspected of suffering
answered when evaluating gait and posture are, first, neurologic disorders. In our experience, the most
which limbs are abnormal, and second, is there evi­ frequent mistake made in observing for, describing,
dence of lameness suggesting a musculoskeletal or and teaching about characteristics of gait and pos­
painful component of any gait or posture abnormality? tural abnormalities is failure to describe accurately
what is seen, before interpreting what any abnormali­
ties might represent. Thus, we do not see ataxia,
weakness, lameness, and pain, but we do see irregular
and unpredictable foot placement, toe dragging,
head nodding, and abnormal postures, respectively,
that can be interpreted as such.

It is important to firstly describe in non-­technical

terms exactly what is abnormal with gait and pos-
ture before interpreting changes as being due to
ataxia, weakness or lameness.

Paresis or weakness can be defined as poor ability

to initiate a gait, to maintain a posture, to support
weight of the body or its parts, and to resist gravity.
Often it can be determined that such weakness is pre­
dominantly involving extensor or flexor muscle
groups or both. As a generality, extensor, antigravity
weakness is most indicative of final motor neuron
paresis. Dependent on where the lesion is, this is
often seen as a bouncing gait with a short-­stride
length, trembling, buckling and bunny hopping, and
a lowered neck carriage. This can result in an appar­
ent weight-­bearing lameness due to the exaggerated
head nodding, particularly when it is asymmetric.
For clarification, bunny hopping is a nonspecific gait
characteristic, more often seen with musculoskeletal
Figure 2.13 Heavy patients with various neuromusculoskeletal disor-
ders can have difficulty rising. Such patients, especially ruminants and
disorders. When representing paresis, bunny hop­
pigs that adopt a dog-­sitting posture for several seconds to minutes ping likely reflects the added weight support offered
while getting up, usually have lesions caudal to the thoracic limbs and to when two limbs are used together.
T2. However, adult ruminants are seen to rest in the field in such a In distinction, central motor pathway paresis is
­posture without having an overt neuromusculoskeletal explanation. often seen as a delay in initiating movement, there­
Also, occasionally patients such as this horse suffering from mild caudal
cervical spinal cord compression caused by CVM may also adopt and
fore usually involving flexor muscles. Thus, a slow
maintain such postures. This horse was also a tongue sucker (see onset of the protraction or swing phase and a swing­
Chapters 5 and 18). ing, longer stride with decreased joint flexion
34 Large animal neurology

(degrees of hypometria) are characteristics of central not a contest between examiner and patient! For this
motor pathway paresis. Paradoxically, patients with assessment, it is best to apply constant lateral tension
this kind of weakness retain strong reflex extensor to the tail and determine what voluntary pull the
tone and strongly resist against dorsal pressure, thus patient exerts against that tension while it is weight-­
often being described as spastic paresis. bearing on the nearest limb during the stance phase.
Based on this, with a prominent C6–T2 lesion
involving gray and white matter in a smaller patient, Interpretation of results of tail pull test
one can see a very characteristic gait whereby there is
a short-­stride, bouncing gait in the thoracic limbs • Abnormal standing test: Suggestive of ipsilateral final
and a slower, long-­stride with toe dragging in the pel­ motor neuron lesion, L3 to S2 gray matter or nerves.
vic limbs. This can be called a two-­engine gait, with • Normal standing and abnormal walking tests:
final motor neuron, extensor paresis in thoracic Lateralizing only, ipsilateral brainstem to S2 central
limbs and central motor pathway, flexor paresis in motor and/or general proprioceptive pathways.
pelvic limbs.
The tail and halter pull test is performed by pulling
on a lead rope and on the tail while circling the horse
Such two-­engine gaits that can be seen with p­ rominent
around the examiner who is testing a postural reac­
C6–T2 lesions involving gray and white matter can also be
tion and also evaluating voluntary strength. In addi­
seen, probably less often, with forebrain, b­ rainstem, and
tion, it can exaggerate a patient’s tendency to pivot on
cervical, thoracic and lumbar spinal cord lesions. Thus,
a hindlimb demonstrating either flexor weakness or
this syndrome is not pathognomonic for C6–T2 lesions.
hypometria and to exacerbate maneuvering limbs in
an ataxic fashion. Again, ease in pulling the patient
In addition to observing for signs of abnormal gait to the side during circling occurs usuall because of
and posture indicative of weakness, the three most weakness resulting from central motor pathway
useful postural reaction tests for determining the involvement, from a lesion that involves final motor
presence of weakness in the limbs of a horse suffering neurons in either ventral horn gray matter level with
from spinal cord disease are the tail pull, the tail and the limb or the peripheral nerves, from a lesion
halter pull, and thoracic limb hopping. Pulling the tail involving muscle, or as a result of a painful process.
while the patient remains standing initiates an exten­ With final motor neuron, muscle, and painful condi­
sor, quadriceps contraction, mimicking the perfor­ tions, extensor weakness is often profound, and it is
mance of a patellar reflex. As an example, this reflex is easy to pull such a patient to the side while it is stand­
poor when there is a final motor neuron lesion at the ing still and while circling. In contrast, a weak animal
level of L4–5, and therefore such a patient will demon­ with a lesion of the central motor pathways can usu­
strate weakness in poorly resisting a tail pull while ally reflexly fix the limb in extension when pulled to
standing still as well as voluntary weakness with poor one side by the halter and tail, whereas while circling,
resistance offered while the patient is moving. In con­ the patient does not have the voluntary motor strength
trast, an example of a wobbler horse with a central necessary to forcibly resist against the examiner’s pull.
motor pathway cervical lesion will have good resting Hopping a patient laterally on one thoracic limb
muscle tone and will be difficult to pull to the side by while the pelvic limbs are free to move may reveal that
the tail in a singular progressive movement while a horse is weak by a tendency for it to tremble on a
standing still, but will easily be pulled to the side while thoracic limb when the opposite thoracic limb is held
walking. The first example demonstrates depressed up to initiate the hopping test. Such a patient will also
extensor reflexes in the pelvic limbs, while the wobbler have difficulty in hopping to the side and may stumble
demonstrates intact or even hyperactive extensor when pushed away with the examiner’s shoulder;
reflexes in the pelvic limbs in the face of voluntary, this test being best performed on soft ground.
central motor pathway weakness. Ease at causing the Flexor paresis is often evident when an animal drags
patient to sway sideways with lateral pull on the tail its toes, has worn hooves, and has a low arc and long
likely reflects the loss of hindlimb strength and/or pro­ swing phase to the stride. When an animal bears weight
prioceptive abilities. However, the tail pull test is very on a limb demonstrating extensor weakness, the limb
useful in detecting extensor weakness in the ­pelvic often trembles and the animal may even collapse on
limbs, but it is often performed far too vigorously; it is that limb because of the lack of support. While circling,
 Neurologic evaluation 35

walking on a slope, and walking with the head elevated, The patient is observed while standing still, walk­
such an animal frequently will stumble on a limb hav­ ing, trotting, turning tightly, and backing up, and
ing extensor weakness and will knuckle over at the fet­ while the patient moves in a serpentine path with the
lock. This compares nicely with the patient having head held elevated and while moving on a slope. The
central motor pathway weakness, and ataxia, that walks best way of accomplishing the latter maneuvers is to
stiff legged with the thoracic limbs but usually without walk backward in a zigzag manner while holding the
knuckling over at the fetlock. lead rope high to extend the patient’s head and neck.
With severe weakness in all four limbs, but with no The aim is to alter the intended direction of the
ataxia, neuromuscular disease must be considered. patient’s limbs while they are in protraction by turn­
Profound weakness in only one limb is suggestive of ing the lead abruptly such that there must be a change
a peripheral nerve or muscle lesion in that limb. in direction of each foot to be placed in the site the
Weakness occurs with central motor pathway lesions examiner intends for it to be placed. Some horses will
in the brainstem and spinal cord, and it is present in not obligingly turn in tight or even large circles for
the limb(s) on the same side and caudal to the lesion. examination. With practice, circling can be best
A patient with a peracute peripheral vestibular syn­ accompanied by walking the horse forward and then
drome may appear weak in the limbs on the same starting to turn in one direction slowly making the
side as the lesion because of the decreased extensor turn slightly tighter as the examiner moves from in
tone and tendency to fall in that direction and the front of the horse to level with the shoulder, then to
increased extensor tone in the contralateral limbs. It level with the middle of the trunk, while coaxing the
can be difficult to be sure that a patient with promi­ horse by flicking the rump with the free end of the lead
nent ataxia but no pathologic evidence of motor rope. This way the patient turns around the examiner,
pathway problems such as with cerebellar abiotrophy not the examiner around the horse. Essentially, these
or perennial ryegrass toxicity is not clinically weak. maneuvers comprise the postural reaction tests for large
Such patients can be readily made to move laterally animals. These tests alter input to the central motor
with constant tail pulling but will pull forcibly against pathways through changes in many modalities, includ­
such lateral pull when standing and when the lateral ing the visual horizon, vestibular stimulation, and neck
force is applied firmly only when the limb is in the and limb proprioception, that is synthesized with cer­
propulsive phase of stride. ebellar input into refined motor system signals. Subtle
neurologic abnormalities, which may be compensated
for under conditions of normal gait, are exaggerated
Markedly asymmetric weakness and/or pain can result during these maneuvers. Ataxic movements can be
in the sidewinder syndrome with the patient “crab seen as irregular and mostly unpredictable foot flight
walking” or moving “on two tracks”14 (see Chapter 25). and placement. To detect subtle asymmetry in limb
protraction and the length of stride, it can be useful
Ataxia is a term that, by its Greek derivative, means to walk parallel to, or behind the animal, matching
a lack of order or an inconsistency. In this context, step-­for-­stride. An ataxic gait is sometimes most
ataxia is a proprioceptive dysfunction causing abnor­ pronounced when an animal is moving freely in a pad­
mal rate, range and force of movement, and place­ dock especially when attempting to stop abruptly from
ment of the limbs and other body parts, including a trot or canter when the limbs may be wildly adducted
head, neck, trunk, and even at times the eyes. Ataxia or abducted.
thus essentially reflects changes in function of the Three descriptors are often used to characterize
subconscious proprioceptive mechanisms. What the the inconsistent movements that comprise ataxia.
examiner must see to interpret as ataxia is irregular Hypermetria is used to describe a lack of direction
and mostly unpredictable movement and placement and increased range of movement, and is seen as an
of the limbs, head, neck, or trunk. overreaching of the limbs with excessive joint flexion.
Hypermetria without paresis is characteristic of spi­
nocerebellar and cerebellar disease. Hypometria is
It is important for the examiner to observe the patient
seen as a stiff movement of the limbs with little flex­
performing these maneuvers from a distance and also
ion of the joints, particularly the carpal and tarsal
from close-­up by handling the patient oneself while
joints. This is generally indicative of increased exten­
making it perform the same maneuvers.
sor tone, and of a lesion affecting the central motor,
36 Large animal neurology

or spinocerebellar pathways from that limb. A hypo­ often exaggerates ataxia, particularly in the pelvic
metric gait, particularly in the thoracic limbs, is seen limbs. This maneuver also frequently allows the
best when the animal is backed up or when it is expression of a hypermetric or a hypometric compo­
maneuvered on a slope with the head held elevated. nent of ataxia in the thoracic limbs. When a weak and
The thoracic limbs may move almost without flexing ataxic animal is turned sharply in circles, it leaves the
and resemble a marching tin soldier. The short-­ affected limb in one place while pivoting around it,
stride, staggering gait seen with vestibular disease particularly so for the pelvic limb. This may also
may be considered hypometria. Also, movement of a occur when backing up.
limb with prominent flexor weakness, as with botu­ Ataxia can also be classified into three syndromes
lism, can result in poor joint flexion and dragging of by the quality of the signs seen and the system or
toes as with hypometria, but the abnormal move­ pathway involved in the nervous system. These are
ment and placement of the weak limb is relatively subconscious proprioceptive or spinal ataxia, cere­
repetitive and predictable. Finally, dysmetria is a term bellar ataxia, and vestibular ataxia; and after observ­
that incorporates both hypermetria and hypometria ing characteristics of a gait abnormality in a patient,
(and all others from the Ministry for Funny Walks). it is reasonable to attempt to define which of one or
Animals with severe cerebellar lesions may have a more of these syndromes are present.
high stepping ataxic gait, but have limited movement Subconscious proprioceptive (spinal) ataxia results
of the distal limb joints, especially in thoracic limbs; from involvement of afferent proprioceptive path­
this is best termed dysmetria. And in this context, it ways in sensory nerves and more commonly in spinal
is worth consideration of the characteristic stringhalt cord and brainstem tracts. These proprioceptive defi­
gait with marked flexion of all pelvic limb joints cits are caused by lesions affecting the general pro­
made during onset of a flexor movement. This is not prioception pathways relaying information on limb
a form of ataxia as it is particularly predictable, even and body position to the cerebellum for subconscious
though it may be markedly variable in degree. In all proprioception. In contrast, general proprioceptive
these various situations, we do need to take other conscious pathways pass to the thalamus and cerebral
abnormalities into consideration in defining the cortex for conscious proprioception and are more
presence and characteristics of ataxia. involved in position sense at rest, i.e., posture. With
Ataxic movements are thus seen as a swaying from subconscious proprioceptive ataxia, the gait is irregu­
side to side of the pelvis, trunk, neck, and sometimes larly irregular and prominently unpredictable. There
the whole body. These may also appear as a weaving is a delay in onset and a swaying or floating swing
of the affected limb during the swing phase. Such phase and subsequent variable foot placement exag­
abnormalities can be well evident while an assistant gerated by maneuvering the patient. This movement
maneuvers the patient and also while the horse is and placement may include adduction and abduction.
walked with the head elevated and the examiner is Hyperflexion in hindlimbs and hypoflexion or
pulling on the tail. The examiner should also walk hypometria in forelimbs are common. Subconscious
backward on a serpentine course with the patient’s proprioceptive deficits likely contribute to scuffing
head raised while watching the pattern of stride and toes and stumbling, especially on thoracic limbs.
placement of limbs. The aim of these maneuvers is to Obviously, some of these signs are also associated
change the direction of limb flight during mid-­stride with motor pathway weakness, but because general
to promote errors due to proprioceptive abnormal­ proprioception and central motor tracts are adjacent
ities. Any irregular, abnormal foot placement in in large parts of the central and peripheral nervous
abducted or adducted positions, irregular crossing of system, and involved in disease processes together, it
the limbs, and intermittent stepping on the opposite usually is not necessary to distinguish which gait char­
foot especially while the animal is circling or turning acteristics is due to dysfunction of one or the other.
tightly all can be seen as possible evidence for ataxia. Cerebellar ataxia can have characteristics of spinal
Any animal that is substantially ataxic for any reason ataxia, but changes in limb placement and movement
tends to pace when walking with both feet on the same tend to be more abrupt in onset and to be excessive;
side off the ground at the same time. Circumduction the best definition of cerebellar ataxia being alterations
of the outside limbs when turning and circling is also in the rate, range, and force of movement.15 Thus, jerky
considered a proprioceptive abnormality. Walking an onsets of movement and hypermetria are often seen,
animal up and down a slope with the head elevated becoming more pronounced with more complex
 Neurologic evaluation 37

maneuvers such as hurriedly regaining an upright pos­ to rest on the dorsum for prolonged periods. Horses
ture from recumbency, abruptly turning to flee from need to have almost total paralysis of the limb or to
being frightened, or changing direction while run­ have a nociceptive sensory deficit in the limb before
ning. There is no central motor pathway or final motor they allow such postural anomalies to be maintained.
neuron paresis accompanying cerebellar disease, but Other tests, such as manually crossing the limbs or
other signs of cerebellar involvement including head placing one limb on a sack and slowly sliding the sack
tremor and defective menace responses are often pre­ to the side, have been tried to test conscious proprio­
sent. Less commonly, signs of vestibular involvement ception, but again in our hands have proven to be
can also be present with pan-­cerebellar disease. noncontributory to the examination process. Rather
Concerning vestibular ataxia, although the limb than manually placing limbs in abnormal positions,
movement and foot placement accompanying mild it appears more reliable to maneuver the horse rap­
to moderate vestibular disease are irregular, and idly, say in a circle, and stop the maneuver abruptly
therefore can be called ataxic, they are somewhat less (Figure 2.14). This often results in an initial awkward
unpredictable. For example, if thoracic limb move­ placement of the limbs, and then the examiner can
ment is forced to change in direction while the
patient is lead with its head raised, the resulting cor­
rection will be predictably abducted. Also, on turn­
ing a patient with mild vestibular disease, the wide
movement and placement of an outside hindlimb
will not usually be accompanied by hypermetria, and
any hurried movements to maintain a balanced pos­
ture will be strong and multiple, thus again being
somewhat predictable.
Normal animals react in different ways to blind­
folding, from extremes of excitement or distress to
acting imobile. Subsequent movements they make
while blindfolded then often depend on this variable (A)
behavioral response. Vestibular ataxia and loss of bal­
ance will often be markedly exacerbated when a
blindfold is applied to a patient suffering from ves­
tibular, diffuse spinocerebellar, or cranial cervical
spinal cord disease. On the other hand, blindfolding
a horse suspected of suffering from typical mid to
caudal cervical spinal cord compression usually does
not add anything substantial to the neurologic evalu­
ation. Damage to the sensory, C1–3 dorsal nerve roots
can produce vestibular ataxia, and this may be
expected to exacerbate with blindfolding the horse.24
Regarding the assessment of posture and postural
abnormalities, flexing the foot to attempt to make the
animal stand on the dorsum of the pastern and deter­
mine how long the animal leaves the foot in this state
before returning it to a normal position is said to be a (B)
test for conscious proprioception in dogs and cats.
Almost certainly, this involves somatic afferent (tac­ Figure 2.14 Stopping a patient abruptly after maneuvering it may result
tile) pathways as well, and a very weak patient may in abnormal limb postures being adopted and maintained. This is evident
not be able to move the foot from many abnormal here in a pony (A) and a young ram (B), both of which have cervical spinal
positions. This test can be attempted in large animals, cord compression, and this may be taken as evidence for abnormal
­conscious proprioceptive input from the limbs to the forebrain. On the
but in our hands has not been helpful in adding accu­ other hand, an obtunded patient or one with prominent weakness may
rate information to lesion location. Inactive and som­ not correct such abnormal limb positioning without having any specific
nolent patients, especially calves, often allow the foot conscious proprioceptive pathway lesion.
38 Large animal neurology

determine how long the horse leaves the limbs in c­ ervical arthritis and synovial cyst formation, result­
such an abnormal posture to determine the presence ing signs can wax and wane quite dramatically over
or not of conscious proprioceptive deficits. This pro­ periods of hours to days. Such signs usually stabilize
cedure probably does test for deficiencies in con­ with subacute to chronic lesions. For example, a
scious proprioception. Examination of horses horse that has suffered a single insult of cervical spi­
walking across kerbs has not proven to be a useful nal cord compression a year prior to the examination
test of proprioceptive dysfunction. Normal horses, may have an unusual, perhaps hypermetric, mild
particularly if distracted, will often trip and those ataxia in the pelvic limbs with no evidence of pelvic
that are moving cautiously, even if quite weak and limb weakness and no signs in the thoracic limbs
ataxic, can often maneuver such obstacles. other than a questionably poor response to hopping.
Gait alterations can occur in all four limbs with The anatomic diagnosis in such cases may be a lesion
lesions affecting the white matter in the caudal brain­ in the thoracolumbar or cervical spinal cord, or dif­
stem when head signs such as cranial nerve deficits fuse or multifocal spinal cord disease. A moderate or
are used to help define the site of the lesion. Subacute severe abnormality in the pelvic limbs, and none in
to chronic lesions affecting the forebrain usually the thoracic limbs, is however far more consistent
cause no substantial change in gait. However, pos­ with a thoracolumbar spinal cord lesion. With a very
tural reactions, such as hopping, are abnormal and mild and a very severe neurologic abnormality in the
sometimes the gait is slowly initiated on the thoracic thoracic and the pelvic limb gaits respectively, one
limb contralateral to the side of a forebrain lesion. must also consider a severe thoracolumbar lesion plus
In smaller patients, other postural reactions can be a mild cervical lesion or a diffuse spinal cord disease.
performed. These primarily help detect signs of sub­ Lesions involving the brachial intumescence at C6–
tle proprioceptive and motor system lesions when T2, with involvement of the gray matter supplying the
the straight-line gait is normal. Wheelbarrowing the thoracic limbs, and diffuse spinal cord lesions may
patient to make it walk on just the thoracic limbs, both result in a severe gait abnormality in the tho­
hopping it laterally on each individual thoracic and racic limbs and the pelvic limbs. A severely abnormal
each individual pelvic limb, and hemistanding and gait in the thoracic limbs, with normal pelvic limbs,
hemiwalking the animal by making it stand and then indicates final motor neuron involvement of the tho­
walk sideways on both left and then both right limbs racic limbs; a lesion is most likely present in the ven­
are three useful postural reactions to perform. Even tral gray columns at C6–T2 or involving thoracic limb
in large, adult animals, particularly horses, it is pos­ peripheral nerves or muscle (Chapter 26).
sible to perform a modified hopping response test
with the thoracic limbs. This is performed by lifting
each thoracic limb in turn while using the shoulder Localizing findings in spinal cord disease
to make the horse hop laterally on the other thoracic Neck and forelimbs
limb. This test can help the clinician decide if there If a gait alteration was detected in the thoracic limbs
are subtle neurologic abnormalities involving the and there were no signs of brain involvement, then
control of a thoracic limb. Brainstem and spinal cord this part of the examination can confirm involve­
lesions appear to result in postural reaction deficits ment of the C1–T2 spinal cord or thoracic limb
on the same side as the lesion, whereas cerebral peripheral nerves or muscles; it should also help
lesions produce contralateral abnormalities. localize the lesion within these regions.
At the conclusion of the examination, a most likely Results of the thoracolaryngeal adductor response
site of any acute nervous system lesion frequently can or the slap test can be a useful part of the complete
be defined accurately by determining the precise neurologic evaluation of horses suspected to be suf­
characteristics and severity of any gait and posture fering from lesions of the vagal or recurrent laryngeal
abnormalities present. The degree of weakness, nerves, caudal medulla oblongata, or cervical and cra­
ataxia, hypometria, hypermetria, and conscious pos­ nial thoracic spinal cord. As most emphasis is placed
tural deficits should be graded for each limb on its utility in diagnosing cervical spinal cord disease
(Table 2.4). in wobbler horses, some aspects of testing will be reit­
With peracute lesions, particularly those of an erated here. The test can be performed in cooperative
inflammatory nature and those with soft tissue com­ horses by palpating the dorsal and lateral laryngeal
pression of the spinal cord such as with caudal musculature while simultaneously slapping the
 Neurologic evaluation 39

c­ontralateral dorsolateral thoracic region from the Importantly, as musculoskeletal diseases are far
cranial withers to near the last rib, while the horse is more common than neurologic disease and as disuse
exhaling. If there is difficulty in interpretation of this atrophy can occur within at least weeks of the onset
test, observing the larynx via an endoscope while of lameness, muscle atrophy, especially common over
performing the test may be necessary. It should be the scapula, should be taken as evidence of an under­
emphasized that the thoracolaryngeal response is not lying lameness until there is additional evidence that
consistently absent in horses with cervical spinal cord it is neurologic in origin.
disease or caudal brainstem disease and can be absent Clearly delineated regions of cervical and thoracic
in horses with no evidence of CNS disease.27,28 sweating can be useful indicators of localized spinal
However, a reduced or absent slap reflex on the left cord or peripheral nerve disease in that they can repre­
side of the larynx must be taken as strong evidence for sent sympathetic denervation or decentralization of
the presence of idiopathic recurrent laryngeal neu­ the vasculature in the skin, resulting in increased cir­
ropathy or prior laryngeal surgery, although exercise culating adrenalin stimulating sweat glands to secrete.
and endoscopic examination of the horse will be nec­ Care must be taken in interpreting patchy sweating
essary to confirm any clinical problem of reduced that is not well delineated. Very asymmetric patchy
laryngeal function and of roaring. Bilateral absence of sweating can occur in horses that are excited or
the response without other signs of severe laryngeal distressed, particularly when in a draughty area,
or cervicomedullary disease must be interpreted cau­ without a specific sympathetic lesion being present.
tiously, particularly in an excitable horse. A normal Involvement of the peripheral pre-­and postganglionic
response on the left side of the larynx and absent sympathetic neurons in the horse results in localized
response on the right side will indicate a neurologic sweating; this can be an extremely helpful localizing
disease, most likely right-­sided brainstem or spinal sign. Horner syndrome will result if the cervical sym­
cord C1 to cranial-­thoracic, other than classical idio­ pathetic trunk is damaged. In the horse, dermatomal
pathic recurrent laryngeal neuropathy. Thus to repeat, patterns of sweating on the neck and cranial shoulder
the only useful result from the right to left test is a occur with involvement of the C3–C8 branches of the
positive test, whereas both unequivocal positive and sympathetic fibers. These arise segmentally from the
negative test results from left to right have utility. vertebral nerve that follows the vertebral artery up
the neck after the vertebral nerve has left the stellate
ganglion near the thoracic inlet (see Figure 2.10).
The commonest cause of acute, acquired, severe bilat- When the skin of the lateral neck of a horse just
eral laryngeal paralysis is hepatoencephalopathy. above the jugular groove from the level of the atlas to
the shoulder is prodded firmly with a blunt probe,
Observation and palpation of the neck and fore­ the cutaneous coli muscle contracts, which causes
limbs will detect gross skeletal defects, asymmetry in skin flicking. With stronger stimuli, the sternoce­
the neck and muscle atrophy. These signs may be phalicus and brachiocephalicus muscles often con­
associated with neurologic disease and thus be local­ tract, causing the shoulder to be pulled cranially and
izing findings. The neck should be manipulated to even the head to be flexed laterally. This response
assess a normal range of movement. Interpretation of tends to be less obvious in other species. In horses,
what appears to be reluctance to move the neck pas­ there is also flicking of the ear rostrally, blinking of
sively or actively in any direction as indicating neck the eyelids, and lip retraction when the test is per­
pain is fraught with difficulties. On the other hand, if formed. Originally introduced by Rooney,30 these are
a horse will not lower or bend its head to eat, drink, termed the local cervical and cervicofacial responses,
or reach for a treat, or the head and neck gets “locked” respectively. The precise anatomic pathways are not
in an abnormal position/posture, this usually indi­ entirely clear, although they must involve several cer­
cates a mechanical or painful disruption to move­ vical segments and the facial nucleus in the medulla.
ment of the cervical vertebrae, particularly involving At least in the cranial cervical region, even the local
intervertebral disk damage in the caudal neck and cervical reflex may well be a cervical/trigeminal–facial
cranial thoracic region.29 Cervical vertebral arthrosis, reflex associated with the anastomoses between the
involvement of cervical nerve roots, and marked cer­ cervical branch of the facial nerve with cutaneous
vical spinal cord disease can cause scoliosis and even branches of the C2–C6 segmental nerves.31 Cervical
torticollis. lesions that involve gray and white matter can cause
40 Large animal neurology

depressed or absent cervical responses; however After pausing to allow the patient to settle, a second,
inter­pretation of abnormal responses may need to be sharp skin pinch is applied to determine superficial
expressed as imprecisely as for example “consistent sensation. There may be reflex withdrawal of the part,
with a right-side caudal cervical lesion” or “consistent with or without a cerebral response such as vocalization
with a cranial cervical lesion.” In contrast, the seg­ or moving the whole body away from the stimulus;
mental absence of the cutaneous trunci reflex can be the latter events being taken as representing the
very useful in delineating the precise cranial extent conscious perception of the noxious stimulus.
of a thoracic spinal cord lesion particularly when If a large, adult animal has significant gait abnor­
such a lesion is asymmetrical. mality and it is feasible to cast it to lateral recum­
Sensory perception from the neck and forelimbs bency, then this should be done to assess the spinal
must be assessed. This can be difficult to evaluate accu­ reflexes. If the animal is ambulating well, it may be
rately in stoic and in excited animals. Perception of a assumed that the flexor and extensor spinal reflexes
noxious stimulus is noted by observing the animal’s are at least intact. These reflexes can be studied in all
behavioral response while observing the local cervical smaller patients.
responses and continuing the skin prodding over the When evaluating wobblers with evidence of a neu­
shoulders and down the limbs to include testing the rologic abnormality in both thoracic and pelvic limbs
autonomous zones for the thoracic limbs (Figure 2.15). and no evidence of brain disease, one should allow
As with any cutaneous sensory test, a two-­step tech­ for a lesion to be present anywhere from C1 through
nique is recommended.32 This is accomplished by T2. Conversely, when there is evidence of a mild neu­
initially tenting and grasping a fold of skin between rologic gait abnormality in the pelvic limbs but not
the jaws of heavy duty hemostats or needle holders. the thoracic limbs, then the possibility of a lesion

Figure 2.15 Autonomous zones are areas of desensitivity that can be detected when individual peripheral spinal nerves to the limbs are not function-
ing. Source: Adapted from Blythe33; Blythe and Engel34; Blythe and Kitchell35.
 Neurologic evaluation 41

anywhere from C1 through S2 must be considered. If the trunk and pelvic limb nerves or muscles. This
the signs of pelvic limb ataxia and/or paraparesis in a part of the examination helps localize such lesions
large adult patient are moderate or even marked, more precisely. However, the examiner must remember
then a lesion can be considered anywhere in these that with a subtle grade neurologic gait abnormality
segments. The reason to include lesions sites at C6–T2 in the pelvic limbs, the lesion may be anywhere
is because such lesions, when intramedullary, can be between the rostral brainstem and the mid-­sacral
very selective and spare white matter tracts and gray spinal cord.
matter involving the thoracic limbs resulting in no The trunk and hindlimbs must be observed and
definitive thoracic limb signs. Such has been the case palpated for malformation and asymmetry
in adult horses suffering from S. neurona myelitis, (Figure 2.17). Lesions affecting thoracolumbar gray
fibrocartilagenous thromboembolism, granuloma­ matter cause muscle atrophy, which is a helpful local­
tous meningoencephalomyelitis, and migrating hel­ izing finding. With asymmetric myelopathies, scolio­
minth parasites affecting C6–T2 spinal segments. sis of the thoracolumbar vertebral column often
occurs, initially with the concave side opposite the
Trunk and hindlimbs lesion, but changing with subsequent fibrous contrac­
If the examination of the head, gait and posture, and ture setting in. Once again, evidence of muscle atro­
neck and thoracic limbs reveals evidence of a nerv­ phy, especially common over the gluteal region
ous system lesion(s), then an attempt should be made (Figure 2.18), should be taken as evidence of an
to associate such lesions with any further signs found underlying lameness until there is additional evidence
during examination of the trunk and hindlimbs. If that it is neurogenic.
there are only signs in the trunk and hindlimbs
(Figure 2.16), then the lesion(s) must be between C1
and S2, but most probably between T3 and S2, or in

(A)

(B)

Figure 2.16 This Holstein calf (A) suffered from vertebral trauma during
an assisted delivery that resulted in paraplegia due to an epiphyseal Figure 2.17 Very occasionally, portions of muscles, whole muscles, or
separation at caudal L4 vertebra. With nursing care, the calf recovered muscle groups are found to be absent and often there are no definitive
quite well to be able to stand and walk but with a tendency to knuckle neurologic signs present. Such was the case with this horse in which a
over on its fetlocks as shown. The residual gross lesion shown below (B), large portion of the left medial thigh muscles, at least including the
particularly the focal necrosis of dorsal gray and white matter at L4-­5, medial quadriceps group, was missing with no evidence of weakness or
explains the clinical syndrome that related mostly to bilateral deficits of ataxia in either hind limb. Whether individual cases are congenital or
the sciatic/peroneal nerve distribution with very poor flexor reflexes acquired (from say S. neurona) is usually very difficult to determine when
­present in the pelvic limbs. present for such a long time.
42 Large animal neurology

cord in thoracolumbar dorsal spinal nerve roots at the

level of the site of stimulation. Transmission is then
cranial in the spinal cord to C8–T1, where the final
motor neuron cell bodies of the lateral thoracic nerve
are stimulated resulting in contraction of the cutane­
ous trunci muscle. Lesions anywhere along this path­
way may cause suppression of the response, which is
easiest to detect with an asymmetric lesion. In addi­
tion to this, an assessment of sensory perception from
the trunk and hindlimbs (Figure 2.19) must be made.
This appears as a cerebral, behavioral response to a
two-­pinch stimulus described above, which includes
the assessment of the autonomous zones for the pelvic
limbs (Figure 2.15). Degrees of hypalgesia have been
detected caudal to the sites of thoracolumbar spinal
cord lesions, but only when they are severe.

The cutaneous trunci reflex should not be referred to as

the panniculus reflex as panniculus refers to the subcu-
ticular fat depots over the abdomen.

Stroking firmly with a blunt probe or pinching and

pressing down firmly with the fingers over the thora­
columbar paravertebral muscles causes a normal ani­
mal to extend into a slightly lordotic stance and fix the
thoracolumbar vertebral column. The patient also
resists the ventral motion and usually does not flex
the thoracic or pelvic limbs. Continuing this stimulus
to the dorsal sacral region and caudally along the
rump results in a degree of vertebral flexion and a
kyphotic stance. A weak animal usually is not able to
Figure 2.18 Proximal limb atrophy more often is due to disuse mostly resist the pressure by fixing the vertebral column, and
because of orthopedic disease. However, selective middle gluteal muscle
thus it overextends or overflexes the back and begins
atrophy in the absence of lameness and the absence of atrophy of other
proximal limb musculature as seen on the left side in this horse is likely to to buckle in the pelvic limbs. The onset of buckling
be due to final motor neuron disease such as that caused by S. neurona can be viewed as the patella pops out of its “stayed”
myelitis at L6 as was the case here. position during these maneuvers. With additional
proprioceptive lesions, the patient can sometimes
Sweating in the horse over the trunk and hindlimbs, react to this test by sinking but with irregular swaying
excluding the neck and face, can be a helpful localiz­ movements of the pelvic region on sinking and on
ing sign. Ipsilateral sweating caudal to the lesion sig­ recovery – truncal ataxia. Prominent back pain can
nals involvement of the descending sympathetic tracts result in poor responses and evidence of pain percep­
in the spinal cord caudal to T3. Lesions involving spe­ tion by, say, a grunt from the patient. With lumbosa­
cific pre-­or postganglionic peripheral sympathetic cral and sacroiliac orthopedic lesions, such responses
fibers that are second-­and third-­order neurons cause may be more localized to be most evident with
saddles or patches of sweating at the level of the lesion. downward pressure on each tuber sacrale in turn.
Firm prodding of the skin over the trunk, particu­
larly the mid-­lateral aspects of the thoracic wall, causes
Lordosis refers to extension, and kyphosis refers to
a contraction of the cutaneous trunci muscle, seen as a
flexion, of the vertebral column. There is no such thing
flicking of the skin over the trunk—­the cutaneous
as dorsiflexion.
trunci reflex. The sensory stimulus travels to the spinal
 Neurologic evaluation 43

(A) (B)

Figure 2.19 This foal developed sciatic paralysis after being treated for Klebsiella sp. sepsis. This resulted from the development of severe empyema
over the caudal hip, entrapping the sciatic nerve onto the pelvis. The knuckled fetlock while standing (A) and walking suggests peroneal branch involve-
ment, and the analgesia from the caudal cannon region (B) is consistent with tibial nerve involvement.

Recumbent patient there can be poor tone and little observable voluntary
Every effort should be made to help a recumbent effort in a limb that has suffered pressure damage
patient stand and walk unless there is suspicion of from been lain upon. A severe central motor pathway
bone fracture. By so doing, one can learn as much or lesion to the thoracic limbs at C1–C6 causes poor or
more about voluntary effort and lesion localization absent voluntary effort, but there will be normal or
than one can from reflex testing (Figure 2.20). Heavy sometimes increased muscle tone in the limbs. This
animals should be moved early in the course of is because there is a release of the final motor neuron
recumbency to avoid secondary problems such as that is reflexly maintaining normal muscle tone under
decubital sores, decreased blood supply to limbs and the calming influences of the descending central motor
dehydration, which makes evaluation difficult. pathways. Interestingly, such a spastic (hypertonic)
A patient that has recently become recumbent but paralysis only in the pelvic limbs can also be seen with
uses the thoracic limbs well to get up likely has a lesions between C6 and T2 if little or no thoracic limb
lesion caudal to C6, most often caudal to T2. If such an gray matter is affected. A Schiff–Sherrington phe­
animal cannot attain a dog-­sitting posture, the lesion nomenon of short duration (hours to a few days),
is likely to be in the cervical spinal cord (Figures 2.13 with excessive extensor tone in the thoracic limbs in
and 2.20). If only the head, but not the neck, can be the presence of good voluntary activity and normal
raised off the ground, there is probably a severe cra­ reflexes, has been seen rarely in horses and usually
nial cervical lesion. With a severe caudal cervical follows a cranial thoracic vertebral fracture.36
lesion, the head and neck usually can be raised off the Finally, spinal reflexes are tested in the thoracic
ground, although thoracic limb effort decreases, and limbs. The flexor reflex in the thoracic limb involves
the animal usually is unable to maintain sternal stimulation of the skin of the distal limb with needle
recumbency. Assessments of limb function cannot be holders and observing for flexion of the fetlock, knee,
relied on while a heavy animal is lying on the limb elbow, and shoulder (Figure 2.21). This reflex arc
being tested. Muscular tone can be determined by involves sensory fibers in the median and ulnar
manipulating each limb. A flaccid limb, with no nerves, spinal cord segments C6 to T2, and motor fib­
motor activity, is typical of a final motor neuron ers in the axillary, musculocutaneous, median, and
lesion to that limb, but in heavy recumbent animals ulnar nerves. Lesions cranial to C6 may release this
44 Large animal neurology

(A) (B)

(C) (D)

Figure 2.20 Complete paraplegia with good function in the thoracic limbs is seen in these young ruminants (A to D). This will often be consistent with
a lesion caudal to T2 and sometimes (B) the tone in the pelvic limbs will be increased indicating a lesion most probably from T3 to L3. In this case, the
pelvic limb reflexes were hyperactive, also consistent with spastic paraplegia due to a lesion from T3 to L3. Such a patient often will struggle around using
the thoracic limbs (C). However, when a young ruminant postures and moves around (D), with the thoracic limbs not extended, the possibility of an
additional lesion cranial to T3 must be considered.

(A) (B)

Figure 2.21 The only important spinal limb reflexes to perform on any patient that can be placed in lateral recumbency are the flexor reflexes in the
thoracic limbs (A) and the pelvic limbs, and the extensor or patellar ligament reflex in the pelvic limbs (B). All other reflex testing can be problematic in
interpretation, and results of such tests rarely change an anatomic diagnosis. Appropriate hyperactive reflexes and crossed extensor reflexes were present
as expected in this normal neonatal calf. Reflexes should be tested in both pairs of limbs while uppermost, and while dependent, the most prominent
result being taken as real, with prominently asymmetric reflexes helping to lateralize a lesion. Rarely, a reflex cannot be elicited in a normal patient, usu-
ally bilaterally.
 Neurologic evaluation 45

reflex from the calming effect of the central motor reflex present that subsides through the first weeks
pathways and cause an exaggerated reflex with rapid of life.
flexion of the limb. The limb may remain flexed for The pelvic limb spinal reflexes may also be evalu­
some time and even show repetitive movements or ated in all animals that can be restrained in lateral
clonus. Such lesions may also result in a crossed recumbency and in all recumbent patients. In addi­
extensor reflex, with synchronous extension of the tion, the amount of voluntary effort and muscle tone
untested limb. This usually occurs only with severe present in the pelvic limbs is assessed in recumbent
and chronic central motor pathway lesions. Thus, an patients. As described for the thoracic limbs, this can
animal affected by such a lesion may demonstrate be performed while watching the animal attempt
considerable reflex movement following stimuli, but to get up or by observing its struggle in response
usually will have little coordinated voluntary motor to stimuli while lying in lateral recumbency.
activity in the limbs being tested. A spinal reflex can Consideration must be given to possibly exacerbat­
be intact without the animal perceiving the stimulus, ing a fracture.
and the latter must be observed independent of the The patellar reflex and the flexor reflex are the two
local reflex movement. Cerebral responses associated most clinically important spinal cord reflexes involv­
with the perception of the skin pinch include changes ing the pelvic limbs. The patellar reflex is performed
in facial expression, head movement, and phonation. by supporting the limb in a partly flexed position,
Conscious perception of the stimulus will be intact tapping the middle patellar ligament with a neuro­
only if the afferent fibers in the median and ulnar logic hammer or a heavy metal plexor, and observing
nerves, the dorsal gray columns at C6–T2, and the a reflex contraction of the quadriceps muscle result­
central sensory pathways in the cervical spinal cord ing in extension of the stifle (Figure 2.21). The sen­
and brainstem are intact. sory and motor fibers for this reflex are in the femoral
Interpreting results of testing the tendon reflexes—­ nerve, and the spinal cord segments involved are pri­
triceps, biceps, extensor carpi radialis, etc.—­in the marily L4 and L5. The flexor reflex is performed by
thoracic limbs is problematic and does not usually pinching the skin of the distal limb with needle hold­
assist in defining the site of neurologic lesion, perhaps ers and observing for flexion of the limb. The afferent
except for neonatal animals. Also, patients with pro­ and efferent pathways for this reflex are in the sciatic
found diffuse neuromuscular paresis can have reflexes nerve and involve spinal cord segments L5 to S3
that are at least present. However, a general descrip­ (Figure 2.16).
tion of two of these reflexes follows—descriptions for Although two other reflexes can be elicited in most
the remainder being superfluous. To perform the neonatal animals, they are frequently not clearly
triceps reflex, the relaxed limb is held slightly flexed, reproducible in adult patients, and thus results of
and the distal portion of the long head of the triceps testing them do not usually contribute to defining the
and its tendon of insertion is balloted with a rubber site of neurologic lesions. The gastrocnemius reflex is
neurology hammer in smaller patients or a heavy performed by balloting the gastrocnemius tendon
metal plexor in larger patients while observing and and observing and palpating the contraction of the
palpating for contraction of the triceps muscle, which gastrocnemius muscle, which is accompanied by an
causes extension of the elbow. The triceps reflex extension of the hock. This reflex involves the tibial
involves the radial nerve for its afferent and efferent branch of the sciatic nerve and spinal cord segments
pathways and spinal cord segments C7 to T1. The L5 to S3. Second, the cranial tibial reflex results in
triceps reflexes, although present, can be extremely contraction of the cranial tibial muscle with hock
difficult to demonstrate in heavy, adult, recumbent flexion occurring when the muscle is balloted and
patients. The musculotendinous portion of the the relaxed limb is held partially extended. Variable
extensor carpi radialis muscle can be balloted to limb movement and direct impact muscle contrac­
produce an extension of the knee when the relaxed tion in response to mechanical stimulation may be
limb is held in a partially flexed position. This exten­ interpreted falsely as a positive reflex muscle contrac­
sor carpi radialis reflex involves afferent and efferent tion when both these reflexes are tested.
fibers also in the radial nerve, but the reflex may not Distinguishing characteristics of final motor neu­
always be present in normal adult animals. ron paresis and paralysis and central motor pathway
All these reflexes are usually active in normal neo­ paresis and paralysis are given in Table 2.5. Such dis­
nates in which there is a prominent crossed extensor tinctions can be straightforward in assisting to
46 Large animal neurology

Table 2.5 Common clinical features with lesions involving central apparent. Some horses with no known neurologic
motor pathway and final motor neurons lesion(s) hold their tail to one side, and others are
Clinical sign Clinical features with lesion in considered natural tail wringers and flick their tails
vertically and laterally while moving. A crooked tail
Central motor pathway Final motor neuron carriage appears to be more prevalent in lame horses
Muscle tone Normal to hypertonic Hypotonic to flaccid than non-lame horses.39
Muscle atrophy None or disuse* Significant Fixed torticollis of the caudal vertebrae, or wry tail
Muscle fasciculations NOT present Present (caudal vertebral scoliosis), should alert the exam­
Reflexes Normal to hyperactive Hypoactive to absent iner to the possibility of the presence of other spinal
malformations, but it may, particularly in adult cattle,
*
With lameness and disuse in fit horses, this becomes quickly evident in
proximal muscles. be due to overzealous twisting of the tail.
The perineal reflex is elicited by briskly prodding
the skin of the perineum and anus while observing
a­ natomically localize the site and extent of spinal cord reflex contraction of the anal sphincter and clamping
and peripheral nerve lesions in many patients, but in down of the tail. The sensory fibers are contained
recumbent heavy patients and those with chronic dis­ within the perineal branches of the pudendal nerve
ease and disuse these classic characteristics can merge from S1–S3. Contraction of the anal sphincter is medi­
such that this distinction becomes problematic. ated by the caudal rectal branch of the pudendal nerve,
Skin sensation from the pelvic limbs should be and tail flexion is mediated by the sacral and caudal
assessed independently from reflex activity using the segments and nerves, S1–Ca. Light tactile rubbing of
two-­pinch technique focussing on the autonomous the anus will usually result in reflex tail extension that
zones (Figure 2.15). The femoral nerve is sensory to in adult cows at least can herald the onset of a micturi­
the skin of the medial thigh region, the peroneal nerve tion reflex. An animal with a flaccid tail and anus due
to the dorsal tarsus and metatarsus, and the tibial nerve to a final motor neuron lesion will not have an anal or
to the plantar surface of the metatarsus and fetlock. As tail reflex. However, it may still have normal sensation
for the thoracic limbs, lesions of the peripheral nerves from the anus and tail provided that the sensory nerves
to the pelvic limbs, such as the femoral and peroneal and spinal cord and brainstem white matter nocicep­
nerves, result in specific motor deficits; however, the tive pathways are intact. Thus, as with all other reflex
precise sensory deficits can be difficult to define. testing, the sensory perception of the stimulus must be
The patellar reflex is hyperactive in newborn foals, evaluated separately from segmental reflex action.
lambs, calves and kids, and probably in all large animal The spinal cord ends at the level of the first or
neonates. Also, the cranial tibial and gastrocnemius second sacral vertebra in large animals. Therefore,
tendon reflexes are easily performed in healthy, coop­ focal lesions of the last lumbar and of the sacral and
erative newborn patients. As with the forelimbs, these caudal vertebrae may involve components of the
patients have normal, strong, crossed extensor reflexes. cauda equina, hence the afferent and efferent spinal
In addition, an extensor thrust reflex is obtained, in nerve roots from many sacrocaudal spinal cord seg­
very young patients, by rapidly overextending the ments. Depending on the level, this causes varying
toe while the limb is already partially extended. This degrees of hypalgesia, hyporeflexia, hypotonia, and
results in a forceful extension of the limb and possibly ultimately muscle atrophy of the tail, anus, perineum,
represents a Golgi tendon organ reflex that becomes hips, and caudal thighs. A rectal examination may
suppressed as the animal matures. detect a space-­occupying lesion or fracture or luxa­
tion of the lumbar, sacral, or caudal vertebrae. In
Rectum, bladder, anus, perineum, and tail addition, assessment should be made of urinary blad­
Tail tone can be assessed prior to testing the per­ der volume and the tone of the bladder and rectal
ineal reflex, and it is exceedingly variable between walls. Adult animals, especially male horses, that are
patients. A completely flaccid tail with no voluntary recumbent for any reason, often do not urinate. Thus,
movement is indicative of a lesion of sacrocaudal they usually have a distended bladder that eventually
spinal cord segments, nerves, or muscles. Decreased results in urine dribbling. Manipulating such an ani­
movement of the tail can be detected with lesions mal to help it stand, or violent attempts by the animal
cranial to the caudal segments, but usually the spinal itself to stand, can result in rupture of a bladder wall
cord lesion must be severe for the weakness to be that is already weakened by pressure necrosis.
 Neurologic evaluation 47

It is reasonable to interpret that an animal that is horse with accompanying gluteal muscle asymmetry.
ambulatory and has nonobstructive distension of the Unless marked, such asymmetric muscle atrophy
urinary bladder with urinary incontinence probably should be taken as evidence for disuse due to lame­
has a lesion that affects the sacral spinal cord segments ness until proven otherwise.
or the pelvic nerves or urinary detrusor muscle, a final
motor neuron lesion bladder. In such cases, there will Clinico-pathologic categories of peripheral
usually be excess feces in the rectum, but this usually nerve damage.
will not cause overt constipation unless there is a
dense, diffuse, sacral, final motor neuron lesion. • Neurapraxia is temporary loss of function with no
Paraplegic large patients frequently contuse the morphological changes.
perineum and tail while dog-­ sitting and while • Axonotmesis is damage to axons with preservation
attempting to stand. Also, tail ropes and various of myelin sheaths resulting in prolonged loss of
forms of sling support frequently damage these areas. function until axonal regrowth re-­establishes inner-
An assessment of the neurologic function must be vation of the target organ (muscle).
made as soon as possible because perineal and tail • Neurotmesis is severance of axons and their myelin
contusion results in edema, quickly followed by sheaths with prolonged to permanent loss of function,
hypotonia, hyporeflexia, and hypalgesia. sometimes with partial reinnervation depending on both
By this stage of the examination, the clinician the distance between the proximal and distal nerve
should have a clear idea of the presence and location stumps and between the lesion and the muscle.
of lesions in the brain, spinal cord, and the peripheral
nerves and muscles of the thoracic and pelvic limbs. From a practical point of view, peripheral nerves
The more peripheral the lesion, the better defined the are very difficult to injure directly or to stretch unless
sensory and motor deficits. Syndromes resulting they are fixed in situ, or they overlie a bony structure
from lesions involving specific limb peripheral such as the case for portions of the facial and supras­
nerves involve characteristic abnormalities of gait, capular nerves, or there is a sharp penetrating injury.
paralysis of specific muscles with resulting muscle Presumed peripheral nerve irritation and vascular
atrophy, specific reflex loss, and sensory deficits that compromise can result in unusual syndromes in
are discussed further below. horses. Perhaps the best example of these is the
abrupt onset of distress involving one limb when the
horse will kick out and repeatedly stomp the foot on
Interpretation of signs of peripheral
the ground. This is occasionally seen following an
nerve disease
intramuscular injection, presumed to have been
For an accurate interpretation of signs of peripheral deposited adjacent to a peripheral sensory or mixed
nerve disease, some consideration must be given to nerve. The other example would be the similar syn­
the neuropathological classification of damage to drome that can appear upon recovery from general
peripheral nerves that can result in degrees of loss of anesthesia wherein there is no overt evidence of a
function termed neurapraxia, axonotmesis, and myopathy or a motor neuropathy, the most likely
neurotmesis. explanation being the onset of paresthesia or, as it is
With loss of somatic efferent motor innervation referred to in humans, pins and needles. Such unu­
due to axonal or whole nerve fiber damage, there is sual syndromes can occur spontaneously in horses,
muscle atrophy, which occurs relatively rapidly sometimes with no associated or predisposing inci­
although in large patients it may take up to 2 weeks dent and sometimes are associated with exertion.
to become clinically prominent. Electromyographic Most often these signs dissipate rapidly, with occa­
changes indicating denervation of muscle may take sional notable and enigmatic exceptions.
even longer and may take 3–4 weeks to become Compared to small animals, the specific areas of
prominent in the horse. Surprisingly, disuse atrophy desensitivity relating to each major spinal nerve,
appears to occur quite rapidly in the (fit) horse and referred to as autonomous zones, are quite variable
therefore distinguishing neurogenic atrophy from from horse to horse (Figure 2.15). The variable anal­
disuse atrophy clinically can be blurred. A good gesic zones found following tibial and peroneal, and
example of the significance of this would be an median and ulnar nerve blocks undertaken during
unusual asymmetric hindlimb gait abnormality in a orthopedic evaluations attest to this. Determining
48 Large animal neurology

such precise areas of analgesia can be extremely use­ a week or two. Shoulder abduction that occurs on
ful, albeit often frustrating, in helping to localize a weight-­bearing, or so-­called shoulder slip, that is
peripheral neuropathy although their absence should seen with thoracic limb trauma is presumed to be lat­
not exclude such syndromes. On the trunk and prox­ eral laxity to the shoulder joint. This sign likely
imal limbs, the two-­pinch technique outlined above results from loss of lateral support of the shoulder,
is preferable for sensory testing. but although it can occur when local anesthetic solu­
Except for those affecting the cauda equina, tion is deposited in the region of the suprascapular
peripheral spinal nerve lesions most often result in a nerve it may well not be due to suprascapular nerve
gait abnormality involving only one limb. Classically, paralysis alone.37 Other signs, such as sensory deficits
the further the lesion is away from the central nerv­ over the caudal neck and shoulder and ensuing mus­
ous system, the more selective are any motor and cle atrophy elsewhere in the limb, must make the cli­
sensory deficits. This is less true in the horse com­ nician suspicious of more than suprascapular nerve
pared to small animals for several reasons, perhaps involvement such as additional damage to neural
because of peripheral nerve anastomoses and second components from the brachial plexus.
because incomplete peripheral neuropathies fre­ The femoral nerve is incredibly well protected
quently occur. from external injury although damage to it will ulti­
The gait abnormalities present after several days mately result in quadriceps atrophy. Even with mod­
following onset of selective median or ulnar neu­ erate muscle atrophy and posturing with the pelvis
ropathies are minimal. The same can be said of distal flexed and back arched, horses with partial unilateral
tibial and peroneal nerve lesions although sometimes femoral nerve lesions can have a remarkably normal
there will be a change in stride with occasional stum­ gait at the gallop although athletic performance
bling associated with hock and fetlock flexion with probably is curtailed. Femoral nerve lesions must be
the former and with hock extension with the latter. quite proximal in the limb before medial thigh hypal­
The radial nerve is probably rarely damaged alone gesia resulting from saphenous nerve branch involve­
due to its protected course. However, the commonly ment can be detected.
recognized signs of typical proximal radial nerve Cauda equina involvement most frequently results
paralysis, including a lack of carpal and fetlock exten­ from a fractured sacrum or from polyneuritis equi.
sion and an inability to bear weight on the limb with Such signs may begin acutely or may be delayed fol­
a dropped elbow, usually result from partial brachial lowing the onset of the disease. A slightly abnormal
plexus involvement. Theoretically, this syndrome gait may be detected in the pelvic limbs, but the cause
should be distinguishable from myopathy involving may not be identified until the perineal region is
the triceps or the extensor carpi radialis muscles, evaluated closely when other signs of cauda equina
elbow joint lameness, humeral fracture, and bicipital involvement became apparent.
bursitis. However, in practice, such distinction can be Other characteristic gait abnormalities do strongly
difficult to achieve without a thorough evaluation suggest peripheral nerve disease. Stringhalt is one
usually requiring ancillary aids, including ultrasonog­ example where there is exaggerated flexion of the
raphy, radiography, synovial fluid analysis, and elec­ limb during protraction with excessive hock flexion
tromyography. Because partial brachial plexus lesions and digital extension resulting from inappropriate
are quite common following proximal thoracic limb contraction of the digital extensor muscles or lack
impact injury, this problem should be considered fore­ of opposition from digital flexor muscles. This
most when an inability to bear weight on an otherwise syndrome can occur with spinal cord disease but
pain-­free thoracic limb is being evaluated. most commonly—­in regions where flat weed plants
Musculocutaneous nerve problems are rarely, if are abundant—­due to toxic peripheral axonopathy.
ever, encountered alone, and after some initial stum­ A thorough musculoskeletal examination including
bling any permanent gait abnormality may be diffi­ ultrasound evaluation of the affected limb may reveal
cult to detect. abnormalities detected within the lateral digital
Immediately after an episode of shoulder injury, extensor muscle, tendon or sheath, or in the hock.
signs of damage to the motor suprascapular nerve Any abnormalities detected are often assumed to ini­
often include a degree of lameness, presumably tiate the abnormal neural reflexes, thus increasing
associated with adjacent soft tissue and periosteal tone in the digital extensor muscles during protrac­
damage. Suprascapular muscle atrophy will ensue in tion. Another interesting gait that results from
 Neurologic evaluation 49

mechanical interference to contraction of caudal a degenerative cerebellar nuclear axonal lesion as

thigh muscles, or perhaps sometimes because of possibly being related to this enigmatic syndrome.38
reflex hypertonia involving these muscles, is referred
to as fibrotic myopathy. In this syndrome, the gait Final interpretation: where and what is
classically results in excessive slapping of the foot to the lesion?
the ground at the end of protraction, thus shortening
the stride length. Mild to moderate fibrotic myopa­ Results of the neurologic examination should be
thy usually does not appear to interfere with high-­ ­documented and not left to memory (Figure 2.1).
speed performance; however, dressage horses, show After completion of the neurologic examination,
horses, and trotters and pacers do show an abnormal the examiner may be able to decide if and where any
gait during their performance. possible lesion exists. Sites include the basic areas of
Variations in these characteristic gait abnormalities the following body components:
occur. These include repetitive or intermittent mild
abduction of the hindlimb during protraction and cau­ 1. Forebrain
dal jerking of the distal hindlimb after the initiation of 2. Brainstem
protraction. It is possible to explain these and other 3. Peripheral cranial nerves
movement disorders by an initiation of abnormal mus­ 4. Cerebellum
cle spindle activity, as in Stringhalt, with a result that 5. Spinal cord
certain muscles or groups of muscles contract too early 6. Peripheral spinal nerves and nerve roots
or too late, or excessively or poorly, at a particular phase 7. Neuromuscular junctions
of the stride. Thus, intermittent abduction and caudal 8. Muscles
jerking in the hindlimb may result from hypertonia 9. Autonomic nervous system
and hyperreflexia involving the biceps femoris muscle
Often the exact location of a lesion or lesions within
during the swing phase of the stride.
these divisions will be able to be defined precisely,
Cantering with synchronous movement of the
albeit cautiously (see Figure 2.22). If the location of a
hindlimbs is referred to as bunny hopping and is seen
lesion is not clear, then it is often worthwhile returning
with numerous pelvic limb musculoskeletal, often
bilateral, problems. It is rarely the result of acquired
neurologic disease but can occur with certain con­
genital or acquired spinal cord malformations. Overt
evidence of peripheral nerve or spinal cord disease,
or the identification of bilateral and synchronous
hindlimb reflexes determined during recumbency,
needs to be present before such neurologic causes for
bunny hopping can be confirmed.
Finally, horses diagnosed with shivers demonstrate
a wide variety of signs. These include slightly exces­
sive flexion of the hindlimbs along with thigh muscle
and tail trembling at the onset of backing, reluctance
to have the hindlimbs picked up with degrees of thigh
muscle trembling, inability to back-­up, and sponta­
neous and induced episodes of muscle trembling
with hindlimb and forelimb and neck extension, all
Figure 2.22 In a case of limb ataxia and weakness and based on
of which may wax and wane. Interestingly, an absolute, definitive neurologic findings, the thought process at this stage
acquired lameness can abruptly exacerbate the syn­ of the workup may be that
drome. A few horses demonstrating shivering also “All or part of the lesion(s) is between A and D.”
suffer from mild spinal cord disease, some from Any additional information that is not definitive or is ill-­defined can be
marked lumbar arthropathy, some from destructive used to modify the working hypothesis that the lesion is
“Probably between B and C.”
lesions of the lumbosacral vertebrae, and others from This way, further scrutiny with repeated examinations and ancillary test-
painful conditions involving the distal hindlimbs. ing can be focused without losing sight of unusual, additional, or partial
However most do not, and recent evidence points to lesion(s).
50 Large animal neurology

to the patient and performing an even more critical rule out certain disease processes, a therapeutic plan,
evaluation. Thus, if facial weakness is suspected but and a plan for client education, including economic
not clearly seen, the examiner can return to observe advice, herd health management, and prognostic
the horse for facial asymmetry while it is standing considerations.
quietly in its stall without any stimulation. Also, a
blindfold may be applied to exaggerate evidence of
vestibular disease. Finally, a very fractious or a very References
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ness in the limbs may be exercised before a re-­ Vet Rec] 1984; 6: 43–53.
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6 Lorenz MD, Coates J and Kent M. Chapters 1 and 2, in
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15 Holliday TA. Clinical signs of acute and chronic experimental
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Initial plan 16 Herron MA, Martin JE and Joyce JR. Quantitative study of the
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newborn foals according to age. Equine Vet Educ 2011; 23(1):
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lesion may be suspected but is usually not proven 19 Ozgel O, Duzler A, Dursun N and Beyaz F. The morphology of
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21 Jenkinson DM, Elder HY and Bovell DL. Equine sweating and
• Shivering • Rearing violently when first ridden anhidrosis Part 2: anhidrosis. Vet Dermatol 2007; 18(1): 2–11.
• Stringhalt-­like movements • Extreme difficulty in rising 22 Usenik EA. Sympathetic innervation of the head and neck of
• Hyperreflexic movements • Localized hypertonia and tremor the horse: neuropharmacological studies of sweating in the
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23 Cohen LA. Role of eye and neck proprioceptive mechanisms in 32 Bailey CS and Kitchell RL. Cutaneous sensory testing in the
body orientation and motor coordination. J Neurophysiol dog. J Vet Intern Med 1987; 1(3): 128–135.
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24 Biemond A and De Jong JM. On cervical nystagmus and Comm. 1988.
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26 Bankoul S and Neuhuber WL. A cervical primary afferent neurological examination. Vet Clin North Am Equine Pract
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26 Greet TR, Jeffcott LB, Whitwell KE and Cook WR. The slap test 1511–1524.
for laryngeal adductory function in horses with suspected cer­ 36 Chiapetta JR, Baker JC and Feeney DA. Vertebral fracture,
vical spinal cord damage. Equine Vet J 1980; 12(3): 127–131. extensor hypertonia of thoracic limbs, and paralysis of pelvic
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HO. Evaluation of the thoraco-­laryngeal reflex (’slap test’) as Vet Med Assoc 1985; 186(4): 387–388.
an aid to the diagnosis of cervical spinal cord and brainstem 37 Firshman AM, Valberg SJ, Bender JB, Annandale EJ and
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28 Newton-­Clarke MJ, Divers TJ and Valentine BA. Evaluation of the skeletal muscle fixation techniques for the diagnosis of poly­
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355–357. 38 Valberg SJ, Lewis SS, Shivers JL, et al. The equine movement
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 3
Ancillary diagnostic aids

DiseasePage Computed tomography 62

Routine clinicopathological tests 53 Magnetic resonance imaging 63
Thermography65
Genetic markers 53 Scintigraphy 65
Cerebrospinal fluid analysis 54
Ultrasonography65
Spinal endoscopy 65
Electrodiagnostic testing 59
Brain biopsy 65
Neuroimaging59
Plain and contrast radiography 59 References65

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Ancillary diagnostic aids 53

Routine clinicopathological tests tumors can often be detected using current endo-
crinologic testing procedures.5,6
A routine hemogram can assist in the diagnosis of Specific serum antibody titers, particularly when
some infectious and inflammatory diseases, lympho- assayed on acute and convalescent sera, are helpful
sarcoma and trauma with blood loss. Results of in diagnosing infectious diseases such as equine
routine blood chemistry tests, many of which can be viral encephalitis, equine infectious anemia, equine
obtained at animal side by the use of convenient herpesvirus-­ 1 myeloencephalopathy, louping ill,
point-­of-­care devices, assist in defining many meta- malignant catarrhal fever, pseudorabies, and bovine
bolic diseases affecting the nervous system, particu- leukemia virus infection. Blood and tissue toxin and
larly liver failure, hyperammonemia, renal failure/ nutrient concentrations can assist in diagnosing
uremia, hypocalcemia, hypercalcemia, hypomagne- intoxications and nutritional disorders.
semia, hypokalemia, hyperkalemia, and hypogly-
cemia. Special serum enzyme and other assays and
organ biopsies may be performed to confirm liver
and muscle disease, and routine urinalysis has its
Genetic markers
place in monitoring pigment excretion in systemic With accurate phenotypic identification, screening
diseases (Figure 3.1). Detecting circulating pyrrolic with genetic markers is now available to make the
metabolites of pyrrolizidine alkaloids from plants precise identification of several neural and muscular
responsible for huge losses of herbivores from liver diseases in large animals possible (see text box).
disease is possible,1 and in future more use may well be These include hyperkalemic periodic paralysis and
made of detection of plant toxins in blood samples of glycogen branching enzyme deficiency in horses, cit-
patients suspected of suffering other plant poisonings. rullinemia and complex vertebral malformation in
Assays for toxic chemicals and their effector compounds cattle, and scrapie susceptibility in sheep and goats.
in body fluids and tissues depend on knowledge of New genetic markers are certainly becoming available
the particular intoxicant, e.g., cholinesterase activity all the time. Testing for many of the genetic markers
for organophosphate intoxication2,3 and cantharidin for neuromuscular disorders in large animals is
for blister beetle poisoning.4 offered by Veterinary Genetics Laboratory, University of
Only rarely do pituitary tumors result in overt California, Davis, CA, USA; although there are numer-
neurologic syndromes such as blindness and collaps- ous commercial laboratories offering such tests.
ing episodes, but those that are functionally excreting A selection is presented in the adjacent text box.

Figure 3.1 In the appropriate clinical setting, red to brown discoloration to urine normally indicates the presence of globin pigments that is positive for
same on a dip stick assay and is an excellent ancillary aid to diagnosis. Myoglobinuria is seen in these urine samples from a horse recovering from acute
rhabdomyolysis. The acute sample taken is on the left through to the sample taken after recovery on the right. Although myoglobin is usually brown and
hemoglobinuria is usually red, as seen here there can be poor distinction based on color alone.
54 Large animal neurology

Selection of neuromuscular genetic tests that are available

Alpha-­Mannosidosis Dwarfism/Chondrodysplasia Myotonia in New Forest Ponies

Arthrogryposis Multiplex Friesian Dwarfism/Hydrocephalus Neuropathic Hydrocephalus
Beta-­Mannosidosis Glycogen Branching Enzyme Deficiency Occipitoatlantoaxial Malformation
Bovine Pseudomyotonia Hyperkalemia Periodic Paralysis Progressive Ataxia of Charolais Cattle
Cerebellar Abiotrophy Idiopathic Epilepsy of Hereford Cattle Spider Lamb Syndrome
Ceroid Lipofuscinosis Lavender Foal Syndrome Stationary Night Blindness
Citrullinemia Malignant Hyperthermia
Complex Vertebral Malformation Myosin Heavy Chain-­1 Disorders

Selection of Large Animal Veterinary Genetic Testing Laboratories (URLs logged March 2022)

Animal Genetics Inc. Neogen Corporation

Biogenetic Services, Inc. Quantum Genetix
Equine Neuromuscular Diagnostic Laboratory UC Davis list of Cattle Genetic Testing Laboratories
Eurofins AgriGenomics UC Davis Veterinary Genetics Laboratory
Genetic Testing at Gluck VetGen
Genetic Visions-­ST Zoetis Animal Genetics
Illumina Inc.

Cerebrospinal fluid analysis

The routine collection procedures for cerebrospinal
fluid (CSF) sampling from large animals (Figure 3.2)
have been described and simplified,7–12 and tech-
niques for the analysis of CSF samples have also been
published.12–19 Techniques for CSF collection from the
horse are shown in Figures 3.3, 3.4, and 3.5, and those
described for other large animals (Figure 3.6) can be
extrapolated directly from the horse and from rumi-
nants.20–22 Ultrasound-­guided collection of CSF can
also be considered,23,24 and such ultrasound-­guided
techniques for the collection of fluid from the atlan-
tooccipital (Figure 3.7) and atlantoaxial spaces
(Figure 3.8) in standing, adult horses can be useful in
certain circumstances.20–22,25 These are safe procedures
using effective chemical restraint, although the possi-
bility of inadvertent movement resulting in spinal
cord penetration is always of concern. It is likely that
worrisome signs of somnolence, stiff neck, and fever
that resolves in a day or so following the cervical cen-
tesis occurs in a few cases. In neonatal foals, calves,
camelids, and piglets, as well as sheep and goats, it is
advantageous to use a 40–50 mm (1.5–2 inches), 20 ga
disposable hypodermic needle with a plastic hub for
all atlantooccipital CSF c­ ollections. These needles are
exceedingly atraumatic, and in obtunded and in Figure 3.2 Multiple tests were performed on this patient suspected of
lightly sedated recumbent patients they cause mini- having a neuromuscular disorder. These included lumbosacral cerebrospi-
nal fluid collection (1), needle electromyography (2), and muscle biopsies
mal or no patient reaction. More importantly, CSF
of type I and type II muscle-­fiber-­predominant muscles taken from sacro-
appears in the hub of the needle immediately after it caudalis dorsalis medialis and semitendinosus muscles at sites (indicated
enters the subarachnoid space. A sample can be by 3 and 4), respectively.
 Ancillary diagnostic aids 55

Figure 3.3 Atlantooccipital cerebrospinal fluid collection from the

recumbent horse. Spinal needle in position with stilette removed. Palpable
landmarks are the cranial borders of the atlas (filled circles) and the exter-
nal occipital protuberance (cross) on the dorsal midline. (Source: From
Mayhew11 with permission.

Figure 3.5 Lumbosacral spinal fluid collection from the horse. Transverse
dissection through lumbosacral articulations, cranial view. Spinal needle
passes through the skin, thoracolumbar fascia adjacent to the inters-
pinous ligaments, interarcuate ligament, dorsal dura mater and arach-
noid, dorsal subarachnoid space, and conus medullaris. Needle point is in
the ventral subarachnoid space. Inset shows the cranial view of pelvis,
sacrum, and the area of dissection. Source: From Mayhew11 with
permission.

cellular debris than a stylet-­ in technique using a

standard CSF ­styletted needle.26
If a patient is in an intensive care facility showing
severe focal or diffuse brain injury, then considera-
tion might be given to inserting a separate
­subarachnoid or subdural cranial catheter at the time
of anesthesia for sampling CSF from the AO site to
allow the assessment of intracranial pressure and the
derivation of an estimate of cerebral perfusion pres-
sure.27,28 This can be of use in determining the effec-
Figure 3.4 Lumbosacral cerebrospinal fluid collection from the standing
horse. Spinal needle in position with stilette removed. Palpable landmarks
tiveness of ongoing management of such cases.
are the caudal borders of each tuber coxae (filled circles), the caudal edge Patient-­ side observations and tests are extremely
of the spine of L6 (star), the cranial edge of the second sacral spine (filled important at this stage. For example, if initial CSF is
triangle), and the cranial edge of each tuber sacrale (filled triangle). pink but clears, iatrogenic hemorrhage is likely the
Source: From Mayhew11 with permission. cause. With a sick neonatal patient, cloudy CSF with
a low glucose content detected on urine test strips
obtained, and the needle withdrawn much more rap- likely indicates suppurative meningitis. Particularly
idly than if a styletted needle is used—­very important during lumbosacral sampling, small particles can
in nonanesthetized patients. Indeed, during CSF col- often be seen to swirl in the aspirated sample. These
lection from the cisterna magna of anesthetized dogs, are usually determined to be epidural fat and small
it was shown that a stylet-­out technique was per- aggregates of collagenous tissue introduced into the
formed more r­ apidly and yielded a sample with less sample at the time of collection, likely reasons for
56 Large animal neurology

(A) (B)

Figure 3.6 Performing CSF collection from the atlantooccipital (AO) (A) and lumbosacral (LS) (B) sites is very straightforward with appropriate restraint,
sedation, and/or general anesthesia. In very young patients light sedation is adequate, and in obtunded patients simple restraint suffices to perform an
AO collection. Collection of CSF from the LS site is easier with the patient standing as the landmarks are more easily palpable and symmetric.
The landmarks are shown for the AO procedure in a calf (A) with the superficial site for skin penetration indicated by . This site is at the intersection
of a line joining the cranial borders of the wings of the atlas indicated by linear marks, with the midline, indicated by the spot over the occipital protuber-
ance, while the head is flexed 90° to the neck as shown. A 19–21g, 30–45 mm hypodermic needle with plastic hub is ideal for this procedure, allowing
for CSF to appear in the hub instantly the subarachnoid space is penetrated. The basic site for an LS procedure (B) is where a line joining the caudal
aspects of the wings of the ilia (yellow dotted line) crosses the midline, as indicated by . This coincides with a palpable depression between the paired
tubers sacrale (TS) laterally and the dorsal spines of L6 and S2 on the midline—­the spine of S1 normally being too short to palpate. An 8–20 cm, 18 or
20 g spinal needle with fitted stilette is used for all adult animals depending on their size.
Penetration of the terminal spinal cord during an LS procedure is essentially inconsequential. Damage to the medulla oblongata, which occurs on
pathologic inspection more often than is clinically suspected, can result in additional neurologic signs.

falsely elevated CSF-­CK activity. When CSF analysis e­ rythrocytes and usually less than 6 × 106/L (=6/μL)
cannot proceed immediately following collection, small mononuclear cells. Protein content is usually
the addition of a small, quantified volume (~10%) of between 0.5 and 1.0 g/L (=50–100 mg/dL) in the
autologous serum to an aliquot of the sample may horse with an absolute range of 0.1–1.2 g/L depending
help support cells for better cytologic harvesting, at on the laboratory and can be up to 1.8 g/L in normal
least for 24 h. neonatal foals. Ruminants and pigs usually have CSF
with a protein content of less than 0.75 g/L.18 Specific
electrophoretic protein fractions in CSF can be
Of note is that estimates of protein content in CSF may assayed by numerous methods,17 but the utility of
be substantially higher, at least when tested by the pyro- these results in changing the clinical course of cases is
gallol red method, when CSF is collected into commonly doubtful at present. Neonates of all species may have
used red vacutainer tubes containing clot activator.(29) slightly xanthochromic CSF.
To help account for the blood contamination of
CSF samples and to help determine the local versus
The results of CSF analysis can reflect diseases in systemic source of measured CSF immunoglobulin
the brain and spinal cord just as a hemogram detects content, the determination of the albumin quotient
many systemic disease states. Thus, CSF analysis is and the IgG index, respectively, can be of some
one of the most helpful aids in determining the use.30,31 Additionally, on the assumption that all red
nature of current and progressive CNS lesions. blood cells are from the circulation and not the result
Normal CSF is clear and colorless with a refractive of previous subarachnoid bleeding, arithmetical
index of 1.3347–1.3350. In addition, it contains no ­corrections can be made for all measured co­mponents
 Ancillary diagnostic aids 57

tissue damage, but its measurement is somewhat

complex and the interpretation of results of its
­content in CSF in disease states is not extremely spe-
cific. Total CK activity in CSF may well vary with dis-
ease states,36 and the utility of such assays in general
­disease states has been questioned.37 In specific neu-
romitochondrial disorders, lactate and pyruvate
measurements may well be of diagnostic use.
Assays are available for proteins in and antibodies to
infectious agents in CSF.38,39 These tests are probably
best for the subacute to chronic infections with par-
ticular viruses and protozoa. Indeed, testing for the
presence of antibodies to Sarcocystis and Neospora sur-
face antigens in CSF and blood has become popular
and is very useful to assist in the diagnosis of equine
protozoal myeloencephalitis,40,41 especially when
Sarcocystis neurona vaccines were used.38 In particular,
the ratios of specific antibody in serum to CSF are
used to reveal locally produced (i.e., intrathecal) anti-
bodies indicative of CNS infection.42 Unfortunately,
(A)
while this antibody ratio technique is highly specific
and sensitive for EPM diagnosis, it is not accurate for
the diagnosis of equine neuroborreliosis.43 As with
many of such tests, a negative result with S. neurona
immunotesting using CSF (and serum) is very useful
to rule out the disease in a case with clear clinical signs
in an area where the background frequency of expo-
sure is low. However, debate arises as to interpretation
of marginal test results when clinical signs are equivo-
cal and there is a high exposure rate in the sample
population. This is particularly true for a negative
(B) result, as the negative predictive value declines with
increasing disease (exposure) prevalence, and for EPM
Figure 3.7 Collection of CSF from the atlanto-­occipital cistern in a the consequences of a f­alse-­negative result (failure to
standing sedated horse. After the ears have been secured in a forward treat) are more serious than a false-­positive result
position and the area clipped and surgically prepared, a 3.5­ inch (unnecessary treatment). Again, with a high rate of
(8-10 cm) 18g spinal needle is introduced and advanced as described for
the procedure in recumbent anesthetized horses (A). When a distinct
false-­positive and false-­negative results occurring with
change in resistance (“pop”) is felt, the stylet is removed, and CSF is borreliosis testing, there can be no reliance on serology
gently aspirated into a syringe attached to extension tubing (B). The nee- for the confirmation of that disease.
dle may be advanced under ultrasound guidance as described by One aspect of CSF chemistry that may well
Depecker et al.20 Source: Images courtesy of Carol Clark, Peterson Smith become useful in future is the analysis of levels of
Equine Hospital & Complete Care, Ocala, FL, USA.
neurotransmitters, neurohormonal metabolic prod-
ucts, and antibodies directed against constitutive
of CSF. Such corrections for routinely ­measured CSF proteins to help categorize some disease states.44–49
components have not proven to consistently improve This will most likely relate to those diseases that have
the utility of absolute measurements of amounts of CSF no recognized morbid neuropathologic basis, such
constituents.32–34 Repeat thecal puncture from the lum- as shivers, headshaking, narcolepsy, cataplexy,
bosacral or from the atlanto-­axial space 2 weeks apart self-­
­ mutilation, rage syndrome, acquired tremor
has been shown not to impact results of CSF analysis.35 ­syndromes, spastic syndrome, and spastic paresis,
Many constitutive and induced enzymes have although some progress has recently been made on
activities expressed in CSF. The cytosolic BB-­CK iso- the search for a putative genetic component to the
enzyme almost certainly is quite specific for neuronal latter two syndromes.50
58 Large animal neurology

(A) (B) (C)

Figure 3.8 Ultrasound-­guided collection of CSF from between C1 and C2 in a standing sedated horse (A and B). In C, the spinal cord (SC) and dura
mater (green arrows) are imaged using a transversely oriented ultrasound transducer. A 3.5­inch (8-10 cm) 18 g styletted needle is introduced from below
the transducer and advanced into the subarachnoid space, then the stylet is removed and CSF is aspirated into a syringe attached to extension tubing.
The dashed orange line in C indicates a typical dorsolateral to ventromedial path of needle placement. The “Z” symbol at the top marks the dorsal aspect
of the ultrasound image. Source: Images courtesy of Sally DeNotta, University of Florida, USA.

With most CNS malformations, the CSF analysis expected modest pleocytosis, usually mononuclear,
will be normal, although those anomalies that result and, extrapolating from canine practice, it may well
in tethering of neural tissues such as complex verte- be worth sampling CSF from both the cervical and
bral deformations can result in progressive disease lumbar regions to maximize the likelihood of identi-
with ongoing traction injury to CNS neural tissues fying the major CSF cytologic response.51 This rec-
during growth, thus potentially resulting in CSF ommendation also likely holds true for many of the
changes consistent with trauma. If a malformation of infectious spinal disorders.
the calvaria or vertebral column damages underlying With traumatic injury to the CNS, there is often
nervous tissue, the CSF may reflect compression with some hemorrhage into the CSF with resulting yellow
evidence of subtle hemorrhage. discoloration that can persist for days after the insult.
Infectious diseases can result in CSF pleocytosis This xanthochromia remains after red cells have been
and the elevation of protein content. The cell type centrifuged off. Neutrophils, not showing toxic
present varies considerably, but generally neutrophils changes, followed by macrophages, will usually
predominate with bacterial diseases and small mono- appear in the CSF in response to hemorrhage.
nuclear cells with viral diseases. Notable exceptions In most toxic, nutritional, and metabolic neuro-
to this are high neutrophil numbers with Eastern logic diseases, the results of routine CSF analyses are
equine encephalitis and high mononuclear cell generally normal. However, for those diseases in
numbers with listeriosis and equine neuroborreliosis. which there can be considerable tissue destruction,
Fungal and protozoal diseases u ­ sually cause mixed such as lead poisoning, sodium salt/water i­ ntoxication
cell responses. Protozoal, and particularly helminth and polioencephalomalacia in ruminants, and moldy
parasite infestations, may produce an eosinophilic corn-­associated leukoencephalomalacia in horses,
and neutrophilic response in the CSF, as well as hem- there may be some protein leakage into, and a mono-
orrhage. In contrast to bacterial meningitis where the nuclear cell response within, the CSF.
neutrophils are degenerate and show toxic changes, Typically, there is leakage of protein and some xan-
with parasitic invasions and specific viral diseases the thochromia without any significant pleocytosis in
polymorphonuclear cells are nondegenerate and many vascular diseases. If the hemorrhage is large,
multilobulated due to their age. In most chronic then neutrophils and macrophages may also be seen.
inflammatory states and in diseases in which there is Primary genetic (degenerative) diseases do not
much CNS tissue necrosis, the CSF can contain many typically cause any changes in CSF constituents, and
large mononuclear cells or macrophages. most frequently, the CSF analysis is normal. Early in
Although immune-­associated CNS disorders such the course of cell degeneration and especially in very
as canine steroid-­responsive meningitis have not yet young patients, some protein and even cellular
been reported in large animals, there would be an response may be expected. Those resulting in the
 Ancillary diagnostic aids 59

accumulation of products such as occurs in the stor- states.87–89 This and the additional use of more elabo-
age diseases may result in macrophages containing rate but error-­ prone quantitative EMG investiga-
waste material in the CNS and thence in CSF. tions58,60,62,70 should allow more accurate identification
Neoplasms can act like other space-­ occupying of neuromuscular disorders.
lesions, such as abscesses, granulomas (such as cho- Finally, measuring conduction velocity across
lesterinic granulomas in horses) and hematomas, and the cauda equina can be simply performed by using
can increase intracranial pressure. The most frequent one stimulating electrode placed over the dura
CSF change in patients with neoplasia is a slight eleva- mater at the lumbosacral space and another stimu-
tion in protein content. Sometimes there is evidence of lating ­electrode in the sacrocaudal cauda equina,
mild injury, xanthochromia, and a few macrophages. with anode in adjacent skin. Induced motor action
Rarely, there have been atypical lymphocytes detected potentials are recorded using electrodes in a ventral
in CSF from cattle with CNS lymphosarcoma. Atypical coccygeal muscle. No conduction from the cranial
cells such as melanoblasts have been detected in CSF stimulating site, with some potentials recorded from
samples, but it is worth considering whether such cells the caudal site early in a case of a fractured sacrum,
may have been disrupted from meningeal sites during can reasonably be taken as the cauda equina being
the course of CSF collection. totally severed. In this context, measuring the maximal
Because of the lymphatic-­like drainage system of bladder contraction pressure and maximal urethral
the CNS from perivascular and Virchow–Robin closure pressure is a technique90 that should assist in
spaces ultimately to the subarachnoid space, any pro- better defining the site of a lesion and should particu-
cess that is contained within the parenchyma of the larly assist in monitoring the use of drugs that can be
CNS may ultimately cause the leakage of pigments or used to treat patients suffering from urinary incon-
protein, or the exfoliation of cells into the CSF. tinence. Of note is the fact that there appears to be
discrepancies in reported n ­ ormal ­values.90 However,
the measurement of ­ intravesicular and urethral
Electrodiagnostic testing pressure profiles could well be useful in monitoring
Electroencephalography (EEG), needle electromyo- horses with urinary incontinence.91,92
graphy (EMG) (Figure 3.2), quantitative EMG, and
nerve stimulation and conduction testing contribute Neuroimaging
to a complete neurological evaluation. The tech-
Plain and contrast radiography
niques are used in large animals52–63 and are the same
as those used in small animal neurology.64–66 An Radiography of the calvaria and vertebral column
ambulatory EEG system has been described that (Figure 3.11) is indispensable for identifying normal
allows telemetric recording from freely moving variations, bony malformations, fractures and osteomy-
horses.67 Considerable experience in using these elitis,93–104 and even evidence of reactivity to parasites.105
ancillary aids is required to be able to interpret elec- Undoubtedly, the use of digital radiography will con-
trophysiologic studies in large animals because find- tinue to be used more widely allowing better routine
ings in normal animals are not well defined.60,68–70 radiographic imaging and decreased radiation
This fact, and the expense of the equipment, makes exposure.
these procedures rather out of reach for most large Almost certainly, the cervical region is the
animal clinicians. However, visual evoked, brainstem area most often radiographed in neurologic large
auditory evoked, and other evoked potential testing animal patients. However, even though the radio-
(Figure 3.9) definitely have become more widely used graphic anatomy of equine cervical vertebrae is well
in large animal neurology over the last decade or so, described, many normal variations and inconse-
and references can be consulted for techniques and quential findings must still be realized in interpreting
initial methods of interpretation.71–84 such radiographs.99,104,106,107 The frequent finding in
Certainly, the reasonably innocuous testing for <5% of Thoroughbred and Warmblood horses of
transcranial magnetic and electrical motor evoked transposition of ventral p ­ rocesses of C6 onto C5 and
potentials (Figure 3.10) now has received attention in more often onto C7 on one or both sides must be
large animal neurology,85,86 and it appears to be a very ­considered when vertebrae are being identified on
sensitive and quite specific electrophysiologic test for radiographs.104,108 This can also occur occasionally in
the disruption of somatic motor pathways in disease other breeds including ponies.
60 Large animal neurology

Figure 3.9 Brainstem auditory evoked potential (BAEP) recording is a minimally invasive procedure as being performed here in a patient suspected as
having vestibulocochlear (CN VIII) nerve disease. Broad band clicks are generated (1) and passed to insert earphones. The electroencephalogram is
recorded with subcutaneous electrodes and passed through a preamplifier (2) to be recorded in an electrodiagnostic unit (3). By signal averaging many
individual electrical responses, a waveform is produced that represents electric activity in the brainstem because of the clicks, which can be printed out
as a BAEP trace (shown below). This horse indeed is deaf in the left ear as shown by there being no brainstem electrical activity resulting when the left
ear is stimulated (top two traces) compared to the normal responses recorded from the left (third trace down) and right (bottom trace) sides of the brain
when the right ear is stimulated.

Notable though usually inconsequential radiographic find- • Serpentine lucent vascular channels on the spine of C2.
ings on equine cervical radiographs include the following: • Relative lucencies of the pedicles of the arches of the
• Variations and asymmetry in the shape of the interver- vertebral canal of C1 and C2.
tebral notch or orifice at the cranial border of C2. • Irregular border to the caudal aspect of the spine of C2.
• Irregularities to the dorsal aspect of the caudal p­ hyses • Circular 3-­20 mm, cyst-­like lucencies occasionally pre-
of C2–C7 projecting into the intervertebral space. sent in the arches or bodies of all cervical vertebrae
• Separate ossification of the caudal projection of the • Variable size of, and irregular dorsal border to spines
transverse processes of C6. of C3-­6
• One or two transverse processes of C6 sometimes • large and cranially-­projecting, irregularly-­mineralized,
transferred onto C5 or onto C7. dorsal spinous process on C7 and T1
 Ancillary diagnostic aids 61

Figure 3.10 Magnetic motor evoked potential (mMEP) recording can be undertaken in the fully conscious cooperative patient or with the patient
sedated with alpha-­2 and synthetic narcotic drugs. A magnetic stimulator (1) creates a very brief magnetic pulse in the attached coil (2) held centrally
over the forebrain of the patient. At the onset of the stimulus, the generator triggers an electrodiagnostic unit (not shown—­see Figure 3.9) to begin
recording from the skin clip electrodes (3) placed over muscles such as cranial tibial (CT) and extensor carpi radialis (ECR) limb muscles. One or a few
traces can be summated to produce mMEP waveforms that indicate the time for impulses to be produced in the brain motor centers and propagated
along the central motor pathways to the peripheral nerves and ultimately the muscles from which a summated motor unit action potential can be
recorded. Inset (4) shows a printout of the mMEP waveforms recorded from the ECR (top) and CT (bottom) muscles. Conduction times from stimulus till
muscle response for these recordings were 24 ms to the ECR muscle and 46 ms to the CT muscle.

oblique radiographic views (Figure 3.13) can be u ­ seful

in lateralizing changes seen on vertebral (and skull)
radiographs especially where DV views are difficult or
impossible to obtain.97 Interpretation of plain radio-
graphs of other large animal species111,112 is less fre-
quently undertaken and thus more problematic113
such that control images often need to be consulted.18
The techniques of positive contrast myelography
have been described in large animals, particularly
horses.103,114–122 These procedures are useful for defining
spinal cord compression and swelling of the s­ pinal cord,
although experience is required to be able to obtain sat-
isfactory studies (Figure 3.14). Complications do occur,
Figure 3.11 Radiographic evidence of a chronic lesion in the area of the and the procedures can be prolonged and distressing to
occipital bursa such as the irregular mass of mineralized tissue seen here the patient.123,124 Consequently, it is suggested that these
(arrows) has been suggested to be one cause for headshaking in horses. procedures be performed only by an experienced radi-
This horse was not a headshaker, and the radiographs were taken for
other reasons.
ographer who has the correct equipment and only when
the clinician is prepared to attempt whatever surgical
Obtaining high-­quality radiographs is absolutely and medical approach is indicated, including euthanasia,
paramount to the accurate quantification of any as necessary at the end of the procedure. We do not con-
measurements such as minimal sagittal diameter of done performing positive contrast myelography on non-
the vertebral canal (Figure 3.12).96,109,110 Standardized anesthetized large animal patients.125 Notwithstanding
62 Large animal neurology

Figure 3.13 Oblique lateral radiographs can assist in lateralizing altera-

tions to vertebral articular processes in wobblers and horses suffering
from neck pain and unusual thoracic limb gait abnormalities. This results
in skyline views of the articular surfaces as shown here using a 34°
(A) (above lateral) oblique projection for one of the C2–3 articulations
(between yellow arrows). One of the C3–4 articulations (between green
arrows) is not quite as well defined on this projection as the more caudal
cervical articular surfaces are on a greater angle such that at C6–7 the
X-­ray beam needs to be directed from at least 45° above horizontal with
the horse’s neck on a horizontal axis.

(B)

Figure 3.12 Obtaining accurate measurements such as minimal sagittal

diameters from radiographs does depend upon obtaining a true lateral pro-
jection and good exposure factors—­the latter being more readily obtained
with digital radiography. A and B are images from the same average quality,
standing radiograph of the C3–4 intervertebral articulation of a yearling
with CVM using different postprocess exposures. The sites that need to be
precisely identified to accurately measure the sagittal ratios are indicated by
circles in A and are very indistinct. With image manipulation, reasonable
measurements can be obtained for the intravertebral (white bar) and
intervertebral (yellow bar) sagittal diameters. Part of the problem with mak-
ing measurements lies with the superimposition of structures including the
pedicles of the articular processes overlying the laminae of the dorsal arch
Figure 3.14 Thinning of ventral (yellow arrows) and dorsal (white arrow
of the vertebral canal. Also blurred and paired lines of the dorsal and espe-
heads) myelographic contrast columns as shown here in two cases of
cially ventral margins of the vertebral canal due to obliquity, add to the
EPM with swollen spinal cords at C6–7 can be mistaken for epidural
imprecision of measurements.
compression and thus possible evidence for spinal cord compression and
CVM.

Computed tomography
these issues, contrast myelography and subjective and
objective assessment of measured parameters of com- Computed tomography (CT) and CT contrast myelog-
pression of spinal cord taken from these studies are use- raphy have some advantages over unenhanced radiog-
ful to define lesions prior to corrective surgical raphy but at an expense. More detailed imaging of bony
procedures being carried out99,121, 126–132 and to help focus structures such as vertebrae and petrosal, basilar and
diagnostic postmortem studies.53,113, 133,134 hyoid bones, being able to view structures in three
 Ancillary diagnostic aids 63

(A) (B)

(C)

Figure 3.15 A, B & C are transverse, dorsal, and median plane views, respectively, of CT myelogram centered on the C3-­4 intervertebral site of a
16-­month-­old ataxic Thoroughbred colt with Type-­I CVM. The dashed blue line in A traces the outer circumference of the C3-­4 intervertebral disc.
Transverse (A) and dorsal (B) projections were reconstructed in the planes shown as a and b in C. Although dorsal flaring of the caudal vertebral body of
C3 (arrow) and a kyphotic angle between C3 and C4 are obvious in C, spinal cord compression is not clearly revealed in A. Conventional radiographic
myelography was required to demonstrate dynamic dorsoventral spinal cord compression at this site. Early osteochondral degenerative changes are
evident in the articular process joints. There are osteophytes at the dorsal joint margins, sclerosis of the articular aspects of the C3 processes and cavita-
tion of articular surfaces of C4 with possible bony fragmentation (orange circles).

planes and perform anatomical reconstructions can be cord MR morphology of large animals are availa-
definite advantages for diagnostic purposes.102,135–141 CT ble.164–166 Identifying pathologic changes has assisted in
also images some soft tissue lesions well.113,142–163 The diagnosing a wide range of diseases, including brain
utility of CT for imaging of large animals has been abscess, brain injury, pituitary adenoma, nigropallidal
enhanced at a few high-­end referral centers by the encephalomalacia, otitis media, hydrocephalus, cere-
development of large-­ bore mobile scanners and bellar disorders, aplasia of corpus callosum, inflam-
robotic-­controlled, gantry-less digital systems. Both of matory foci, and coenurosis.144,150, 151,164–173 An example
these methods enable high-­resolution CT imaging of of the clinical application of MR imaging to equine
the heads and cervical v­ertebrae of standing, awake brain disorders is given in Figure 3.17.
horses. Examples of the detail in image definition and
some aspects of the diagnostic utility of CT myelogra- In making judgements from any test procedure such as
phy are shown in Figures 3.15 and 3.16. cervical radiographs, it is axiomatic that, depending on
cutoff criteria taken from reference values, there will
Magnetic resonance imaging be variable proportions of false-­positive and false-­
negative diagnoses. As well as considering normal vari-
Undoubtedly, magnetic resonance (MR) imaging with
ance, test error, and clinician bias, any test is only a
and without gadolinium contrast is superior for iden-
snapshot in time so that results may well have changed
tifying lesions primarily involving nervous tissues, and
since the onset of the problem.
studies of the normal variability of brain and spinal
 (A) (B) (C)

Figure 3.16 CT myelograms of an 18-­month-­old ataxic Thoroughbred horse that underwent ventral stabilization surgery at C6-­7 for Type-­II CVM. A,
B & C are cranial views (left is to the right side) of transverse plane images at C5-­6, C3-­4, and C6-­7, respectively. The stainless-­steel basket implant can
be seen ventrally in C. In A, there are prominent osteophytes on the dorsal margins of the APJs and the left intervertebral foramen at that site is markedly
narrow with adjacent sclerotic changes suggesting contact across the foramen (orange circle). In B there is marked, asymmetric osteochondral modeling
of APJs that is much worse on the left, narrowing of the joint spaces bilaterally, a region of osteolysis (arrow) and patchy areas of bony attenuation in
the left C6 articular process. There is extensive modeling of both sets of APJs and joint spaces and intervertebral foramina are markedly narrow at C6-­7 in
C, although as in B, such narrowing seen on one slice does not constitute reason to diagnose foraminal stenosis with intervertebral neurovascular bundle
compression. Spinal cord compression is not evident in any of these views.

(A) (B)

(C) (D)

Figure 3.17 Brain 3T MR images of a horse with presumptive equine protozoal myeloencephalitis {EPM]. Rostral is to the left in panel C and towards
the top of panel D; the left side of the brain is to the right of images A, B & D. The images in A, B & C are T2-­weighted sequences and D is a short-
­T1 inversion recovery (STIR) sequence. The transverse images A & B were obtained at the planes indicated by a & b in C. Image C is a sagittal section at
plane c in A. D is a ventral view of a dorsal plane just ventral to the mesencephalic aqueduct.
This 15-­year-­old Holstein hunter gelding had a 2-­week history of somnolence, right-­sided central blindness, and predominantly right-­sided limb ataxia
and weakness. snSAG serum:CSF ratio was 6 (values <100 consistent with EPM). The horse was given nonstandard 7x doses of ponazuril on 2 successive
days. The day before presentation, he suddenly developed mild right-­sided head tilt and facial paresis. There are at least 3 areas of increased signal
intensity in the basilar regions: (i) left midbrain extending from the junction with the pons well into the diencephalon (thalamus/hypothalamus; white
arrows); (ii) right midbrain (yellow arrows); and (iii) left rostral thalamus (blue arrows). These areas did not enhance with gadolinium. The visible lesions
may account for the blind right eye (left thalamus), for persistent somnolence (sleep centers in the reticular formations of the midbrain and thalamus)
and forelimb weakness and conscious proprioceptive deficits but spinal/cerebellar ataxia, facial paresis and head tilt may have resulted from additional
un-­sectioned medullary, cerebellar or spinal cord foci. Unfortunately, the horse was unable to regain its feet after the MRI procedure and was euthanized.
Histopathologic examination revealed moderate to severe lymphoplasmacytic and histiocytic encephalitis of the midbrain and thalamus, with multifocal
neuronal degeneration and gliosis. Protozoal stages were not seen, possibly because of previous antiprotozoal treatment. The authors have successfully
treated several other horses with similar MR lesions consistent with EPM.
 Ancillary diagnostic aids 65

Thermography thrombosis193,199–202 and musculotendinous lesions203,204

and muscle atrophy.205 This imaging modality can also
Infrared, electronic thermography is a completely non-
be used to confirm the site of v­ ertebral arthritis and
invasive method of determining skin temperature.174,175
discospondylitis177,187 and the presence of clinical or
Thermography should be well suited for horses because
subclinical otitis media in calves.206 Recently, ultra-
of their short, even hair coat and because radiography
sonographic examinations performed per rectum
of the thoracolumbar vertebral column, which is so
have been used to find abnormalities of lumbosacral
useful in smaller patients, often contributes less to the
and L5–6 intervertebral discs and foramina and
neurologic workup of large patients.
associated lumbosacral nerves of horses.207,208 The
­
Superficial temperature primarily depends on
technique also had favor in ­confirming the ­presence of
cutaneous blood flow. Because many neurologic dis-
enlarged vertebral articular processes seen radio-
orders can be associated with local alterations in
graphically and in guiding the administration of intra-
blood flow, this diagnostic modality can help localize
­and periarticular injections of medicaments at these
neuromuscular lesions.174–177 In this manner, exercise-­
sites,209–214 whether they are indicated or not.
exacerbated focal, thoracolumbar myopathies with
associated pelvic limb gait abnormalities have been
corroborated by focal and asymmetric thermographic Spinal endoscopy
patterns before and after exercise. Also, neurologic The advent of microcameras has allowed the interesting
and disuse muscle atrophy have been associated with but orphan technique of epidural and subarachnoid
a lower overlying superficial temperature, when flexible endoscopy to be developed,215,216 but these tech-
compared with the normal, opposite side. However, niques are really awaiting disorders for evaluation.217
any such changes in skin temperature are very varia-
ble and not specific such that cutaneous t­ hermography
is not regarded as very useful for diagnosis and moni- Brain biopsy
toring of spinal cord and nerve root diseases in Sounding heroic in large animal neurology circles,
humans178,179 and large animals. Its utility in cases of brain biopsy is actually a relatively straightforward
back pain in horses175,177, 180 is also dubious. surgical exercise in human and small animal neurol-
Because loss of sympathetic innervation in the ogy,218,219 and the goal of obtaining a histologic diag-
horse causes demarcated cutaneous vasodilation and nosis is laudable. But of course the damage caused in
hyperhidrosis, thermography can be of great a­ ssistance attaining a biopsy for histologic evaluation must be
in localizing any lesion affecting the sympathetic nerv- kept minimal, and clinically vital regions of the brain
ous system, particularly those involving peripheral must be avoided. However, with training,220 the appli-
nerves that contain sympathetic fibers. For example, cation of new imaging techniques with neuronaviga-
the well-­known facial hyperthermia of Horner syn- tional guidance procedures will allow diagnostic
drome in the horse produces a characteristic, abnor- brain biopsies to be obtained efficiently.221
mal thermographic pattern.180–186

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 4
Pathologic responses of the nervous system

Disease  Page Mechanisms of disease 83

Gross changes 76
References87

Histologic reactions 80

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
76 Large animal neurology

This chapter reviews the gross and cellular r­ eactions the temporohyoid region or the cervical vertebrae—­
of nervous tissue in disease states and covers the gen- cranial base to T1-­and continue to harvest further
eral clinicopathologic characteristics of the mecha- tissues if no gross explanation for the signs becomes
nisms of neurologic disease. The aim is not to review evident. Histopathologically, most compressive
veterinary neuropathology, but to provide a basic lesions of the spinal cord, whether they are caused by
understanding of clinically ­important, neuropatho- previous external injury, a stenotic vertebral canal,
logic principles. The reader is referred to pathology osteomyelitis, or a tumor, are the result of trauma.
references for a more detailed coverage of most of Thus, the burden is often on the prosector to supply
these aspects of neuropathology.1–6 such pertinent etiologic information.
General reactions seen in tissues in response to path- A technique for a full postmortem examination
ologic insults and the associated terminology should be including removal of the brain and spinal cord from
understood. We must be able to communicate with the adult horse can be consulted.7,8 In lieu of the tech-
each other about neurologic diseases and understand nique outlined which requires facilities and time,
the pathogenesis of these diseases. Importantly, such an there are other suitable techniques for brain removal.
understanding allows us to sensibly investigate a A midline saw or hatchet cut allows for the removal
neurologic disorder of unknown cause and to under- of the brain halves. It is probably better to make two
stand, evaluate, and clinically interpret pathology transverse saw cuts through the calvarium, one at the
reports on animals dying of neurologic diseases. This level of the external auditory meatus (except for ves-
becomes economically significant when dealing with tibular syndromes) and the other at a level halfway
an outbreak of a neurologic disorder. between the caudal aspect of the bony orbit and the
external auditory meatus. This preserves most midline
structures and allows for removal of four sections of
Gross changes visible in nervous tissues brain after the cerebellar peduncles are cut to separate
the cerebellum. For all cases, particularly for smaller
Finding the lesion
heads, the dorsal neurocranium can be removed piece-
A complete necropsy, including the removal of the meal starting at the foramen magnum using bone
entire brain and spinal cord from a large animal, is an cutters, thus allowing the whole brain to be lifted out
arduous task. Nervous tissue shows the effects of autol- from the olfactory lobes and progressing caudaly cutting
ysis rapidly and is extremely susceptible to distortion cranial nerves as they exit the brain cavity (Figure 4.1).
before it is well fixed. There is nothing more frustrating The spinal cord can be harvested by preparing cervi-
for a pathologist than scanning numerous histologic cal, thoracic, and thoracolumbosacral vertebral column
sections of tissue soup because of careless and rushed sections. Then, a dorsal laminectomy is performed
processing of samples of neural tissue. However, using bone cutters for smaller samples allowing for
because of these facts and because so much vital infor- removal of the spinal cord sections using traction
mation can be gained by a thorough neurologic nec- applied to the dura mater and careful sharp section-
ropsy, it is worth doing if it is performed well. Failing ing of neural and vascular attachments. Alternatively,
this, a compromised or no pathologic diagnosis can be the spinal cord sections can be exposed by making a
expected. With the submission of inadequately pre- sagittal saw cut along the vertebrae exposing the ver-
pared specimens for study, cases such as harvesting tebral canal and lateral spinal cord and removing and
only the cervical spinal cord from a wobbler horse with labeling each section of cord for orientation. A spinal
a thoracic lesion, or only the brain from a lamb with cord removal instrument9 can be useful in removing
tetraplegia, or no peripheral nerves and muscles from a long sections of spinal cord from trimmed blocks of
calf with monoplegia all can be expected to frustrate vertebral column in large animals (Figure 4.2). The
both clinician and pathologist. Sometimes an abbrevi- dura mater should be carefully split along the dorsal
ated necropsy will suffice in obtaining a diagnosis. surface and almost complete transverse sections
Thus, there is no need to remove the petrosal bones made with a new razor blade through the cord at least
and vestibular nerves from a cow with only tail paraly- at every segment. Alternatively, in wobblers, the cer-
sis, although this does presuppose that an accurate vical vertebrae may be disarticulated and each seg-
neuroanatomic diagnosis has been made! ment of spinal cord labeled and oriented as to cranial
A practical approach to the postmortem examina- versus caudal. If there is good evidence from clinical
tion of a large animal with neurologic disease is to and imaging studies of the site of a focal spinal cord
begin at the site suspected of having a lesion such as lesion, then the preparation of the site of interest can
 Pathologic responses of the nervous system 77

not be available to perform a laminectomy or sagittal

vertebral cut to remove the spinal cord, and it may be
unpractical to preserve large sections of vertebral
column for the pathologist. A hatchet may then be
used to remove the vertebral bodies from the vertebral
arches using a ventral approach. The cuts are made in a
slightly medial direction, from the angle between the
vertebral bodies and the transverse processes in the
cervical and lumbar regions, or from the rib remnants
in the thoracic region. Alternatively, a spinal cord
removal tool9 may be used (Figure 4.2).

Gross artifacts
Vertebral and cranial fractures and separations some-
times occur at the time of euthanasia and during any
manipulation of the cadaver of both immature and heavy
large animals. This may be the result of falling, electrocu-
tion, dragging, and slinging. Surprisingly, considerable
hemorrhage may be present around such fracture sites,
and the histologic appearance can be difficult to interpret.
Figure 4.1 To remove the brain intact, a craniectomy can be performed as Irrespective of this, large, mainly subarachnoid, spinal
depicted here. Two saw cuts through the bones of the cranium are made and cranial hemorrhages also occur, especially if decapi-
(between arrows 1 and between arrows 2) on each side and then a trans-
tation is performed immediately after death.
verse cut is made over the rostral frontal region just caudal to the level of the
caudal extent of the bony orbits (arrows at 3). With further careful sawing Gross estimates of an excessive (or deficient) volume
and leverage (arrowhead) with a hand wedge (4), the cranial roof can be of CSF are almost impossible to make, and except for
removed. The brain is then removed by tilting the nasal region up and over noting any other major malformation, the evaluation
while cutting the exposed cranial nerves as they exit the calvarium. of an apparent slight increase in the size of ventricles
should await measurements made after fixation.
be more focused and carefully performed. As a rule, Areas of postmortem damage to nervous tissue
there will be no epidural fat evident on opening each can appear as a softening (malacia) and discoloration.
dorsal intervertebral space at sites of spinal cord com-
pression. This then becomes a signal of a likely com-
pressive lesion, warranting care when that segment of
cord is harvested. If in large wobbler cadavers the site
of a suspected compressive lesion(s) is not known,
the cervical vertebral column can be sectioned trans-
versely through the middle of each vertebral body so
that each ­segment of spinal cord can be removed
after cutting the spinal nerve roots. After spinal cord
removal, each block of vertebral sections or adjacent
halves of two vertebrae can be cut on the median
plane to expose all intervertebral sites where most
compressions occur in the neck of large animals.
Because the removal of the entire spinal cord from
an adult large animal is particularly difficult, the proce-
dure of sectioning the entire or appropriate parts of the Figure 4.2 With the vertebral column cut into cervical, cranial thoracic, and
vertebral column with enclosed spinal cord, trimming thoracolumbosacral sections, a laminectomy may be performed to remove the
spinal cord sections or a spinal cord removal instrument as shown can be
off excess soft tissues, and immersing the sections of
used to gently cut the spinal nerves in the epidural space allowing withdrawal
vertebral column in large volumes of 10% formalin is of the spinal cord segments. Such an instrument as shown at top is ~60–
an appropriate alternative means of preservation for 80 cm long and has a blunt-­ended, curved blade with indented cutting
shipment to a pathology laboratory. A band saw may surface at one end (two close-­up views are shown beneath).
78 Large animal neurology

Saw cuts and sites of tension may be apparent, but the

spinal cord in particular must be removed carefully to
avoid an effect akin to squirting toothpaste from a
tube; tension or compression on the spinal cord
within its dura mater easily causes constrictions,
areas of softening, discoloration, and dislocation of
parts of spinal cord tissue.
A common error in preserving large masses of ­neural
tissue is underestimating the volume of aldehyde fixa-
tive to use resulting in autolysis of tissues and even bac-
terial growth in the cramped samples sitting in a small
volume of fixative! A ratio of one-­part nervous tissue to
ten parts fixative is ideal, and changing the fixative after
24 h is good practice and helps reduce any blood stain-
ing of the preserved specimens. Partial and differential
fixation can produce localized changes in texture and Figure 4.3 Small volumes of necrosis of CNS tissue result in astrocytic
color, so comment is best reserved until fixation is com- scars. Such lesions of many millimeters and greater usually result in cystic
plete. This does not preclude initial sectioning of the cavities lined by astrocytic fibers and residual inflammatory cells. The lat-
ter may include cells such as hemosiderin-­laden macrophages as was the
brain and spinal cord, as this also aids in fixation. case here in a yearling foal that recovered completely from a perinatal
hypoxic–ischemic event as a neonatal foal leaving porencephalic, fluid-­
Gross lesions filled cysts such as the one shown here in one internal capsule on this
transverse section of the fixed brain.
Malformations of the CNS usually are apparent on
careful gross inspection. However, associated struc-
CNS, so an effort must be made to maintain orientation
tures such as eyeballs, peripheral nerves, bones, and
of the parts. If one suspects the presence of a gross
muscles as well as midline structures such as heart and
lesion, then an examination of newly made cut sur-
great vessels should be scrutinized for accompanying
faces of the fixed tissue should provide clarification.
defects. The outside of the brain and spinal cord
should be studied for abnormalities in color, configu-
Blocking tissues
ration, regional size and texture, and the brain can
then be cut into four to six transverse sections to assist If it is worth harvesting tissues at postmortem exami-
in fixation. Examining these freshly cut surfaces, espe- nation, then it is worth routinely blocking tissues in
cially for symmetry, can help locate areas of malacia, all cases. This will obviously be modified where there
hemorrhage, atrophy, and swelling. Small (and even is a specifically known site (e.g., right cerebrum, left
large) lesions may not be clinically significant in sev- vestibular nuclei, right T6, etc.) and when collection
eral regions of the forebrain (Figure 4.3). If cerebellar of, and particularly blocking of, tissues will focus on
atrophy or hypoplasia is suspected, the cerebellum to those sites in the first instance.
total brain weight ratio should be calculated (normal For a routine case with signs relating to a brain
>7%). Parasite tracts and inflammatory lesions can be lesion, the entire brain should be harvested along
inconspicuous. A culture taken from the meninges with at least one trigeminal ganglion lying slightly
and saving a small portion of brain tissue for viral and lateral and projecting rostral to the optic chiasm. If
bacterial isolation, especially from areas of discolora- vestibular signs are indicated, the skull should be sec-
tion, is advisable. In animals suspected of having tioned transversely after brain removal at the level of
rabies, appropriate samples need to be prepared for the external acoustic meati for an inspection of the
submission to the local animal health authorities. This ear cavities. If no specific lesion site is indicated clini-
may entail preparing the whole head or all/part of the cally or grossly, routine brain harvesting and fixation
brain for shipment and requires that appropriate pre- should proceed. The brain can then be cut into trans-
cautions be followed during harvesting and shipping. verse 5–10 mm slices except for the cerebellum that
If care is used in removing the spinal cord, areas of should be sectioned initially on a median plane after
compression and discoloration associated with necro- sectioning its peduncles. The brain histopathology
sis, hemorrhage, or inflammation can be detected eas- blocks would routinely be taken from the sites indi-
ily. Obviously, one cannot section every part of the cated in Figure 4.4, taking samples from the right
 (A)
Structures Section
Frontal cortex A

Caudate nucleus including internal capsule A

Thalamus just caudal to optic chiasm B

Hippocampus and adjacent cortex A/B

Midbrain at the level of oculomotor nerves C

Occipital cortex (preferably at the site of occipital lobe herniation) D

Medulla oblongata at the level of confluence of cerebellar E

peduncles

Medulla oblongata just rostral to obex F

Caudal cerebellar hemisphere (medium plane) G

Trigeminal ganglion (TG)

(B) D

TG
(C) A B C E F

A B C

E F G

Figure 4.4 Suggested levels for taking routine brain sections for histopathologic study. Selected brain regions to be routinely viewed (A). Sites for routine
sectioning (B). Examples of final routine brain histologic sections (C).
80 Large animal neurology

side of the preserved brain as a routine unless other- system of such histopathologic sleuthing is depicted
wise indicated. These sites are selected based on sites in Figure 4.5.
of lesions for commonly occurring and for important In a neurologic case involving final neuronal path-
diseases (e.g., rabies, cerebellar abiotrophy, and neu- ways, especially when the lesion site(s) is unknown,
roaxonal dystrophy), and should be varied and added proximal and distal major nerves along with nerve
to depending on clinical signs, gross pathologic find- roots and selected dorsal root, paravertebral and
ings, funding available, and the regional experience autonomic ganglia, and selected muscle samples
of the neuropathologist. should also be harvested. Longitudinal as well as
With spinal cord cases where clinical documen- transverse sections of peripheral nerves and muscles
tation or gross findings indicate a specific site, then should be clearly identified as to orientation for
sections from this area should take priority. With processing.
no clinically or grossly documented focal lesion
identified, then in addition to spinal cord, periph- General histologic reactions of cells
eral nerves (e.g., median and sciatic) and the brain
should be harvested. Routine blocking of spinal
of the nervous system
cord should include two cervical, two thoracic, and Of some importance in histologic interpretation are
one lumbar set of sections, each sampled on a occult and aging changes that can be quite impres-
transverse plane, a dorsal longitudinal plane, and a sive.10–12 These include the presence of polyglucosan
median longitudinal plane orientation (Figure 4.5). accumulations or Lafora bodies in cattle,13 cerebro-
Again, a documented focal or multifocal lesion will vascular siderosis,14 mineralization,15 dense micro-
dictate sampling sites. The remainder of the cord spheres and axonal spheroids in adult, and especially
should be replaced in fixative such that the orienta- aged animals16 and processing-­related neuropil vacu-
tion of parts is still evident for future sub-­sectioning. olation,17 all in the CNS. Peripheral nerves do show a
As with the brain tissues, unless focal or multi- depletion of large myelinated fibers with aging,18,19
focal sites of lesions are grossly very clear, a and normal equine nerves often contain a few to
methodical approach of sectioning selected spinal spectacular concentrations of Renaut bodies
­
cord segments should be taken. This enables the (Figure 4.6).20,21 Although when profuse, these latter
identification of sections being above and sections structures may indicate sites of pressure on, or tension
being below focal lesions so that such focal lesions of, nerves.22 Equine skeletal muscle can contain many
can be pinpointed to assess possible cause. One nonpathological degenerative sarcoplasmic masses.23

Cranial
WM GM WM WM GM WM

Cranial
WM GM WM WM GM WM

Caudal

Caudal
Cranial
WM GM WM

Dorsal Ventral

Caudal

Figure 4.5 The recommended planes of sections to be taken for histologic examination at each selected spinal cord site are depicted here. [WM = white
matter; GM = gray matter]. At the center is the standard transverse plane section. Additional routine histologic sections to be taken on the dorsal plane (left
and right) and the sagittal plane (bottom) are strongly recommended. The major sensory (↑) and motor (↓) tracts that allow detection of where a lesion(s) is
located are indicated by arrows.
 Pathologic responses of the nervous system 81

surrounding such altered neurons, this is referred to as

satellitosis. Where there is actual neuronophagia, then
the change is irreversible. Shrinkage of a neuronal soma
(cell body) is often seen in hyperthermia, hypoxia, and
trauma. The process of shrinkage with loss of Nissl sub-
stance, eosinophilic homogenization or chromatolysis
of the cytoplasm, and a shrunken, densely basophilic
nucleus is referred to as ischemic neuronal cell change.
It can be indicative of ischemia, hypoglycemia and other
toxic and metabolic insults, and these cells are some-
what simplistically referred to as ischemic neurons.
Simple atrophy of CNS neurons with axonal loss is part
Figure 4.6 Renaut bodies (arrows) may be described as often forgotten of the aging process. When chronic, trans-­synaptic
endoneural structures seen here on routine low power histologic view of atrophy occurs, and is present in many delayed onset,
a sciatic nerve fascicle of a horse. They consist of loose connective tissue degenerative disorders, or abiotrophies. Neurofibrils in
substances often arranged in loose whorls on transverse section, contain-
ing little collagen and few nuclear remnants. Usually they are in a sub-
affected atrophic axons undergo shrinkage, hyperchro-
perineural location where they can occupy a large proportion of space in mia, and beading.
a fascicle (arrow heads). These normal structures in equine peripheral Injury to neuronal processes can be divided func-
nerves do not appear to represent pathologic processes by themselves tionally and morphologically into three stages.
and should not be misinterpreted as pathologic in their own right on Neurapraxis is the state of loss of function only;
pathology reports. However, Renaut bodies can accumulate dramatically
and appear to distend nerves undergoing changes such as pressure-­
axonotmesis is the severance of axons; and neurotmesis
induced neuronal fiber atrophy as occurs with suprascapular nerve is the severance of the entire neuronal fiber, both axon
entrapment. and myelin sheath. In the PNS, degeneration and
regeneration occur following interruption of axons.
The nerve fiber that is distal to the site of damage dis-
An understanding of the ways that cells of the nerv- integrates in 3–4 days, and more slowly the myelin
ous system respond to pathologic and artefactual degenerates as ellipsoids and droplets to be phagocy-
insults is paramount to the clinical interpretation of tosed. The end plate, or receptor organ, atrophies and
pathology reports.(1-­3) disintegrates, and Schwann cells begin proliferation.
The nerve fiber proximal to the site of damage disinte-
grates minimally back toward the cell body, but the cell
A précis of the recognized pathologic responses by body shows a reactive change, including central chro-
cells in neural tissues thus follows. matolysis and swelling with margination of the
nucleus. Regeneration of several axonal stumps, with
Neurons
budding into proliferated Schwann cell membranes
Artifactual changes in neurons are extremely common and endoneurial columns, begins within days, with
in microscopic specimens and are usually the result of further axonal growth at about 1–4 mm a day.
fixation, sectioning, and staining procedures. Individual fiber replacement can be complete, but
Disappearance of neurons is good evidence of a lesion, total quantitative nerve function is not. This degenera-
but this is usually subjective. Neuronal changes, with- tive and regenerative process was elegantly described
out associated glial or other cellular reactions, must be in frog glossopharyngeal and hypoglossal nerves after
interpreted cautiously. Neuronal fiber (axon and mye- axonotomy in a seminal paper24 by the British physi-
lin sheath) degeneration can be a useful sign of a neu- ologist Augustus Volney Waller (1816–1870) at the age
ronal defect even at a site distant from the cell body. of 34 years. The overall pathologic process is referred
Swelling and shrinkage are two changes frequently to as Wallerian or Wallerian-­like degeneration and
seen in neurons and are reasonably reliable findings if regeneration, and is now generally applied to injury to
they are present in well-­preserved tissue. Pale, baso- both peripheral and central axons due not only to
philic swelling of the cytoplasm and nucleus is often the trauma but also to inflammatory, immune-­mediated,
earliest observable change in infections, toxicities and and other mechanisms.25,26
hyperthermia, and it might be reversible. When there In the CNS, Wallerian-­like degeneration occurs
are excessive numbers of glial cells, notably microglia, following focal axonal damage, but the regenerative
82 Large animal neurology

process is markedly curtailed. The mapping of degen- they appear to act as a guide to migrating neurons dur-
erated, distal neuronal fibers following damage is ing development. They tend to be relatively resistant to
used to help define the site(s) of lesions in the CNS, noxious stimuli and are associated with reparative pro-
particularly in the brainstem and spinal cord (see cesses. The common response to CNS damage is astro-
Figure 4.5 for a depiction of spinal cord histologic cyte hyperplasia and hypertrophy with prominence of
sectioning that can assist in mapping out the precise their processes—­ fibrillary astrogliosis. For poorly
site of focal CNS lesions.). Thus, in a pathology understood reasons, the repair of larger areas of dam-
report, if degeneration is only described in fibers in aged CNS parenchyma often does not occur, leaving a
sensory (afferent) white matter pathways cranial to void that is occupied by CSF-­like fluid surrounded by a
C6, and only in motor (efferent) fibers caudal to C6, lamina of astrocyte processes. Shrinkage and necrosis
then a focal lesion at C6 is most likely present. of astrocytes occurs with the death of other CNS ele-
However, if afferent and efferent fiber degeneration is ments during infarction, hemorrhage, and pressure.
present in the T10 segment, there must be at least one Astrocytes imbibe tissue fluid after it has leaked into
lesion cranial to T10 and one lesion caudal to T10, or extracellular spaces, and this is an early finding in vari-
diffuse degeneration of neuronal fibers-­QED. ous edematous states such as trauma, infarction, and
With many metabolic, toxic, and nutritional insults, vascular disorders. Astrocytes do act as phagocytes but
axons may undergo degenerative changes that are to a lesser degree than resident microglia and invading
often recognized as swelling. Such swollen axons, or macrophages. Reactive astrocytes are often found at the
spheroids, can be prominent in particular nuclear periphery of subacute and chronic lesions, surround-
regions where neuroaxonal dystrophy is occurring. ing any remaining holes left from larger loss of brain
This process is common in some nutritional diseases tissue (Figure 4.3). They often show prominent
and intoxications, and in certain hereditary disorders; nuclear enlargement and eosinophilic cytoplasmic
it also occurs during the aging process. swelling and are then called gemistocytes.
Accumulation of pigments containing iron and
calcium in and especially around neurons and blood
Oligodendrocytes
vessels may indicate a previous influx of blood pig-
ments to the area. Such pigmentations occur with The oligodendrocyte cell bodies can show hydropic
aging, along with often spectacular intraneuronal swelling in many edematous states, although the
accumulation of lipofuscin: the aging or wear and edematous fluid is often quickly transferred to astro-
tear pigment. Accumulation of specific lysosomal cytes and microglial cells. The delicate oligodendro-
products is the hallmark of the inherited lysosomal cyte processes, including those producing lipid-­rich,
storage diseases as well as a few intoxications mim- myelin sheaths, are very susceptible to noxious stimuli.
icking these enzyme deficiencies. With such insults, often the enclosed axons are also
damaged, but several immune-­mediated, infectious
and toxic insults cause selective disintegration of mye-
Axonal swellings (spheroids) and pigment accumula- lin sheaths with or without oligodendrocyte loss. This
tions (mainly lipofuscin) can be prominent in basal way the functionally vital oligodendrocyte/axon rela-
nuclear regions, the medulla oblongata, and intermedi- tionships are disturbed, and this process is termed
ate zone of spinal gray matter of aged animals. Effete, demyelination. If such a perturbation occurs prior to
or worn-­out, cells tend to accumulate at subependymal the final developmental, perinatal process of myelina-
sites, particularly adjacent to the rostral ventricles. tion, it is termed hypomyelination. Some toxic and
These changes are often accompanied by mineral and inherent disorders of oligodendrocytes result in dis-
iron deposits near vessels in older patients making turbances of the myelin sheath, which are seen as vac-
cautious histopathological interpretation necessary. uoles or fluid in the white matter, referred to as status
spongiosus. Many of the disorders that affect myelin
alone cause asynchrony of axonal conduction due to
ephaptic coupling (short-­circuiting), seen clinically as
Astrocytes
congenital or delayed onset whole body tremor.
Astrocytes that are present in the gray and white matter Remyelination of demyelinated CNS axons can
are a major component of the cytoskeleton framework occur under various conditions but is not consistent.
of the CNS. Their processes, with basal laminae, form Interestingly, remyelination in the superficial areas of
part of the blood–brain and blood–CSF barriers, and the CNS is just as likely to be performed by resident
 Pathologic responses of the nervous system 83

and immigrant peripheral Schwann cells as by Neuropathologic responses in the various

oligodendrocytes. mechanisms of disease
Interpretation of neurohistopathologic sections and
Microglia reports can be made with consultation of current refer-
These fixed histiocytes or tissue macrophages of the ence books2,6 and especially e-­ libraries such as the
CNS respond quickly to any insult that results in Cornell University Atlas of Veterinary Neuropathology27
necrosis and tissue debris, which they phagocytose. and others.28,29
They thus can hypertrophy into macrophages. During Just as each mechanism of disease has its own
proliferation, these histiocytes may form nodules or clinical characteristics as outlined in Chapter 2, so
stars at sites of damage to CNS parenchyma and may each has certain morphologic characteristics. Thus,
also accumulate in perivascular cuffs along with one must understand that vascular disorders result in
monocytic and polymorphonucleated inflammatory abrupt, localized hypoxia and tissue necrosis, as well as
cells. They are involved with removal of dead neurons the leakage of blood protein and pigments. This is as
in the process of neuronophagia. Focal or diffuse clinically relevant as understanding that such diseases
microgliosis often remains for years as the last recog- usually have a sudden onset of signs that remain static
nizable change following lesions in the CNS. or, more frequently, improve with time: consider fibro-
With prominent damage to CNS parenchyma, cartilaginous emboli in pigs and equine herpesvirus
often phagocytic mononuclear cells filled with mye- myeloencephalopathy.
lin lipid debris accumulate. These are gitter cells and
for the most part are believed to arise from an influx Malformations
of circulating monocytes, as opposed to proliferation Neurologic signs can result from malformations that
of microglial cells. involve nervous tissue or involve the tissues surrounding
the neuraxis, particularly the cranium and vertebral col-
Meningeal, choroidal, and ependymal cells umn. Cranial and vertebral malformations do not always
affect the nervous system, but when they do, it is affected
These cells tend to be relatively nonreactive. Invasion by by trauma and often signs are progressive. Malformations
infectious agents and direct injury result in an influx of may be congenital or acquired, and in both cases can
circulating inflammatory and phagocytic cells around have a hereditary, infectious, toxic, traumatic, or even
them, with some cell proliferation. Subependymal and vascular basis. The type of nervous tissue malformation
subpial gliosis can be prominent in some superficial that results often depends more on the time and site of
CNS infections. These cells become flattened when CSF action rather than the causative factors. Thus, certain
pressure is increased within the neuraxis. Fibroblasts infections and toxins may result in the same malforma-
associated with the meninges are effective in prolifera- tion such as cerebellar hypoplasia or arthrogryposis
tion and migration, and they cover any meningeal or when acting at the appropriate developmental stage.
submeningeal defects that occur with damage.
Infectious, inflammatory, and immune
Schwann cells disorders
Proliferated Schwann cells mainly guide and ensheath With a few important exceptions, these result in
regrowing axons during the process of Wallerian regen- degrees of inflammatory cell infiltrate, at least in the
eration in the PNS. Thus, following focal or diffuse PNS early stages.
axonal lesions, such proliferation is evident. Schwann
cells, like oligodendrocytes, are subject to immune and Viruses
toxic attack and are sometimes affected by inherent Most viral diseases cause nonsuppurative inflamma-
metabolic disorders. This may occur before or after nor- tion with lymphocytes, plasma cells, and monocytes,
mal developmental myelination, causing hypomyeli- especially accumulating as perivascular cuffs. A few
nation or demyelination, respectively. Unlike fulminant viral infections, particularly those that
oligodendrocytes, Schwann cells are quite efficient at result in considerable necrosis of CNS tissue, are char-
recoating bare PNS axons and repairing lesions. They acterized by neutrophil invasion. Neurotropic viruses
do not appear to contribute to the often impressive such as rabies and the arboviral encephalitides destroy
Renaut body formation in peripheral nerves (Figure 4.6). neurons so there is neuronal degeneration, satellitosis,
84 Large animal neurology

and neuronophagia. The rarer “slow-­viral” infections

such as Maedi/Visna virus infection may not induce
much of an inflammatory response and are slowly
progressive.

Bacteria
Suppurative meningitis is most common in neonatal
animals, especially those with failure of passive transfer
of immunoglobulin. Often there is considerable pro-
tein exudate with tissue swelling. When subacute to
chronic accumulations of predominantly polymor-
phonuclear inflammatory cells become sectioned off
from CNS parenchyma with astrofibrosis, then a Figure 4.8 The most frequently seen type of herniation of brain tissues
true brain abscess is formed and can act as a space-­ resulting from brain swelling is shown here. This is a caudal view of the
occupying lesion causing compression and edema of occipital lobes and transverse section of midbrain (center), and a median
adjacent tissue. Because of the rigidity of the calvaria, section of the caudal cerebellum (left lower) from a pony that died from
leukoencephalomalacia associated with feeding moldy sweet corn. The
these forms of brain swelling can result in herniation swollen brain has flattened gyri, and there has been herniation of the
of adjacent parts of the brain (Figures 4.7 and 4.8).30 ventromedial portions of both occipital lobes caudally (arrows) under the
Vertebral osteomyelitis most often causes spinal cord tentorium cerebelli to push ventrally on the midbrain. The right side
compression rather than myelitis, and at least initially shows greater herniation resulting in it deviating to the left side and
even septic emboli damage CNS tissue because of compressing the right side of the midbrain more than that occurring on
the left. A further herniation has occurred with the cerebellar vermis
ischemic and hemorrhagic infarction. being pushed caudally into the foramen magnum producing a bulging of
the tonsil of the vermis (arrow head).
Fungi
Fungal infections of the nervous system are rare
(Figure 4.9). The usual result is a mixed neutrophilic
and mononuclear inflammation, and granulomata

Figure 4.9 Septic thromboemboli can lodge in any vessel in the CNS but
will often arrive via the major carotid supply and thus seed the forebrain
as was the case with this foal suffering from Aspergillus sp. superinfec-
tion after neonatal sepsis and abdominal surgery. The necrotic inflamma-
tory lesions seen on this transverse section of the fresh forebrain and
midbrain (arrows) are particularly in gray matter that usually has a
greater blood supply than white matter.

Figure 4.7 In distinction from caudal herniation of cerebrum and cere-

may form. Sometimes immunocompromisation is
bellum with cerebral and brain swelling (Figures 4.8 and 4.10), occasion-
ally a space occupying cerebellar lesion can cause unusual herniation of associated with fungal infections.
brain tissue. This is seen here in a dorsal view of the brain from a yearling
heifer that suffered from a rostral cerebellar abscess (situated under the Protozoa and amoeba
arrow) causing rostral herniation of the cerebellar vermis under the ten- Encysted protozoal forms may be associated with
torium cerebelli. The position of the removed lateral portions of the
little cellular reaction. With dividing forms such as
tentorium cerebelli is depicted by the yellow bars. Ultimately, the mid-
brain, with the CN-­III oculomotor nerves beneath, will be compressed Sarcocystis sp. merozoites, there is often severe necrosis
ventrally by such herniated tissue. with hemorrhage and inflammation comprised of
 Pathologic responses of the nervous system 85

lymphocytes and macrophages, sometimes neutro-

phils, eosinophils, and multinucleated giant cells. Injury causing only loss of function is referred
Amoeba usually only invades the CNS following to as concussion in the brain, spinal shock in
massive exposure via portals such as the olfactory the spinal cord and neurapraxis in the PNS.
turbinates. These agents also take advantage of
immunocompromised states. Physical and chemical disorders

Helminth and arthropod parasites Concussion, with loss of function, is only the mildest
Penetration of the CNS by fly larvae (myiasis) and effect of CNS trauma, whereas contusion or bruising
roundworms (nematodiasis) is usually accidental and and laceration with tissue disruption cause morphologic
random, whereas invasion by some nematodes and lesions with degrees of cell death, hemorrhage, edema,
tapeworm cysts (coenurosis) is part of the respective and neutrophil and macrophage infiltration. Microglial
life cycles. In the natural host, minimal damage may then astrocytic activation, proliferation, and hypertro-
result. In unnatural hosts, however, massive tissue phy all occur in adjacent viable tissue. The site of major
destruction, hemorrhage, protein exudate, and an tissue damage may not be directly related to the site of
influx of neutrophils and macrophages with variable traumatic impact on the calvaria or vertebral column.
numbers of eosinophils and giant cells occur. Such Parenchymal and subarachnoid bleeding is common,
parasites can arrive in the CNS through natural foram- but subdural and epidural hematoma formation is
ina or via the blood supply. Subsequent meanderings less frequent in domestic animals than in man.
can be tortuous and surprisingly may simply separate Hematomas, cerebral abscesses and other space-­
the tissues without causing much inflammation. Also, occupying lesions, create local pressure and edema
parasites can leave the CNS after creating devastation. that can cause brain swelling and herniation of parts
of the brain (Figures 4.7, 4.9, and 4.10).30 Destroyed
tissue is removed by activated microglia, but if it is
Immune mechanisms
more extensive, it is removed by infiltrating monocytic
Type I, anaphylactic immune responses in the CNS are
macrophages. This results in pools of lipid-­laden mac-
rare, partly because the CNS is a relatively privileged site,
rophages with net-­like cytoplasm—­gitter cells. Such large
somewhat isolated from the immune system. Cytotoxic,
autoimmune, type II reactions directed against natural
or altered antigens such as myelin do occur in the CNS
and PNS, causing nonsuppurative encephalitis or neuri-
tis, respectively. Antigen–antibody complex, type III
mediated vasculitis occurs in the CNS in some diseases,
and, like other forms of vasculitis, CNS damage results
more from infarction than from inflammation. The lat-
ter can be neutrophilic, lymphocytic, or mixed.

Prion agents
The transmissible spongiform encephalopathies or
prion diseases are caused by novel infectious agents that
do not incite a detectable immune response in the host.
Generally, they are endemic diseases of low incidence,
have a prolonged incubation period, and are uniformly
fatal. Although evidence of the infectious agent can usu-
ally be detected in several peripheral tissues, particularly
those of the lymphoreticular system, pathological lesions Figure 4.10 This is a caudal view of the occipital lobes and section
are confined to the nervous system. The lesions consist through the midbrain of a neonatal foal that suffered birth asphyxia and
of vacuolation of neurons, neuronal loss, astrocytosis demonstrated bizarre behavior and somnolence prior to developing
and microglial activation, and accumulation of protease-­ intractable seizures. Diffuse forebrain swelling that resulted from the cer-
ebral neuronal necrosis caused by the asphyxia is evident by the herni-
resistant, self-­propagating forms of the host-­encoded
ated ventral portions of the occipital lobes of the cerebrum (arrows).
protein PrP, termed PrPSc. In some cases, accumulations Additionally, softening and necrosis (malacia) is present in both rostral
of PrPSc as amyloid plaques and scrapie-­associated fibrils colliculi (arrowheads) that likely also resulted from the effects of oxygen
occur in the brain. deprivation on these sensitive regions of gray matter.
86 Large animal neurology

lesions may heal to form an astroglial scar, but more ruminants, neuroaxonal dystrophy in adolescent
so a fluid-­filled cavity lined by astrocytes. Secondary horses, or motor neuron disease in older horses.
neuronal fiber degeneration will occur along fiber tracts
that are separated from their cell bodies by the injury. Metabolic diseases
Heat, cold, chemicals, and ionizing irradiation can
Many metabolic disorders such as hypocalcemia,
cause immediate cell death with massive vascular
hypomagnesemia, and ketoacidosis alter nervous
breakdown and tissue infarction. Some delayed effects,
tissue function, especially electrical transmission, when
particularly on the maintenance of myelin, may be
there are no morphologic lesions. Some cause degen-
noted with irradiation.
eration of neurons and ultimately necrosis, often in
selective areas of the CNS. These include hypoglycemia,
Toxic diseases
hypoxia, and hepatoencephalopathy, the latter produc-
Some toxins such as cyanide interfere with oxygen ing a striking hypertrophy and hyperplasia of astrocytes.
transport. Water and salt intoxications directly alter Most are characterized by a lack of inflammation. The
osmolality of cells, interrupting many metabolic perinatal disease referred to as hypoxic and ischemic
functions associated with swelling or shrinking cells. encephalopathy (Figure 4.10) also fits this category but
Lesions, if present, are usually symmetrical, often diffuse is likely complex in its specific pathophysiology.
and usually end with tissue necrosis, sometimes with Inherited, neuronal, metabolic disorders are often
subsequent brain swelling (Figure 4.8). Some plant (e.g., expressed as abiotrophy with selective, delayed neu-
yellow star thistle) and microbial (e.g., Clostridium roaxonal degeneration, or as lysosomal storage dis-
perfringens type D) toxins produce extremely selective ease with an accumulation of metabolic products in
and focal lesions, suggesting that they are mediated by macrophages and neurons. Other metabolic disor-
selective neurotransmitter disruption or more likely by ders result in hypomyelination or demyelination.
selective vascular derangements.
Some such as botulinum toxins affect neurotrans- Vascular lesions
mission directly while others like lolitrem-­B in per-
Interruption of the blood supply results in hemor-
ennial ryegrass staggers interfere with membrane ion
rhagic or ischemic infarction and tissue necrosis
channels resulting in an acquired channelopathy.
(Figure 4.3), with neutrophilic and then monocytic
And finally, other toxins interfere with (macro)
phagocytosis of debris. Emboli and thrombi may be
molecular biosynthesis as occurs with corynetoxins
septic, parasitic, or fibrocartilaginous. More general-
in annual ryegrass toxicity disrupting glycoprotein
ized infarction may occur with cardiopulmonary failure,
synthesis, and fumonisins in equine leukoencephalo-
disseminated clotting abnormalities, and septicemia.
malacia/moldy corn poisoning disrupting sphingolipid
Hypertension, perhaps on a compartmental basis,
metabolism.
may play a role in the vascular accidents associated
with the neonatal hypoxic and ischemic encephalop-
Nutritional diseases
athy seen most often in foals.30
Starvation and disorders associated with inadequate
vitamin A, vitamin D, calcium, and phosphorus intake Degenerative processes
can be associated with vertebral fractures. Thiamine
Many of these diseases that involve morphologic
deficiency can cause cerebrocortical ­neuronal necrosis
degeneration of CNS tissue are familial or hereditary
in ruminants, hemorrhagic necrosis of white matter in
and may be considered metabolic disorders. Of the
felidae and axonal degeneration in horses. Lesions of
remaining, most are of unknown origin, although
cell death tend to be symmetrical with nutritional dis-
hereditary, toxic, metabolic, nutritional, and viral
eases. Of course, dietary imbalances involving cal-
factors are often suspected.
cium, phosphorus, vitamin A, vitamin D, copper, etc.,
can result in neurocrania and vertebral defects that
Neoplasms and other tumors
impinge on CNS and PNS structures asymmetrically,
especially when secondary trauma plays a role. With the exception of neurofibroma and lymphosar-
Antioxidant failure effects various syndromes coma in cattle, neoplasms involving nervous tissue are
depending on age, and species especially. Thus, as rare in domestic large animals. Neoplasms replace and
exemplified by vitamin E deficiency, this may be compress nervous tissue, and both forms of intrusion
­cardiomyopathy in growing pigs, myopathy in young often cause adjacent edema because of local vascular
 Pathologic responses of the nervous system 87

perturbations. Indeed, vascular compromise can result

in considerable necrosis of CNS tissues as well as of the
tumor itself. As a result of the space-­occupying effect
and any associated edema, brain herniations occur with
brain neoplasms just as they occur with cerebral
abscesses and hematoma. These include herniations of
the cingulate gyrus under the falx cerebri, the occipital
lobes under the tentorium cerebelli, and the cerebellar
vermis through the foramen magnum (Figures 4.8
and 4.10). All these tissue movements cause compres-
sion of parts of the brain. Primary CNS tumors are
extremely rare in large animals, but can arise from
meningeal, ependymal, choroidal, glial, and endothelial Figure 4.11 Granulomatous meningoencephalomyelitis (GME) is not com-
cell lines. Neuronal cell line neoplasms are even less fre- mon in horses but can present with fluctuant and progressive focal and
quently encountered. However, a proliferation of primi- multifocal signs related to brain and/or spinal cord disease, thus can result
tive neuroepithelial cells from the late developing brain in syndromes akin to those seen with EPM caused by S. neurona in horses
from the American continents. Small to coalescing lesions of granulomatous,
sometimes occurs in young patients as a medulloblas- nonsuppurative inflammatory lesions (arrows), sometimes focused around
toma. Ganglion and Schwann cell neoplasms occur in vessels in the white matter, can be seen grossly on this transverse section of
the PNS. Neoplasms involving the skull and vertebrae as forebrain at the level of the corona radiata and internal capsule from a horse
well as metastatic neoplasms usually compress nervous with progressive behavioral and visual abnormalities suffering from GME.
tissue, the effects being identical to those of external
injury. Lymphosarcoma probably is the most common
between infectious diseases as we know them, toxicities
neoplasm involving the brain and spinal cord in large
impacting on immune-­responsiveness, and neoplasms
animals, and probably it should be considered a pri-
that allow cells and tissues to express their own varied,
mary tumor when it is in the epidural space and when it
albeit unacceptable, phenotypes.
encompasses the peripheral nerves of cattle.
There is an interesting group of neural tumors that
include usually focal, disorganized proliferation of References
normal neural and other tissue elements in abnormal
1 Cantile C and Youssef S. Nervous system. In Jubb, Kennedy &
groupings or abnormal sites, collectively referred to Palmer’s Pathology of Domestic Animals, 6th ed, Maxie MG,
as hamartomas.31–33 These expansile tissue masses Editor. Elsevier, St. Louis, MO, USA. 2016; 250–406.
disrupt the function of adjacent neural tissues with- 2 Summers BA, Cummings JF and de Lahunta A. Veterinary
Neuropathology. Mosby, St. Louis, M.O. 1995.
out usually causing tissue destruction. 3 Innes JRM and Saunders LZ. Comparative Neuropathology.
Academic Press, London. 1962.
4 Jahns H, Callanan JJ, McElroy MC, Sammin DJ and Bassett HF.
Idiopathic disorders Age-­related and non-­ age-­related changes in 100 surveyed
horse brains. Vet Pathol 2006; 43(5): 740–750.
In many clinical neurologic syndromes such as self-­ 5 Vandevelde M, Higgins RJ and Overmann A. Veterinary
mutilation, no consistent gross or light microscopic Neuropathology: Essentials of Theory and Practice. Wiley-­
Blackwell, Hoboken, NJ. 2012; 216.
findings exist. In some cases, a thorough search for 6 Love S, Perry A, Ironside J and Budka H. Greenfield’s
lesions is not undertaken for various reasons. Neuropathology. 9th ed. CRC Press. 2015.
Biochemical, not morbid, lesions likely account for 7 Rech R and Barros C. Neurologic Diseases in Horses. Vet Clin
North Am Equine Pract. 2015; 31(2): 281–306.
some of these syndromes. Other problems such as 8 Buergelt CD. Necropsy (Ch. 3). In Equine Medicine and
recurrent laryngeal neuropathy, stringhalt, and Surgery, Collahan PT, Mayhew IG, Merritt AM, Moore JM,
acquired equine polyneuropathy may be associated Editors. Vol. 1. St Louis, MO. 1999; 119–133.
9 Walzer C, Kubber-­Heiss A and Robert N. A simple field
with consistent neuropathologic lesions, but the etiol- method for spinal cord removal demonstrated in the cheetah
ogy is still uncertain. A further subcategory is diseases (Acinonyx jubatus). J Vet Diagn Invest 2002; 14(1): 76–79.
that involve impressive clinical syndromes and present 10 Singh R, Kumar R, Singh PP, et al. Neurohistopathological
lesions in brains of Indian cattle. Indian J Anim Sci 2008;
impressive florid lesions and yet defy our understand- 78(10): 1063–1074.
ing as to their biology. Such are the inflammatory dis- 11 Verma A, Singh R, Ingale AM and Singh K. Spontaneous lesions
orders cumulatively expressed as granulomatous and other unusual cell types in bovine brain. Indian J Vet Pathol
2014; 38(1): 1–4.
meningoencephalomyelitis (Figure 4.11). This latter, 12 Borras D, Ferrer I and Pumarola M. Age-­related changes in the
catch-­all diagnosis currently falls in the hinterland brain of the dog. Vet Pathol 1999; 36(3): 202–211.
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13 Simmons MM. Lafora disease in the cow? J Comp Pathol 1994; 25 Stoll G and Muller HW. Nerve injury, axonal degeneration and
110(4): 389–401. neural regeneration: basic insights. Brain Pathol 1999; 9(2):
14 Saunders LZ. Cerebrovascular siderosis in horses. AMA Arch 313–325.
Pathol 1953; 56: 637–642. 26 Stoll G, Jander S and Myers RR. Degeneration and regeneration of the
15 Hurst EW. Calcification in the brain of equidae and bovidae. peripheral nervous system: from Augustus Waller’s observations to
Am J Pathol 1934; 10: 795–798. neuroinflammation. J Peripher Nerv Syst 2002; 7(1): 13–27.
16 Furuoka H, Yamada M, Miyazawa K, Taniyama H and Matsui T. 27 Huxtable C, Summers BA and de Lahunta A. Atlas of Veterinary
Dense microspheres in normal horse brain. Acta Neuropathol (Berl) Neuropathology. Cornell University, College of Veterinary
1996; 91(4): 440–443. Medicine, Ithaca, NY. 2002. Available from: https://secure.
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ducible histological processing artefact. J Comp Pathol 1989; 2022_01_28.
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peripheral nerve: teased fibre studies. Res Vet Sci 1990; 48(2): Available from: https://peir.path.uab.edu/library/index.php?/
145–151. category/19. Accessed 2022_02_28
19 Wheeler SJ and Plummer JM. Age-­related changes in the fibre 29 Science T. M. I. o. M. (2011). Essential Brain Anatomy &
composition of equine peripheral nerve. J Neurol Sci 1989; 90(1): Neuropathology (EBA&N). Retrieved from The Neuropathology
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­production of Renaut bodies. J Neurol Sci 1983; 62(1–3): 233–241. 31 Miranda IC, Taylor KR, Castleman W, et al. Schwannosis in
23 Aleman M, Lecouteur RA, Nieto JE, et al. Sarcoplasmic masses three foals and a calf. Vet Pathol 2019; 56(5): 783–788.
in equine skeletal muscle. Neuromuscul Disord 2005; 15(2): 32 Taylor KR, MacKay RJ, Nelson EA, et al. Spinal cord hamar-
147–153. tomatous myelodysplasia in 2 horses with clinical neurologic
24 Waller A. Experiments on the section of the glossopharyngeal deficits. Vet Pathol 2016; 53(4): 844–846.
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 Part II
Clinical Problems in Large Animal
Neurology
Chapter 5 Disorders of behavior 91 Chapter 20 Deafness156

Chapter 6 Seizures and epilepsy 97 Chapter 21 Disorders of posture and

movement159
Chapter 7 Sleep and acute collapse
disorders103 Chapter 22 Incoordination of the head,
neck, trunk and limbs:
Chapter 8 Coma and other altered states cerebellar diseases  171
of consciousness107
Chapter 23 Tetraparesis, paraparesis,
Chapter 9 Blindness111 and ataxia of the limbs:
spinal cord diseases 175
Chapter 10 Miosis, mydriasis, anisocoria,
and Horner syndrome 114 Chapter 24 Diffuse weakness 181

Chapter 11 Strabismus121 Chapter 25 Paresis and paralysis of one limb:

monoparesis185
Chapter 12 Dropped mandible and
masticatory muscle atrophy 125 Chapter 26 Bilateral brachial paresis
to paralysis191
Chapter 13 Decreased and Increased facial
sensation129 Chapter 27 Urinary bladder distention,
dilated rectum and anus, and
Chapter 14 Facial paralysis and facial spasm 133 atonic tail: cauda equina
syndrome194
Chapter 15 Pharyngeal dysphagia 137
Chapter 28 Pruritus, self-­mutilation,
Chapter 16 Dilated esophagus 142 headshaking, complex
regional pain syndrome, and
Chapter 17 Laryngeal paresis and paralysis: miscellaneous distressing
roaring144 disorders198

Chapter 18 Tongue Paralysis 147 Chapter 29 Autonomic nervous system

dysfunction206
Chapter 19 Head tilt, circling, nystagmus,
and other signs of vestibular Chapter 30 Vertebral and paravertebral
dysfunction150 problems: stiff neck and sore
back210
 5
Disorders of behavior

The location of lesions resulting in disorders of

behavior essentially involves the forebrain, and such Frantic behavior of a bull during the mating season,
lesions can be focal, multifocal, and diffuse. Because jerky collapsing in a white pig with sunburn in full sun,
normal behavior is extremely variable among spe- bizarre antics of a mare in diestrus, and violent kicking
cies, breeds, individuals, and especially stages of in a colt having a new bandage applied over the hock
reproductive cycles, if after a neurologic examination all attest to unusual behavior syndromes that can eas-
the only finding is a history of or evidence of a subtle ily be mistaken for morbid brain disorders.
change in expected behavior, the examiner must be
cautious while assuming that a morbid lesion in the Subtle alterations in behavior resulting from organic
forebrain accounts for the signs. brain disorders include the following: continual

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
92 Large animal neurology

yawning—­that can be prominent in hepatoencepha-

lopathy; a tendency to drift to one side when walking—­
that is often present with asymmetric lesions; and a lack
of recognition of familiar animals (Figure 5.1), people,
and objects—­that is often the earliest expression of cer-
ebral disease in foals. More prominent signs are sei-
zures (Chapter 6), compulsive walking and circling
(Figure 5.2), pressing the head on objects, running
around frantically, biting at animate (including self)
(Figure 5.3) and inanimate (Figure 5.4) objects, leaving
food in the mouth, and adopting bizarre postures of the
head, neck, trunk and limbs. Such syndromes are usu-
ally referable to lesions in the frontal lobes, temporal
lobes, internal capsule, limbic system, thalamus or
basal nuclei, or due to diffuse brain disease.
Usually, localized and diffuse lesions affecting only
the forebrain result in combinations of behavioral
Figure 5.2 A patient that is variably obtunded and spontaneously
changes (including seizures), blindness, and lethargy. turns and walks toward one side will have an asymmetric lesion in the
forebrain, usually worse on the side toward which it turns—­right in this
case. This lamb has a chronic suppurative and granulomatous epend-
ymitis and ventriculitis on the right side. Additional signs of forebrain
involvement were poor vision and poor menace response in the left eye
(with normal pupils) and decreased sensation perceived from the left
nasal septum compared with the right. Typical of many lesions associ-
ated with perilesional edema, and especially those involving forebrain,
the signs would wax and wane in severity so that at times the lamb
would walk, trot, and run quite well in both directions. The only consist-
ent abnormality with gait and posture was a delay in protracting the
left limbs, especially the left forelimb as shown here, while turning right
and while attempting to hop on each left limb in turn. This likely repre-
sents abnormal conscious proprioceptive processing from the left side
of the body and limbs.

Although often sluggish in movement, little or no

alteration in gait occurs, at least in the subacute to
chronic stages. Central motor pathways to and sen-
sory inputs from cranial nerves can be disrupted, and
such syndromes are discussed under the individual
cranial nerve disorders. Particularly with metabolic
diseases such as hyperammonemia, and with those
focal and diffuse disorders accompanied by inflam-
matory lesions or by perilesional edema, there can be
dramatic fluctuations in the severity of behavioral
signs displayed over periods ranging from minutes to
weeks. This can even mean that there are no overt
signs demonstrated at a point in time, and within a
few hours there may be prominent behavioral
changes and even an uncontrollable patient.
Nondomesticated and unhandled ­domestic large ani-
mals, particularly adult bulls, boars and horses, can
Figure 5.1 A newborn Thoroughbred foal that is not distracted by the
become exceedingly defensive when incapacitated by all
presence of people, does not attend to the dam, and postures with its head
flagging alongside its flank is behaving very abnormally and is likely suffer- sorts of disorders and behave quite violently and aggres-
ing from forebrain disease. With such a syndrome, this foal did have an sively. Additionally, Equidae routinely respond to ­visceral
undiagnosed, aseptic meningoencephalitis from which it survived. pain in surprisingly violent ways (Figure 5.5) such that
 Disorders of behavior 93

Figure 5.3 Self-­inflicted lesions caused by biting are quite unusual and
can be spectacular with horses suffering from the self-­mutilation syndrome.
In the Arabian stallion shown here, such signs were due to rabies virus Figure 5.4 This milking Friesian cow likely was suffering from ketosis
infection, as was a proclivity to assault learned professors wearing white with episodes of bizarre behavior characterized by vigorously attacking
coats. Possibly associated with aggressive anti-­inflammatory therapy, these animate and especially inanimate objects such as the metal bars of her
signs progressed slowly over many days, with the patient surprisingly sur- pen as shown; she recovered fully with treatment. Such extremes of
viving for well over a week after the onset of abnormal behavior. Self-­ abnormal behavior in cattle can also be seen with many morbid and func-
inflicted biting trauma can also be seen in horses with other tional encephalopathies including rabies, hepatoencephalopathy, ammo-
encephalomyelitides and with metabolic encephalopathies. nia intoxication, and lead poisoning.

colic always needs to be considered differentially when of wildly abnormal behavior can have a positive out-
dealing with aberrant behavior in these species. come, and therefore euthanasia must be given careful
consideration while sedation takes effect. Examples of
A period of calm or of induced sedation may be taken those diseases with a more favorable prognosis include
as an opportunity to search for localizing signs of brain thiamine-­responsive polioencephalomalacia, hypoad-
disease that are often overshadowed by any accompa- renocorticism,1 neonatal hypoxic and ischemic
nying wildly aberrant behavior. These will include sub- encephalopathy, salt poisoning, hypomagnesemia,
tle signs such as asymmetric menace responses, hypocalcemia, hypoglycemia, hepatic, exogenous and
anisocoria, asymmetric nasal sensation, head tilt, head intestinal ammonia intoxication, ketosis, metaldehyde
turn, facial hypotonia, and drifting to one side walking toxicosis, macrocyclic lactone overdose, and immedi-
undirected with blindfold applied. ate post-head trauma delirium.
Asymmetric forebrain lesions frequently cause an ani-
mal to hold its head and neck turned to one side, usually
Faced with an animal showing aggressive or violent toward the same side as the lesion. This can be difficult
behavior, for safety reasons the clinician must consider to distinguish from a vestibular head tilt where there is
sedating the patient. Most times diazepam will not be rotation of the poll around the muzzle. In a more promi-
at hand but expedient IM or IV administration of nent form, a head turn due to vestibular or cerebral dis-
moderate to high doses of a readily available α-­2 ease may involve bending of the whole neck and head
agonist drug combined with a synthetic opioid drug is toward the flank. The presence or absence of a vestibular
perfectly satisfactory in most circumstances. Obviously, head tilt is best evaluated after the nose and neck have
with a patient from a rabies-­endemic area, this diagno- been held back into a midline position. In some animals
sis must be considered of paramount importance. with forebrain lesions, the eyes are also deviated and the
Some diseases that result in such a fulminant syndrome whole body spins in circles in the direction of the head
94 Large animal neurology

Figure 5.5 Painful processes, perhaps espe-

cially abdominal pain, frequently cause unex-
pected and abnormal behavior in large
animals frequently, and such actions need to
be distinguished from those caused by morbid
neurologic diseases. This racehorse would
unexpectedly rear uncontrollably while being
walked. There were no other signs of brain
abnormalities, and the only lesions detected
clinically were focal, suppurative pleuritis and
pneumonia from which he recovered with
appropriate treatment.

(A) (B)

Figure 5.6 The Thoroughbred racehorse shown here (A) is a tongue sucker and demonstrated this stereotypic behavior frequently. The horse appeared
to appreciate having its tongue grasped and manipulated, and such a maneuver would set off an episode of the tongue-­sucking behavior shown. The
mare (B) also demonstrates this behavior. Her healthy newborn foal accompanied her into the hospital and within days was seen to demonstrate the
same repetitive and nonproductive behavior (inset).
 Disorders of behavior 95

Figure 5.8 Radiographs of the atlantooccipital region of a horse dem-

(A) onstrating headshaking. There is marked modeling of the caudal aspect
of the occipital protuberance (arrows). This riding horse would only
perform persistent dorsoventral head movements while fully tacked-­up
with a bridle for ridden work. Local anesthetic solution deposited
around the region of bone modeling almost stopped the syndrome
occurring for about an hour, and infiltrating a repository glucocorticoid
drug in the region attenuated the syndrome markedly for over a week.
Ultimately, surgical exploration and removal of much of the new miner-
alized tissue was undertaken, and after healing of the surgical site the
syndrome did not occur while the horse was ridden for several months
before the case was lost to follow-­up. It is however worth recalling that
horses without the problem of headshaking can have various radio-
graphic changes present in this region (see Figure 3.9).

used for chronic sedation and sulpiride used for lacta-

tion induction protocol. Included in these can be epi-
sodes of unusual, monotonous movements of the
(B)
limbs and of the head and neck with the thoracic limbs
extended and the head touching the ground—­even
Figure 5.7 Horses diagnosed as headshakers usually have little else in flexed between them in a “praying” posture.2 Episodes
the way of physical and neurologic signs. They usually display the syn- of bradykinesia or freezing can also occur. Such signs
drome best during some form of movement or exercise such as this can be interrupted by unpredictable, violent events
Clydesdale gelding (A) and gray Thoroughbred mare (B) while being that render the situation dangerous although most
lunged. In addition to the dorsoventral and sometimes lateral flicking
cases have responded to anticholinergic therapy with
movements of the head on the neck, some will repeatedly snort and
attempt to rub their nasal region on the ground (B) or forelimbs while diphenhydramine and/or benztropine.3 These syn-
moving to cover their distal face with dirt (inset). The syndrome is aptly dromes can be compared to the extrapyramidal side
explained by the adage “acting as if it has a bee up its nose.” Riding effects seen in people with antipsychotic and antido-
becomes dangerous or impossible with severe cases. After demonstrating paminergic drugs including fluphenazine and meto-
the signs, some horses will rub their muzzle and face on objects.
clopramide, but they can also occur in animals
suffering from brain injury and from meningitis.
turn. Such episodes may be precipitated by any stimulus With no other neurologic signs, it can be difficult
to either side of the animal, when such a response can be to be sure whether subtle behavioral syndromes are
regarded as an adversive movement. This sign of cere- learned repetitive behavioral traits—­ or simply
bral disease is mostly seen with prominently asymmetric actions perceived as being unacceptable responses to
lesions, such as lateral ventricle cholinisteric granuloma, human-­induced management restrictions placed on
forebrain abscess, parasitic thromboembolism or ver- domestic animals rather than being due to acquired
minous migrations, and with head trauma. morbid neurologic lesions. Examples of these include
Quite bizarre syndromes can be seen as idiosyn- repetitive licking and sucking (Figure 5.6), head
cratic reactions to intramuscular injections of depot shaking (Figures 5.7 and 5.8), tail wringing, aggres-
forms of antipsychotic drugs including fluphenazine siveness, self-­mutilation, and refusing to follow
96 Large animal neurology

learned instructions such as taking jumps. Some of 5 Hahn CN. Behavior and the Brain. In Equine Behavior: A
Guide for Veterinarians and Equine Scientists, McGreevy P,
these syndromes are discussed in Chapter 28, Editor. Saunders, Philadelphia, PA. 2004.
although for a more detailed evaluation of equine 6 Kiley-­Worthington M. Stereotypes in horses. Cause, function
behavioral aberrations, the reader is directed to fur- and prevention. Equine Pract 1983; 5(1): 33–40.
7 Kiley-­Worthington M, Wood-­Gush D. Stereotypic Behavior, in
ther literature.4–15 Although tempting to speculate, Current Therapy in Equine Medicine, Robinson NE, Editor.
there is not ample evidence that many forms of var- 2nd ed. Philadelphia. 1987; 131–134.
ied behavior, regarded as unacceptable in domesti- 8 Beaver BV. Aggressive behavior problems. Vet Clin North Am
Equine Pract. 1986; 2(3): 635–644.
cated animals by humans, are genetic for the most 9 Houpt KA. New perspectives on equine stereotypic behavior.
part,16 and indeed many clinicians would rather suggest Equine Vet Educ 1995; 27(2): 82–83.
they are acquired, even when appearing in successive 10 Luescher UA. Porcine behavior problems. Comp Cont Edu
Pract Vet 1998; 11: 515–518.
offspring. 11 McGreevy P. Equine Behavior: A Guide for Veterinarians and
Finally, the potential role of painful sensory Equine Scientists. Saunders, Philadelphia, PA. 2004; 369.
inflammatory or degenerative lesions such as gangli- 12 Price EO. Farm animal behavior. Vet Clin North Am Food
Anim Pract 1987; 3: 217–481.
oneuritis17 in causing unacceptable and dangerous 13 McGreevy PD, French NP and Nicol CJ. The prevalence of
behavior needs further ratification. abnormal behaviours in dressage, eventing and endurance
horses in relation to stabling. Vet Rec 1995; 137(2): 36–37.
14 McAfee LM, Mills DS and Cooper JJ. The use of mirrors for the
control of stereotypic weaving behaviour in the stabled horse.
References Appl Anim Behav Sci 2002; 78(2–4): 159–173.
1 Couetil LL and Hoffman AM. Adrenal insufficiency in a neona- 15 Houpt KA. Domestic Animal Behavior for Veterinarians and
tal foal. J Am Vet Med Assoc 1998; 212(10): 1594–1596. Animal Scientists. 6th ed. Wiley-­Blackwell, Hoboken, NJ. 2018;
2 McCrindle CM, Ebedes H and Swan GE. The use of long-­acting 448.
neuroleptics, perphenazine enanthate and pipothiazine palmi- 16 Hemmann K, Ahonen S, Raekallio M, Vainio O and Lohi H.
tate in two horses. J S Afr Vet Assoc 1989; 60(4): 208–209. Exploration of known stereotypic behaviour-­related candidate
3 Baird JD, Arroyo LG, Vengust M, et al. Adverse extrapyramidal genes in equine crib-­biting. Animal 2014; 8(3): 347–353.
effects in four horse given fluphenazine decanoate. ­J Am Vet 17 Story MR, Nout-Lomas YS, Aboellail TA et al. Dangerous
Med Assoc 2006; 229(1): 104–110. Behavior and Intractable Axial Skeletal Pain in Performance
4 Crowell-­Davis SL and Houpt KA. Behavior. Vet Clin North Am Horses: A Possible Role for Ganglioneuritis (14 Cases; 2014–
Eq Pract 1986; 2: 465–671. 2019). Front Vet Sci, 2021; 8: #734218.
 6
Seizures and epilepsy

Seizures, abnormal sleep patterns, myotonic episodes, being observed, 24-­h video recording can be useful
and syncopal episodes can be difficult to distinguish to capture suspected episodes of sleep disorders and
apart. The last of these, occurring in the absence of epilepsy when they are not otherwise overt.
heart failure, is incredibly rare but the first two are Exposure to stray electric currents can be the cause
quite distinguishable if observed or preferably cap- of unusual repetitive recumbency akin to epilepsy.1
tured on video. Particularly because they both more There are also many nonepileptic disorders imitating
often occur at quiet periods when patients are not ­generalized idiopathic epilepsy that need to be

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
98 Large animal neurology

considered when evaluating patients for repeated

motor and hypotonic events. These include movement
disorders classified as paroxysmal dyskinesia,2 benign
myoclonus, hypotension, hyperekplexia, and many
metabolic and toxic insults.3,4 Indeed, even severe
Psoroptes ovis infestation (sheep scab) has been seen to
induce convulsions in sheep5 and Otobius megnini
(spinose ear tick) will cause fits in horses,5b and both of
these syndromes resolve with antiparasitic therapy.
Acquired metabolic derangements including
hypomagnesemia, hypocalcemia, hyponatremia,
hypernatremia, hepatoencephalopathy, hyperam-
monemia, and uremia all can result in seizures, as
also seen with terminal events in many toxicities.
Dyskinesias, although not apparently confirmed in
large animals, do deserve mention here.2 These disorders
are differentiated from epileptic seizures by there being
no impairment to consciousness and no autonomic or
postictal signs. Many of these phenotypic syndromes are
yet to be specifically defined, but some involve genetic
alterations to proteins involved in transmembrane con-
ductance. Interestingly, the paroxysmal, familial ataxia in
lambs (see Chapter 31) fits these criteria,6 but as with The onset of a focal or generalized seizure in large ani-
several inherited spinocerebellar ataxias in humans mals often begins with an altered facial expression
and dogs this ­disorder is likely a channelopathy.7 The such as grimacing.
onset of a myotonic episode in patients with myotonia
(Chapter 31) can be exceedingly abrupt with whole body
rigidity and recumbency that mimics a seizure, although ing from human neurology studies, consciousness is
again there is no loss of consciousness. lost in generalized seizures.9 Autonomic involvement
A seizure, fit, ictus, or convulsion is considered expressed as urination or defecation may intervene at
abnormal behavior. Seizures are the physical expres- any time. A postictal phase of poor responsiveness,
sion of abnormal, synchronous, electrical discharges restlessness, and temporary blindness may last for min-
spreading through forebrain neurons that reach the utes to hours, although central blindness may be appar-
somatic and visceral motor areas to initiate spontane- ent in foals for several days following severe generalized
ous, paroxysmal, involuntary movements. These cere- seizures. More than one seizure constitutes epilepsy
bral dysrhythmias tend to begin and end abruptly, and this, most often, is not an inherited condition in
having a finite duration8 and may be very brief. There large animals. More than one seizure over several min-
may or may not be a preictal phase or aura for seconds utes to hours, without full normalcy between, is
to hours when the animal is distracted from its envi- referred to as a cluster of seizures, and continuous sei-
ronment and is usually restless. The beginning of the zure activity with seizures immediately following each
ictus may be a localizing f­inding with one part of the other without an interictal period is status epilepticus
body, usually part of the head, involved in motor activ- that is always given a bad prognosis. Notwithstanding
ity first. If the seizure begins affecting one side of the this, several cattle, sheep, and horses have been
face, head, or body, it can be referred to as a focal sei- observed to have generalized tonic and clonic seizures
zure and may or may not progress further (Figure 6.1). with prolonged periods of having a startled expres-
These muscle contractions can spread to the whole sion, hyper-­responsiveness, and repetitive, jerky face,
body, thus resulting in a generalized seizure with the jaw, head, neck and trunk movements that ultimately
animal falling to the ground. Initially, the motor event resolved without therapy between epileptic attacks.
is one of tonic muscle contractions that then proceeds Fortunately, large animals have a relatively high
to clonic muscle contractions with the patient showing seizure threshold as it seems to take a considerable
limb paddling while in lateral recumbency. Based on perturbation to forebrain function to precipitate con-
observations of absent responsiveness and extrapolat- vulsions. Notwithstanding, seizures often accompany
 Seizures and epilepsy 99

(A) (B)

Evidence of prior self-­inflicted trauma over bony promi-

nences or on the tongue or gums as seen here can herald the
onset of epilepsy as seen by an upper lip lesion in this foal.

(C) (D) (E)

Figure 6.1 Most cases of seizures and epilepsy in large animals are Large animals, especially horses, often become
acquired. Some accompany inherited neurologic disorders (Chapter 31) violent in response to painful processes and when
and others are associated with metabolic problems including electrolyte
disturbances and liver disease, and with some specific toxicities such as
attempting to regain their footing. These intermittent
Tutu (Coriaria arborea) and metaldehyde poisoning. In neonates, seizures and sometimes continuous episodes of struggling
can accompany birth asphyxia in calves (A) and the hypoxic–ischemic and thrashing are difficult to distinguish from con-
encephalopathy syndrome in foals (B). The seizures in these two cases vulsions. Secondary head trauma often ensues,
were heralded by tonic movements of the head and neck that were sym- ­usually adding to the delirious state. Primary processes
metric in the calf (A) and asymmetric in the foal (B), prior to generalizing
to tonic and clonic contractions of the whole body. Focal seizures, and
that fall in this category include colic, myopathy, ver-
mild generalized seizures, where the patient does not lose consciousness tebral injury, long bone fractures, and acute spinal
to become recumbent, may be restricted only to the face and head as cord, brainstem, and particularly vestibular disease.
shown by the early ictal movements in two other foals (C and D). The Because suspected epilepsy does appear to be more
consequences of generalized seizures are seen in a horse (E) that had frequently a presenting problem in horses, and some
epilepsy and focal seizures with secondary generalization causing self-­
inflicted head trauma.
attempts have been made to classify these,13,14 a few spe-
cific comments are warranted for that species. Repeated
generalized seizures that persist, with no active under-
lying disease process identified, and occurring in fami-
many focal and diffuse acquired diseases of the lies of purebred animals, are true or idiopathic epilepsy.
­forebrain, often as part of terminal syndromes.10,11 This does not appear to have been demonstrated in
Neonatal animals, particularly foals, convulse more adult horses, although it may have been seen in some
readily than adults, and foals frequently demonstrate breeds of cattle.15 However, a patient that has had one
mild generalized seizures seen as periods of jaw seizure from any cause is more likely to have another—­a
chomping (“chewing-­gum fit”),12 tachypnea, tremor process referred to as kindling. Thus, epilepsy begin-
and grimacing of facial muscles, and jerky head move- ning in adulthood in horses can be regarded as acquired
ments without evolving from a focal seizure. Epilepsy until proven otherwise. Any morbid or biochemical
may occur in conjunction with other signs of forebrain forebrain lesion potentially can act as a seizure focus,
disease persistent during the interictal period. These and the resulting epileptic syndrome may begin days to
may be quite subtle and consist of degrees of partial years after the initial lesion. Also, a nonprogressive cer-
blindness seen as an asymmetric menace response, ebral lesion such as an old glial scar may result in epi-
partial facial hypalgesia seen as asymmetric reactions lepsy that resolves, progresses, or remains stable.
to touching the sides of the nasal septum, an asymmet- Repeated seizures in neonatal foals most frequently
ric hopping response on the thoracic limbs, and a ten- indicate sepsis or neonatal encephalopathy,16–18 and a
dency to drift to one side when blindfolded and similar syndrome has been seen in calves suffering
verbally coaxed, but not led, to walk straight forward. birth asphyxia with resuscitation (Figure 6.1). Equine
100 Large animal neurology

familial isolated hypocalcemia (EFIH) in Thorough­ of an epileptic syndrome using larvicidal doses of
bred foals, hypoglycemia, and possibly hyperbiliru- anthelmintics and short-­ term nonsteroidal anti-­
binemic encephalopathy (kernicterus) should also be inflammatory or glucocorticosteroid therapy. And
considered in young patients,19,20 and in adults under third, cases with bacterial granulomatous ependymitis
appropriate situations.21 Adolescent foals, especially and choroiditis, true brain abscesses, and cholinis-
of the Arabian breed, can suffer from epilepsy that is teric granuloma can be insidious in their clinical
of genetic origin22,23 and can also suffer from severe progression, and one or more seizures may be the
seizures associated with the lethal Lavender foal initial overt sign. Indeed, in an aged horse with epi-
syndrome.22,24 In the genetic adolescent epilepsy, sei- lepsy that may be responsive to glucocorticosteroid
zures are usually symmetrical and generalized, and drugs for quite some time, cholinisteric granuloma
the first seizure may accompany an episode of sepsis must be given strong consideration.28 Various surgical
or other acquired diseases. Control of the seizures and antibacterial therapeutic regimens are feasible,
with medication is usually successful, and the patients but heroic approaches in such cases. Rare occurrences
appear to grow out of the condition. Finally, although of ear tick infestation, hypoglycemia associated with
not true epilepsy, foals and calves with severe cere- pancreatic neoplasia, intracranial neoplasia, and vas-
bellar disease have been seen to have convulsive epi- cular dysplasia might be considered.29–31
sodes regarded as cerebellar fits, but they are aware of Guidelines aimed at assisting in the handling of
their environment during these attacks. large animal epileptic patients and in advising own-
On a practical note, the recommendation to pro- ers are not available, thus recommendations are
ceed with straightforward epilepsy cases having no rather empiric. To begin with, it must at least be
interictal signs ­to advanced diagnostic imaging is not reported to the owner that a patient with epilepsy is
really helpful unless everything possible, including unsafe to ride until seizure free and not on anticon-
heroic intracranial surgery, is to be entertained. The vulsant medication for at least 6 months. Also, if the
utility of electroencephalography and MR imaging in horse injures itself to require veterinary attention,
improving the outcome of such cases has been dis- and thus documentation of the injury for the record,
cussed,25,26 but is not widely accepted. then euthanasia must be considered (Figure 6.1).
Signs that may relate to a focal forebrain lesion that With respect to this decision, and in reporting to an
is a potential seizure focus must be searched for insurance company, it is reassuring to have a video of
during an interictal—­ not postictal—­ neurologic one of the seizures and to have some, albeit subtle,
examination. Such signs include asymmetric menace interictal sign to corroborate the horse having epi-
responses, asymmetric nasal sensation, anisocoria, a lepsy associated with an acquired intracranial mor-
head deviation with or without blindfold applied, bid disease process. On the other hand, a sensible
facial paresis and facial hypertonia, and asymmetry owner can be advised that the vast majority of sei-
in hopping on the forelimbs. If an epileptic horse is zures will occur at quiet times and not while working;
essentially healthy with minimal or no neurologic however, the written report must state that the horse
signs evident between seizures, then most possible is unsafe to ride.
causes of forebrain disease that include viral enceph- The client should be encouraged to keep an accu-
alitis, hepatoencephalopathy, leukoencephalomala- rate diary of known and suspected seizure episodes
cia (Fusarium sp. mycotoxicosis), and other toxicities particularly noting preictal signs, site on the body
are exceedingly unlikely to be the cause of the epi- where the motor disturbance begins, and the severity
lepsy. Three diseases at least should however be given and timed duration of each seizure. This will allow a
consideration as underlying specific causes in such best prediction as to whether the epilepsy is stable,
situations. In horses that have been on the American resolving or progressing, to be made. Should individ-
continents, equine protozoal myeloencephalitis caused ual seizures be occurring say fewer than one every
by Sarcocystis neurona or Neospora hughesi must be month and the patient does not injure itself to require
considered.27 Serum and cerebrospinal fluid immu- veterinary attention, then medication is probably not
noassay tests can be performed so that appropriate indicated. If there are cluster seizures, status epilepti-
treatment can be initiated and continued if the cus or more than one seizure a month, or if the patient
tests are positive. In most countries, consideration injures itself to require veterinary attention and the
should be given to treatment for thromboembolic and client does not accept euthanasia as an option, then
migratory verminous encephalitis at the beginning anticonvulsant therapy must be considered.
 Seizures and epilepsy 101

The following points are a guide to maintenance anti- • After control, monitor serum concentrations and aim
convulsant therapy to help control seizures in epileptic to keep them in the therapeutic ranges (e.g., pheno-
adult horses: barbital, 15–40 μg/mL; bromide, 1000–4000 μg/mL).
• Have the owner keep a diary of seizure activity and all • Seizure threshold may be lowered with estrogen,
medication given. therefore anticonvulsant dosage may be increased
• All anticonvulsant drugs are not licensed for use in prior to onset of and during estrus activity.
large animals. • If the patient is completely seizure free for 6 months.
• Begin phenobarbital at 5 mg/kg BID, PO. then slowly wean the patient off one drug at a time
• Increase the dose about 20% every 2 weeks until per- over 3 months. If seizures begin, raise the dose again.
sistent sleepiness occurs or seizures are not • Interactions must be considered when other drugs are
controlled. to be administered to an animal already on anticon-
• Reduce dose say by 20% and add KBr at 25–90 mg/kg vulsant therapy.
SID, PO, with or without loading doses of 120–200 mg/kg These guidelines may be extrapolated to other species.
SID, PO for 1–5 days.41 Metabolic disorders especially hypocalcemia and hypo­
• Consideration then can be given to incorporating phe- magnesemia must be considered in ruminants. All ruminants
nytoin, carbamazepine, gabapentin or levetiracetam, that have seizures of uncertain cause should receive gram
etc., to the regimen if further control required and/or doses of thiamin immediately after any diagnostic samples
side effects are unacceptable. have been drawn for red cell transketolase activity.

For acute control of seizures in adult horses, IV References

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suspected. Then, 50 mg IV doses of diazepam or horse. Vet Rec 1998; 142(3): 68.
midazolam can be used.32, 33 Benzodiazepine drugs 2 Lowrie M and Garosi L. Classification of involuntary move-
ments in dogs: paroxysmal dyskinesias. Vet J 2017; 220: 65–71.
should not be left in a plastic container or syringe for 3 Caraballo RH, Cersosimo RO and Fejerman N. Benign focal
more than a few minutes as they may become inacti- seizures of adolescence: a prospective study. Epilepsia 2004;
vated. If diazepam or an alternative benzodiazepine 45(12): 1600–1603.
4 Fejerman N. Nonepileptic disorders imitating generalized idi-
drug is not available, then standard doses of alpha-­2 opathic epilepsies. Epilepsia 2005; 46(Suppl 9): 80–83.
agonist drugs, or IV levetiracetam can be used. If these 5 van den Broek AH and Huntley JF. Sheep scab: the disease,
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at this stage euthanasia must be strongly considered. 5b Miller, S. M. (2020). Putative Otobius megnini-associated
Midazolam can also be considered as first line therapy clinical signs in horses in South Africa (2012–2018). J S Afr Vet
for neonatal seizures in foals,32,34 and intranasal equiv- Assoc, 91(0), e1–e6. 10.4102/jsava.v91i0.1983
6 Mayhew IG, Jolly RD, Burnham D, et al. Familial episodic
alent doses may expedite seizure control.35 ataxia in lambs. N Z Vet J 2013; 61(2): 107–110.
Pharmacokinetic and related drug disposition 7 Dittmer KE, Jolly RD, Mayhew IG, et al. Familial episodic
studies on phenobarbital,36–39 potassium bromide40,41 ataxia in lambs is potentially associated with a mutation in the
fibroblast growth factor 14 (FGF14) gene. PLoS ONE 2017;
and phenytoin in horses,42–44 potassium bromide in 12(12): e0190030.
sheep,45 and phenobarbital46 and levetiracetam47 in 8 Wong M. Advances in the pathophysiology of developmental
foals have been published. Gabapentin,48 pregaba- epilepsies. Semin Pediatr Neurol 2005; 12(2): 72–87.
9 Blumenfeld H. Impaired consciousness in epilepsy. Lancet
lin,49 and imepitoin50 may need to be considered if Neurol 2012; 11(9): 814–826.
the starting drugs are ineffective at giving some sei- 10 Chigerwe M and Aleman M. Seizure disorders in goats and
zure control. Several other human anticonvulsant sheep. J Vet Intern Med 2016; 30(5): 1752–1757.
11 Lacombe VA. Seizures in horses: diagnosis and classification.
drugs may be worth considering if control of seizures Vet Med Auckl 2015; 6: 301–308.
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foals with unsubstantiated anticonvulsant results are mic neonatal foals: four cases. Aust Vet J 2014; 92(12):
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14 Lacombe VA, Mayes M, Mosseri S, Reed SM and Ou TH.
of antiseizure medication in small animals51 and in Distribution and predictive factors of seizure types in 104
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15 Braun U, Schweizer G and Hilbe M. Epileptiform convulsions Retrieved 2022_02_28 from https://www.ivis.org/library/aaep/
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150(9): 281–282. to-control-equine-neonatal-seizures
16 Galvin N and Collins D. Perinatal asphyxia syndrome in the 35 Charalambous M, Volk HA, Tipold A, et al. Comparison of
foal: review and a case report. Ir Vet J 2004; 57(12): 707–714. intranasal versus intravenous midazolam for management
17 Toribio RE. Equine neonatal encephalopathy: facts, evidence, of status epilepticus in dogs: a multi-­center randomized
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20 Loynachan AT, Williams NM and Freestone JF. Kernicterus in administration of the drug. Am J Vet Res 1992; 53(5):
a neonatal foal. J Vet Diagn Invest 2007; 19(2): 209–212. 706–710.
21 Aleman M, Costa LR, Crowe C and Kass P H. Presumed neu- 38 Ravis WR, Duran SH, Pedersoli WM and Schumacher J. A
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Intern Med 2018. oral dosing. J Vet Pharmacol Ther 1987; 10(4): 283–289.
22 Aleman M, Finno C J, Weich K and Penedo MCT. Investigation 39 Reimer JM and Sweeney RW. Pharmacokinetics of phenobar-
of known genetic mutations of Arabian horses in Egyptian bital after repeated oral administration in normal horses. J Vet
Arabian foals with juvenile idiopathic epilepsy. J Vet Intern Pharmacol Ther 1992; 15(3): 301–304.
Med 2018; 32(1): 465–468. 40 Gamble KC, Lacasse C, Way SI and Boothe DM. Management
23 Lichter-­Peled A, Polani S, Stanyon R, Rocchi M and Kahila of idiopathic epilepsy in a female Grevy’s zebra (Equus grevyi)
Bar-­Gal G. Role of KCNQ2 and KCNQ3 genes in juvenile idi- with potassium bromide and therapeutic drug monitoring. Proc
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24 Page P, Parker R, Harper C, Guthrie A and Neser J. Clinical, May 2009; 59–64.
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Vet Intern Med 2006; 20(6): 1491–1494. 42 Guan F, Uboh CE, Soma LR, et al. Quantification of phenytoin
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imaging characteristics of equine head disorders: 84 cases performance liquid chromatography. J Chromatogr B Biomed
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27 Reed SM, Furr M, Howe DK, et al. Equine protozoal myeloen- 44 Soma LR, Uboh CE, Guan F, et al. Disposition, elimination,
cephalitis: an updated consensus statement with a focus on and bioavailability of phenytoin and its major metabolite in
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Meningocerebral hemangiomatosis resembling Sturge-­ Weber 48 Davis JL, Posner LP and Elce Y. Gabapentin for the treatment
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Ultrasonographic confirmation of a space-­occupying lesion in 49 Mullen KR, Schwark W and Divers TJ. Pharmacokinetics of
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 7
Sleep and acute collapse disorders

The role of sleep in mammalian biology is somewhat whereas others experience great difficulties in being
of an enigma.1 Adult herbivores spend a substantial cross-­tied for several days. The latter appear to go
proportion of time foraging, and only a few hours into a deep sleep state but stagger as not being able to
daily are spent in stages of sleep, a small proportion remain upright, and some can injure themselves.
of which is rapid eye movement (REM) sleep with Thus, the concept of sleep deprivation in horses may
accompanying somatic hypotonia or atonia and well be an individual phenomenon.3,7
recumbency.1–3 For adult cattle and horses, this Without observing episodes, it can be difficult to
amounts to 3–5 h per day in sleep states and about 0.5 distinguish seizures from normal and abnormal
h per day in REM sleep.3–6 Some horses appear to be episodes of sleep and from cardiovascular collapse or
able to perform REM sleep while standing2 and to syncope in otherwise perfectly healthy patients. The
tolerate weeks of being unable to lie down to sleep, last of these show multiple episodes of collapse but

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
104 Large animal neurology

with apparent normalcy between is incredibly rare in

our experience, but seizures and sleep disorders can
be quite distinguishable if observed. In this regard,
24-­h video monitoring and recording can be useful
to capture suspected episodes of sleep and seizures
when they are not overt.8 However, intermittent
paralysis or cataplexy can pose as syncope, epileptic
seizures (particularly pseudocataplexy or atonic sei-
zures), hyperekplexia, and vestibular drop attacks.9
In the context of sudden and unexpected collapse,
there are many systemic issues that can mediate an
abrupt loss of body support,10 but the majority result in
other progressive signs such as weakness and obtunda-
tion or are associated with other factors such as trauma,
diarrhea, or drug usage.11 In about half the cases of epi-
sodic collapse, it may be possible to arrive at a final diag-
nosis with most having signs other than collapse being (A)
evident. Such diagnoses include cardiac arrhythmia,
right-­sided heart failure, hypoglycemia, neurocardio-
genic syncope, and exercise-­induced pulmonary hem-
orrhage. For most other cases, there will be a strong
suspicion of epilepsy (Chapter 6) and sleep disorders.12
Sleep disorders in humans3,13–15 can be categorized
into many groupings, but these usually include narco-
lepsy with cataplexy (narcolepsy type-­ 1, NT-­ 1) (B)
(Figure 7.1), narcolepsy without cataplexy (NT-­2), and
idiopathic hypersomnia (see Chapter 31 for further Figure 7.1 Familial narcolepsy with cataplexy as seen in these two
readings on narcolepsy in large animals).3,16–23 ponies is uncommon compared to other forms of sleep disorders in
horses. These ponies would, spontaneously and particularly with pleasur-
Narcolepsy occurs in 0.02–0.15% of the population, able stimuli such as grooming, feeding, and playing (A), rapidly become
and patients typically demonstrate excessive diurnal somnolent, stagger or sway, and fall passively to the ground in a cata-
sleep, flaccid paralysis with somatic areflexia that con- plectic state (B) with no spinal reflexes demonstrable, where they would
stitutes cataplexy, sleep paralysis, sleep-­onset halluci- remain until they slowly woke up after a minute to an hour or so.
nations, and nocturnal disrupted sleep. Strict EEG and
EOG criteria, including the early onset of rapid eye signaling was related to both familial and sporadic
movement at the beginning instead of the middle of a narcolepsy.3,21,22,24,25 A mutation in the hypocretin
sleep cycle, are in place for confirming the diagnosis receptor-­2 gene was present in dogs with familial nar-
and for distinguishing narcolepsy with cataplexy from colepsy although they had normal levels of hypocre-
narcolepsy without cataplexy and from idiopathic tins in their CSF and hypothalamus. Neurotransmission
hypersomnia. A familial form of narcolepsy with cata- through hypocretin-­1 was likely to be intact indicating
plexy occurs in dogs and humans, and in the latter it is that defective hypocretin-­2 function is more impor-
strongly associated with the genetic allele HLA-­ tant in producing narcolepsy in that model. In con-
DQβ1*0602. An autoimmune basis to at least some trast, dogs with sporadic narcolepsy had no expressed
forms of narcolepsy thus seems likely.13 Narcolepsy hypocretins in the CSF or brain tissue. Hypocretin
without cataplexy shares the same electrophysiological deficiency, as shown by low or absent concentrations
abnormalities and associated signs, but there is no in CSF, has been found in 90% of patients with spo-
demonstrable cataplexy. Purely excessive daytime sleep radic narcolepsy with cataplexy, and less commonly in
attacks, also referred to as unwanted siestas (a well-­ familial narcolepsy26 and in sleep deprivation, suggest-
appreciated term!), occur in idiopathic hypersomnia. ing that disorders with marked cataplexy are more
Two novel neuropeptides (orexins), hypocretin 1 dependent on dysfunctional hypocretin pathways.
and 2, were found to be specifically expressed in cer- In the sporadic and some familial forms of the dis-
tain hypothalamic neurons, and defective hypocretin ease, various pieces of evidence indicate that there may
 Sleep and acute collapse disorders 105

be an autoimmune attack on hypocretin-­producing have been documented. Thus, it is likely that many of
neurons and decreased hypocretin-­expressing neu- these cases of adult-­onset sleep attacks are examples
rons in the hypothalamus have been reported.27–30 of sporadic idiopathic hypersomnia, probably with
Attempts to identify a neural autoantibody in canine influences of sleep deprivation as discussed above.7
and human narcolepsy have been unsuccessful; how- Many factors of animal domestication, including dis-
ever, evidence for the presence of a functional, IgG rupted social hierarchy, confinement, and occupa-
autoantibody in serum of narcoleptic humans and not tional maladies, appear to be involved with lack of
in controls which upregulates cholinergic activity, a restful sleep, and astute observational programs can
characteristic of narcolepsy, has been presented.31 result in very useful management alterations to assist
Further evidence that the immune system plays a role in restoring acceptable sleep–wake cycles.36 A
in canine genetically dependent narcolepsy has been detailed understanding of sleep patterns, including
published.32 One study found that immunosuppres- the associated encephalographic patterns, and deter-
sive and anti-­inflammatory drugs delayed the onset mining the roles, if any, of hypocretin pathways and
and severity of narcolepsy and cataplexy in treated their immune attack in the various sleep disorders
dogs compared to controls.33 Also, there has been an may help better characterize the syndromes and
upsurge in acquired influenza vaccine-­induced narco- perhaps allow the use of specific therapy rather than
lepsy type 1 (Pdmx-­NT1) and a loss of hypocretin-­ palliative treatment of some of these disorders.37–39
producing neurons in this form of narcolepsy as well
as in spontaneous narcolepsy type 1 (narcolepsy with
cataplexy; sNT1). Results of attempts at treating narco- References
lepsy in dogs with prednisolone and systemic and 1 Siegel JM. Clues to the functions of mammalian sleep. Nature
intrathecal hypocretin-­ 1 have been poor, perhaps 2005; 437(7063): 1264–1271.
2 Williams DC, Holliday TA, Aleman MR, et al. Sleep in the
because of depleted hypothalamic neurons.34 However, horse: an electroencephalographic study. Am Coll Vet Int Med
using alternating periods of desipramine and yohim- Forum 2002; ACVIM.
bine (an α-­2 antagonist to activate adrenergic trans- 3 Kryger MH, Roth DT and Dement WC. Principles and Practice
of Sleep Medicine. 4th ed. Saunders, Elsevier, Philadelphia, PA.
mission) therapy for the cataplexy showed promise. 2005; 1552.
Many normal newborn foals can be induced into a 4 Dallaire A and Ruckebusch Y. Sleep patterns in the pony with
sleep-­like state by firm, whole-­body restraint or cud- observations on partial perceptual deprivation. Physiol behav
1974; 12(5): 789–796.
dling to sometimes even lie still on the ground when 5 Ruckebusch Y. The relevance of drowsiness in the circadian
released.35 This phenomenon wanes rapidly over a few cycle of farm animals. Anim behav 1972; 20(4): 637–643.
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of a protective mechanism that stops vigorous reflex Societe de biologie et de ses filiales. 1970; 164(3): 658–665.
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24th Annual Forum Am Coll Vet Int Med, Louisville KY.
2006; 24: 167–169.
8 Pizza F, Antelmi E, Vandi S, et al. The distinguishing motor features
Astute observational studies of of cataplexy: a study from video-­recorded attacks. Sleep 2018;
41(5): zsy026–zsy.
sleep–wake cycling in domestic 9 Pillen S, Pizza F, Dhondt K, Scammell TE and Overeem S.
animals can result in modified envi- Cataplexy and its mimics: clinical recognition and manage-
ronments to facilitate relaxed lean- ment. Curr Treat Options Neurol 2017; 19(6).
10 Lyle CH and Keen JA. Episodic collapse in the horse. Equine
ing behavior, as depicted here for Vet Educ 2010; 22(11): 576–586.
an elephant using a leaning fence 11 Hughes KJ. Diagnostic challenge: lethargy and weakness in an
with horizontal protuberance for Arabian foal with cardiac murmurs. Ventricular septal defect
(VSD). Aust Vet J 2006; 84(6): 209–212.
support. Source: Modified from 12 Lyle CH, Turley G, Blissitt KJ, et al. Retrospective evaluation of
Schiffmann et al.36 episodic collapse in the horse in a referred population: 25 cases
(1995–2009). J Vet Intern Med 2010; 24(6): 1498–1502.
13 Reading PJ. Update on narcolepsy. J Neurol 2019; 266(7):
1809–1815.
Some syndromes of adult-­onset sleep attacks in 14 Young TJ and Silber MH. Hypersomnias of central origin.
large animals—­especially horses—­clinically resemble Chest 2006; 130(3): 913–920.
true narcolepsy with cataplexy; however, confirming 15 de Lecea L and Sutcliffe JG. The hypocretins and sleep. FEBS J
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limb atonia, limb areflexia, as well as onset of REM 16 Mignot E and Nishino S. Emerging therapies in narcolepsy-­
sleep at the onset of an episode does not appear to cataplexy. Sleep 2005; 28(6): 754–763.
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17 Scammell TE. The neurobiology, diagnosis, and treatment of 30 Thannickal TC, Siegel JM, Nienhuis R and Moore RY. Pattern
narcolepsy. Ann neurol 2003; 53(2): 154–166. of hypocretin (orexin) soma and axon loss, and gliosis, in
18 Dauvilliers Y and Buguet A. Hypersomnia. Dialogues clin neu- human narcolepsy. Brain Pathol 2003; 13(3): 340–351.
rosci 2005; 7(4): 347–356. 31 Smith AJ, Jackson MW, Neufing P, McEvoy RD and Gordon
19 Dauvilliers Y, Challamel MJ and Touchon J. (Sleep disorders in TP. A functional autoantibody in narcolepsy. Lancet 2004;
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1937–1946. 32 Liblau RS. Put to sleep by immune cells. Nature 2018; 562(7725):
20 Tafti M, Maret S and Dauvilliers Y. Genes for normal sleep and 46–48.
sleep disorders. Ann med 2005; 37(8): 580–589. 33 Boehmer LN, Wu MF, John J and Siegel JM. Treatment with
21 Black JE, Brooks SN and Nishino S. Narcolepsy and syndromes immunosuppressive and anti-­ inflammatory agents delays
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271–282. ity. Exp Neurol 2004; 188(2): 292–299.
22 Kotagal S and Pianosi P. Sleep disorders in children and adoles- 34 Schatzberg SJ, Cutter-­Schatzberg K, Nydam D, et al. The
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23 ICSD-­ 3 AAoSM. International Classification of Sleep Weimaraner with narcolepsy. J Vet Intern Med 2004; 18(4):
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26 Baumann CR and Bassetti CL. Hypocretins (orexins) and phants. Zoo Biol 2018; 37(3):133–145.
sleep–wake disorders. Lancet Neurol 2005; 4(10): 673–682. 37 Klimova B, Maresova P, Novotny M and Kuca K. A global view
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27(3): 469–474. 27(2): 187–192.
 8
Coma and other altered states
of consciousness

Coma (Gr: deep sleep) is a state of living nonrespon- of these terms in human medicine. It is clearest to
siveness. Stages of increasing levels of obtundation simply state what the patient is and is not aware of.
can be referred to as sleepiness (somnolence), semi- Diffuse and focal lesions resulting in coma and other
coma (Figure 8.1) and coma, and represent a progres- altered states of consciousness involve the forebrain
sive lack of awareness of the environment and and/or the reticular activating system (RAS) in the
decreased responsiveness to physiologic and noxious brainstem, particularly in the midbrain (Figure 1.7).
stimuli. It is wise to avoid the anthropomorphic An alert state is maintained through multiple
terms depression, delirium, oscitancy, torpor, stupor, ­sensory inputs to the RAS in the rostral brainstem
lethargy, etc., because of the subjective connotation and subsequently to the thalamus and cerebral

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
108 Large animal neurology

c­ ortex where conscious awareness in animals pre- To witness a large animal suddenly collapse, or to
sumably is attained. Diffuse cerebral disease and be called urgently to evaluate a patient that has suf-
severe lesions involving just the thalamus, internal fered one or more episodes of collapsing, can be con-
capsule, or frontal lobe can result in an inattentive fusing for the clinician and certainly distressing for
and oblivious mental awareness in animals, often the owner or caregiver. On most occasions, the situa-
expressed as dummy syndrome. Additional signs of tion resolves quickly to one of sudden death, recovery
behavioral aberrations, seizures, and visual distur- with recumbency, a gait abnormality, another neuro-
bances frequently accompany this condition. Coma logic syndrome, recovery with or without evidence of
can result from acute damage to these regions of the a non-­neurologic problem, or repetitive episodes of
forebrain, but particularly so from lesions involving collapsing. Poorly informed clients and children must
the midbrain RAS and especially the thalamus. be reminded of their own safety and should be advised
Almost all of the diffuse inflammatory, metabolic, to keep clear of a collapsing large animal until the vet-
nutritional, toxic, traumatic, and vascular CNS dis- erinarian arrives. An informed client may be directed
eases can ultimately result in coma prior to death. to stop any massive bleeding or roll a heavy animal
Mentally obtunded animals do not respond appro- that might be cast. In the event that the animal arises,
priately to noxious stimuli such as loud noises and the client can guide it if it is ambulatory to soft ground,
prodding with a blunt instrument (Figure 8.1). Also, away from potentially harmful objects.
lesions involving the thalamus, internal capsule, or Upon arriving at the scene of a collapsed patient,
sensory parietal lobe of the cerebrum can be associ- the ABCs of acute care must be attended to concur-
ated with decreased sensation on the contralateral side rently. It must be determined that the patient has a
of the face, most prominent on the nasal septum. This patent airway and is breathing adequately. Oxygen or
exceeds degrees of nonresponsiveness that can be assisted ventilation may be necessary. Obstructing
expected from any associated obtunded mental state. fluids or objects should be removed from the airway,

(A) (B)

Figure 8.1 This neonatal Limousin cross calf suffering from bacterial meningitis (A) demonstrated opisthotonus and was in a semicoma being nonre-
sponsive to physiologic stimuli and inappropriately responsive to noxious stimuli. He would flail around with his head and neck extended when haemostats
were prodded against the nasal septum or they were squeezed across the coronets of a digit. With antibiotic and glucocorticoid therapy, the calf made
a complete recovery (B).
 Coma and other altered states of consciousness 109

and 10 mL 50% ethanol can be given intratracheally ally because of the presence of a cardiac arrhythmia or
and/or furosemide 1 mg/kg IV, if pulmonary edema is a cardiac murmur. Definitive cardiac disease is con-
evident. Hemorrhage should be stopped by packing, firmed in a proportion of these cases.2–4 Such docu-
suturing, and bandaging. Cardiovascular function mented disorders include atrial fibrillation, ruptured
should be quickly assessed, and cardiac resuscitation chordae tendineae, myocardial infarction, myocardial
with thoracic massage, if appropriate, and intrave- fibrosis, dissecting aortic aneurysm, aortic endocardi-
nous or intracardiac adrenalin (3–5 mL of 1:1000 in tis, and pericarditis.
10 mL H2O for adult horse) should be administered if With syncopal attacks, usually there is little or no pre-
asystole or anaphylaxis is evident. Intravenous vol- monitory warning of collapse; because of cerebral
ume expansion with polyionic fluids, plasma, or hypoxia, a temporary, quiet, comatose state ensues.
blood is used as indicated and when available. Some struggling may occur during recovery, before the
The presence of any compound or complicated patient regains its footing, unless of course the patient
fractures that may mean a hopeless prognosis (e.g., has suffered severe head trauma on way to recumbency.
femur), that may be life-­threatening (e.g., ribs) or that Other overt signs of cardiac failure may become evident.
may require splinting (e.g., metacarpus) must be iden- Polycythemia5 and upper airway obstruction—­including
tified, and appropriate measures should be taken. untoward effect of cribbing throat collar—­rarely can also
A thrashing patient may require sedation or even anti- result in syncopal attacks.6
convulsant therapy if it is deemed to be due to cerebral A seizure, convulsion, or fit is the physical expression
seizure. If shock or respiratory depression are not prob- of bizarre but synchronous electrical neuronal dis-
lems, and there is no good evidence of seizure activity, charges in all or part of the cerebrum and is introduced
then an α-­2 agonist sedative drug, pentobarbitone, or in Chapter 6. Often a preictal aura of a few seconds to
even acepromazine can be instituted. Diazepam IV or minutes occurs, then the ictus or seizure lasts seconds to
midazolam IM or IV in 5–10 mg (foal) to 25–100 mg minutes with an accompanying variable period of coma
(horse) doses can be given to control seizures. A horse or semicoma. This is followed by a postictal phase
recumbent for any reason can become terribly violent in lasting several minutes to days. The initial aura may
its frantic attempts to rise and in response to pain, and it cause the animal to be distracted from its environment,
may be impossible to distinguish this behavior from true to have a blank facial expression, and to occasionally
seizures. With the latter, the horse is in a state of uncon- become restless. If the seizure becomes generalized, the
sciousness, and its attention cannot be attracted. Also, patient becomes recumbent and may lay rigid for a
the face and jaw muscles usually show spasmodic or con- while before paddling or thrashing for several seconds
tinuous contractions, the eyeballs move to abnormal to minutes. With status epilepticus, this phase is repeated
positions, opisthotonus tends to occur, and sometimes continually and is fatal unless chemical, anticonvulsant
urine and feces are voided. restraint is used. A postictal animal usually regains
Important facts to be noted include the duration and its footing relatively easily then may pace, act blind,
repetition of the episode of collapse, any exposure to constantly drink or eat, and may not recognize herd
various environmental factors such as recent lightning/ mates, its handler, or its environment. Depending on
thunder storm, proximity to stray voltage sources, the underlying cause, other neurologic signs may be
excessive heat, poisonous plants, exogenous chemicals, evident. Anticonvulsant therapy may be required if
previous or prodromal illness, different feeds, and more than one generalized seizure has occurred;
whether other herd mates have been affected. although if familial juvenile epilepsy of Arabian foals is
A brief physical examination can then be under- suspected, therapy can be started immediately.
taken. The general aim at this stage is to determine Narcolepsy is characterized by uncontrolled epi-
which basic category of acute collapse best fits the par- sodes of sleep. Unlike seizures and many metabolic
ticular case.1 These general categories include syncope disorders, such as hyperkalemia and hypocalcemia,
and seizure (Chapter 6), sleep disorders (Chapter 7), there are no warning signs. With multiple attacks, the
coma, motor paralysis (Chapters 23 and 24), and patient may appear sleepy between episodes. Adult
generalized and metabolic disorders.1 Some of the animals do not always drop to the ground in a para-
characteristics of each of these are given here to assist lyzed state of cataplexy and may catch themselves
in making an accurate diagnosis. after the head suddenly lowers and the thoracic limb
A small number of animals that experience one or stay apparatus begins to fail. Most often prominent
more episodes of acute collapse are suspected of having cataplexy, which entails sudden loss of all voluntary
syncope or a fainting condition. This suspicion is usu- motor effort and somatic limb reflexes, occurs and
110 Large animal neurology

the animal collapses to the ground. Petting about the collapse, hypoglycemia, hypocalcemia, hyperkalemia,
head and neck, hosing down after exercise, begin- hypokalemia, endotoxemia, intestinal hyperammone-
ning to eat or drink, and resting quietly in a barn at mia, anaphylaxis, anaphylactoid reaction, acute exo-
night all seem to have been associated or precipitating toxemia, snake envenomation, and many terminal
factors with various cases. Sleep attacks do not usu- toxic states.10–15 Usually, several body s­ystems are
ally occur while an animal is exercising vigorously. found to be abnormal after a general physical exami-
Coma is a state of recumbency with unconsciousness nation and subsequent, appropriate detailed system
and total unresponsiveness. It is primarily associated examinations, and therapy can be undertaken.
with profound changes in the forebrain or midbrain.
Head trauma, birth asphyxia, bacterial meningoen-
cephalitis, thiamine-­responsive polioencephalomalacia,
References
parasitic infarction/migration, spontaneous hemor-
rhage, moldy corn intoxication, liver disease, intraca- 1 Fejerman N. Nonepileptic disorders imitating generalized idio-
pathic epilepsies. Epilepsia 2005; 46 Suppl 9: 80–83.
rotid injections, and many poisons are some of the more 2 Jesty SA and Reef VB. Evaluation of the horse with acute cardiac
frequent causes of acute coma. Consequently, it is crisis. Clin Tech in Eq Pract 2006; 5(5): 93–103.
important to determine if the animal has a history or 3 Lyle CH, Turley G, Blissitt KJ, et al. Retrospective evaluation of
episodic collapse in the horse in a referred population: 25 cases
evidence of trauma or of other premonitory neurologic (1995-­2009). J Vet Intern Med 2010; 24(6): 1498–1502.
signs. Immediately following head trauma, a temporary 4 Lyle CH and Keen JA. Episodic collapse in the horse. Equine Vet
period of coma often ensues. Thus, the animal does not Educ 2010; 22(11): 576–586.
5 Steiger R and Feige K. Case report: polycythemia in a horse.
require euthanasia during the first 24 h, but at this time Schweiz Arch Tierheilkd 1995; 137(7): 306–311.
appropriate diagnostic and therapeutic approaches 6 Hay WP, Baskett A and Abdy MJ. Complete upper airway
should be instituted. Access to specific toxic compounds obstruction and syncope caused by a subepiglottic cyst in a horse.
Equine Vet J 1997; 29(1): 75–76.
should be sought in order to administer appropriate 7 Landolt GA. Management of equine poisoning and envenoma-
antidotes that can be lifesaving.7,8 Future use of nano- tion. Vet Clin North Am Equine Pract 2007; 23(1): 31–47.
structured biomaterials may well become generally 8 Khan SA, Kuster DA and Hansen SR. A review of moxidectin
overdose cases in equines from 1998 through 2000. Vet Hum
available for unknown toxicities.9 Toxicol 2002; 44(4): 232–235.
Collapse without loss of consciousness can be 9 Muhammad F, Nguyen TDT, Raza A, Akhtar B and Aryal S.
caused by loss of motor function. Motor pathways A review on nanoparticle-­based technologies for biodetoxifica-
tion. Drug Chem Toxicol 2017; 40(4): 489–497.
may be interrupted at the level of the brainstem, ves- 10 Bandarra PM, Pavarini SP, Raymundo DL, et al. Trema
tibular apparatus, spinal cord, peripheral nerve, neu- micrantha toxicity in horses in Brazil. Equine Vet J 2010; 42(5):
romuscular junction, or muscle. A neurologic 456–459.
11 Ozmen O, Sahinduran S, Haligur M and Sezer K. Clinicopathologic
examination is needed to identify where the lesion is. observations on Coenurus cerebralis in naturally infected sheep.
Trauma is the most frequently occurring mechanism Schweiz Arch Tierheilkd 2005; 147(3): 129–134.
at the first three of these anatomic levels. Acute col- 12 Giadinis ND, Psychas V, Polizopoulou Z, et al. Acute coenuro-
sis of dairy sheep from 11 flocks in Greece. N Z Vet J 2012;
lapse without loss of consciousness is also caused by 60(4): 247–253.
botulinum toxins including the shaker-­ foal syn- 13 Ozmen O and Mor F. Acute lead intoxication in cattle housed in
drome, postanesthetic myasthenic syndrome, pos- an old battery factory. Vet Hum Toxicol 2004; 46(5): 255–256.
14 Johnson PJ, Mrad DR, Schwartz AJ and Kellam L. Presumed
tanesthetic neuromyopathy, exercise-­ associated moxidectin toxicosis in three foals. J Am Vet Med Assoc 1999;
rhabdomyolysis, tick and elapid snake bite paralyses, 214(5): 678–680.
and hyperkalemic periodic paralysis. 15 Brownlow MA, Dart AJ and Jeffcott LB. Exertional heat
­illness: a review of the syndrome affecting racing Thorough­
Generalized and metabolic disorders resulting in breds in hot and humid climates. Aust Vet J 2016; 94(7):
acute collapse include hyperthermia, cardiovascular 240–247.
 9
Blindness

The visual and pupillary light pathways should be t­ halamus (lateral geniculate nucleus), optic radiation
reviewed (Figure 2.9) as well as the discussion on part of the internal capsule, or the visual cortex pre-
testing for vision in the neurologic examination sec- dominantly in the occipital lobe of the cerebral hemi-
tion in Chapter 2. Some cases of reduced vision with sphere. These structures constitute the central visual
the associated pupillary changes are given here as pathways. Central to the chiasma, one optic tract
examples of blindness in large animals (Figure 9.1). receives circa >80% of all visual and light pathway
Often animals suffering from forebrain lesions are fibers from the contralateral eye, and these function-
blind with depressed menace responses in one or ally different fibers pass together in the first portion
both eyes. A central blindness or amaurosis, with of the optic tract to the level of the caudal thalamus
pupillary reflexes intact, occurs in an eye con- where the pupillary light fibers separate to synapse on
tralateral to a lesion involving an optic tract, dorsal the pretectal nucleus and thence to the parasympathetic

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
112 Large animal neurology

oculomotor nucleus in the midbrain (Figure 2.7). blind with an absent menace response and a slightly
Thus, one would expect that, as well as central con- dilated pupil in one eye due to an eye or optic nerve
tralateral blindness due to a lesion involving the lesion, and can still have some pupillary constriction
(light and visual) afferent, immediate postchiasmal in response to a very bright strobe light shone in that
optic tract fibers, there should be (bilaterally) sup- eye. This discrepancy comes down to difficulties in
pressed pupillary motor function evident when light determining when an animal is totally blind, and the
is shone in the blind eye. However, clinically this is fact that visual path fibers are probably damaged
very difficult to discern. On the other hand, occa- more readily with various eyeball and optic nerve
sionally it is possible to detect visual field deficits lesions than are light pathway fibers destined for the
with some selective and focal lesions involving these oculomotor nuclei in the midbrain. With respect to
central visual pathways as discussed in the neuro- visual perception, possibly the most sensitive test of
logic examination section in Chapter 2. crude visual pathway input is to place a blind patient
A lesion in the eye or optic nerve on one side, with having no menace responses in a dark enclosed area
the other eye and its optic system normal, results in with a brightly lighted exit available to see if the
blindness and a suppressed menace response in that patient can discern the escape route.
eye with slightly dilated pupils (mydriasis) and poor The swinging light test can be useful to help sort
pupillary constriction in both eyes when light is out difficult visual deficits too, as performing and
shone in the blind eye. The degree of mydriasis evi- interpreting consensual or indirect pupillary light
dent will depend on the ambient light that the other reflexes in large animals is problematic, particularly
normal eye is exposed to. A patient can be clinically with partial lesions, and often having to perform the
examination in daylight without access to a darkened
environment (see case example in Chapter 10).

It is often good to recall that even partial sunlight is

brighter than any commonly used, handheld penlight
or ophthalmoscope.

Here, it must be recalled that blinking in response

to a bright light, the dazzle response, does not involve
the visual pathways from the thalamus to the visual
cortex, and the presence of this response does not
equate with intact vision. Its presence does indicate
that light is stimulating the light pathways into the
midbrain and thence to the facial nucleus, but it
should not replace testing the true pupillary light and
menace responses as outlined. Thus, it is conceivable
that a dazzle response can be present in a centrally
blind patient that also has no oculomotor nerve func-
tion and therefore no pupillary light reflexes, a very
unlikely clinicopathologic scenario.
The prognosis for acquired peripheral blindness is
bad compared to that for central visual pathway
lesions. Apart from eye diseases, most common
causes of only peripheral blindness would be head
Figure 9.1 Following head trauma, bilateral blindness with dilated and trauma,1,2 sphenopalatine sinus infection and neopla-
nonresponsive pupils in a fully conscious horse as in top figure, is most
likely due to bilateral optic nerve injury. In comparison, blindness with a
sia,3 progressive ethmoid hematoma, and various
normally responsive pupil, as in bottom figure, is more likely due to a anthelmintic toxicities.4–7 In comparison, the prog-
contralateral, central, thalamic, or caudal cerebral lesion. nosis for partial central blindness is better as such
 Blindness 113

patients are able to compensate well and at times to 4 Button C, Jerrett I, Alexander P and Mizon W. Blindness in
kids associated with overdosage of closantel. Aust Vet J 1987;
regain quite amazing degrees of apparent visual 64(7): 226.
acuity. 5 Barlow AM, Sharpe JA and Kincaid EA. Blindness in lambs
The postictal period may be associated with tem- due to inadvertent closantel overdose. Vet Rec 2002; 151(1):
25–26.
porary central blindness presumably due to neuronal 6 Borges AS, Mendes LC, de Andrade AL, Machado GF and
exhaustion in central visual pathways. Also neonates, Peiro JR. Optic neuropathy in sheep associated with overdos-
although they can see, have poor menace responses age of closantel. Vet Hum Toxicol 1999; 41(6): 378–380.
7 Pollio D, Michau TM, Weaver E and Kuebelbeck KL.
in the first 1 or 2 weeks of life.8 Electroretinographic changes after intravenous lipid emulsion
Finally, degrees of blindness occur with many ocu- therapy in a dog and a foal with ivermectin toxicosis. Vet
lar diseases. Of some note is that with cases of con- Ophthalmol 2018; 21(1): 82–87.
8 Enzerink E. The menace response and pupillary light reflex in
genital peripheral blindness, there can be associated neonatal foals. Equine Vet J 1998; 30(6): 546–548.
abnormal eyeball positions, with the globe directed 9 Dwyer AE. Management of blind horses. In Equine
dorsally and sometimes wavering, searching eyeball Ophthalmology, Gilger BC, Editor. 3rd ed. Wiley-­Blackwell,
Oxford, UK. 2016; 629.
movements. Removal of obstacles and provision of a 10 Dwyer A. Hello darkness my old friend: management of blind
“buddy” that wears a bell are some of the provisions horses. Equine Vet Educ 2021; 5.
that assist in caring for a blind horse.9,10 The reader is 11 Mayhew IG. Neuro-­ophthalmology. In Equine
Ophthalmology: An Atlas and Text, Barnett KC, Crispin SM,
referred to texts of ophthalmology and particularly Lavach J.D, Matthews AG, Editors. 2nd ed. London, UK.
to chapters on neuro-­ ophthalmology in large 2004; 247–254.
animals.9,11–18 12 Irby NL. Neuro-­ophthalmology in horses. Vet Clin North Am
Equine Pract 2011; 27(3): 455–479.
13 Mayhew IG. Neuro-­ophthalmology: a review. Equine Vet J
Suppl 2010; (37): 80–88.
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Eq Pract 2002; 48: 300–313.
1 Matz K, Gerhards H, Heider HJ and Drommer W. Bilateral 15 Beltran E, Matiasek K and Hartley C. Equine neuroophthal-
blindness after injury in a riding horse. Tierarztl Prax 1993; mology. In Equine Ophthalmology, Gilger BC, Editor. 3rd ed.
21(3): 225–232. Wiley-­Blackwell, Oxford, UK. 2016; 567.
2 Reppas GP, Hodgson DR, McClintock SA and Hartley WJ. 16 Lavach JD. Large Animal Ophthalmology. Mosby, St. Louis,
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 10
Miosis, mydriasis, anisocoria, and Horner
syndrome

Degrees of miosis (constricted pupil), mydriasis (Figure 2.7 and 2.8). Normal resting pupil size will
(dilated pupil), and anisocoria (asymmetric pupil depend on the emotional state of the patient and the
size) occur in many ocular diseases, often accompa- amount of ambient light reaching the retinas. Usually, a
nied by degrees of visual impairment. Large animal nonfrightened large animal patient has a brisk initial
patients are not very frequently presented because of pupillary light reflex (PLR). However, a common prob-
these problems alone; however, identifying them on a lem uncounted during examination is the patient
neurologic examination greatly helps in localizing blinking when a light is directed into one eye—­the daz-
the lesion. Texts discussing the evaluation and treat- zle response—­thus hiding the initial fast constrictive
ment of eye problems in large animals should be con- phase of the PLR. This can be averted by allowing the
sulted for ophthalmic diseases.1–6 patient to accustom to the light, starting at say 30–40 cm
The pupillary constriction (CN III) and dilation from the eyes, swinging it from focusing into each eye
(ocular sympathetic) pathways should be reviewed in turn while moving closer, and observing for tapetal

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Miosis, mydriasis, anisocoria, and Horner syndrome 115

LIGHT ON LIGHT OFF CASE STUDY

Increasing pupil diameter

Picture a patient being examined for visual and light

acuity, but outside in daylight with both pupils some-
what constricted. The right menace response appears
to be less than that for the left eye with no convincing
Postillumination anisocoria detectable in shaded but bright daylight.
Pupil escape pupil response The left pupil responds directly to light shone in the left
eye. The right pupil does respond to light shone in the
right eye, although being in daylight it is not possible
to be convinced of any asymmetry in the rate or degree
0 15 30 45 60 of pupillary responsiveness. Where is the lesion? With
TIME (s) such information available, a partial lesion should be in
Figure 10.1 Diagram of pupillary response to light-­on and to light-­off.
the left central visual pathways, i.e., postchiasmal.
Note that latency to start of constriction from light-on is ~200ms. Source: However, now note the responses to the swinging light
Modified from Hall and Chilcott,9 figure 1 (CC BY 4.0). test using a very bright light source. Light shone in the
left eye results in pupillary constriction in that eye. The
reflexes that highlight pupillary diameters. After light is quickly swung to be redirected into the right
determining pupil size and symmetry, the PLR can be eye, avoiding a dazzle response. Although the right
assessed using a one second bright light flash directed pupil is initially constricted it dilates back to its resting
to the area centralis in the midlateral (temporal) field size as light reaches that eye! When the light is swung
where photoreceptor density is greatest. Interpretation quickly to be redirected into the left eye again the left
should consider the phenomena of pupil escape follow- pupil, that may or may not initially appear somewhat
ing light-on, and the postillumination pupil response dilated, responds by constricting very well. This can be
occurring after light-off (Figure 10.1). repeated as the light is quickly redirected into each eye
Of interest here is the newly recognized, intrinsi- in turn, pausing long enough to observe each pupillary
cally photosensitive, retinal ganglion cells (ipRGCs), size and response. Also, being outside, when the left
which rely on a unique photopigment, melanopsin, eye is covered for 10 s with a hand the right pupil
and they are now known to have a major role in non- dilates to a resting state. When the right eye is covered
visual light pathways including the PLR. Use of red the left pupil remains constricted as appropriate for the
and blue light PLR testing has now allowed the testing degree of bright ambient light. Indeed, such maneuvers
of retinal cell subpopulations.7–9 In general terms, low may allow convincing anisocoria to become more
intensity, dark-­adapted (scotopic), blue light PLR tests apparent with the right pupil becoming less constricted
rod function, high intensity, dark adapted, blue light than the left pupil. At least one lesion is in the right eye
tests ipRGC function, and high intensity, photopic, red or right optic nerve. When a darkened examination
light PLR tests cone function. Better understanding of space becomes available, anisocoria with right relative
the details of such testing and use of handheld pupi- mydriasis should then be noted. Two points are of note
lometers10 will allow for a more accurate assessment of in this case. First, we are often not discerning enough to
visual and light pathways in our large animals.11 visually detect minor degrees of anisocoria; and second,
Results of pupillary responses to the swinging light outside, even in shaded daylight, there is enough ambi-
test are useful here as in the evaluation of vision. ent light entering the normal eye to maintain consider-
Consider a bright and alert patient with rather com- able pupillary constrictor tone in the blind eye.
plex responses to visual and light pathway testing. The
patient has no menace response but has a normal pal-
pebral response to touch, and is blind with a widely the left eye. When the light is then quickly retrans-
dilated pupil, all in the left eye. There is a normal men- ferred to enter the right eye, the right pupil constricts
ace response in the right eye, and light shone in the strongly again. The lesion must involve both the left
right eye results in the right pupil constricting and also retina or optic nerve and the left oculomotor parasym-
in a positive dazzle (blink) response. When the light is pathetic fibers. Retrobulbar empyema, cellulitis, or
then swung briskly to enter the left eye, the left pupil is neoplasm can readily explain these findings. With
and remains dilated and there is no dazzle response in such lesions behind the globe, the sympathetic fibers
116 Large animal neurology

to the dilator muscles of the pupil can also be involved,

confounding this clinical picture further.
With anisocoria, particularly when due to partial
lesions, it can sometimes be difficult to determine
which pupil is abnormal. As a rule, an abnormally
small pupil (i.e., sympathetic denervation) in one eye
will not dilate fully in darkness, but it will respond to
light directed into that eye and into the other, normal
eye. In comparison, a unilateral abnormally dilated
pupil (i.e., parasympathetic denervation) will be
most evident in bright light and will not constrict
fully in response to light shone into either eye. With
reference to bright light, it should be remembered
that daylight, and especially direct sunlight, is so
much more powerful than any portable light source.
It is thus best to perform light pathway tests both in
Figure 10.2 With this degree of bilateral pupillary dilation found in nor-
ambient and in quite dim lighting.
mal ambient room light (yellow bar), the possibility that it is due to a
A mydriatic pupil with normal vision is seen with frightened or painful patient must be considered. Especially if this is
parasympathetic oculomotor nerve involvement in asymmetric, the effects of previous application of a mydriatic have also to
large animals, although this is not commonly seen in be considered. This patient had received one application of atropine in
isolation. The accompanying classical lateral and this left eye 36 h previously and even in sunlight left mydriasis was main-
tained (see also Figure 13.2).
ventral (down and out) strabismus with ptosis due to
somatic motor CN III lesions is also not often seen in
large animals but occurs with basilar and sphenoidal can be seen with retrobulbar lesions involving post-
sinus diseases. When mydriasis with an inability of ganglionic sympathetic fibers. Ptosis is due to paraly-
the iris to constrict is found with no other neurologic sis of the sympathetically innervated Műller superior
abnormalities, previous atropine therapy must be tarsal smooth muscle. In addition, hyperemic mucous
considered (Figure 10.2). Many asymmetric membranes of the head (Figure 10.3), hyperthermia
inflammatory, traumatic, and vascular brain diseases of the face,20,21 and in horses sweating of the face and
can result in midbrain oculomotor involvement and cranial neck are evident with more proximal sympa-
anisocoria. Space-­ occupying and other forebrain thetic lesions (Figures 2.10, 10.5, and 10.6). These
lesions associated with brain swelling can result in latter findings are caused by the interruption of sym-
subsequent ventral pressure on the midbrain and pathetic fibers to the skin (blood vessels and sweat
hence onto the oculomotor nerves (Figure 4.8). glands) of the head and neck.19 Although sweat
When such lesions are asymmetric, they then cause glands in horses, as in other mammals, may not be
anisocoria with poorly responsive pupils that can be directly innervated,22 sympathetic denervation of the
accompanied by degrees of blindness, depending on head causes cutaneous vasodilation so that more cir-
whether the optic nerves and light pathways are also culating adrenalin is brought to the sweat glands, and
affected. this neurohormone has powerful sudomotor effects
In accordance with the global trend for the use of in horses.22,23 If the sympathetic fibers are affected at
nonpossessive eponyms,12 we shall use the descriptor the level of, or distal to, the cranial cervical ganglion
Horner syndrome—­ as opposed to Horner’s syn- in the wall of the guttural pouch, sweating over the
drome—­to describe the signs associated with sympa- head projects caudal only to the level of the atlas.
thetic denervation (decentralization) of the head of Preganglionic lesions proximal to this level, as in the
animals. The degree of miosis seen in sympathetic neck, result in sweating further down the neck to the
denervation of the eye (Horner syndrome) is very level of the axis to C3.18, 21 Cranial thoracic lesions can
variable and not dramatic in large animals, and nei- affect the sympathetic fibers not only in the cervical
ther is enophthalmos and protruding nictitating sympathetic trunk, but also those innervating the
membrane (Figures 10.3 and 10.4).3,13–19 Horner syn- skin of the remainder of the neck traveling with the
drome in horses consists of miosis and ptosis of the vertebral nerve and segmental dorsal spinal nerve
upper eyelid as in other species, and these signs alone roots (Figure 2.10). Then, there is sweating over the
 Miosis, mydriasis, anisocoria, and Horner syndrome 117

(A)

(B) (C)

Figure 10.3 Left Horner syndrome present in this horse (A) is evident as moderate ptosis, lowering of the upper eyelashes and miosis (C) compared
with the unaffected side (B). Note that there is still an angle present at the medial margin of the upper lid that is usually much less apparent with the
ptosis seen with facial CN VII paralysis.

(A) (B)

Figure 10.4 In this case of acute, temporary, experimental Horner syndrome induced by local anesthetic blockade of the cervical sympathetic trunk, a
slightly constricted pupil is evident (A) compared with the normal eye (B). In horses, loss of sympathetic tone to superficial blood vessels induces vasodila-
tion and this can be seen on any affected mucous membrane such as the pharynx and larynx, and the bulbar conjunctiva in this case (A). Ptosis is not
evident as the eyelids are being held open.

whole neck and head (Figures 2.10 and 10.6). A first-­ of Horner syndrome.18 Of some diagnostic interest
order sympathetic neuronal lesion in the descending, is that at least for horses with acute sympathetic
tectotegmento-spinal tract in the brainstem or cervi- lesions and distributions of sweating, the administra-
cal spinal cord results in sweating on the whole side tion of α-­2 agonist sedative drugs will result in
of the trunk, neck, and head as well as the eye signs expected sweating over normal skin of the body but
118 Large animal neurology

(B)

(C) (D)

(A) (E)

Figure 10.5 This horse is suffering from guttural pouch (GP) mycosis with evidence of pharyngeal dysphagia (A) along with left-­sided Horner
syndrome shown as mild ptosis of the upper lid (arrowhead in (B)) and accompanied by facial sweating (A) down to the level of C2 on the neck
and even evident under the eye on the left (D) compared with the right (C) side. This is to be distinguished from facial nerve paralysis in that there
is no weakness to closing the eyelids when there is loss of sympathetic tone to the eyelids. The classical signs of Horner syndrome are seen in the
horse’s left eye (D) when compared to the normal right eye (C). Mild miosis and enophthalmos with slight protrusion of the nictitating membrane
are evident along with the ptosis. A prominent component of the ptosis in this syndrome compared with facial paralysis is the lower angle of the
upper eyelashes (D) rather than marked lowering of the upper lid, especially the medial aspect, that more typifies facial paralysis. A useful test to
help confirm the presence of Horner syndrome is to instill 0.5 mL of 0.5% phenylephrine into the conjunctival sac and observe for correction of
the lowered eyelashes. This is shown in (E) where a case of bilateral Horner syndrome has been treated on the right side to correct the ptosis
(yellow arrows).

Figure 10.6 This horse was injected with local anesthetic

solution in the caudal cervical region. It demonstrated
Horner syndrome and sweating over the face and cranial
cervical region, especially at the base of the ear. Additionally,
there was prominent sweating on the neck over the C3 to C6
dermatomes. The local anesthetic solution almost certainly
spread caudally along the cervical vagosympathetic trunk
to the region of the cervicothoracic ganglion. This would
then produce blockade of the sympathetic supply to the
skin of the neck at the levels of C3 to C6 in addition to
blocking the cervical sympathetic trunk that causes sweat-
ing over C1 and C2 only (See also Figure 2.10).
 Miosis, mydriasis, anisocoria, and Horner syndrome 119

often reverses the vasodilation and sweating over temperature.27 Facial analgesia was present in a cow
the sympathetically denervated skin such that it that had an ocular squamous cell carcinoma invading
becomes dry. the trigeminal nerve. Part of the syndrome included
Sympathetic denervation of the head in cattle a specific and dense infestation of ticks only on the
includes the eye signs of ptosis of the upper eyelid, denervated skin of the face.27 This most probably
miosis, and subtle enophthalmos as described in resulted from cutaneous vasodilation caused by
other species, with dilated vessels on the pinnae, interruption of postganglionic sympathetic fibers
warm face and ears, and an absence of droplets of distal to those innervating the eyeball that had joined
sweat forming on the muzzle (Figure 10.7).24-26 Eye the trigeminal nerve to innervate the skin and blood
signs in Horner syndrome are even less prominent in vessels of the remainder of the face.
large animal species other than horses and cattle.14,15,19 Accompanying generalized signs of autonomic
Interestingly, it may be reasonable to expect ectopar- failure, horses affected by equine dysautonomia,
asites such as ticks to be attracted to skin with altered commonly known as grass sickness, often show bilat-
eral ptosis.28, 29 Muscles (and their innervation) of the
upper eyelid that when paralyzed may result in ptosis
of the upper eyelids are the levator palpebrae superio-
ris (CN III), the levator anguli oculi medialis (CN
VII), and Müller tarsal smooth muscle (sympa-
thetic).30 In grass sickness cases, there is no evidence
for the ptosis being due to somatic facial or oculomo-
tor dysfunction, and the evidence points to this being
due to sympathetic dysfunction. Indeed, the ptosis
can be readily reversed (Figure 10.8) using a low dose
of topical α-­1 adrenergic agonist (0.5 mL of 0.5%
phenylephrine eye drops). Not only does the upper
eyelid ptosis resolve within 10–30 min, but the
lowered angle of the upper eyelashes (i.e., pointing
toward the ground), so characteristic of grass sick-
ness, also resolves and often quite impressively so
compared to the untreated side. This lower eyelash
Figure 10.7 Loss of sympathetic control to the blood vessels and glands angle present in grass sickness cases is likely due to
of the muzzle in cattle results in a loss of fluid production by the nasal paralysis of the smooth muscle innervating the eye-
glands. This cow had a lesion in the left cranial neck causing Horner syn-
drome and a dry muzzle on the left side (arrows). Because of the chronic-
lashes themselves, the arrectores ciliorium, present in
ity of the dry muzzle, desiccation and excoriation had begun to occur horses and cattle but not in humans and dogs. This
(arrowhead). phenylephrine eye drop test is thus useful to assist in

(A) (B)

Figure 10.8 This horse has left-­sided Horner syndrome (A). About 20 min following instillation of 0.5 mL of 0.5% phenylephrine into the left conjunc-
tival sac, the ptosis is resolved (B) helping to confirm hypersensitivity to adrenergic compounds in the sympathetically denervated structures. An appar-
ently excessive sweat response to phenylephrine also is seen around the orbit (B).
120 Large animal neurology

the diagnosis of grass sickness and other causes of 11 Komaromy AM, Abrams KL, Heckenlively JR, et al. Sudden
acquired retinal degeneration syndrome (SARDS): a review
Horner syndrome at least in horses.31 and proposed strategies toward a better understanding of
Third-­order sympathetic neuronal fibers do not pathogenesis, early diagnosis, and therapy. Vet Ophthalmol
pass through the petrosal bone as in small animal 2016; 19(4): 319–331.
12 Gregoline B. Eponyms. Chapter 15 in AMA Manual of Style: A
species; therefore, Horner syndrome is usually not Guide for Authors and Editors. 11th edition. Oxford University
recognized with otitis media in large animals or with Press. 2020.
petrosal bone fractures. Inadvertent perijugular 13 Musk GC, King M and He BL. Horner syndrome in 2 pigs (Sus
scrofa) after vascular grafting of the carotid artery and jugular
injection of drugs is a relatively frequent cause of vein. Comp Med 2017; 67(6): 518–523.
Horner syndrome when the compound spreads to the 14 Samimi AS, Shafiian A, Rezaei M, et al. Horner’s syndrome and
adjacent cervical vagosympathetic trunk. The effect unilateral facial paresis in a goat: a case report. Comp Clin
Pathol 2016; 25(2): 469–472.
with local anesthetic compounds including α-­2 drugs 15 Ding P, Tufano R, Campbell-­Malone R, et al. Horner syndrome
is usually temporary. But depending on the degree of after carotid sheath surgery in a pig: anatomic study of cervical
tissue inflammation caused by other, more irritant sympathetic chain. Comp med 2011; 61: 453–456.
16 Borges AS and Watanabe MJ. Guttural pouch diseases causing
compounds, any resulting Horner syndrome can last neurologic dysfunction in the horse. Vet Clin North Am
for hours to months and may be permanent. In horses, Equine Pract 2011; 27(3): 545–572.
the sympathetic fibers innervating the eye are more 17 Simoens P, Lauwers H, De Muelenare C, Muylle E and
Steenhaut M. Horner’s syndrome in the horse: a clinical, exper-
often damaged in and around the guttural pouch in imental and morphological study. Equine Vet J Suppl 1990(10):
the region of the cranial cervical ganglion. Finally, 62–65.
many systemic toxins, such as those mediated by 18 Mayhew IG. Horner’s syndrome and lesions involving the sym-
pathetic nervous system. Equine Pract 1980; 2(5): 44–47.
atropine-­like alkaloids and the common antimuscarinic 19 Smith JS and Mayhew IG. Horner’s syndrome in large animals.
colic drug butylscopolamine, cause degrees of mydria- Cornell Vet 1977; 67: 529–542.
sis (Figure 10.1), and those acting with anticholinest- 20 Purohit RC, McCoy MD and Bergfeld WA, III. Thermographic
diagnosis of Horner’s syndrome in the horse. Am J Vet Res
erase activity can result in miosis. 1980; 41(8): 1180–1182.
21 Palumbo MIP, Moreira JJ, Olivo G, et al. Right-­sided laryngeal
References hemiplegia and Horner’s syndrome in a horse. Equine Vet Educ
2011; 23(9): 448–452.
1 Beltran E, Matiasek K and Hartley C. Equine neuroophthal- 22 Jenkinson DM, Elder HY and Bovell DL. Equine sweating and
mology. In Equine Ophthalmology, Gilger BC, Editor. 3rd ed. anhidrosis Part 1: equine sweating. Vet Dermatol 2006;17(6):
Wiley-­Blackwell, Oxford, UK. 2016; 567. 361–392.
2 Irby NL. Neuro-­ophthalmology in horses. Vet Clin North Am 23 Jenkinson DM, Elder HY and Bovell DL. Equine sweating and
Equine Pract 2011; 27(3): 455–479. anhidrosis Part 2: anhidrosis. Vet Dermatol 2007; 18(1):
3 Mayhew IG. Neuro-­ophthalmology: a review. Equine Vet J 2–11.
Suppl 2010(37): 80–88. 24 Pace LW, Wallace L, Rosenfeld CS and Sansone J. Intracranial
4 Myrna KE. Neuro-­ophthalmology in the Horse. Vet Clin North squamous cell carcinoma causing Horner’s syndrome in a cow.
Am Equine Pract 2017; 33(3): 541–549. J Vet Diagn Invest 1997; 9(1): 106–108.
5 Lavach JD. Large Animal Ophthalmology. Mosby, St. Louis, 25 Tawfeeq MM, Miura S, Sugimoto K, et al. Thymic lymphosar-
MO. 1990; 395. coma with brain involvement in a Holstein heifer. J Vet Med Sci
6 Barnett KC, Crispin SM, Lavach JD and Matthews AG. Equine 2012; 74(11): 1501–1504.
Ophthalmology: An Atlas and Text. 2nd ed. Saunders, 26 Guard CL, Rebhun WC and Perdrizet JA. Cranial tumors in
Edinburgh. 2004; 274. aged cattle causing Horner’s syndrome and exophthalmos.
7 Park JC, Moura AL, Raza AS, et al. Toward a clinical protocol Cornell Vet 1984; 74(4): 361–365.
for assessing rod, cone, and melanopsin contributions to the 27 Samuel JL, Kelly WR and Vanselow BA. Intracranial invasion
human pupil response. Invest Ophthalmol Vis Sci 2011; 52(9): by bovine ocular squamous cell carcinoma via cranial nerves.
6624–6635. Vet Rec 1987; 121(18): 424–425.
8 Yeh CY, Koehl KL, Harman CD, et al. Assessment of rod, cone, 28 Pirie RS, Jago RC and Hudson NP. Equine grass sickness.
and intrinsically photosensitive retinal ganglion cell contribu- Equine Vet J 2014; 46(5): 545–553.
tions to the canine chromatic pupillary response. Invest 29 McGorum BC and Pirie RS. Equine Dysautonomia. Vet Clin
Ophthalmol Vis Sci 2017; 58(1): 65–78. North Am Equine Pract 2018; 34(1): 113–125.
9 Hall CA and Chilcott RP. Eyeing up the future of the pupillary 30 Hahn CN and Mayhew IG. Studies on the experimental induc-
light reflex in neurodiagnostics. Diagnostics (Basel) 2018; 8(1): 19. tion of ptosis in horses. Vet J 2000; 160(3): 220–224.
10 Kim J, Heo J, Ji D and Kim MS. Quantitative assessment of 31 Hahn CN and Mayhew IG. Phenylephrine eyedrops as a diag-
pupillary light reflex in normal and anesthetized dogs: a pre- nostic test in equine grass sickness. Vet Rec 2000; 147(21):
liminary study. J Vet Med Sci 2015; 77(4): 475–478. 603–606.
 11
Strabismus

Strabismus refers to abnormal deviation of the central the eyeball cannot be moved out of the deviated
axis of the eyeball. Loss of function of the extraocular ­position by movement and manipulations of the head
muscles innervated by the oculomotor nerve should and thus can be described as fixed strabismus
result in a lateral and slightly ventral strabismus. A (Figure 11.1). These are rarely seen alone as acquired
medial strabismus should result with abducent nerve syndromes in large animals. Both bilateral medial
lesions. Finally, rotation of the globe such that the (convergent) strabismus, or esotropia, with exophthalmos
medial aspect of the pupil moves dorsomedial should (Figure 11.2), and lateral (divergent) strabismus, or
result with trochlear nerve involvement. In each case, exotropia, occur in cattle and are believed to be due to

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
122 Large animal neurology

Trochlear
CN IV

Medial Lateral

Abducent
CN VI

Oculomotor
CN III

Figure 11.1 Although rarely encountered alone in large animals, a fixed

strabismus in various abnormal positions occurs with lesions of the ocu-
lomotor, trochlear, and abducent nerves. The abnormal directions in which
the eyeball is pulled due to lesions of individual cranial nerves III, IV, and
VI, due to the lack of opposing muscle strength, are indicated here.

Figure 11.3 Ventral eye deviation, as seen in this donkey’s left eye
while the muzzle is being raised, with or without a left head tilt, is
assumed to be left vestibular disease until proven otherwise. In this
case, there also is left facial paresis evidenced by the right deviation
of the muzzle. These signs were due to involvement of CN VIII and VII
caused by the immune-­associated disease polyneuritis equi.

which may be noticed when they attempt to visually

Figure 11.2 True, fixed, ventromedial strabismus (esotropia) is seen here
from a dorsal view in a Holstein cow. Degrees of exophthalmos usually
fix on an object.13,14 The ventromedial rotational posi-
accompany this inherited disorder that occurs in several breeds of cattle. tioning of the eyeball seen in many newborn foals
A brainstem nuclear defect is believed to cause this problem that may be disappears by a few weeks of age.15
accompanied by some degree of visual impairment (amaurosis). Although many inflammatory, physical, metabolic,
toxic, and nutritional disorders may affect the regions
of the brainstem where the oculomotor, trochlear, and
genetic brainstem nuclear defects.1–9 An eyeball abducent nuclei are located, prominent signs of fixed
deviation, particularly when it stays in a ventral or strabismus are rarely seen alone in large animals.16,17
dorsal position but can be made to move from that However, many severe asymmetric forebrain diseases
abnormal position with head movements, is seen fre- result in turning of the head and neck and drifting
quently. Usually, this is due to lesions involving the toward one side, usually the side of the lesion. This can
vestibular system and is referred to as vestibular also involve the eyes being drawn toward one side,
­strabismus (Figures 11.3 and 11.4).10–12 This may not particularly with thalamic involvement, and these
be very evident with the head in a normal posture signs collectively comprise the adversive syndrome.18,19
but usually is exaggerated when the muzzle is raised. The relative dorsomedial rotation of the eyeballs
Also, performing a fundic examination to focus on (Figure 11.5) seen in diseases such as polioencephalo-
the position of the optic disc can assist in defining malacia, lead poisoning, water intoxication and bacte-
asymmetric positioning of the pair of eyeballs. rial meningitis in ruminants, and with meningitis and
Congenital blindness from many diseases can be hypoxic and neonatal encephalopathy in newborn
associated with abnormal eyeball positions and move- foals, may not be a specific trochlear nerve paralysis.
ments. Also, Appaloosa, miniature, Thoroughbred, This is because the eye can be moved in all four direc-
and Paso Fino horses severely affected with inherited tions and out of this rotated position, so it might reflect
night blindness can have dorsomedial strabismus, severe forebrain disease involving the central motor
 Strabismus 123

(A) (B)

Figure 11.4 Ventral and slight lateral deviation of one eyeball relative to the other is the most frequently seen eye deviation in large animals. It is most
often due to vestibular disease. Although it can be referred to as strabismus, the eye is not fixed and can be moved away from the ventral position by
movement of the head. This lamb is suffering from listeriosis with the encephalitis worse on the left side of the brainstem. Compared with the more
normally responding right eye (A), the left eyeball is ventrally deviated (B) while the head is in a normal posture. The ventral deviation became even more
prominent with elevation of the nose and head extension.

(A) (B)

Figure 11.5 The term dorsomedial (rotational) strabismus is used to describe what is seen here (A and B). The cow (A) has Salmonella sp. sepsis and
meningitis, and the ewe (B) has thiamine-­responsive polioencephalomalacia. Both have rotation of the globe such that the medial aspect of the pupil is
now rotated to a dorsal and caudal position. The images of each eye have been rotated such that the palpebral fissure is shown perfectly horizontal, and
the equators of the eyeballs are indicated by yellow lines. That this is not a fixed strabismus is attested by the fact that with moving the position of the
head the eye can be drawn out of this position.

pathways controlling eyeball posture. A similar dorso- 5 Regan WM, Gregory PW and Mead SW. Hereditary stra-
bismus in Jersey cattle. J Hered 1944; 35(8): 233–234.
medial eyeball rotation can also be seen with congenital 6 Holmes JR and Young GB. A note on exophthalmos with
cerebellar hypoplasia and with cerebellar abiotrophy strabismus in shorthorn cattle. Vet Rec 1957; 69: 148–149.
in several species likely due to alteration in vestibu- 7 Julian RJ. Bilateral divergent strabismus in a Holstein calf.
Vet Med Small Anim Clin 1975; 70(10): 1151.
locerebellar tonic control of extraocular muscles. 8 Distl O and Scheider A. An unusual eye defect in Highland
cattle: diverging unilateral strabismus. Dtsch Tierarztl
Wochenschr 1994; 101(5): 202–203.
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124 Large animal neurology

14 Sandmeyer LS, Bellone RR, Archer S, et al. Congenital station- 17 Myrna KE. Neuro-­ophthalmology in the Horse. Vet Clin
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15 Leiva M, Pena T and Monreal L. Ocular findings in healthy The lateralizing and localizing value of adversion in epilep-
newborn foals according to age. Equine Vet Educ 2011; 23(1): tic seizures. Neurology 1983; 33(9): 1241–1242.
40–45. 19 Schiff MM, Esmond WG and Himwich HE. Forced c­ ircling
16 Jacob SI, Drees R, Pinkerton ME, Bentley EM and Peek movements (adversive syndrome): correction with dinen-
SF. Cavernous sinus syndrome in a Holstein bull. Vet hydrinate (“dramamine”). Arch Otolaryngol 1950; 51(5):
Ophthalmol 2015; 18(2): 164–167. 672–677.
 12
Dropped mandible and masticatory
muscle atrophy

With denervation of the muscles of mastication, the Many normal horses appear to have asymmetric
masseter, temporalis, medial and lateral pterygoid, appearance to the origins of the temporal muscles
and distal belly of the digastricus muscles on the without having asymmetric supraorbital fossae, thus
affected side atrophy rapidly within 1–2 weeks. having equal tissue mass behind the eyeballs
Unilateral neurogenic muscle atrophy is initially not (Figure 12.2). On the other hand, some asymmetry of
associated with any major difficulty in chewing the temporalis and other masticatory muscles occurs
food. With time however there is deviation of the quite frequently that is assumed to be associated with
mandible toward the normal side (Figure 12.1). dental pain, as it can resolve with adequate dental care.

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
126 Large animal neurology

(A) (B)

Figure 12.1 This horse suffered total left trigeminal nerve trauma from direct penetrating trauma to the dorsal guttural pouch several months previ-
ously. Atrophy of the left muscles of mastication resulted in pronounced sinking of the left supraorbital fossa (A) and the mandible became drawn to the
right side with the tongue passively falling from the left side of the mouth (B). The cheek teeth arcades also required dental care.

(A) (B)

Figure 12.2 Interpreting asymmetry of muscles of mastication can be problematic. This is especially so for temporalis muscles that often appear asym-
metric in normal horses. Both these horses (A and B) have asymmetry to the shape of their parietotemporal regions associated with a difference in the
appearance of origin of each pair of temporalis muscles at the temporal crests of the parietal bones (arrows). One good guideline as to whether or not
there actually is an asymmetry of muscle bulk between the pairs of temporalis and masseter muscles is whether or not there is an asymmetry to the depth
(or filling) of the supraorbital fossae (arrowheads). However, any asymmetry in the bulk of tissue in the bony orbit, to include the eyeballs, muscles, and
fat, can result in a change in the appearance of the supraorbital fossae. In actual fact, the first horse (A) had neurogenic atrophy of the temporal muscle
associated with S. neurona encephalitis involving the right motor nucleus of the trigeminal nerve. The muscle asymmetry present in the second horse (B)
was incidental—­very likely due to asymmetric chewing, perhaps resulting from dental disease.

Bilateral atrophy can result in a horse showing pon- with no other neurologic signs rarely occur in large
derous eating habits and dropping food from its animals. An immune-­associated masseter myositis
mouth. Total mandibular paralysis in all large ani- and selective, immune-­associated, transient trigemi-
mals causes the jaw to hang down with food and nal (nongranulomatous) neuritis without systemic
saliva present in the mouth, and usually the tongue polyneuritis do not yet appear to have been docu-
hangs out over the lower incisor teeth. mented in large animals. Bilateral myopathy of mus-
Sudden onset of a dropped mandible in a large ani- cles of mastication occurring in horses, particularly
mal patient should prompt the clinician to suspect those in poor condition, appears to be related to vita-
trauma to the temporomandibular joint or mandible, min E and possibly selenium deficiency.1 This should
with or without fracture of the mandible (Figure 12.3). be differentiated from neurogenic and physical
Neurologic diseases resulting in a dropped mandible causes of loss of mandibular muscle function. The
 Dropped mandible and masticatory muscle atrophy 127

Figure 12.3 Large animals, especially cattle that

develop a jaw that does not close, will have the
tongue resting slightly out from the mouth (A).
That this is not glossal weakness is evident by the
patient being able to withdraw the tongue into
the mouth with stimulation and by the patient
being able to move the tongue to attempt to eat
and to lick its nares (B). This calf was involved in a
squeeze-­shute accident and lost the ability to
close its jaws. No temporomandibular damage
could be detected, and as mandibular function
returned quite quickly within about a week it was
believed that this was due to a motor mandibular
nerve neurapraxia, perhaps associated with (sub)
luxation of the temporomandibular joint, as the (B)
(A)
nerve and its branches pass by the joint.

acute phase of this can result in swollen masseter

muscles (palpation of which eliciting a pain response),
exophthalmos, chemosis, and protrusion of the third
eyelid,2,3 whereas the chronic phase progresses to
muscle atrophy, difficulty in eating, and degrees of
trismus.1,4
Many encephalitides that may involve the pon-
tomedullary region where the motor nucleus of the
trigeminal nerve resides can effect the syndrome of
mandibular muscle atrophy. Degrees of weakness,
ataxia, obtundation, and other cranial nerve palsies
are usually evident. On the American continents, a
syndrome of unilateral and much less commonly
bilateral atrophy of mandibular muscles is seen in
horses suffering from S. neurona and other protozoal
myeloencephalitides, sometimes with no other evi-
dence of brainstem disease. Thus, this mimics periph-
eral CN Vm neuropathy (Figures 12.4 and 12.5).
Ruminants suffering from listeriosis have also been
seen with brainstem disease to include unilateral and
sometimes bilateral mandibular muscle atrophy, some
Figure 12.4 In the absence of other neurologic abnormalities or other
having a flaccid mandible with the latter.5–8
evidence of a lesion in the region of the rostral base of cranium, atrophy of
Marked masseter, temporalis, and pterygoid mus- the muscles of mastication on one side in a horse from the Americas is very
cle atrophy also results in slight degrees of enophthal- likely to be caused by S. neurona encephalitis as was the case here.
mos and drooping of the upper eyelid, at least in Neoplasia and trauma to the basilar region rostral to the guttural pouch
cattle9,10 and horses. This appears to be caused by the also have produced such a syndrome of atrophy of the masseter, temporalis,
pterygoid, and distal digastricus muscles innervated by the trigeminal nerve.
loss of muscle mass behind the globe, which is sig-
naled by sinking of the retrobulbar tissues in the
supraorbital fossa. Non-­ neurologic causes of oral To be differentiated from this problem is the trismus
dysphagia, such as temporomandibular disorders seen with tetanus and the dystonia of jaw and tongue
and particularly dental problems, can be associated muscles seen with equine nigropallidal encepha-
with atrophy of the muscles of mastication that at lomalacia, among other orthopedic and neurologic
times can be very asymmetric (Figure 12.6). disorders.
128 Large animal neurology

(A) (B)

Figure 12.5 This horse was also suffering from S. neurona encephalitis partly involving left and right motor nuclei of the trigeminal nerves in the pontomed-
ullary region. It had normal movement of the facial muscles, lips, and tongue but could not close the jaw (A). Drinking was achieved by lapping like a dog (B).

References
1 Pearson EG, Snyder SP and Saulez MN. Masseter myodegen-
eration as a cause of trismus or dysphagia in adult horses. Vet
Rec 2005; 156(20): 642–646.
2 Conwell R. Hyperlipaemia in a pregnant mare with sus-
pected masseter myodegeneration. Vet Rec 2010; 166(4):
116–117.
3 Step DL, Divers TJ, Cooper B, et al. Severe masseter myonecro-
sis in a horse. J Am Vet Med Assoc 1991; 198(1): 117–119.
4 Aharonson-­Raz K, Milgram J, Chai O and Sutton GA. Fibrosis
of the masseter leading to trismus and dysphagia in a mare. Vet
Rec 2009; 164(19): 597–608.
5 Schweizer G, Ehrensperger F, Torgerson PR and Braun U.
(A) Clinical findings and treatment of 94 cattle presumptively diag-
nosed with listeriosis. Vet Rec 2006; 158(17): 588–592.
6 Braun U, Stehle C and Ehrensperger F. Clinical findings and
treatment of listeriosis in 67 sheep and goats. Vet Rec 2002;
150(2): 38–42.
7 Rebhun WC and deLahunta A. Diagnosis and treatment of
bovine listeriosis. J Am Vet Med Assoc 1982; 180(4):
395–408.
8 Barlow RM and McGorum B. Ovine listerial encephalitis:
analysis, hypothesis and synthesis. Vet Rec 1985; 116(9):
233–236.
9 Divers TJ and Peek SF. Rebhun’s Diseases of Dairy Cattle.
Saunders Elsevier, Philadelphia, PA. 2008.
10 Rebhun WC. Diseases of the bovine orbit and globe. J Am Vet Med
Assoc 1979; 175(2): 171–175.
(B)

Figure 12.6 Asymmetric temporalis (and masseter and pterygoid) mus-

cle atrophy (A) can be associated with severe dental problems as seen in
this teenaged Thoroughbred with a deep supraorbital fossa on the right
side (yellow arrow) compared with that on the left side (white arrow).
Long fibers of chewed forage were present in the feces (B) associated
with the oral dysphagia displayed by the horse. All signs were resolved
with appropriate dental care.
 13
Decreased and Increased facial sensation

Many animals, mentally obtunded because of marked In defining this problem, care must be taken
systemic illness and particularly severe brain disease, to distinguish facial hyporeflexia from facial
are slow to respond to noxious stimuli anywhere on hypalgesia—­and these signs can occur together. The
the body, including the face. The problem of facial reflex (CN V sensory → CN VII motor) can be
decreased facial sensation is identified when the poorly functional with lesions involving the sensory
degree of hypalgesia detected is greater than that to trigeminal nerve, ganglion or nucleus, or the facial
be expected by any accompanying somnolent or motor nucleus or nerve. With lesions involving the
moribund state or is demonstrably asymmetric. sensory branches of the trigeminal nerve, these facial

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
130 Large animal neurology

reflexes will not function. Degrees of facial hypalgesia eye lesions.2,3 Partial facial analgesia resulting from
or analgesia also occur and the animal does not pull trauma to single branches of CN Vs is not common
its head away from the noxious facial stimulus, for and is usually associated with trauma to the face,
example in a cow that had an ocular squamous cell nasal region, and sinuses. Because distal portions of
carcinoma invading the trigeminal nerve resulting in sensory trigeminal nerves are distributed with
facial analgesia.1 branches from autonomic nerves, processes such as
Sensation from at least the rostral third of the perineuritis that affect distal nerves may result in
tongue of horses is mediated via fibers in the signs of autonomic denervation. For example,
­mandibular nerve and that has been inadvertently trigeminal innervation of the nasal membranes
sectioned during surgical debulking of intermand- includes parasympathetic branches of CN VII, thus
ibular tumors, resulting in analgesia and areflexia resulting in rhinitis sicca when these nerves are
from the ipsilateral rostral circa 10 cm of the tongue. damaged (Figure 13.1). A similar involvement of
Expansile retrobulbar tumors including lymphosar- oculomotor branches to the eyeball that are conflu-
coma, melanoma, squamous cell carcinoma, and ent with the ophthalmic branch of CN V may also
parotid adenocarcinoma have caused facial hypal- result in poor pupillary constrictor function
gesia, usually with other overt evidence of face and (Figure 13.2).

Figure 13.1 Facial analgesia is evident in the bright and

alert horse shown here, by the needle holders clamped on the
distal face (arrow). There was a cranial—­believed immune-­
associated—­polyneuritis particularly involving the trigeminal
nerves, with bilateral facial and rostral nasal analgesia. The
presence of severe rhinitis sicca as also shown was unusual.
In the right clinical setting, this sign is regarded as almost
pathognomonic for equine dysautonomia, but this horse had
no other signs of enteric or autonomic nervous dysfunction.
As is the case often with polyneuritis equi, the trigeminal neu-
ritis was accompanied by a prominent perineuritis. Also, the
neuritis involved not just proximal cranial nerves but spread
along the distal branches. It was believed that the more distal
perineuritis involving the maxillary nerve also involved the
autonomic fibers innervating the nasal membranes, mimick-
ing the rhinitis sicca seen with grass sickness.

Figure 13.2 This case of polyneuritis involved the trigeminal nerves, and quite distinctly the ophthalmic branch on the left side was clinically affected.
The latter resulted in conjunctival and corneal hypalgesia demonstrated here in the left eye (OS). Likely because of perineuritis, and the fact that branches
of the ophthalmic nerve are confluent with the oculomotor fibers and the ciliary ganglion, a degree of pupillary dilation was also present in the left eye
(OS) compared with the right (OD) (yellow bars).
 Decreased and increased facial sensation 131

Medullary (and cranial cervical spinal cord) diseases

such as equine protozoal myeloencephalitis and listeri-
osis in ruminants are the more common central causes
of decreased facial sensation due to involvement of the
sensory tract and/or nucleus of the trigeminal nerve in
the caudal medulla oblongata and cranial cervical spi-
nal cord (Figure 13.3).
Central pathways for sensory perception from the
face pass from the trigeminal sensory nucleus to the
contralateral thalamus, contralateral internal capsule,
and somesthetic, sensory cerebral cortex, mostly in
the frontoparietal lobe. Lesions in these structures
rostral to CNs V and VII can result in degrees of con-
tralesional facial hypalgesia or analgesia but no inter-
ruption to the facial (CN V sensory → CN VII motor)
reflex (Figure 13.4). This facial hypalgesia or analge-
sia is most evident when the noxious stimulus is
applied to the sensitive nasal septal membranes on
the side opposite to such rostral lesions. Several
severe, particularly focal or selective, diseases of the
thalamus, internal capsule, and forebrain including
cerebral abscess, cholesterinic granuloma, Fusarium Figure 13.4 Definitive facial hypalgesia and analgesia are best detected
verticillioides (ex. moniliforme) leukoencephalomala- over the distal face as shown and particularly on the nasal membranes.
cia, intracarotid injection, and Sarcocystis neurona When this is found, the main question to arise is whether it is due to a
central forebrain (thalamus or cerebral hemisphere) lesion or it relates to
an afferent sensory lesion of the trigeminal distribution. In this horse with
a lesion in the forebrain causing facial analgesia, the facial reflexes
remained intact and voluntary movement of the face was good. With
peripheral sensory CN Vs lesions, the loss of facial sensation can be very
well demarcated particularly with more distal lesions. Also, facial reflexes
will be reduced or absent to the same degree as the hypalgesia or anal-
gesia. The central distribution of the afferent fibers from the trigeminal
nerve is quite spread out in the medulla oblongata and cranial cervical
spinal cord within the sensory trigeminal nucleus and its tract. Thus, a
central medullary lesion causing dense analgesia over the face would
entail a very extensive lesion such that there would be many other signs
of brain disease such as recumbency and (semi)coma. Thus, dense facial
sensory loss alone, due to an afferent lesion, is most likely in the periph-
eral trigeminal nerve or ganglion.

encephalitis have resulted in this contralesional facial

hypalgesic and analgesic syndrome.
Equine protozoal myeloencephalitis caused by
S. neurona and filariid nematode encephalitis have
caused ipsilesional facial hypalgesia and no interfer-
ence to the facial (CN V sensory → CN VII motor)
Figure 13.3 Oblivious to the presence of a straw stuck in its left nasal reflexes with brainstem lesions involving pontine and
cavity, this lamb suffering from listeriosis is demonstrating facial analge- midbrain sites, but with no lesion(s) in thalamus or
sia. There were accompanying facial and vestibulocochlear nerve deficits cerebrum. It is likely that the ascending impulses for
with ataxia and weakness. Indeed, involvement of the sensory branch of
the trigeminal nerve is a very common sign with listeriosis and possibly
conscious sensory perception from the face cross in
reflects one of the routes of bacterial infection reaching the medulla the region of the rostral brainstem to join the con-
oblongata in that disease. tralateral medial lemniscus on its path to the ventral
132 Large animal neurology

caudal lateral thalamic nucleus. Also, it is probable

that facial sensory input is perceived not only at the
somatosensory cerebral cortex, but also at the level of
the thalamus as a few newborn ruminants with no
cerebral cortices (agenesis) appeared to react with
avoidance movements when the nasal septal region
was stimulated strongly.
Facial analgesia can be seen in cattle with extensive
basilar empyema adjacent to and invading the sen-
sory branches of the trigeminal nerves along with
accompanying signs of dropped mandible, head and
neck extension, bradycardia, peripheral blindness,
dilated pupils, and facial, tongue and pharyngeal
paralysis. The full syndrome results from extension
to involve CNs II, III, V, IX, X, XI and XII, the ventral
brainstem, and the hypothalamus.
Facial and body regional hypersensitivity to firm
stimuli (hyperesthesia) but not to light touch stimuli
(allodynia) is seen with trigeminal and diffuse neuri-
tis in early stages of diffuse bacterial meningitis.
Trigeminal neuritis is the presumed diagnosis in the Figure 13.5 Accompanying the obvious nasal and distal facial hypalgesia
syndrome of pernicious head rubbing in horses, to firm pressure in this case, there was evidence of nasal and facial allo-
dynia to light touch in the form of self-­inflicted injury to the affected area of
wherein there is an acquired, profound irritation the face as indicated here. This horse was suffering from a squamous cell
such that the patient severely self-­traumatizes the carcinoma affecting the left side of the sphenopalatine sinus region and the
side of the face. Such a syndrome has been replicated trigeminal nerve. It rubbed its distal face on objects spontaneously and with
during (presumed) regrowth of infraorbital nerve stimulation to the face, despite the demonstrable hypalgesia, but did not
axons following compression or cauterization of that demonstrate headshaking.
nerve to attempt to ameliorate signs of headshaking
in horses.4 Facial hyperesthesia with allodynia to
References
light touch (Figure 13.5) has been seen in association
with ­fluctuating signs of facial hyporeflexia and hyp- 1 Samuel JL, Kelly WR and Vanselow BA. Intracranial invasion by
bovine ocular squamous cell carcinoma via cranial nerves. Vet
algesia to firm stimuli. This has occurred in cases of Rec 1987; 121(18): 424–425.
paranasal sinusitis and following sinus surgery when 2 Rebhun WC. Diseases of the bovine orbit and globe. J Am Vet
the trigeminal nerve within or adjacent to the sphe- Med Assoc 1979; 175(2): 171–175.
3 Guard CL, Rebhun WC and Perdrizet JA. Cranial tumors in
nopalatine sinus and within the infraorbital canal aged cattle causing Horner’s syndrome and exophthalmos.
have been involved.5,6 The syndrome has resolved Cornell Vet 1984; 74(4): 361–365.
in a few cases as the sinusitis was controlled. The 4 Roberts V. Trigeminal-­mediated headshaking in horses: prevalence,
impact, and management strategies. Vet Med Auckl 2019; 10: 1–8.
absence of true, stable allodynia alone does seem to 5 Tucker R, Windley ZE, Abernethy AD, et al. Radiographic,
differentiate these cases from cases of regional pain ­computed tomographic and surgical anatomy of the equine
syndrome with prominant allodynia as well as from sphenopalatine sinus in normal and diseased horses. Equine Vet
J 2016; 48(5): 578–584.
the enigmatic syndrome of headshaking with no 6 McCann JL, Dixon PM and Mayhew IG. Clinical anatomy of the
facial hypalgesia. (see Chapter 28). equine sphenopalatine sinus. Equine Vet J 2004; 36(6): 466–472.
 14
Facial paralysis and facial spasm

Paralysis of the muscles of facial expression, or facial making it usually easy to recognize in horses
paralysis, is a very common problem in large animals (Figure 14.1). This is less so in other species that tend
with neurologic disorders and is a common part of to have little facial expression, naturally stiff or droopy
the syndromes caused by temporohyoid osteoar­ ears and firm muzzles. However, when quite mild and
thropathy.1–3 Dysfunction of the somatic efferent fib­ when the patient is excited, facial muscle tone can be
ers of the facial nerve produces decreased spontaneous remarkably normal so that the syndrome may be very
and reflex movements of the ear, eyelids, lips, and subtle to observe. In this situation, returning to
external nares. The ear, upper eyelid, and lips on the observe the patient during a resting state, or use of
side of the lesion droop and the muzzle tends to be mild sedation, can help uncover the signs. Ptosis of
pulled to the opposite side with a unilateral lesion, the upper eyelid is a feature of facial paralysis in all

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
134 Large animal neurology

(A) (B)

Figure 14.1 Total left facial paralysis is seen in this horse (A) suffering from direct penetrating trauma to the base of the cranium including the left middle
and inner ears. The horse in (B) suffered direct injury to the buccal branches of the left facial nerve resulting in mild deviation of the muzzle to the right.

large domestic animals and is prominent in horses. It This occurs without flaccid facial paralysis. There is
is due to the paralysis of the strong levator anguli oculi still tone in the muscles of facial expression, and
medialis muscle in these species that is innervated facial reflexes (CN V sensory → CN VII motor) are
by the facial nerve CN VII. It is possible that the bulk intact and may even be hyperactive. However, the
of atonic supraorbital muscles and the paralysis of the expression may be bland or grimacing on one or
frontalis muscle also contribute to the ptosis. Unfortu­ both sides. Needle electromyographic examination
nately, when upper eyelid ptosis is seen in large ani­ of the facial muscles does not reveal denervation
mals, the immediate thought is one of it being Horner because the facial motor nucleus and nerve are still
syndrome (Figure 10.4). However, facial paralysis is intact. Large, focal cerebral lesions such as hema­
vastly more common than sympathetic denervation toma, S. neurona encephalitis, and abscess have pro­
of the eyelids in large animals and always must be duced such signs of supranuclear facial motor
considered the most likely cause. dysfunction that, unlike in humans, appear to be ipsile­
Parasympathetic visceral efferent fibers pass with sional, at least to the muzzle and lips of the distal face.
the somatic fibers to exit the brainstem, pass through Trauma and bacterial infection of the middle and
the internal acoustic meatus, and then leave the main inner ears are the commonest cause of peripheral
facial nerve within the facial canal to innervate the facial nerve paralysis,5–9 most particularly in young
lachrymal gland (and palatine and nasal glands) via patients. With distal, peripheral facial nerve involve­
the major petrosal nerve and pterygoid ganglion.4 ment, usually one or two branches of the nerve, not
When these parasympathetic fibers in the facial nerve all three nerve branches (auricular, palpebral, and
are damaged, then the loss of lachrymal tear produc­ buccal), are involved. Pressure on the side of the face
tion ensues resulting in keratoconjunctivitis sicca. as a result of a tight halter or from recumbency
Damage to the central motor pathways in the fron­ damages buccal branches, paralyzing just the nares
tal cortex, internal capsule, crus cerebri, and brain­ and lips; however, the ear and upper eyelid may
stem that control the facial nucleus and nerve can droop because of separate but direct auricular and
result in abnormal facial expression (Figure 14.2). palpebral nerve trauma. Brainstem lesions, particu­
 Facial paralysis and facial spasm 135

(A) (B)

Figure 14.2 In comparison to facial weakness, these two horses (A and B) have, at times, very good tone and movement in their face but at rest have
a bland facial expression (A). Sometimes with voluntary effort and with facial reflex testing, their face shows hypertonic expression and hyperreflexia (B).
Both horses had lesions in the forebrain without facial nuclear or facial nerve involvement. The first (A) had a vascular lesion involving much of the left
forebrain, and the second had thalamic lesions of equine protozoal myeloencephalitis on the left side. It does appear that the distal facial, functional
abnormalities as seen in these horses are ipsilesional to the damage to the central motor pathways to the facial nuclei.

(A) (B)

Figure 14.3 Facial paralysis is seen as marked loss of facial expression and movement with drooping of the ear, and upper eyelid, and of the lips (A and B).
Bilateral facial weakness seen here can be less evident due to the relative facial symmetry present (B). Collapse of alar folds with inspiratory restriction
(A) occurs far more with bilateral than unilateral paralysis in horses. Also, mild degrees of facial paresis can be difficult to see especially in patients such
as calves and piglets that do not normally have prominent facial expression and facial muscle tone. Re-­examination when a patient is fully relaxed or
sedated can help determine degrees of partial facial weakness. Palpating for decreased muscle tone and observing and palpating for reduced facial
reflexes are also very useful to confirm degrees of facial paresis.

larly those caused by equine protozoal myeloen­ and proliferative inflammatory lesions in and around
cephalitis and listeriosis, can selectively involve facial the facial nerves of calves may be the result of partly
nuclei in the brainstem and can mimic a peripheral treated and chronic bacterial otitis.13–16
lesion by producing selective, partial facial paresis. Large animals accommodate to unilateral facial
Neuritis of polyneuritis equi and equine Lyme neu­ paralysis very well, but bilateral facial paralysis
roborreliosis are causes of unilateral facial paresis,10–12 (Figure 14.3) results in difficulty in prehending food
136 Large animal neurology

and in keeping it in the mouth. Horses with this syn­ 3 Myrna KE. Neuro-­ ophthalmology in the Horse. Vet Clin
North Am Equine Pract 2017; 33(3): 541–549.
drome do sequester food in the flaccid cheek pouches 4 de Lahunta A, Glass E and Kent M. Veterinary Neuroanatomy
and drop a lot of food while eating. Temporary tarsor­ and Clinical Neurology. 4th ed. Saunders, Elsevier, St. Louis,
rhaphy may help alleviate damage to the cornea from MO. 2015.
5 Gosselin VB, Francoz D, Babkine M, et al. A retrospective
the lack of tears, but permanent facial paralysis may study of 29 cases of otitis media/interna in dairy calves. Can
necessitate enucleation of the eyeball because of kera­ Vet J 2012; 53(9): 957–962.
titis sicca and exposure ophthalmitis.3 Exercising 6 Lamm CG, Munson L, Thurmond MC, Barr BC and George
LW. Mycoplasma otitis in California calves. J Vet Diagn Invest
horses may require false nostril surgery as a result of 2004; 16(5): 397–402.
an obstruction to inspiratory airflow.17 Chronic paral­ 7 Francoz D, Fecteau G, Desrochers A and Fortin M. Otitis
ysis with muscle atrophy and fibrous contracture of media in dairy calves: a retrospective study of 15 cases (1987 to
2002). Can Vet J 2004; 45(8): 661–666.
the face can cause twisting of the muzzle and nares 8 Katz L. Left otitis media/interna and right maxillary sinusitis
back across the midline toward the paralyzed side. in a Percheron mare. Vet Clin North Am Equine Pract 2006;
In the early phase of irritative lesions such as bacterial 22(1): 163–175.
9 Ragle CA. Head Trauma. Vet Clin North Am Equine Pract
meningitis, viral meningoencephalitis, neuritis, and 1993; 9(1): 171–183.
focal trauma involving the facial nerve, facial muscles 10 Vatistas N and Mayhew IG. Differential diagnosis of polyneu­
can twitch and even remain in spasm prior to paresis or ritis equi. In Practice 1995; 17: 26–29.
11 Vatistas NJ, Mayhew IG and Whitwell KE. Polyneuritis equi: a
paralysis that may ensue. True, permanent hemifacial clinical review incorporating a case report of a horse display­
spasm with constant contraction of facial muscles, that ing unconventional signs. Prog Vet Neurol 1991; 2: 67–72.
relaxes following facial nerve anesthesia or general 12 Johnstone LK, Engiles JB, Aceto H, et al. Retrospective evalua­
tion of horses diagnosed with neuroborreliosis on postmortem
anesthesia as seen in humans and dogs does not yet examination: 16 cases (2004–2015). J Vet Intern Med 2016;
appear to be recorded in large animals. This might be 30(4): 1305–1312.
expected to occur following recovery from bacterial 13 Jensen R, Maki LR, Lauerman LH, et al. Cause and pathogen­
esis of middle ear infection in young feedlot cattle. J Am Vet
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groups,18 facial muscles are occasionally seen to undergo 14 Maenhout D, Ducatelle R, Coussement W, et al. Space occupy­
repetitive contraction described as facial tic or myo­ ing lesions of cranial nerves in calves with facial paralysis. Vet
Rec 1984; 115(16): 407–410.
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one facial tic in a horse has been seen to become almost space occupying lesions of cranial nerves in calves. Vet Rec
violent when hypocalcemia associated with systemic 1994; 134(22): 579–580.
16 McFadden AM, Mackereth GF, Avery MI, et al. A syndrome of
illness occurred, to then quieten with IV calcium treat­ facial paralysis of dairy calves in the Franklin district of New
ment. The underlying cause for facial and other localized Zealand. N Z Vet J 2009; 57(1): 63–68.
myoclonia is notoriously not found.18–20 17 Torre F. Use of autogenous cartilage graft from auricular
cartilage in treatment of unilateral paralysis of nostril in
Brainstem auditory evoked potential recordings racing standardbred horse. Equine Vet Educ 2003; 15(1):
may be used as proxy for facial nerve function as the 10–14.
facial nerve is intimate with the vestibulocochlear 18 Beech J. Forelimb tic in a horse. J Am Vet Med Assoc 1982;
180(3): 258–260.
nerve for their course in the region of the temporal 19 de Lahunta A, Glass EN and Kent M. Classifying involuntary
bone and its middle and inner ear compartments.21,22 muscle contractions. Comp Cont Ed Pract Vet 2006; 28:
516–529.
20 Kerby MJ. Repetitive facial nerve stimulation in a cow. Vet Rec
References 2006; 158(12): 420.
21 Wrzosek M, Niezwiedz A, Giza E, Borowicz H and Nicpon J.
1 Espinosa P, Nieto JE, Estell KE, Kass PH and Aleman M. Auditory brainstem evoked response (BAER) in the diagnosis
Outcomes after medical and surgical interventions in horses of nervous system diseases in horses. Medycyna Weterynaryjna
with temporohyoid osteoarthropathy. Equine Vet J 2017; 49(6): 2012; 68(9): 557–561.
770–775. 22 Aleman M, Puchalski SM, Williams DC, Kass PH and Holliday
2 Walker AM, Sellon DC, Cornelisse CJ, et al. Temporohyoid TA. Brainstem auditory-­evoked responses in horses with tem­
osteoarthropathy in 33 horses (1993–2000). J Vet Intern Med porohyoid osteoarthropathy. J Vet Intern Med 2008; 22(5):
2002; 16(6): 697–703. 1196–1202.
 15
Pharyngeal dysphagia

Dysphagia is a frequently occurring neurologic prehension, mastication, and deglutition. Central

sign in preterm and neonatal infants1 and in large control of eating is mostly by specific medullary
animals (Figure 15.1). It is reported to occur in centers and their afferent and efferent pathways in
newborn foals2 at a frequency of ~1% and has been the following nerves (and their innervated struc-
reported to occur in ~5% of foals admitted to an tures): trigeminal (CN V- muscles of mastication
equine hospital neonatal ICU.3 The term dysphagia and facial sensation); facial (CN VII- muscles of
is used here in its broadest sense to mean difficulty the lips and cheeks); glossopharyngeal, vagus, and
in eating or drinking and includes disorders of accessory (CNs IX, X and XI- pharynx, and ­larynx);

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
138 Large animal neurology

of yellow star thistle or Russian knapweed poisoning

Physical damage to the naso-­and oro-­pharynx, and the causing nigropallidal encephalomalacia, but can also
larynx, can result in food accumulating in the pharynx be caused by focal lesions of S. neurona protozoal
and airway with resultant nasal or oral food discharge. myeloencephalitis or migrating helminth parasites.
This includes postoperative complications resulting from Prehension and mastication are impaired, but
various laryngeal surgical procedures, especially prosthetic affected animals can usually swallow. Other signs of
laryngoplasty4–6 and from pharyngeal trauma in cattle.7 brain disease may be mild or absent.
The signs of dysphagia seen with medullary lesions
depend on the specific cranial nerve nuclei affected.
and hypoglossal (CN Xll- tongue). The voluntary There are usually other asymmetric signs of medullary
effort in eating and drinking probably is initiated in disease such as somnolence, limb weakness and ataxia,
the cerebral motor cortex and in basal nuclei. and other cranial nerve signs particularly from any
Therefore, disorders of the cerebrum, thalamus, involvement of the vestibular and facial nuclei.9,10 Specific
medulla oblongata, and cranial nerves V, VII, IX, X causes include S. neurona protozoal myeloencephalitis,
and XII can cause dysphagia. migrating metazoan parasites, and trauma to the back of
Development of fully competent swallowing the head with medullary hemorrhage. Diffuse brain dis-
reflexes appear to occur late in gestation, and preterm eases with a medullary component, such as the toga-­and
human infants often have swallowing difficulties that flavi-­viral encephalitides, rabies, meningitis, locoweed
with time most often improve or resolve.1 Newborn poisoning, and hepatoencephalopathy, can include
foals with apparent pharyngeal dysphagia most often dysphagia as part of the clinical syndromes.
also go on to resolve this problem.3 Bilateral involvement of the motor branches of the
Passing a stomach tube, inspecting teeth, auscultat- trigeminal nerve causes paralysis and eventual atrophy
ing the thorax for evidence of feed inhalation, taking of the masseter muscles and of the temporal, pterygoid,
appropriate radiographs, and using an endoscope to see and distal belly of the digastricus muscles (Chapter 12).
the pharynx and larynx and the structures surrounding The resulting weak jaw tone causes difficulty in mastica-
the guttural pouches are helpful ancillary aids. In par- tion and allows the tongue to hang from the mouth.
ticular, this should exclude many of the most common Unilateral trigeminal paralysis does not cause signifi-
non-­neurologic causes of dysphagia including dental cant dysphagia but may result in slight deviation of the
problems, esophageal choke, pharyngitis, oropharyn- jaw, initially away from the affected side. Damage to the
geal foreign body, pharyngeal abscess, or phlegmon and sensory branches of the trigeminal nerve (CN Vs) sup-
neoplastic masses.4, 8 When evaluating animals from plying the face, mouth, and rostral tongue does not pro-
rabies-­endemic regions that have had signs of dysphagia duce severe dysphagia but may cause food accumulation
for less than 2 weeks, consideration must be given to in the cheeks and laceration of the tongue by teeth.
this possibility early during evaluation. Paralysis of the lips due to facial nerve (CN VII;
Forebrain diseases do not cause actual paralysis of Chapter 14) damage on one side causes minor problems
the muscles involved in eating but can impair volun- in prehension of food, perhaps only with pasture and
tary control of these muscles, resulting in uncoordi- grain. Food-­stained saliva may dribble from the com-
nated, dystonic, and weak movements of the face, missure of the lips, and food often adheres to the gums
tongue, mouth, and pharynx. Diffuse cerebral disease and lips. Bilateral facial paralysis does however cause
can cause dysphagia in addition to lack of ability to marked problems in prehending forages and dry grain,
find or eat food due to other gross behavioral and atti- but slurries of food are usually handled reasonably well.
tudinal abnormalities such as mental obtundation, head Marked bilateral paralysis of the pharyngeal and pala-
pressing, circling, and blindness. Characteristically, there tine muscles innervated by cranial nerves IX, X, and XI
is some weakness and protrusion of the tongue, droop- makes swallowing impossible. Attempts at eating are fol-
ing of the lower lip, and drooling of saliva. Unweaned lowed by choking, dorsal displacement of the soft palate,
patients lose the suckling reflex. Included in these and food and saliva exiting the nostrils in horses and the
diffuse diseases are the arboviral encephalitides, mouth in other herbivores. Unilateral paralysis causes
rabies, hepatoencephalopathy, diffuse meningitis, less severe signs. Aspiration of food may lead to necrotic
neonatal encephalopathy, head trauma with brain bronchopneumonia and is particularly likely if there is
swelling, leukoencephalomalacia, and hydrocephalus. concurrent paralysis of the larynx due to damage of the
Dysphagia caused by lesions of the basal nuclei laryngeal fibers of the vagus nerve. In affected horses,
occurs in horses in western North America as a result collapse of the atonic pharyngeal walls, displacement of
 Pharyngeal dysphagia 139

the soft palate, and poor abduction of the vocal folds Affected horses usually have other signs of the primary
cause abnormal respiratory noises, especially during disease in addition to dysphagia. Polyneuritis equi can
exercise and during attempts at swallowing. cause dysphagia by affecting any or all of cranial nerves
Damage to CN Xll, the hypoglossal nerve, causes V, VII, IX, X, XII.17–19 Dysphagia, along with laryngeal
lingual paralysis and eventual atrophy. This is accom- paralysis, is also a common sequel to chronic lead poi-
panied by quidding of poorly chewed food and soning. Seven of 16 horses with Lyme neuroborreliosis
drooling of saliva, with poor tongue retraction only if had pharyngeal dysphagia, five had tongue weakness,
bilateral. This may occur with the ingestion of young and four had facial paralysis associated variously
bamboo plants by horses.11 with meningoencephalitis, radiculitis, or neuritis
Various combinations of cranial nerve deficits may affecting any or all of CNs VII, IX, X, and XII.20
have synergistic effects in producing dysphagia. Botulism is associated with generalized paresis of
Examples of these combinations are facial and lin- striated muscles, including those of prehension, mas-
gual paresis, motor trigeminal and lingual paresis, tication, and swallowing.21–26 The toxins produced by
and sensory trigeminal and vagal motor deficits. Clostridium botulinum block neuromuscular trans-
Some diseases (and the CN involvement) resulting in mission by interfering with the action of acetylcho-
dysphagia include guttural pouch mycosis (IX, X, XI, line. Early clues of dysphagia in botulism cases can be
XII), ruptured rectus capitus ventralis muscle (IX, X, XI), slow and relatively quiet prehension and mastication,
fractured hyoid bone (V or Xll depending on the site of prolonged eating times, and excess saliva in the
fracture), excessive traction on the tongue (XIl), and retro­ mouth and on the tongue which is readily grasped
pharyngeal lymph node abscessation (IX, X, and Xll).12–16 and held, albeit very slimy (Figure 15.1).

A C

Figure 15.1 Esophageal choke must be the most common cause of dysphagia in large animals, particularly associated with anhydrous feed in horses,
and bulky forage items in cattle. Botulism and guttural pouch mycosis are also accompanied by pharyngeal choke with nasal and even oral return of food,
saliva, and sometimes purulent exudate. With botulism (A and B), the food returning is usually not accompanied by exudate until a chronic state is
reached when there is secondary necrotic respiratory disease. Quiet, slow and cumbersome chewing may be characteristic in some cases (A), and with
oral dysphagia in botulism cases the material is usually soaked with saliva making the mouth and tongue extremely wet (B) and slippery to examine.
Perhaps surprisingly, unilateral guttural pouch catarrh, empyema, and mycosis (C) often cause degrees of pharyngeal paralysis with mucopurulent exu-
date (and sometimes blood) accompanying the chewed food appearing at the nares.
140 Large animal neurology

The neurotoxin produced by Clostridium tetani 6 Dixon RM, McGorum BC, Railton DI, et al. Long-­term survey
of laryngoplasty and ventriculocordectomy in an older, mixed-­
facilitates firing of final motor neurons throughout breed population of 200 horses. Part 1: Maintenance of surgical
the CNS. This toxin has a slight predilection for the arytenoid abduction and complications of surgery. Equine Vet
medullary nuclei that control eating. Thus, besides J 2003; 35(4): 389–396.
7 Gomez DE, Desrochers A, Francoz D, et al. Pharyngeal
generalized muscle tetany, there is hypertonicity of trauma in dairy cattle: 27 cases. J Vet Intern Med 2019; 33(4):
the muscles that control eating, particularly the 1833–1839.
masseter muscles, resulting in trismus or lockjaw. 8 Hudson NPH, McGorum BC and Dixon PM. A review of 4
cases of dysphagia in the horse: buccal abscess, lingual abscess,
A high prevalence of dysphagia (milk aspiration) retropharyngeal foreign body and oesophageal obstruction.
occurred in full-­term, unrelated, neonatal foals on a Equine Vet Educ 2006; 18(4): 199–204.
breeding farm in Pennsylvania close to unconven- 9 Covington AL, Magdesian KG, Madigan JE, et al. Recurrent
esophageal obstruction and dysphagia due to a brainstem
tional natural gas (hydraulic fracturing, also called melanoma in a horse. J Vet Intern Med 2004; 18(2): 245–247.
fracking) operations.2 Of 28 foals born over three 10 McConkey S, Lopez A and Pringle J. Extramedullary plasma-
years, there were 17 (61%) foals affected with dyspha- cytoma in a horse with ptyalism and dysphagia. J Vet Diagn
Invest 2000; 12(3): 282–284.
gia for which no specific cause could be determined. 11 Barbosa JD, de Oliveira CMC, Duarte MD, et al. Poisoning of
Fourteen of the affected foals regained swallowing horses by bamboo, Bambusa vulgaris. J Equine Vet Sci 2006;
ability over a median of 11 days, although three foals 26(9): 393–398.
12 Divers TJ, de Lahunta A, Ducharme NG, Irby NL and Scrivani
required hand rearing having never gained suckling PV. Temporohyoid osteoarthropathy. Clin Tech Eq Pract 2006;
ability. There was strong toxicologic evidence for a 5(1): 17–23.
role of environmental contamination by polycyclic 13 Pease AP, van Biervliet J, Dykes NL, Divers TJ and Ducharme
NG. Complication of partial stylohyoidectomy for treatment
aromatic hydrocarbons, and the problem of neonatal of temporohyoid osteoarthropathy and an alternative surgical
dysphagia was eliminated by the installation of a technique in three cases. Equine Vet J 2004; 36(6): 546–550.
water filtration and treatment system.2 14 Walker AM, Sellon DC, Cornelisse CJ, et al. Temporohyoid
osteoarthropathy in 33 horses (1993–2000). J Vet Intern Med
Myopathy involving pharyngeal and other muscles, 2002; 16(6): 697–703.
such as caused by doxycycline and other toxicities 15 Greet TR. Outcome of treatment in 35 cases of guttural pouch
in ruminants, can include dysphagia in the overall mycosis. Equine Vet J 1987; 19(5): 483–487.
16 Lepage OM and Piccot-­Crezollet C. Transarterial coil emboli-
syndrome.27, 28 sation in 31 horses (1999–2002) with guttural pouch mycosis:
Finally, equine dysautonomia or grass sickness is a 2-­year follow-­up. Equine Vet J 2005; 37(5): 430–434.
an important differential in animals with dysphagia 17 Hahn CN. Miscellaneous disorders of the equine nervous sys-
tem: Horner’s syndrome and polyneuritis equi. Clin Tech Eq
in endemic areas. Affected horses drop food, drool Pract 2006; 5(1): 43–48.
saliva, reflux through the nostrils, and have difficul- 18 Vatistas N and Mayhew IG. Differential diagnosis of polyneu-
ties in swallowing. The exact mechanism causing ritis equi. In Pract 1995; 17: 26–29.
19 Vatistas NJ, Mayhew IG and Whitwell KE. Polyneuritis
dysphagia in grass sickness has not been clearly equi: a clinical review incorporating a case report of a horse
defined.29–31 displaying unconventional signs. Prog Vet Neurol 1991; 2:
67–72.
20 Johnstone LK, Engiles JB, Aceto H, et al. Retrospective evalua-
References tion of horses diagnosed with neuroborreliosis on postmortem
examination: 16 cases (2004–2015). J Vet Intern Med 2016;
1 Sitton M, Arvedson J, Visotcky A, et al. Fiberoptic endoscopic 30(4): 1305–1312.
evaluation of swallowing in children: feeding outcomes related 21 Wilkins PA and Palmer JE. Botulism in foals less than 6 months
to diagnostic groups and endoscopic findings. Int J Pediatr of age: 30 cases (1989–2002). J Vet Intern Med 2003; 17(5):
Otorhinolaryngol 2011; 75(8): 1024–1031. 702–707.
2 Mullen KR, Rivera BN, Tidwell LG, et al. Environmental 22 Whitlock RH. Botulism, type C: experimental and field cases
­surveillance and adverse neonatal health outcomes in foals born in horses. Eq Pract 1996; 18(10): 11–17.
near unconventional natural gas development activity. Sci Total 23 van der Lugt JJ, Henton MM and Steyn BG. Type C botulism in
Environ 2020; 731: 138497. sheep associated with the feeding of poultry litter. J S Afr Vet
3 Giguère S, Weber EJ and Sanchez LC. Factors associated with Assoc 1996; 67(1): 3–4.
outcome and gradual improvement in survival over time in 24 Schoenbaum MA, Hall SM, Glock RD, et al. An outbreak of
1065 equine neonates admitted to an intensive care unit. Equine type C botulism in 12 horses and a mule. J Am Vet Med Assoc
Vet J 2017; 49(1): 45–50. 2000; 217(3): 340, 365–368.
4 Vidovic A and Delling U. Aryepiglottic fold augmentation as 25 Kelch WJ, Kerr LA, Pringle JK, Rohrbach BW and Whitlock
treatment for late-­onset dysphagia following surgical treatment RH. Fatal clostridium botulinum toxicosis in eleven Holstein
of recurrent laryngeal neuropathy. Tierarztl Prax Ausg G cattle fed round bale barley haylage. J Vet Diagn Invest 2000;
Grosstiere Nutztiere 2017; 45(4): 219–225. 12(5): 453–455.
5 Barakzai SZ, Dixon PM, Hawkes CS, Cox A and Barnett TP. 26 Braun U, Feige K, Schweizer G and Pospischil A. Clinical find-
Upper esophageal incompetence in five horses after prosthetic ings and treatment of 30 cattle with botulism. Vet Rec 2005;
laryngoplasty. Vet Surg 2015; 44(2): 150–155. 156(14): 438–441.
 Pharyngeal dysphagia 141

27 Brihoum M, Amory H, Desmecht D, et al. Descriptive study of 29 Araya O, Vits L, Paredes E and Ildefonso R. Grass sickness in
32 cases of doxycycline-­overdosed calves. J Vet Intern Med horses in southern Chile. Vet Rec 2002; 150(22): 695–697.
2010; 24(5): 1203–1210. 30 Vörös K, Bakos Z, Albert M, Barátossy G and Fejér B.
28 Botha CJ, Schultz RA, Van der Lugt JJ, Retief E and Occurrence of grass sickness in Hungary (Hungarian). Magyar
Labuschagne L. Neurotoxicity in calves induced by the Allatorvosok Lapja 2003; 125(2): 67–74.
plant, Nierembergia hippomanica Miers var. violacea 31 Cottrell DF, McGorum BC and Pearson GT. The neurology
Millan in South Africa. Onderstepoort J Vet Res 1999; and enterology of equine grass sickness: a review of basic
66(3): 237–244. mechanisms. Neurogastroenterol Mot 1999; 11: 79–92.
 16
Dilated esophagus

Dilated esophagus can be due to obstruction or common than primary neuromuscular esophageal
­primary dysfunction of the esophagus. Permanent dysfunction that does however occur in the proximal
dilation of the esophagus or megesophagus is not fre- esophagus as a complication of laryngeal surgery.1
quently seen in large animals. However, it has been Regional aganglionosis and deficiency of neural
observed with chronic intra-­and extraluminal elements have been purported to be congenital neu-
esophageal obstruction caused by lower esophageal ral causes of megaesophagus.2 Also, some young
sphincter scarring and ulceration, persistent right foals showing nasal regurgitation of milk may have pri-
aortic arch, severe pneumonia with dyspnea and with mary esophageal muscular lesions seen at postmor-
gastroesophageal ulceration, and associated bruxism, tem examination; however, others diagnosed as
retching and aerophagia. Such causes are far more having neonatal encephalopathy do well with

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Dilated esophagus 143

Several drugs influence esophageal motility, and

certainly the α-­2 agonist sedatives will result in air
detectable in the esophagus radiographically. Also,
isoproterenol, terbutaline, and oxytocin reduce
the contractility of esophageal smooth muscle of
horses.8
Consideration may be given to other infrequent
(A) causes of signs of regurgitation and suspected
esophageal paralysis including neuroborreliosis,
polyneuropathies, polymyopathies, and myasthenia
gravis.9 Finally, local brainstem encephalitis in
horses can result in persistent esophageal dilation
and obstruction.10

References
1 Barakzai SZ, Dixon PM, Hawkes CS, Cox A and Barnett TP.
(B) Upper esophageal incompetence in five horses after prosthetic
laryngoplasty. Vet Surg 2015; 44(2): 150–155.
2 Broekman LEM and Kuiper D. Megaesophagus in the horse.
Figure 16.1 Dilation of the esophagus with regurgitation in large ani- A short review of the literature and 18 own cases. Vet Q 2002;
mals is most frequently due to upper gastrointestinal obstruction or due 24(4): 199–202.
to functional disorders such as equine dysautonomia and ruminant vagal 3 Mullen KR, Rivera BN, Tidwell LG, et al. Environmental sur-
indigestion. Megaesophagus can accompany botulism, but otherwise it is veillance and adverse neonatal health outcomes in foals born
only rarely seen without an esophageal stricture. These two cases demon- near unconventional natural gas development activity. Sci
strated with contrast esophagram (A and B) had acquired, mild, general- Total Environ 2020; 731: 138497.
ized, fluctuant, somatic weakness and poor esophageal function of 4 Giguère S, Weber EJ and Sanchez LC. Factors associated with
outcome and gradual improvement in survival over time in
several months duration for which there was no definitive pathologic
1065 equine neonates admitted to an intensive care unit.
lesion determined. Equine Vet J 2017; 49(1): 45–50.
5 Toribio RE. Equine Neonatal encephalopathy: facts, evidence,
s­upportive care so euthanasia should not be and opinions. Vet Clin North Am Equine Pract 2019; 35(2):
363–378.
embarked upon too quickly.3–5 6 Komine M, Langohr IM and Kiupel M. Megaesophagus in
A dilated esophagus is seen in several diffuse Friesian horses associated with muscular hypertrophy of the
myasthenic syndromes, many of which defy specific caudal esophagus. Vet Pathol 2014; 51(5): 979–985.
7 Ploeg M, Grone A, Saey V, et al. Esophageal dysfunction in
diagnosis (Figure 16.1), and some degree of paresis friesian horses: morphological features. Vet Pathol 2015; 52(6):
and dilation of the esophagus is one of the hallmarks 1142–1147.
of the paralytic gastrointestinal syndrome in horses 8 Wooldridge AA, Eades SC, Hosgood GL and Moore RM.
in vitro effects of oxytocin, acepromazine, detomidine, xylazine,
from Europe and from Patagonia, known as grass butorphanol, terbutaline, isoproterenol, and dantrolene on
sickness and Mal Seco, respectively. smooth and skeletal muscles of the equine esophagus. Am J
A familial form of megaesophagus particularly Vet Res 2002; 63(12): 1732–1737.
9 Johnstone LK, Engiles JB, Aceto H, et al. Retrospective evalua-
involving the thoracic esophagus occurs in Friesian tion of horses diagnosed with neuroborreliosis on postmortem
horses in Europe which is associated with increased examination: 16 cases (2004–2015). J Vet Intern Med 2016;
deposition of disorganized collagen mainly in the 30(4): 1305–1312.
10 Green EM, Roth JE and McClure RC. Recurrent esophageal
nondilated portion of the esophagus and a decrease obstruction in the horse: neurologic considerations. 32nd Ann
in neural elements.6,7 Conf Am Assoc Equine Pract 1986.
 17
Laryngeal paresis and paralysis: roaring

This is a common idiopathic disorder in most tall neurogenic muscle atrophy in the intrinsic laryngeal
horses of light breed, warmblood, and draft breeds in muscles innervated by the rln, and a small propor-
which Wallerian-­ like neuronal fiber degeneration tion used for some kind of athletic performance will
and attempts at reinnervation occur in the recurrent demonstrate an inspiratory noise, roaring, and/or
laryngeal nerve (rln), the left far more so than the curtailed performance at exercise.1–3
right, and as such is referred to as recurrent laryngeal Many families of horses have a high frequency
neuropathy (RLN). These horses have degrees of of roaring, although no specific genetic defect has

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Laryngeal paresis and paralysis: roaring 145

been determined. One previously popular hypo­thesis Pyrrolizidine alkaloid-­associated liver failure with
for the idiopathic disorder in horses involves physical hepatic encephalopathy frequently results in bilateral
forces associated with the left rln having a longer laryngeal paralysis with loud inspiratory stridor
course than the right nerve. The syndrome occurs occurring at rest or with minimal exercise.7–9 The
most commonly on the left side in large horses with laryngeal paralysis may be temporary, worsening
long necks and deep thoraxes. The left rln has a during exacerbations of encephalopathy and resolv-
longer course around the aortic arch than the right ing with the restoration of hepatic function. No gross
nerve does around the costocervical artery. The lev- or histopathological abnormalities have been identi-
erage effect created by neck movement could then fied in laryngeal muscles, rln, and other peripheral
result in tension on the nerve and compromise to its nerves of affected horses. Thus, the laryngeal paral-
blood supply with ischemia resulting in local and ysis of liver failure in horses may reflect neuromus-
distal nerve fiber degeneration. Whether such nerve-­ cular dysfunction rather than an axonopathy or
specific factors are more important than the presence myelinopathy.
of a generalized neuropathy with selective predispo- Uncommonly, following general anesthesia, horses
sition to damage of the rln is not known: i.e., is RLN may develop postanesthetic laryngeal paralysis with
a mononeuropathy or a polyneuropathy?2 Several variable recovery of laryngeal function. This may
toxic, metabolic, genetic, and other factors have been result from excessive head and neck extension com-
put forward as possible causative factors for RLN, but promising nerve blood flow or from compression
obviously at present the exact pathogenesis of the and/or stretching of the recurrent laryngeal nerve
disease is unknown.3 over a rigid structure in the neck. Myopathy, persis-
Clinical evaluation of cases of RLN has been stand- tent hypoxia, and pre-­existing laryngeal dysfunction
ardized by use of endoscopy during high-­speed tread- are additional factors that may contribute to the
mill and overground exercise, and relatively successful development of this complication.
surgical procedures are available for palliative treat- Several toxic peripheral neuropathies cause
ment of the condition. Denervation potentials can be equine laryngeal paralysis including intermediate
recorded in left laryngeal muscles, slowing of the and delayed organophosphate induced toxic-
thoracolaryngeal response can be identified and longer ity, 11–13 pasture-­associated stringhalt, lead poison-
left rln conduction latency (viz. reduced velocity) can ing, ingestion of Lathyrus spp. and Cicer arietinum
be calculated with electrodiagnostic equipment, none (chick pea), and other plant poisonings, all with evi-
of which really add to diagnostic accuracy and prog- dence of a generalized disorder that affects multiple
nosis for RLN (see Chapter 38). nerves and so presents little diagnostic problem.
In addition to cases of idiopathic RLN, about Finally, a syndrome of bilateral rln neuropathy can
5–10% of cases of equine laryngeal paresis or paraly- accompany the more general lesions of copper defi-
sis have a detectable cause.4 Non-­ RLN laryngeal ciency, at least in goats.14
paralysis may be a sequel to localized injury to the As an aside, diaphragmatic paralysis can be men-
vagus or recurrent laryngeal nerves such as guttural tioned here as a very unusual neurologic disease
pouch mycosis, rupture of the rectus capitis ventralis resulting in variable signs of respiratory distress with
muscles, temporohyoid fracture, retropharyngeal no evidence of respiratory tract obstruction or of
abscessation, perivascular/perineural cervical injec- ­pulmonary lesions and can result from mid cervical
tion reaction, inadvertent ventral neck intraoperative (C3-5) spinal cord or bilateral nerve root, or phrenic
nerve damage, and retropharyngeal and cranial tho- nerve, or diaphragmatic muscle lesions. Abdominal
racic neoplasia. Non-­RLN paralysis may also be a collapse during inspiration and thoracic expansion, is
manifestation of myopathy and polyneuropathy the characteristic syndrome.15–19
including neuroborreliosis.5 Bilateral laryngeal paral-
ysis,6 which is considerably less common (2–6%)
than unilateral paralysis, almost invariably results References
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hepatoencephalopathy7–9 and hyperkalemic periodic neuropathy. Havemeyer Foundation Monograph Series No. 11:
R & W Publications. 2004.
paresis. A similar array of disorders is likely associ- 2 Draper ACE and Piercy RJ. Pathological classification of equine
ated with non-­RLN laryngeal paralysis in other large recurrent laryngeal neuropathy. J Vet Intern Med 2018; 32(4):
animal species.10 1397–1409.
146 Large animal neurology

3 Parente EJ. Fifty years of recurring struggles with recur- 11 Rose RJ, Hartley WJ and Baker W. Laryngeal paralysis in
rent laryngeal neuropathy. Equine Vet J 2018; 50(2): Arabian foals associated with oral haloxon administration.
155–158. Equine Vet J 1981; 13(3): 171–176.
4 McGorum B and Dixon PM. Non-­recurrent laryngeal neu- 12 Coppock RW, Mostrom MS, Khan AA and Stair EL. A review
ropathy (RLN) causes of equine laryngeal paralysis. In Equine of nonpesticide phosphate ester-­induced neurotoxicity in cat-
Recurrent Laryngeal Neuropathy, Dixon PM, Robinson E, tle. Vet Hum Toxicol 1995; 37(6): 576–579.
Wade JF, Editors. Havemeyer Foundation Monograph Series 13 Thompson JC, Thompson AH and Thornton RN.
No 11: R & W Publications. 2004; 55–56. Accidental poisoning of a group of yearling cattle by the
5 Johnstone LK, Engiles JB, Aceto H, et al. Retrospective evalua- organophosphate insecticide trichloronat. N Z Vet J 1993;
tion of horses diagnosed with neuroborreliosis on postmortem 41(2): 87–90.
examination: 16 cases (2004–2015). J Vet Intern Med 2016; 14 Sousa RFA, Almeida VM, Neto JE, et al. Laryngeal neuropathy
30(4): 1305–1312. in adult goats with copper deficiency. Vet Pathol 2017; 54(4):
6 Duncan ID and Brook D. Bilateral laryngeal paralysis in the 676–682.
horse. Equine Vet J 1985; 17(3): 228–233. 15 Amory H, Lomba F, Lekeux P et al. Bilateral diaphragmatic
7 Hughes KJ, McGorum BC, Love S and Dixon PM. Bilateral paralysis in a pony. J Am Vet Med Assoc 1994; 205(4): 587–591.
laryngeal paralysis associated with hepatic dysfunction and 16 Bedenice D, Mazan MR, Kuehn H and Hoffman AM
hepatic encephalopathy in six ponies and four horses. Vet Diaphragmatic paralysis due to phrenic nerve degeneration in
Rec 2009; 164(5): 142–147. a llama. J Vet Intern Med 2002; 16(5): 603–606.
8 McGorum BC, Murphy D, Love S and Milne EM. 17 Byers S, Barrington G, Nelson D et al. Neurological Causes of
Clinicopathological features of equine primary hepatic disease: Diaphragmatic Paralysis in 11 Alpacas (Vicugna pacos). J Vet
a review of 50 cases. Vet Rec 1999; 145(5): 134–139. Int Med 2011; 25(2): 380–385.
9 Pearson EG. Liver failure attributable to pyrrolizidine alkaloid 18 Johnstone LK, Engiles JB, Aceto, H et al. Retrospective
toxicosis and associated with inspiratory dyspnea in ponies: Evaluation of Horses Diagnosed with Neuroborreliosis on
three cases (1982–1988). J Am Vet Med Assoc 1991; 198(9): Postmortem Examination: 16 Cases (2004–2015). J Vet Int
1651–1654. Med 2016; 30(4): 1305–1312.
10 Bushby VE, Woodford NS and Little DR, Huxley JN. Laryngeal 19 Kokatnur L and Rudrappa M. Diaphragmatic Palsy. Diseases
hemiplegia in a heifer. Vet Rec 2004; 155(22): 715. (Basel, Switz) 2018;, 6(1): 16.
 18
Tongue Paralysis

Paresis or paralysis of the tongue rarely occurs as a Guttural pouch diseases, particularly mycosis, can
selective process alone, and it is more commonly part cause tongue (hemi) paralysis among numerous
of the diffuse neuromuscular diseases especially bot- other cranial nerve syndromes.3,4 Fractured hyoid
ulism and various medullary diseases such as listeri- bones can cause protrusion of the tongue with dys-
osis, West Nile virus encephalitis, and S. neurona phagia in the horse, although this can resolve when
protozoal myeloencephalitis. If there is evidence of the hyoid bones heal. Cattle in squeeze-­shute acci-
local disease process such as a swollen tongue, exces- dents can develop a dropped mandible and rostral
sive salivation, fever and halitosis, then processes protrusion of the tongue, with or without a fractured
such as glossitis due to Actinobacillus lignieresi mandible or luxated temporomandibular joint.
(wooden tongue), pharyngeal trauma,1 and foreign Whether or not the hypoglossal nerves are involved
bodies must be ruled out.2 in individual cases can be difficult to determine as

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
148 Large animal neurology

the tongue lolls out of the mouth because of the low- myeloencephalitis caused by S. neurona is unusual
ered mandible. Calves and lambs born following dys- because it can produce extremely localized lesions
tocia can have edematous heads, and a swollen, that may selectively affect individual cranial nerve
protruded tongue can be a prominent impairment nuclei, even causing hemiatrophy of the tongue with
associated with this syndrome. Occasionally, new- no other signs of brainstem disease. The so-­called
born foals have been found to have a protruding pituitary syndrome in cattle can result from basilar
tongue that has poor tone. These foals can require empyema and pituitary neoplasia, and along with
assistance to suck and drink milk, but often tongue signs such as somnolence, star-­gazing, and bradycar-
function returns within a week or so suggesting there dia indicating thalamic and hypothalamic dysfunc-
was a form of neurapraxia occurring during birth or tion, such lesions can extend caudally to effect tongue
delayed reflex development as with neonatal pharyn- weakness and other cranial nerve-­related signs.7
geal dysphagia. Bamboo (Bambusa vulgaris f. vulgaris) toxicosis in
The generalized neuromuscular paralysis caused horses may result in a tongue remaining out of the
by Clostridium botulinum neurotoxins can result in mouth,8 and doxycycline overdosing of calves may
prominent tongue paralysis. A feature of this is that also result in selective tongue paresis.9
the tongue is readily grasped and drawn from the Diffuse and focal forebrain syndromes caused by
mouth, and it feels like a slippery eel due to flaccidity diseases such as cerebral abscess and hematoma,
and coating with excess saliva (Figure 18.1). polioencephalomalacia, Eastern equine encephalitis,
Lesions in the medulla oblongata such as equine Fusarium verticillioides (previously F. moniliforme)
protozoal myeloencephalitis,5 brainstem trauma, fumonisin B1 toxin-­induced leukoencephalomalacia,
West Nile encephalitis, and listeriosis6 usually result and hepatoencephalopathy may result in poor con-
in degrees of somnolence, asymmetric ataxia, and trol and apparent weakness of the tongue when the
tetraparesis in addition to signs of cranial nerve dys- patient allows it to remain out of the mouth even
function such as tongue paralysis. Equine protozoal though it can be retracted. There is no final motor
neuron lesion, flaccid paralysis, or atrophy, and the
needle electromyogram does not indicate denerva-
tion. These signs indicate that the final motor neuron
is intact and that this is a central motor neuronal
pathway or supranuclear (pseudobulbar) paresis.
Some adult horses and occasionally foals that are
‘tongue suckers’ are often seen leaving the tongue out
of the mouth (see Figure 5.6). In addition, they do
not seem to mind having their tongue pulled from
the mouth. The tongue may appear to be flaccid,
although no dysphagia or other neurologic signs are
present. This can be regarded as an acquired behavio-
ral trait or stereotypic behavior.

References
1 Gomez DE, Desrochers A, Francoz D, et al. Pharyngeal trauma in
dairy cattle: 27 cases. J Vet Intern Med 2019; 33(4): 1833–1839.
2 Pusterla N, Latson KM, Wilson WD and Whitcomb MB.
Metallic foreign bodies in the tongues of 16 horses. Vet Rec
2006; 159(15): 485–488.
3 Borges AS and Watanabe MJ. Guttural pouch diseases causing
neurologic dysfunction in the horse. Vet Clin North Am Equine
Pract 2011; 27(3): 545–572.
4 Kipar A and Frese K. Hypoglossal neuritis with associated lin-
Figure 18.1 With most alert, strong large animals, it is usually very dif- gual hemiplegia secondary to guttural pouch mycosis. Vet
ficult to hold the tongue out of the mouth with minimal restraint as Pathol 1993; 30(6): 574–576.
shown here. This recumbent but alert calf was suspected as suffering from 5 Gray LC, Magdesian KG, Madigan JE and Sturges BK. Suspected
botulism, the tongue being very weak and the mouth containing a lot of protozoal myeloencephalitis in a two-­month-­old colt. Vet Rec
saliva. The calf was from a rabies-free region! 2001; 149(9): 269–273.
 Tongue paralysis 149

6 Schweizer G, Ehrensperger F, Torgerson PR and Braun U. 8 Barbosa JD, de Oliveira CMC, Duarte MD, et al. Poisoning of
Clinical findings and treatment of 94 cattle presumptively diag- horses by bamboo, Bambusa vulgaris. J Equine Vet Sci 2006;
nosed with listeriosis. Vet Rec 2006; 158(17): 588–592. 26(9): 393–398.
7 Wippermann W, Schoniger S, Gerlach K, et al. Pituitary syn- 9 Brihoum M, Amory H, Desmecht D, et al. Descriptive study of
drome caused by neoplasia in a 17-­month-­old Holstein Friesian 32 cases of doxycycline-­overdosed calves. J Vet Intern Med
heifer. Tierarztl Prax Ausg G Grosstiere Nutztiere 2016; 44(3): 2010; 24(5): 1203–1210.
180–186.
 19
Head tilt, circling, nystagmus, and other
signs of vestibular dysfunction

From peripheral to central, the major sites of lesions head. The receptor end organ is in the inner ear,
resulting in afferent vestibular abnormalities are the consisting of the three semicircular canals and
membranous labyrinth of the inner ear, vestibular gan- the utricle and saccule. Movement of endolymph in
glion, vestibular branch of CN VIII, vestibular nuclei in the semicircular canals, induced by movement of the
the medulla oblongata and the floccular lobes, nodulus head and by the restraining effects of gravity, stimu-
and fastigial nuclei of the cerebellum (Figure 2.11). lates receptors that transmit impulses by way of the
The vestibular system is a special proprioceptive vestibular nerve and its ganglion in the internal
system that helps the animal maintain orientation acoustic meatus, to three of the four pairs of vestibu-
within its environment with respect to gravity—­and lar nuclei in the medulla oblongata. There is a
consequently to movement. The system helps to direct afferent connection to small parts of the cere-
maintain the position of the eyes, trunk, and limbs bellum, the flocculonodular lobe and fastigial
in relationship to movements and positioning of the nucleus. The caudal pair of vestibular nuclei receive

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Head tilt, circling, nystagmus, and other signs of vestibular dysfunction 151

only proprioceptive input from the neck via cranial r­elative ipsilateral extensor tonus and contralateral
cervical nerves. Importantly, the facial nerve, CN flexor tonus ­ promoting ipsilateral support of the
VII, travels through the edge of the middle ear to limbs, trunk, and neck against gravity. Conversely, a unilat-
then accompany the vestibulocochlear nerve eral vestibular lesion usually results in increased
through the internal acoustic meatus and pass to its ipsilateral flexor tonus and increased contralateral
central nucleus that is close to the vestibular nuclei extensor tonus, forcing the animal toward the side of
in the medulla oblongata. From the vestibular nuclei, the lesion (Figure 19.1).
the vestibulospinal tract descends ipsilaterally
through the length of the spinal cord. These neurons
are facilitators to ipsilateral final motor neurons Cranial cervical dorsal spinal nerve root lesions and
going to extensor muscles of the limbs and trunk, spinovestibular tract lesions can result in prominent
are inhibitory to ipsilateral flexor muscles, and after signs of vestibular disease,1,2 although nystagmus,
crossing are inhibitory to contralateral extensor though documented with such lesions in primates, has
muscles. Thus, the principal effect of unilateral stim- not yet been seen in our species with such lesions.
ulation of this system on the limbs and body is a

(A) (B) (C)

Figure 19.1 Immediately following a lightning storm, the foal shown here had prominent signs of right peripheral vestibular disease and facial paralysis.
The right head tilt (A) and a ventral deviation of the right eyeball were present outside but became much more evident when the foal was in a darkened
area (B and C). The foal was ultimately euthanized, and transverse sections of the right (AD) and left (AS) temporohyoid regions and ear cavities are
shown. The left middle and inner ear cavities are normal. There were no fractures discerned in the right petrosal bone, but there is hemorrhagic necrosis
within the right ear cavities. This was believed to be the result of lightening and/or trauma.
152 Large animal neurology

The nuclei of cranial nerves III, IV, and VI that vestibular disease. There is a major input to the ves-
control eye movement are also connected with the tibular system also from the visual system. This vis-
vestibular system by way of a tract, the medial lon- ual input complements input from the effects of
gitudinal fasciculus (MLF). Coordinated eye move- gravity in maintaining balance. Thus, blindfolding
ments are orchestrated via the MLF in response to and blindness often exacerbate the signs seen with
changes in positioning and movement of the head. vestibular disease (Figure 19.2), and it is believed that
Just as limb and body postural tone is being main- compensation from vestibular deficiency is largely
tained via the vestibulospinal tract, the MLF con- due to visual correction of head, neck, and eye
ducts impulses to maintain ipsilateral antigravity orientation.
tone to the eyeballs keeping them from lowering in There are additional vestibular efferent projections
the bony orbits. Thus, unilateral vestibular disease to the reticular formation, cerebellum, and central
often results in lowering of the eye in the bony orbit motor pathways. Through all these various afferent
on the same side as the lesion due to loss of antigrav- and efferent pathways, the vestibular system coordi-
ity tone. Additionally, the contralateral eye often rests nates movement of the eyeballs, trunk, and limbs
with an upward or dorsal deviation. with head movements. It maintains equilibrium of
As introduced in the neurologic examination the entire body during motion and rest.
(Chapter 2, Figure 2.11) and iterated above, special Signs of vestibular disease vary depending on
proprioceptive input from the cranial cervical verte- whether there is unilateral or bilateral involvement,
bral ligaments and muscles passes via at least the C1–3 and whether the disease involves peripheral or central
dorsal spinal nerve roots to ascend the spinal cord in components of the system. General signs of symmetric
a spinovestibular tract to the medial vestibular vestibular system dysfunction are irregular limb
nuclei.1,3,4 These nuclei receive no other afferent placement, truncal sway, leaning, falling, drifting
inputs. Lesions in the cranial cervical region involv- sideways when walking, and a wide base stance and
ing these vestibular afferent inputs also cause signs of gait with cautious raising of only one foot off the

(A) (B)

Figure 19.2 A head tilt due to neurologic disease almost always is due to vestibular disease but can be accompanied by a head turn. This patient is
suffering from lesions in the medulla oblongata involving the vestibular nuclear regions caused by S. neurona. There is a head (and neck) turn to the left,
which became prominent when blindfolded (A), as well as asymmetric ataxia and tetraparesis, worse on the left. However, when the head and neck were
held along the median plane, a right head tilt was present (B). This syndrome is consistent with central vestibular and medullary disease. In contrast, with
most patients suffering from forebrain diseases that have a head turn and tendency to walk toward the side of the lesion, there will not be a head tilt
consistently detected when the head and neck are straightened into the median plane.
 Head tilt, circling, nystagmus, and other signs of vestibular dysfunction 153

ground at any one time. This relatively predictable,

staggering gait with slow onset but fast movement
limb positioning and tendency to hypometria are the
signs of vestibular ataxia, to be differentiated from
general proprioceptive (spinal) and from cerebellar
ataxia. Various changes in eye position (strabismus)
and movement (nystagmus) occur. Large patients,
particularly horses with peracute vestibular disease,
can be violent because of profound disorientation,
which is described as vertigo in humans.
In the case of unilateral and asymmetric involve-
ment, an asymmetry in posture (Figure 9.2) and in
resulting staggering movements occurs, with a ten-
dency for a base-­wide posture to be adopted and the
patient often being reluctant to move. Interestingly,
piglets more than other patients with severe vestibu-
lar (and cerebellar) disease learn to use their snout as
a fifth support against falling—­which pigs also do
when very weak. The animal tends to drift, lean, and
roll toward the side of the lesion. In some cases, the
animal circles to the affected side. A head tilt is a
relatively constant sign with the acute phase of asym-
metric vestibular disease (Figure 19.3), along with
nystagmus. The nystagmus tends to regress, but
changes in head position may reactivate it. With
unilateral, peripheral vestibular disease, nystagmus is
horizontal or partly rotary (or more precisely mov-
ing across an arc) with the fast phase directed away
from the side of the lesion. With bilateral peripheral Figure 19.3 This horse suffered head trauma and showed classical
vestibular disease, vertical nystagmus has on rare ­vestibular signs, the most obvious being a vestibular head tilt to the right
occasions been recognized, and, as in people, it is indicated by the yellow line. The poll is rotated to the right (white curved
temporary.5 In central vestibular disturbances, the arrow) about the axis of the vertebral column (indicated by black disc) and
nystagmus may be horizontal, rotary, or vertical. the muzzle rotated to the left (yellow curved arrow) about the same axis.
Head elevation on the median plane also exaggerates
any tendency for eye deviations. These are often a reticular formation, cerebellar signs, and signs of the
ventral deviation of the eye on the same side as the involvement of other cranial nerves all indicate a
lesion and a dorsal deviation on the other side. To more extensive lesion. As indicated, acute, asymmet-
uncover for compensation of vestibular nystagmus ric vestibular disease quite consistently results in a
and strabismus, smaller, co-­operative patients can be head tilt, sometimes only evident when the animal is
positioned in perfect dorsal recumbency when resting, sedated, or blindfolded (Figure 19.2). This
appropriate. This challenging position seems to be a can be difficult to distinguish from the head turn
profound stimulation to the vestibular complex such seen with asymmetric forebrain lesions. The pres-
that any tendency for altered eye posture and move- ence or absence of a vestibular head tilt is only evalu-
ment can become apparent. Note that some abnormal ated for when the neck and poll are moved to the
eyeball positioning and movements may be induced median plane. Occasionally, large animals with cen-
with this maneuver in neonatal patients. tral vestibular disease have been noted to have a head
True limb voluntary weakness does not occur with tilt away from the side of a cerebellomedullary lesion,
peripheral vestibular disease, but can occur in the which is the same as the paradoxical vestibular syn-
case of central disease because of the involvement of drome described in small animals (Figure 19.2).6,7
adjacent central motor tracts, when additional signs The side that the lesion is on is defined by the side of
such as somnolence caused by involvement of the hemiparesis and of other cranial nerve involvement,
154 Large animal neurology

and has also been recorded in a goat with a caudal fossa a temporary, idiopathic, acute, usually unilateral ves-
brain abscess and in Kenyan sheep with Coenurus tibular syndrome occurs in horses. It mimics a
cerebralis cysticercosis.8 peripheral vestibular lesion without any associated
Bilateral vestibular lesions are characterized by signs such as facial paralysis and is likely to be a viral-
more symmetric signs, which strongly resemble ­or immune-­mediated labyrinthitis or neuritis. Horses
generalized cerebellar disease with wide swaying
­ appear to recover completely, irrespective of therapy.
movements of the head and sometimes the trunk. With Strongylus vulgaris becoming quite an unusual
Significantly, no physiologic vestibular nystagmus parasite in modern horse practice, selective, focal
can be induced with induced lateral head motion in vascular accidents are incredibly rare in large ani-
cases of dense, bilateral vestibular disease. mals, but in considering cases of acute onset of brain-
Objective detection of postural sway by studies of stem disease, including central vestibular signs, such
changes in the center of pressure measurements on a processes must be considered.11,12
force plate may well give a more accurate assessment Prominent symmetric, central vestibular signs
of vestibular function.9,10 However, such variations in often dominate the diffuse vestibulocerebellar signs
positioning may also reflect weakness as well as static of perennial ryegrass and Dallis grass intoxication. In
vestibular ataxia. addition to the typical, excitement-­provoked, vestibu-
The most common causes of vestibular disease in locerebellar ataxia, these signs include eye deviations
all large animals are head trauma and suppurative and rapid, variable eyeball tremor, seen best on direct
otitis media and otitis interna. Cases in which signifi- fundic examination. Central vestibular signs can also
cant facial paralysis is found are more serious and accompany many diffuse brain diseases such as
carry a more unfavorable prognosis. Special attention rabies, Eastern, Western, and West Nile equine viral
should be paid to the eye if a facial palsy is present encephalomyelitis and hepatoencephalopathy. Space-­
because keratitis and corneal ulceration rapidly occur occupying lesions such as neoplasms, abscesses, and
in many of these cases. Hemorrhage into the middle cholesterinic granulomata involving the choroid
and inner ear cavities results in vestibular and facial plexus of the fourth ventricle can also affect the ves-
nerve signs consisting of a head tilt toward the lesion, tibular system.
facial paralysis on the same side as the lesion, and a An exaggerated ventral eye deviation seen when
horizontal or rotary nystagmus with the fast phase the head is extended on the neck and a slight head
away from the side of the lesion. If the hemorrhage tilt when the patient is blindfolded are often the
has occurred around or in the medulla oblongata, last remaining signs to be seen following convales-
or if meningitis results from an open fracture of the cence from vestibular disease. Vision is a major
neurocranium, additional central signs such as adjunctive input modality to the vestibular system,
somnolence, ataxia, weakness, and other vestibular and it is required to fully accommodate for vestib-
and cranial nerve signs often appear. Hemorrhage or ular deficits. Thus, blind animals do not accom-
leakage of cerebrospinal fluid from the external ear or modate well.
nares is usually an indication that the basilar, petrosal, Ancillary aids to help refine a diagnosis for the
or ethmoidal bones have been fractured. Chronic exact site and cause of vestibular disease are plain
osteoarthrosis of the temporohyoid articulation may radiographs, CT and MR imaging, guttural pouch
be associated with acute hemorrhage into the middle endoscopy, and auditory testing.13–16 Because the
and inner ear cavities, resulting in an abrupt onset of afferent arm of the vestibular system, being the mem-
facial palsy and vestibular signs respectively. branous labyrinth in the inner ear, the vestibular
Large animals can be presented with asymmetric branch of CN VIII, and the vestibular nuclei in the
central vestibular signs caused by listeriosis, equine medulla oblongata all run in parallel with the first
protozoal myeloencephalitis (Figure 19.2), and by the components of the auditory system, then lesions
migrating metazoan parasites Parelophostrongylus affecting one system are very likely to affect the other.
tenuis, Strongylus vulgaris, Draschia megastoma, and Thus, by assumption, brainstem auditory-­ evoked
Hypoderma spp. larvae. In a horse, evidence of multi- potential (BAEP) recordings can be used as an indi-
focal disease would make equine protozoal myeloen- rect assessment of vestibular pathway function.17
cephalitis more likely than larval migrations. In Several horses suffering from head trauma and
ruminants, listeriosis is the most common cause of others with temporohyoid osteoarthropathy show-
vestibular syndromes due to medullary disease. Also, ing signs of vestibular disease have been followed
 Head tilt, circling, nystagmus, and other signs of vestibular dysfunction 155

with repeated BAEP testing.15 Although not predic- References

tive, it has been noted that horses with a flat BAEP 1 Biemond A and De Jong JM. On cervical nystagmus and
tracing at 100 dB testing level have tended to remain related disorders. Brain 1969; 92(2): 437–458.
with residual vestibular signs compared to horses 2 Frigast C. Equine C1–3 Dorsal Nerve Root Blocks. Pers. comm.
Denmark. 1999.
with acquired vestibular disease of comparable mag- 3 Bankoul S and Neuhuber WL. A cervical primary afferent
nitude but with some appreciable and repeatable input to vestibular nuclei as demonstrated by retrograde trans-
BAEP waveforms, even if that has only been a resid- port of wheat germ agglutinin-­horseradish peroxidase in the
rat. Exp Brain Res 1990; 79(2): 405–411.
ual delay of and suppression of wave V being the only 4 Cohen LA. Role of eye and neck proprioceptive mechanisms in
demonstrable wave form present. body orientation and motor coordination. J Neurophysiol
Treatment of vestibular disease can be discourag- 1961; 24: 1–11.
5 Peele TL. The Neuroanatomic Basis for Clinical Neurology.
ing at times, although with nonprogressive disorders 3rd ed. McGraw-­Hill Book Company, New York. 1977; 144.
some patients can accommodate amazingly well to 6 Thomson C and Hahn C. Veterinary Neuroanatomy: A
vestibular functional loss. Suppurative otitis media Clinical Approach. 1st ed. Saunders Elsevier. 2012; 208.
7 Palmer AC. Introduction to Animal Neurology. 2nd ed.
and otitis interna should be treated vigorously with Blackwell Scientific Publications, Oxford. 1976; 91–113.
appropriate antibiotics and initially with anti-­ 8 Oryan A, Akbari M, Moazeni M and Amrabadi OR. Cerebral
inflammatory drugs. Many neglected cases develop and non-­cerebral coenurosis in small ruminants. Tropical bio-
medicine 2014; 31(1): 1–16.
granulomatous inflammatory reactions in and around 9 Bialski D, Lanovaz JL, Bohart GV, Mullineaux DR and Clayton
the ear cavities, and these cases are irreversible—­ HM. Effect of detomidine on postural sway in horses. Equine
although accommodation to the vestibular (and Comp Exerc Physiol 2004; 1: 45–50.
10 Clayton HM, Bialski DE, Lanovaz JL and Mullineaux DR.
auditory) loss of function can still occur. Sclerosis of Assessment of the reliability of a technique to measure pos-
bone surrounding the ear cavities has been found on tural sway in horses. Am J Vet Res 2003; 64(11): 1354–1359.
radiographs of the skull of animals with vestibular 11 Pilo C, Altea A, Pirino S, et al. Strongylus vulgaris (Looss,
1900) in horses in Italy: is it still a problem? Vet Parasitol 2012;
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known. Cases attributable to trauma respond better 12 Anderson WI, de Lahunta A, Vesely KR and Tucker GW.
as a whole than those cases attributed to suppurative Infaction of the pons and medulla oblongata caused by arte-
riolar thrombosis in a horse. Cornell Vet 1990; 80(3):
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lesions of the hyoid and temporal bones, although 13 Blanke A, Fischer ML, Fuchs M and Schusser GF. Endoscopic
hyoid surgery van be curative for the latter tem- findings of the external ear canal in a group of clinically nor-
mal horses and horses with head shaking or vestibular disease.
porohyoid osteoarthropathy (Chapter 33). Some Berl Munch Tierarztl Wochenschr 2014; 127(3–4): 99–107.
cases do not fully regress but appear to ­compensate, 14 Inui T, Yamada K, Itoh M, et al. Computed tomography and
presumably using vision and general proprioceptive magnetic resonance imaging findings for the initial stage of
equine temporohyoid osteoarthropathy in a Thoroughbred
modalities, and are able to function almost normally. foal. J Equine Sci 2017; 28(3): 117–121.
Concurrent blindness, which may accompany head 15 Aleman M, Spriet M, Williams DC and Nieto JE. Neurologic
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It is generally recommended to allow patients con- 16 Crowell WA, Divers TJ, Byars TD, et al. Neomycin toxicosis in
valescing with residual vestibular signs to exercise calves. Am J Vet Res 1981; 42(1): 29–34.
17 Marshall AE, Byars TD, Whitlock RH and George LW.
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18 Deveze A, Bernard-­Demanze L, Xavier F, Lavieille JP and
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useful in human patients.18 44(1): 49–57.
 20
Deafness

Deafness is rarely recognized alone in large animal response of the body and limbs to loud noise at a sub-
practice. Lesion sites that can result in deafness are the conscious level, and this response may well be initi-
external ear, middle ear, spiral organ and ganglion, ated via the vestibular branch of the VIII cranial nerve
auditory nerve, cochlear nucleus, trapezoid body, as a vestibular-evoked myogenic potential.1,2
caudal colliculus of midbrain, medial geniculate Brainstem auditory-­evoked potential (BAEP) test-
nucleus of thalamus and auditory, temporal cortex. ing is ideal for the evaluation of the auditory path-
From entering the brainstem this is a bilaterally pro- ways in animals3 and has been studied in cattle,4–6
jected system. At the midbrain, the descending tecto- calves,7 llamas,8 alpacas,9 pigs,10 goats,11 sheep,12
spinal tract arises that probably mediates the startle horses,13–16 and foals.17 The BAEP waveforms from a

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Deafness 157

horse are shown in Chapter 3 (Figure 3.9). Evoked References

otoacoustic emission testing can be performed in 1 Bianchi E, Cantoni AM and Poncelet L. The acoustically
anesthetized patients and gives some evaluation of evoked short latency negative response (ASNR) in a unilater-
inner ear hair cell function; however, it can be ally deaf cat with histologically-confirmed cochleosaccular
degeneration. BMC Vet Res 2020; 16(1): 215.
­difficult to get true recordings from all ears.18 2 Rosengren SM, Welgampola MS and Colebatch JG. Vestibular
Several of the diffuse and focally severe brain dis- evoked myogenic potentials: Past, present and future. Clin
eases, including bacterial meningitis, polioencephalo- Neurophysiol 2010; 121(5): 636–651.
3 Mayhew IG. The clinical utility of brainstem auditory
malacia, equine neonatal encephalopathy, and arboviral evoked response testing in horses. Equine Vet Educ 2003; 15:
encephalitides, cause an animal to be poorly responsive 27–33.
to external stimuli including auditory cues that likely 4 Arai S. Brainstem auditory evoked potentials in cattle sedated
with xylazine. Can J Vet Res 2008; 72(3): 287–290.
represent degrees of deafness.19,20 As an example of a 5 Arai S and Matsui Y. Brainstem auditory evoked potentials in
diffuse forebrain disease, the course of neuronal ceroid Japanese Black and Holstein cattle. J Vet Med Sci 2008; 70(10):
lipofuscinosis in South Hampshire lambs21 includes 1139–1142.
6 Arai S, Matsui Y, Fukuda S, Okada H and Onoe S. Brainstem audi-
an unresponsive state seen early in the progression of tory evoked potentials in experimentally-­induced bovine spongi-
disease and includes deafness revealed by suppressed form encephalopathy. Res Vet Sci 2009; 87(1): 111–114.
and delayed BAEP waveforms as well as visual loss 7 Crowell WA, Divers TJ, Byars TD, et al. Neomycin toxicosis in
calves. Am J Vet Res 1981; 42(1): 29–34.
confirmed as obliteration of visual evoked potential 8 Gauly M, Vaughan J, Hogreve SK and Erhardt G. Brainstem
recordings. Calves with bilateral, severe, suppurative, auditory-­evoked potential assessment of auditory function
otitis media, and otitis interna have been found to be and congenital deafness in llamas (Lama glama) and alpacas
(L. pacos). J Vet Intern Med 2005; 19(5): 756–760.
clinically and electrophysiologically deaf. 9 Aleman M, Crowe C, Dechant J, Bellone RR and Avila F.
Congenital and acquired peripheral deafness Brainstem auditory evoked responses and bone conduction
results in an absence of waveforms and a flat BAEP assessment in alpacas. Res Vet Sci 2021; 136: 297–302.
10 Strain GM, Tedford BL and Gill MS. Brainstem auditory
trace following the stimulus artifact (Figure 3.9). evoked potentials and flash visual evoked potentials in
Although congenital sensorineural deafness is well Vietnamese miniature pot-­bellied pigs. Res Vet Sci 2006; 80(1):
shown to be quite common in particular breeds of 91–95.
11 Steffen F, Jaggy A, Gaillard C, et al. Reference values of electro-
dog,22,23 it has more recently been shown in diagnostic and laboratory studies in young Wallis Schwarzhals
horses,24,25 cattle,26 pigs,27 and in llamas8 and alpacas.28 goats. Tierarztl Prax 1996; 24(1): 22–28.
Congenital, inherited, sensorineural deafness should 12 Konold T, Phelan LJ, Cawthraw S, et al. Abnormalities in
brainstem auditory evoked potentials in sheep with transmis-
be considered in patients suspected of being deaf at a sible spongiform encephalopathies and lack of a clear patho-
young age, particularly in those breeds and families logical relationship. Front Vet Sci 2016; 3: 60.
that have extensive white markings of the head and 13 Mayhew IG and Washbourne JR. Brainstem auditory evoked
potentials in horses and ponies. Vet J 1997; 153(1): 107–113.
limbs and a propensity for white or blue irises,22 i.e., 14 Marshall AE, Byars TD, Whitlock RH and George LW.
markedly modified black coloring. Brainstem auditory evoked response in the diagnosis of inner
The commonest causes of acquired peripheral ear injury in the horse. J Am Vet Med Assoc 1981; 178(3):
282–286.
deafness in young and mature horses probably are 15 Marshall AE. Brain stem auditory-­evoked response in the non-
head trauma and temporohyoid osteoarthropathy.14 anesthetized horse and pony. Am J Vet Res 1985; 46(7):
Aminoglycoside antibiotics are known to be ototoxic 1445–1450.
16 Rolf SL, Reed SM, Melnick W and Andrews FM. Auditory
to both the vestibular and auditory systems, and gen- brain stem response testing in anesthetized horses. Am J Vet
tamicin ototoxicity may have occurred in a horse.29 Res 1987; 48(6): 910–914.
However, experimental ponies receiving 15 mg/kg 17 Steiss JE, Brendemuehl JP, Wright JC and Sorrs DP. Nerve con-
duction velocities and brain stem auditory evoked responses in
per day, for 7 or 14 days and monitored with BAEP normal neonatal foals, compared to foals exposed to
testing, failed to show any definitive evidence of endophyte-­infected fesue in utero. Prog Vet Neurol 1991; 2:
auditory ototoxicity.30 Abnormal BAEP waveforms 252–260.
18 McBrearty A, Auckburally A, Pollock PJ and Penderis J.
have been found in calves with neomycin toxicity7 Evoked otoacoustic emissions: an alternative test of auditory
and may well occur in horses following routine function in horses. Equine Vet J 2013; 45(1): 60–65.
­dosing of gentamycin.31 19 Aleman M, Holliday TA, Nieto JE and Williams DC.
Brainstem auditory evoked responses in an equine patient
population. part I: adult horses. J Vet Intern Med 2014; 28(4):
Aging deafness or presbycusis, as occurs commonly in 1310–1317.
20 Aleman M, Madigan JE, Williams DC and Holliday TA.
humans, occurs in older horses32,33 and likely occurs in Brainstem auditory evoked responses in an equine patient
most mammals that live long enough! population. Part II: foals. J Vet Intern Med 2014; 28(4):
1318–1324.
158 Large animal neurology

21 Mayhew IG, Jolly RD, Pickett BT and Slack PM. Ceroid-­ 27 Du Y, Ren L-­l, Jiang Q-­q, et al. Degeneration of saccular hair
lipofuscinosis (Batten’s disease): pathogenesis of blindness in cells caused by MITF gene mutation. Neural Dev 2019; 14.
the ovine model. Neuropathol Appl Neurobiol 1985; 11(4): 28 Webb AA, Cullen CL and Lamont LA. Brainstem auditory
273–290. evoked responses and ophthalmic findings in llamas and
22 Strain GM. The Genetics of deafness in domestic animals. alpacas in Eastern Canada. Can Vet J 2006; 47(1): 74–77.
Front Vet Sci 2015; 2: 29. 29 Pickles KJP, Pirie S and Prince DP. Choke, pleuropneumonia
23 Strain GM. Aetiology, prevalence and diagnosis of deafness in and suspected gentamycin vestibulotoxicity in a horse. Equine
dogs and cats. Br Vet J 1996; 152(1): 17–36. vet Educ 2003; 15: 27–30.
24 Magdesian KG, Williams DC, Aleman M, Lecouteur RA and 30 Nostrandt AC, Pedersoli WM, Marshall AE, Ravis WR and
Madigan JE. Evaluation of deafness in American paint horses Robertson BT. Ototoxic potential of gentamicin in ponies. Am
by phenotype, brainstem auditory-­ evoked responses, and J Vet Res 1991; 52(3): 494–498.
endothelin receptor B genotype. J Am Vet Med Assoc 2009; 31 Aleman MR, True A, Scalco R et al. Gentamicin-­induced
235(10): 1204–1211. sensorineural auditory loss in healthy adult horses. J Vet Int
25 Magdesian KG, Madigan JE, Williams DC, Kortz GD and Med 2021; 35: 2486–2494.
LeCouteur RA. Deafness of suspected congenital origin in 32 Wilson WJ, Mills PC and Dzulkarnain AA. Use of BAER to
American paint horses. 16th Am Coll Vet Int Med Forum. identify loss of auditory function in older horses. Aust Vet J
J Vet Int Med 1998. 2011; 89(3): 73–76.
26 Philipp U, Lupp B, Moemke S, et al. A MITF mutation associ- 33 Wrzosek M, Niezwiedz A, Giza E, et al. Auditory brainstem
ated with a dominant white phenotype and bilateral deafness evoked response (BAER) in the diagnosis of nervous system dis-
in German Fleckvieh cattle. Plos One 2011; 6(12). eases in horses. Medycyna Weterynaryjna 2012; 68(9): 557–561.
 21
Disorders of posture and movement

DiseasePage Sinking with dorsal lumbar pressure 166

Back problems 166
Pure postural deformities 161
Toe dragging 167
Opisthotonus and tetanus 161 Stringhalt 167
Pasture-associated stringhalt 167
Tetany and tremor 163
Fibrotic myopathy 168
Spastic paresis of calves and goat kids 164 Upward fixation of the patella 168
Spastic syndrome of ruminants 164 Rupture of the peroneus tertius tendon 168
Shivering 165 Other subtle gait abnormalities 168
Stiff horse syndrome similar 166 Osteochondrosis 168

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
160 Large animal neurology

A large group of clinical syndromes result in altered and the clinical signs does not exist. In fact, several
muscle tone and movement that are described as of them have no consistent lesion and many have
degrees of opisthotonus, tetanus, myoclonus, tet- diffuse lesions.
any, tremor, muscle spasms, and movement disor- The paroxysmal dyskinesia syndromes warrant
ders.1 These syndromes are characterized by specific mention because of the interesting interac-
alterations in muscle contraction and changes in tions between genetic alterations, immunology, age,
head, body, and limb posture and movement and nutrition.2,5 These disorders are characterized by
(Figure 21.1) that are characterized neither by episodic, hyperkinetic, disturbed movement lasting
changes in mental alertness, by seizure activity nor seconds to hours with no loss of consciousness.
by ataxia and weakness. The postures adopted tend Neurological examination is typically normal between
to be reasonably predictable, and the movements episodes. Dietary hypersensitivities (e.g., to gluten)
made tend to be regular and repetitive. As a group can be associated with some of these specific disor-
they can probably best be classed as postural and ders. The dopamine D2 antagonist drug toxicities seen
movement-related disorders.2,3,4 Some characteris- in foals and adult horses with metoclopramide and
tics of the various syndromes may be referrable to fluphenazine, for instance, fit the classification of dys-
disturbances in cerebral function, cerebellar func- kinesia, and due to the slowness of movement and the
tion, and diffuse spinal cord function, or to distur- drug induction may be termed tardive dyskinesia.6
bances in neuromuscular or muscle function. For The motor system maintains skeletal muscle tone by
several of these quite distinctive disorders, how- a balance between muscle contraction and muscle
ever, no morbid or biochemical lesions are known. relaxation via the neuromuscular spindle and myotatic
Partly because of this, there is not a clear subclas- reflex arc. A variety of feedback mechanisms influence
sification of the clinical syndromes, and one dis- the motor system at spinal and supraspinal levels, one
ease can result in different syndromes. Thus, a of which is the input to and from the neuromuscular
single, progressive case of Clostridium tetani intoxi- spindle. Figure 21.2 shows this general setup with effer-
cation may begin with mild muscle contractions ent tracts influencing both alpha and gamma motor
and muscle tremor, proceed to tetany, then to teta- neurons: α–γ coactivation. The γ-­motor neurons set
nus, and finally to stable opisthotonus and limb tone in muscle spindle intrafusal fibers allowing the
rigidity with recumbency. In many of these disor- muscle spindle annulospiral organ to reflexively, via
ders of posture and movement, a strong correlation 1a-­afferent fibers and α-­motor neurons, maintain tone
between the site of the known or suspected lesions in extrafusal skeletal muscle fibers. Such mechanisms

Figure 21.1 A hypermetric gait and diffuse tremor with hypertonia of face (Inset), neck, and tail muscles were associated with multiple metabolic
derangements including hypocalcemia in this horse that occurred postoperatively. Signs resolved as the metabolic derangements stabilized.
 Disorders of posture and movement 161

Annulospiral
1a-afferent axon

DESCENDING
TRACTS
Proprioceptive
1b-afferent axon

NEUROMUSCULAR
SPINDLE

Intrafusal
muscle fiber

Gamma motor axon

Alpha motor axon

Extrafusal
muscle fiber

Figure 21.2 This is a simplified drawing of the gamma motor system that is very important in helping to control skeletal muscle tone. Descending
gamma motor neuronal pathways in the spinal cord are heavily influenced by the cerebellum but do not themselves effect voluntary movement. These
gamma motor pathways, running in conjunction with the central, voluntary, alpha motor neuronal pathways, influence gamma motor neurons that
control the intrafusal muscle fibers in muscle spindles. The latter small muscle fibers act to set the tension within the spindle. Altered tension can change
the sensitivity of the associated annulospiral afferent endings to stretch stimuli induced from changes in tone in the skeletal muscle in which the spindle
is located, the so-­called extrafusal muscle fibers. This is achieved via the afferent endings in the spindle passing via dorsal spinal nerve roots in annulo-
spiral (and other) fibers to directly influence alpha motor neurons. This influence augments the impulses from Golgi tendon organ, 1b-­afferent fibers, and
voluntary, central motor tracts on those alpha motor neurons and their innervated muscle fibers. In this way, there are controls set on muscle tone at two
levels: at the level of the cerebellum influencing central gamma motor pathways and at the muscle spindle influencing final alpha motor neurons.

thereby alter the amount of muscle tone at rest and dur- are referred to Palmer,7 Peele,8 Afifi and Bergman,9
ing movement, thus influencing the timing and rate of Rossignol et al.,10 Thomson and Hahn,11 Lowrie
onset and force of muscle contractions. et al.3,4,5 and de Lahunta et al.1,12,13
It is proposed that many of the syndromes dis-
cussed here resulting in abnormal muscular function Pure postural deformities
occur because of defects in these sensory and motor
system interactions depending on the degree of Orthopedic variations and anomalies account for the
altered muscle tone and force of contraction of the majority of purely limb positional changes, but many
varied agonist and antagonist muscles affected in congenital and acquired postural deformities defy
each clinical syndrome. For a more detailed discus- thorough explanation (Figure 21.3). Some are due to
sion of the thinking behind these syndromes, readers abnormal collagen development and maturation but
others, variously defined as knuckling syndromes,
are undoubtedly neuropathies.14,15 Arthrogryposis
Concerning these myotatic reflex control mechanisms and associated problems are discussed in Chapter 31.
and numerous other sensorimotor interactions and
their perturbation, “The more we dig into the details of Opisthotonus and tetanus
these sensorimotor interactions, the more it seems
Opisthotonus literally means backward tone and
improbable that they should work so smoothly, but
refers to tonic contraction of epaxial and limb mus-
they do.”10
cles resulting in hyperextension of the neck and head,
162 Large animal neurology

thoracolumbar lordosis, and rigid extension of the

limbs. Tetanus is the state of continuous, tonic con-
traction of muscles without tremor. Because normal
resting, antigravity, extensor muscle tone is necessar-
ily greater than flexor tone, extensor hypertonus pre-
dominates in diffuse tetanus. The most common
cause of this syndrome is intoxication from
Clostridium tetani neurotoxins (Figure 21.4). Head
trauma, with rostral cerebellar damage alone, may
rarely produce opisthotonus in a conscious large ani-
mal. Massive cerebral and midbrain damage may
result in opisthotonus, but the animal is severely
obtunded or in a coma. Many toxins may terminally
cause similar posturing, but they rarely do so without
other more widespread signs. Bacterial meningitis
and other severe diffuse inflammatory diseases can
Figure 21.3 Congenital and acquired postural deformities often defy ortho- be mistaken for C. tetani intoxication, especially in
pedic and neuromuscular explanation. Some, such as the apparent flexural young animals. Severe congenital cerebellar disease,
deformity shown here in a young foal, possibly represent a collagen disorder, at least in calves and foals, may result in opisthotonus
but as likely is a neuromuscular defect that yet has to be characterized. with recumbency.

(A) (B)

(C) (D)

Figure 21.4 Fulminant, unremitting tetany exemplified by Cl. tetani intoxication (A) is quite readily recognized and warrants consideration for immedi-
ate euthanasia unless rapidly responsive to Ca++ treatment. Signs of early onset and mild cases of tetanus (B–D) are not easy to diagnose and without
definitive confirmation being forthcoming, must be considered a diagnosis by exclusion. The signs of diffuse Cl. Tetani induced tetanus can include overt
startle response—­especially to auditory cues and to tactile stimuli to the muzzle (B), along with hypertonus of extensor and flexor limb and tail muscles
on voluntary or reflex movement (C), and with facial muscle hypertonus (D). Metabolic causes of tetany such as hypocalcemia, meningitis/encephalitis,
cerebellar disorders, and particular toxicities such as metaldehyde poisoning all must be considered in the diagnosis of moderate tetany. Although indi-
vidual cases of Cl. tetani tetanus are the norm, outbreaks do occur especially in ruminants (C). Such syndromes have been seen as multiple cases of acute
death, bloat, recumbency, and misadventure heralding an outbreak. These have sometimes been preceded by a change in management such as feeding
frozen turnips (C) or access to pasture sprayed with poultry manure or to a newly ploughed field.
 Disorders of posture and movement 163

Tetany and tremor but is not incapacitating. Signs are most often seen at
4–6 months of age and regress over several weeks.20
The state of tetany is characterized by repeated, We all experience acquired, usually temporary,
sometimes violent, intermittent muscle spasms over localized, facial muscle tremor at some time or other.
the whole body, which frequently develop into a sei- Likewise, numerous cases of localized repetitive con-
zure. Again, extensor tone often predominates. traction of one or several muscles at 0.5–5 Hz involv-
Tremor can be regarded as a milder form of tetany ing facial, particularly periorbital muscles, have been
characterized by involuntary muscle contractions, seen in cattle and horses (Figure 21.5). These are also
which are frequently so mild that they are regarded as seen involving other muscles, and notoriously a cause
trembling or shivering, and are often localized. Thus, is not found.21 Sometimes misinterpreted as increased
there is a gradation in severity of such involuntary sensitivity, repetitive contraction of individual mus-
muscle movements involving individual muscle fib- cles or groups of muscles more likely are aberrations
ers, whole muscles, muscle groups, body regions, or of final motor neuron function and can all be referred
the whole body, and referred to as fasciculation, shiv- to as forms of myoclonus. When these are widespread
ering, tremor, tetany, or seizure. When a tremor and involve limbs, trunk, neck, head, and even eyes,
appears to spread in a wave-­like or writhing manner they are referred to as tremor disorders. Complex
over the body part, the term myokymia is used. Some movements of parts of the body are collectively called
of these contractile syndromes are believed to be due movement disorders. There is overlap between sei-
to extraneous, ephaptic (cross-­ talk) transmission zure disorders and all of these, although most times
occurring between axons denuded of myelin.16 The with more severe or generalized seizures the patient
congenital syndromes typified by that occurring in has reduced or loss of consciousness.
newborn polled Hereford calves associated with dys-
functional glycine receptors17 are indeed tetany and
not myoclonus; the latter refers to sudden contrac-
ture of a group of muscles followed by immediate
relaxation. Newborn Arabian foals of Egyptian line-
age that suffer from a hair color dilution defect also
have congenital tetany and have demonstrable opis-
thotonus upon stimulation.18
Whole body muscle tremoring with no other neu-
rologic signs is not common in large animals. Those
patients that are weak or suffering markedly painful
conditions, especially as a result of conditions such as
shaker foals with botulism, rhabdomyolysis, severe
cervical spinal cord lesions, and even fractured pelvis
or long bones, often tremble, particularly prior to
becoming recumbent. One neonatal foal suspected of
suffering from a perinatal hypoxic and ischemic
myelopathy in the cervicothoracic spinal cord had
limb and body tremor and severe spasms to tetany of
one thoracic limb. It recovered with conservative
therapy and nursing care but had residual weakness
and slight ataxia in the limb and muscle atrophy of
the suprascapular and forearm musculature, indicat-
ing final motor neuron involvement. One
18-­month-­old Quarter Horse is described with a tic
or severe tremor, as well as paresis, localized to the
right front limb.19 Landrace Trembles is a disease of Figure 21.5 The patient shown here had sporadic, right, hemifacial
myoclonia of unknown cause that became continuous and repetitive
Landrace pigs that have tremor of the tail and ears,
when the mare became hypocalcemic in association with an intestinal
which is exacerbated by backing the animal. problem. With calcium therapy, the myoclonia subsided and reverted to
Occasionally, the tremor involves more of the body being intermittent.
164 Large animal neurology

Benign, acquired whole body tremor and tetany generally does not result from cerebellar lesions
occurs in adult horses, but it is not understood what alone and indicates a more diffuse disease.
mechanisms operate; mild cases of tetanus, meningi- Congenital and genetic causes of tremor syn-
tis, and plant and fungal toxins cannot always be dromes are discussed in Chapter 31, and some exam-
excluded from the diagnosis. Usually, affected ani- ples of acquired, toxic tremor syndromes are
mals survive. Almost always, examples of these rare summarized in Table 34.2 and Chapter 34.
syndromes that have involved the face, neck, or a limb Finally, frightened animals frequently demonstrate
do not appear to bother the patient, but more so the tremor of the head and neck that has a relatively high
owner. With no other evidence of brainstem or spinal frequency of 5–10+ Hz, but it dissipates with relaxa-
cord disease, it is more than likely that the initiating tion. This is often seen as trembling ears in those
lesion is peripheral. However, old, small scars, caused animals with soft and upright ears such as alpaca.
for example by the Sarcocystis neurona, might be And, the true orthostatic, high-­frequency tremors of
capable of setting up a central pacemaker focus to ini- ~15 Hz occurring quite often in aging humans and
tiate repetitive discharges in selected muscles, facilely, dogs are seen in body parts that are supporting weight,
a spinal seizure focus. Very rarely, adolescent foals and the tremor disappears completely when weight
have been affected with chorea-­like, repetitive invol- support is removed while resting the body part – viz.
untary muscular contractions of the trunk or of a orthostatic tremor.26
limb or the whole body. The severity of contractions
has varied with rest verses exercise. Where postmor- Other localized muscle spasms,
tem studies have been carried out, sometimes unusual movement disorders, and gait
focal or diffuse spinal cord axonal lesions that may
well have been congenital have been found.22
abnormalities
Quarter Horses affected by hyperkalemic periodic Spasticity usually refers to stiffness when a limb is
paralysis can show focal and diffuse muscle tremor positioned or moved. In veterinary neurology the
during a mild attack that can abate fully and rapidly. term specifically indicates a state of muscular hyper-
A severe paroxysm results in prominent trembling tonia and hyperreflexia resulting from loss of inhibi-
and tetany of many muscles leading to recumbency tion of final motor neurons when it will also be
and sweating. accompanied by degrees of voluntary weakness. This
In the early stages of diffuse, particularly bacterial being so, the term should only be used when hyper-
and viral meningoencephalomyelitides, prominent reflexia has been demonstrated. If there is spinal cord
trembling or shivering may occur. Tetany and tremor or caudal brainstem disease, usually ataxia also
can be caused by diffuse brain, cerebellar, and spinal occurs. The syndromes discussed herein do not,
cord diseases. Those involving CNS myelin fre- for the most part, relate to a focal CNS lesion and
quently result in asynchrony and spread of electrical thus do not include weakness and ataxia. Such syn-
transmission and consequently in tremor syndromes. dromes include spastic paresis of calves and goat
Such congenital tremor syndromes can also be seen kids and spastic syndrome of ruminants
with diffuse neurotransmitter defects as has been (Figure 21.6).27 In man, lesions in areas of the extrap-
seen in foals and calves.23,24 Because the tremor often yramidal central motor neuronal pathways, particu-
causes repeated movement of limbs and other body larly in the basal nuclei, can cause intermittent
parts, these can be referred to as action-­related myo- writhing or flailing movements, referred to as atheto-
clonus.1 Also, alterations in normal axonal and syn- sis or ballismus, respectively. Whether or not these
aptic transmission can cause tremor. For these occur in large animals is not clear, but specific central
reasons, many neurotoxins can cause this syndrome; motor neuron functional lesions may be suspected in
perhaps the tremorgenic mycotoxicoses like peren- several of these syndromes. More likely, these syn-
nial ryegrass staggers are the best example here. dromes involve other components of the motor path-
Animals with various cerebellar diseases may pre- ways and myotatic reflexes controlling muscle tone,
sent with prominent head tremor often referred to as as outlined above.
an intention tremor, and in these diseases a truncal On occasion, a large animal may show intermit-
sway may also be thought of as a whole body, axial tent, usually irregular, muscle spasms of part of the
tremor.25 However, tremor involving not just the neck or trunk or a limb. Some of these signs disap-
head and neck but also the trunk occurring at rest pear, and others remain constant. Partial damage to
 Disorders of posture and movement 165

(A) (B)

(C) (D)

Figure 21.6 A cluster of fascinating but baffling, idiopathic syndromes that tend to occur persistently and in several species are represented here. These
include so-­called spastic paresis in calves (A), spastic syndrome (Syn: Barn cramps; crampiness; stretches) in cattle (B) and sheep (C), and stiff horse
syndrome (D). These all involve degrees of hypertonicity of muscle groups without evidence of final motor neuron disease, but with no consistent patho-
physiological explanation. Some evidence for altered neurotransmitter biochemistry has come forward for some of these syndromes (A and D).

peripheral nerves or muscles or mild localized mye- The following examples of these syndromes occur
lopathies are usually considered as causes, but mostly most prominently during movement, either volun-
not proven. tary or induced. The clinical spectrum of shivering
Myoclonus describes a tremor with shock-­like, usu- (Figure 21.7) is very variable but probably can be
ally brief, intermittent contractions of muscle groups interpreted collectively as involving reflex hypertonia
that may even involve most of the body and occur with of extensor and particularly flexor muscles of the
variable rhythmicity, synchrony, and symmetry. ­pelvic limbs.28 Shivering, with mild muscle tremor
166 Large animal neurology

involving the whole body such that the horse becomes

immobilized. These ‘attacks’ appear to be brought on
by fright. Cases do bear resemblance to so-­called
spastic syndrome of adult cattle (Figure 21.6)32 and to
complex, abnormal gaits seen with a few cases of
equine protozoal myeloencephalitis.
Lesions—­morbid or functional—­in the sensory or
motor pathways, anywhere from the brainstem and
cerebellum to the affected muscles and associated
joint and tendon sensory receptors, potentially could
initiate such abnormal muscle tone and movement. It
is likely that cerebellar nuclear lesions play a role in at
least some cases of equine shivers.33, 34 Some cases do
have histologic evidence consistent with polysaccha-
(A) (B) ride storage myopathy,35 but there is likely not a direct
relationship between these two conditions,36 and
there is only minimal evidence that equine shivers
is associated with metabolic problems such as
hypothyroidism.37
Cases of a stiff horse syndrome similar to stiff
person syndrome in people have been recorded
(Figure 21.6).38 Clinical signs appear to wax and wane
and range from mild muscle stiffness to sudden and
often violent muscle contractions. Generally, there is
an insidious onset. Between episodes the horse may
appear normal, although, if present, the generalized
muscle stiffness may persist (see Chapter 38).
Perennial ryegrass staggers and related mycotoxic
channelopathies must be strongly considered when
such syndromes are encountered.
Sinking with application of dorsal lumbar pres-
(C) (D)
sure in an otherwise healthy horse, which can render
Figure 21.7 Horses can temporarily behave with unusual hyperflexion
the horse unsuitable for riding, is probably never due
of a pelvic limb when a dressing or device is applied to a pelvic limb (A) to kidney disease alone as has been alluded to in the
and occasionally when an injection is made into a pelvic limb muscle. past. Unusual forms of myelitis, thoracolumbar dis-
Even minor limb irritation such as that caused by Chorioptes bovis in this cospondylosis, and longissimus myopathy in race-
horse (B) can cause horses to raise the pelvic limbs in a repetitive, exces- horses have been associated with this syndrome.
sive manner mimicking the syndrome of shivering (C). Horses affected
with shivers (C) are often of heavy breeds. The various induced and spon-
When such a syndrome is seen to abate, particularly
taneous unusual flexion movements and trembling of the pelvic limbs in a young animal, it is possible that it is physiological
and tail—­and even sometimes trembling of the thoracic limbs, neck, rather than pathological in origin. This is because
head, and face—­are best seen on initiation of movements after rest and back extension and hindlimb flexion are reflexly ini-
especially while backing and when a hind foot is lifted. Many variations tiated by dorsal lumbar stimulation such as firm
of the syndrome referred to as shivering occur such as unusual movement
and trembling of the limb when walking (D). Cerebellar nuclear axonal
stroking with a blunt probe and because there can be
lesions may be the basis of some of these cases.30 a very wide range in responsiveness of normal ani-
mals when testing any reflex. With respect to unto-
ward spontaneous and reflexly induced posturing of
involving the hind quarters and tail and occurring the thoracolumbar region, new and better imaging
with induced or voluntary movement, especially (ultrasound, radiographic, thermographic, and even
backing, particularly affects draft and warmblood CT and MR) studies of the thoracolumbar region will
breeds.28–31 A severe form of shivering occurs far less more precisely define existing back problems but in a
commonly wherein there is intermittent hypertonia proportion of cases, especially in younger animals,
 Disorders of posture and movement 167

the signs will abate. One report implicates polysac- alized debility, occult orthopedic problems, and sim-
charide storage myopathy as a cause of back pain in ple laziness.
showjumpers and dressage horses.39 In lay parlance, it is sometimes thought that a
Some heavy patients suffering marked generalized horse with an intermittent gait abnormality has
weakness will not lie down but keep changing posi- ‘trapped a nerve’ to account for the elusive cause of
tion of their limbs. If they do go down, they can be the signs. This may well be possible, but going by the
very reluctant to rise. Also, some horses with promi- evidence available it is medically more logical to pur-
nent orthopedic problems such as chronic spavin or sue orthopedic problems first—­after the back man
vertebral, pelvic, or limb fractures may not lie down. and chiropractor have given the patient temporary
Others may prefer to lie down and get up only reluc- relief—­before condemning the patient to having a
tantly, sometimes in an awkward manner such as with morbid neurological lesion.
the rear limbs first (horse) or with a tell-­tale grunt. Horses with signs of spinal cord disease can have
Weak horses will not improve with analgesic drugs, prominent hypermetria in one or both hindlimbs with
whereas those with orthopedic problems may well do. hyperflexion, thus mimicking stringhalt (Figure 21.8).
Some horses drag their toes while walking, and In the absence of other signs of spinal cord disease,
trotting yet appear to have no other orthopedic or such hyperflexion to the point of almost striking the
neuromuscular signs. Without ataxia, the only con- trunk or elbow with the toe is more likely to be caused
sistent neural reason for toe dragging is flexor weak- by peripheral nerve or muscle lesions. Where horses
ness. If flexor weakness is suspected, then this should graze poor, weedy, dry pastures, particularly with
be exaggerated with forced exercise, complex maneu- Hypochaeris radicata present, then pasture-­associated
vers, and particularly with hopping on the thoracic stringhalt with bilateral involvement is more com-
limbs. In the absence of other neurological signs, monly seen.40 The mechanical explanation for the syn-
most causes of this syndrome are being unfit, gener- drome rests with the presence of the reciprocal apparatus

(A) (B)

Figure 21.8 Stringhalt typically is a very distinctive, dynamic clinical syndrome seen as excessive flexion of one or both pelvic limbs during protraction,
being most obvious in horses because of the obligatory reciprocal apparatus causing all joints to move in relative synchrony, much more so than in other
species (A). Both these horses with stringhalt (A and B) are shown at the mid phase of advancing the left limb during a stride. In (A), there is relative digi-
tal extension that explicably results from excessive contraction of at least the lateral digital extensor (LDE) muscle. Because the LDE tendon runs distally
over the laterodorsal hock, with its contraction there is flexion of the hock and thus of proximal limb joints. This is regarded as typical stringhalt. Horse
(B) shows proximal limb flexion but a relative flexion also of the fetlock joint. The question raised is whether such a difference in biomechanism warrants
consideration that the latter represents a different process to include excessive contraction of digital flexor muscles as well as digital extensor muscles.
Both horses with signs solely in the left hind limb were treated as having unconfirmed S. neurona protozoal myelitis and both improved with time.
168 Large animal neurology

in the hindlimb of horses, the course of the digital spastic paresis of calves, from which it is differenti-
extensor tendons across the dorsolateral aspect of the ated by there being no constant tension in the gas-
center of motion of the hock joint, and the induction trocnemius tendon. Severe cases have disuse atrophy
of peripherally-­(or centrally-­) mediated hypertonia of the quarter. Medial patellar ligament splitting or
and hyperreflexia involving particularly the lateral desmoplasty,43 which is supplanting the previous
digital extensor muscle. In monomelic cases of string- practice of medial patellar desmotomy44 and/or
halt, full scanning of the mid-­hindlimbs is indicated, improving general muscle conditioning and strength,
and asymmetric ultrasonographic changes have been usually resolves the problem without long-­ term
detected in the digital extensor muscles in a few cases. complications.
Variations of stringhalt-­like gait with, for example, Rupture of the peroneus tertius tendon results in
flexion of the digits accompanying proximal limb flex- loss of any reciprocal apparatus controlling move-
ion (Figure 21.8B), limb abduction, and caudal thrust ment of the hock and stifle that is seen as overexten-
of the limb at the onset of protraction may well indi- sion of the hock when the stifle is flexed. This
cate involvement of other muscles in the disease pro- asynergy is seen most dramatically different from
cess. Although lateral digital extensor myotenectomy normal in the horse in which the intact peroneus ter-
has been successful in treating bilateral stringhalt for tius is a fibrous band producing full reciprocity of
centuries,41,42 in these cases with variations in stride hock and stifle movement. In at least the horse, llama,
pattern it may be predicted that such selective surgery camel and cattle such injuries can result in the distal
could be less effective in resolving the syndrome if limb being passively flicking forward during the
other muscles are also prominently involved. Multiple swing phase of limb protraction, again almost mim-
limb involvement, seen in the forelimbs as extensor icking stringhalt.
hypertonus causing stiff limbs, usually indicates Many horses with subtle gait abnormalities, in the
generalized neural involvement such as due to a pelvic limbs in particular, are considered to show
neurotoxin and can be present in severe cases of some evidence of ataxia, weakness or dysmetria, with
pasture-­associated stringhalt. no proof of a specific neurologic disorder. Many of
Fibrotic myopathy describes a gait in which the these patients are casually referred to as having back,
hind foot is slapped to the ground at the end of the hip, or stifle problems. Occasionally, evidence of pol-
swing phase causing a shortening of the stride length. yneuropathy or myelitis becomes evident on thor-
Most cases are associated with lesions such as muscle ough evaluation, but in the majority a complete
tears and injection reactions in the region of the cau- neurologic workup is inconclusive.
dal thigh (hamstring) muscles. The signs are either An animal with osteochondrosis involving the prox-
due to scarring, adhesions, and mechanical shorten- imal limb joints and particularly the intervertebral
ing of the semitendinosus muscle; the same as a ham- joints can present with degrees of reluctance to move
string injury in sportspeople, or due to induced reflex and a stiff, apparently weak gait, which mimics spinal
hypertonia in caudal thigh muscles. Some relief can cord or peripheral nerve disease. Osteochondrosis
be obtained with radical resection of the lesion and/ most often occurs in young feeder pigs and in horses.
or various forms of tenotomy/tenectomy. Diagnostic A thorough physical examination and a lameness
ultrasound probably best defines the nature and examination should reveal the cause of such pseu-
extent of the inciting lesion. doneurologic gait abnormalities.
Upward fixation of the patella is a musculoskele- Back problems (also see Chapter 30) in horses - as in
tal disorder, but it warrants consideration as a differ- people - are a clinical enigma.45–48 With the exclusion
ential diagnosis for several of the above syndromes. of fractures and overt exercise-­associated rhabdomy-
This syndrome may be congenital and occurs in olysis, definitive etiologic and morphologic diagnoses
horses and cattle as an apparently acquired disorder. are the exception rather than the rule, hence data on
The patella and its medial patellar ligament become any effectiveness of therapies is anecdotal.49 One major
momentarily or permanently caught above the reason for this is the wide range of biomechanical
medial trochlear of the femur. When the patella and pathologic changes that can be detected in appar-
releases, the limb flexes forward rapidly resembling a ently normal horses.50–54 A procedure for examining
stringhalt-­like action; some cattlemen refer to the horses suspected of having a non-­neurologic back
acquired condition as stringhalt. More permanent problem has been suggested, and such a procedure
fixation results in a syndrome almost identical to allows cases to be classified into suspected causes.55,56
 Disorders of posture and movement 169

However, a cautious interpretation of additional 7 Palmer AC. Introduction to Animal Neurology. 2nd ed.
Blackwell Scientific Publications, Oxford. 1976; 91–113.
detailed studies of normal horses and clinical cases, 8 Peele TL. The Neuroanatomic Basis for Clinical
using ultrasound, infrared thermography, nuclear Neurology. 3rd ed. McGraw-­Hill Book Company, New York.
scintigraphy, and computer-­ assisted radiographic 1977; 144.
9 Afifi AK and Bergman RA. Functional Neuroanatomy: Text
imaging and electrophysiologic testing should pro- and Atlas. 2nd ed. McGraw-­Hill Professional, New York.
vide a more precise definition of etiopathologic syn- 2005.
dromes.45,46,51,57–59 The possibility of primary or 10 Rossignol S, Dubuc R and Gossard JP. Dynamic sensorimotor
interactions in locomotion. Physiol Rev 2006; 86(1): 89–154.
secondary myopathies such as polysaccharide stor- 11 Thomson C and Hahn C. Veterinary Neuroanatomy: a Clinical
age disorders should not be overlooked and multiple Approach. Saunders Elsevier. 2012; 208 p.
muscle biopsies should be considered,39 although 12 de Lahunta A. Veterinary Neuroanatomy and Clinical Neurology.
2nd ed. W.B. Saunders Company, Philadelphia. 1983.
caution may be required in drawing any conclusion 13 de Lahunta A, Glass E and Kent M. Veterinary Neuroanatomy
between evidence for a myopathy and unusual clini- and Clinical Neurology. 4th ed. Saunders, Elsevier, St. Louis,
cal signs.36 MO. 2015.
14 Furuoka H, Okamoto R, Kitayama S, et al. Idiopathic peripheral
Numerous movement disorders, particularly neuropathy in the horse with knuckling: muscle and nerve lesions
involving the pelvic limbs in horses, may well involve in additional cases. Acta Neuropathol Berl 1998; 96(4): 431–437.
a primary neuropathy; however, most have not been 15 Furuoka H, Mizushima M, Miyazawa K and Matsui T.
Idiopathic peripheral neuropathy in a horse with knuckling.
investigated in detail. One of these syndromes would Acta Neuropathol Berl 1994; 88(4): 389–393.
be intermittent abduction of one pelvic limb during 16 Smith KJ, Felts PA and Kapoor R. Axonal hyperexcitability:
the protraction phase of stride. This syndrome could mechanisms and role in symptom production in demyelinat-
ing diseases. Neuroscientist 1997; 3(4): 237–246.
well be explained by an interruption to the 1a-­afferent, 17 Harper PA, Healy PJ and Dennis JA. Inherited congenital myo-
γ-­efferent pathway that almost certainly explains the clonus of polled Hereford calves (so-­called neuraxial oedema):
abnormal movements occurring in stringhalt for a clinical, pathological and biochemical study. Vet Rec 1986;
119(3): 59–62.
example. It must be clearly stated here that if there is 18 Fanelli HH. Coat colour dilution lethal (’lavender foal syndrome’):
any suspicion of mechanical or weight-­bearing lame- a tetany syndrome. Equine Vet Educ 2005; 17(5): 260–263.
ness or some sensory stimulus such as parasitic der- 19 Beech J. Forelimb tic in a horse. J Am Vet Med Assoc 1982;
180(3): 258–260.
matitis involving the distal limbs of horses, those 20 Gedde-­Dahl TW and Standal N. A note on a tremor condition
factors should be given due consideration before a in adolescent pigs. Anim Prod 1970; 12: 665–668.
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astounding postural and movement aberrations in 22 Seahorn TL, Fuentealba IC, Illanes OG and Storts RW.
the limbs of horses. This is especially so for the pelvic Congenital encephalomyelopathy in a quarter horse. Equine
limbs where even tight leg wraps applied to the distal Vet J 1991; 23(5): 394–396.
23 Gundlach AL, Dodd PR, Grabara CS, et al. Deficit of spinal
thoracic limbs may cause a horse to walk with a cord glycine/strychnine receptors in inherited myoclonus of
stringhalt action of the pelvic limbs. Likewise, an Poll Hereford calves. Science 1988; 241(4874): 1807–1810.
acutely painful lameness such as septic pododermati- 24 Gundlach AL, Kortz G, Burazin TC, Madigan J and Higgins RJ.
Deficit of inhibitory glycine receptors in spinal cord from
tis of one hind foot may result in the syndrome of Peruvian Pasos: evidence for an equine form of inherited myo-
tremors in that or even the contralesional limb. clonus. Brain Res 1993; 628(1–2): 263–270.
25 Kidd AR, Done JT, Wrathall AE, Pampiglione G and Sweasey
D. A new genetically-­determined congenital nervous disorder
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26 Garosi LS, Rossmeisl JH, de Lahunta A, Shelton GD and
1 de Lahunta A, Glass EN and Kent M. Classifying involuntary Lennox G. Primary orthostatic tremor in Great Danes. J Vet
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516–529. 27 Lafortune JG. Une Affection Spasmodique Des Bovins. Can J
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3 Lowrie M and Garosi L. Classification of involuntary movements movement characteristics of forward and backward walking in
in dogs: Tremors and twitches. Vet J 2016; 214: 109–116. horses with shivering and acquired bilateral stringhalt. Equine
4 Lowrie M and Garosi L. Classification of Involuntary Vet J 2015; 47(2): 175–181.
Movements in Dogs: Myoclonus and Myotonia. J Vet Int Med 29 Davies PC. Shivering in a thoroughbred mare. Can Vet J 2000;
2017; 31(4): 979–987. 41(2): 128–129.
5 Cerda-­Gonzalez S, Packer RA, Garosi L et al. International vet- 30 Mitchell WM. Some further observations on pathological
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ment: Terminology and classification. J Vet Int Med 2021; 35(3): significance. Vet Rec 1930; 10(25): 535–537.
1218–1230. 31 Deen T. Shivering, a rare equine lameness. A case report.
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32 Goeckmann V, Rothammer S and Medugorac I. Bovine spastic 46 Turner AS. Back Problems in Horses. Proc Ann Conv Am
syndrome: a review. Vet Rec 2018; 182(24): 693. Assoc Equ Pract, New Orleans, LA, USA 2003; 43: 71–74.
33 Valberg SJ, Lewis SS, Shivers JL, et al. The equine movement 47 Landman MA, de Blaauw JA, van Weeren PR and Hofland LJ.
disorder “Shivers” is associated with selective cerebellar Field study of the prevalence of lameness in horses with back
purkinje cell axonal degeneration. Vet Pathol 2015; 52(6): problems. Vet Rec 2004; 155(6): 165–168.
1087–1098. 48 Groesel M, Zsoldos RR, Kotschwar A, Gfoehler M and Peham
34 Aman JE, Valberg SJ, Elangovan N, et al. Abnormal locomotor C. A preliminary model study of the equine back including
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and Purkinje cell distal axonopathy. Equine Vet J 2018; 50(5): 2010(38): 401–406.
636–643. 49 Riccio B, Fraschetto C, Villanueva J, Cantatore F and Bertuglia
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Orcutt RS. Clinical and pathologic findings in two draft horses part. Front Vet Sci 2018; 5: 195.
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and abnormal gait characteristic of shivers syndrome. J Am tebral articulations in warmblood horses with and without
Vet Med Assoc 1999; 215(11): 1661–1665. back pain and their clinical significance. Europ Vet Diag
36 Firshman AM, Baird JD and Valberg SJ. Prevalences and clinical Imaging Congress. Vet Radiol Ultrasound 2019; 61: 110.
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draft horses. J Am Vet Med Assoc 2005; 227(12): 1958–1964. graphic and scintigraphic findings of the spinous processes in
37 Saadi A, Dalir-­ Naghadeh B, Akbari H, Rashedi M and the equine thoracolumbar region. Vet Radiol Ultrasound 2011;
Mohammadi R. Improvement of the clinical signs of gait abnor- 52(6): 661–671.
mality after treatment with levothyroxine in a horse with shiver- 52 Cousty M, Retureau C, Tricaud C, Geffroy O and Caure S.
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horse syndrome” caused by decreased gamma-­ 2010; 166(2): 41–45.
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40 El-­Hage CM, Huntington PJ, Mayhew IG, Slocombe RF and 18(2): 107–112.
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41 Torre F. Clinical diagnosis and results of surgical treatment of 56 Jeffcott LB. Conditions causing thoracolumbar pain and dys-
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 22
Incoordination of the head, neck, trunk
and limbs: cerebellar diseases

Syndromes with combinations of limb ataxia and Evidence of cranial nerve dysfunction should alert
weakness and those consisting of dysmetria of the the examiner to vestibular disease (Chapter 19)
pelvic limbs, all four limbs, and sometimes of the and other brainstem and cranial nerve disorders
head, and even less commonly cases of episodic (Chapters 7–18). Diseases with additional signs
weakness, have been referred to as wobblers, par- such as widespread tremor, tetanus or muscle
ticularly in horses. The sites of lesions that result spasms, and those that particularly involve one
in such signs include the brainstem, cerebellum limb, or both thoracic limbs or involve the tail and
and cervical, thoracic, lumbar and sacral spinal anus, are discussed in Chapters 21, 25, 26 and 27,
cord, the spinal nerve roots, peripheral nerves, while purely spinal cord disorders are covered in
neuromuscular junctions, and the muscles. Chapter 23.

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
172 Large animal neurology

At the conclusion of a neurologic examination of or high stepping, hypometric (reduced joint move-
such cases, the clinician should be able to identify ment) or stiff legged, or a combination of these signs
cerebellar involvement (Figure 22.1). Although pure when the term dysmetria is applicable. In addition,
cerebellar diseases result in ataxia of the limbs, unlike head signs are usually present to include ataxia of the
in humans, overt weakness is not evident, distinguish- head and neck with wide, swinging, head excursions,
ing cerebellar disease from most of the other disorders jerky head bobbing, an intention tremor involving the
producing ataxia. Notwithstanding, the slow onset of head but not the body and limbs, and an abnormal
movements that are usually variably dysmetric can menace response. With the last finding, the animal
appear to be weakness. Cerebellar ataxia can be defined is able to see and to blink its eyelids but does not
as alterations in the force, speed, and range of move- blink consistently in response to a menacing gesture
ment of body parts, notably the limbs and neck.1 The directed toward each eye, although it may withdraw its
ataxic gait seen with diffuse cerebellar disease is char- head from the threatening gesture—­a visual avoidance
acteristically hypermetric (excessive joint movement) response. This can be seen ipsilateral to unilateral

(A) (B)

(C) (D)

Figure 22.1 These patients with evidence of cerebellar disease have lesions consistent with severe cerebellar hypoplasia associated with BVD virus (A),
inherited cerebellar abiotrophy (B), mild caprine lentivirus encephalitis (caprine arthritis-­encephalitis) (C), and congenital hypomyelination possibly associ-
ated with BVD infection (D). The gait and postural deficits seen with various cerebellar diseases often include hypermetria (A and B) and degrees of
extensor hypertonus with additional hypometric or dysmetric movements (D). Some diseases affect the cerebellar regions involved with vestibular
­function such as in the Nubian goat (C) with a very wide-­based stance, vestibular ataxia, and worsening of signs upon blindfolding. In all cases, a poor
or absent menace response may be detected (central inset) with a normal startle response to a visual threat eliciting head withdrawal and an intact dazzle
(blink) response to a noiseless flash of bright light. The severity of signs of cerebellar diseases shown by a patient do not relate well to the severity or
extent of morphologic lesions present.
 Incoordination of the head, neck, trunk and limbs: cerebellar diseases 173

c­erebellar lesions. It is probable that the cerebellum As with other CNS sites, the cerebellum can now
positively influences the classic menace or eye preser- be imaged, and such ancillary aids can assist with
vation reflex. Thus, cerebellar lesions might suppress specific diagnoses.6–9
the reflex (see Chapter 2—­Neurologic Evaluation). The term cerebellar abiotrophy is used here to
describe a clinical syndrome that is familial and that
most often begins after the animal has had a normal
In all large animals, cerebellar syndromes, when severe, gait for a period of time.10 Signs progress and active
can be misdiagnosed as cerebral disease, although a degeneration of the cells of the cerebellum, particu-
thorough neurologic examination is usually all that is larly cortical neuronal (Purkinje) cells, may be demon-
required to distinguish between these anatomic sites strated. Thus, the clinical syndromes of the cerebellar
of disease processes. abiotrophies are taken to be familial and degenerative,
but not usually congenital. Isolated cases of acute, dif-
fuse cerebellar degeneration, which mimic abiotro-
Temporary exacerbations of cerebellar signs, seen phies, are seen in several breeds of cattle including
when severely affected animals are disturbed, Limousin11 and Aberdeen Angus cattle. They are most
restrained firmly, or suddenly released from lateral easily explained by an environmental toxic or infec-
recumbency, can result in extensor hypertonus, tious insult, but a genetic defect could be operative.
thrashing, and opisthotonus without loss of con- Congenital cerebellar disease may accompany the
sciousness. Such episodic events (seizures) can be congenital tremor syndromes discussed in Chapter 31,
referred to as cerebellar convulsions.2 These occur which includes in utero exposure to organophos-
especially in the familial and toxic cerebellar syn- phates.12,13 The (Arnold) Chiari malformation with
dromes and most often in calves and goats, but also cerebellar vermian displacement, as well as the
in foals and adult horses. In cats, it has been shown Dandy–Walker syndrome that includes agenesis of
that cerebellar lesions alter the nature of seizures the caudal cerebellar vermis, have been related to
induced by convulsant drugs.3 Also, electroencepha- cerebellar signs, although other signs resulting from
lograms taken from piglets4 and Arabian foals5 with hydrocephalus and arthrogryposis and to agenesis of
cerebellar syndromes may be abnormal. Interestingly, the corpus callosum may predominate.14–17
piglets, more than other patients with severe (vestib- Prominent cerebellar syndromes accompany the
ulo) cerebellar disease, learn to use their snout as a mannosidoses seen in calves and goats. Angus calves
fifth support against falling, which pigs also do when with α-­ mannosidosis show progressive cerebellar
very weak, but this is of course a normal (intended) ataxia, aggressiveness, and weight loss, whereas
investigative behavior of healthy pigs. Anglo Nubian goats with β-­mannosidosis are severely
The floccular lobes of the lateral cerebellar hemi- incapacitated early in life, with severe dysmetria and
spheres, the nodular lobe of the caudal vermis, and recumbency. The α-­mannosidase inhibition caused
the pair of fastigial or medial cerebellar nuclei all are by swainsonine-­containing endophyte/plant symbi-
interconnected with the vestibular nuclei within the onts also results in cerebellar signs (Chapter 34).
medulla oblongata. Thus, severe, acquired cerebellar Acquired diseases that may involve the cerebel-
diseases can include signs of vestibular derangement. lum, often resulting in asymmetric signs, include
Resulting vestibular syndromes associated with these equine myeloencephalitis caused by S. neurona,
central vestibular connections can include paradoxi- migrating metazoan parasites,18 nonsuppurative
cal, contralesional signs with leaning, turning and meningoencephalitis,19 caudal fossa neoplasia, and,
head tilt all away from the side of the lesion, and the rarely, head trauma. Subtle cerebellar signs can
fast phase of any nystagmus toward the side of the accompany prion-­ related diseases, at least bovine
central lesion. spongiform encephalopathy and scrapie.
Newborn ungulates frequently have a slightly The relationship between site of lesions in the
hypermetric gait reminiscent of cerebellar dysfunc- cerebellum and specific neurologic syndromes is well
tion. In the context of congenital, cerebellar syn- discussed by Holliday.1 Interestingly, how incapaci-
dromes, clinical signs are present from birth or from tating a particular cerebellar syndrome is does not
when the neonatal animal is expected to ambulate always relate to the severity of the gross and histo-
well. Such syndromes may be inherited, but even if logic lesions detected. Also, clearly evident lesions,
they are familial, there may be other environmental detected unexpectedly at postmortem examination,20
in utero factors that play a pathogenetic role. may or may not have been clinically relevant.
174 Large animal neurology

If the cerebellum is found to be small, this could be 10 Scott EY, Woolard KD, Finno CJ and Murray JD. Cerebellar
abiotrophy accross domestic species. Cerebellum 2018; 17(3):
the result of cerebellar atrophy when it formed, then 372–379.
shrank, cerebellar hypoplasia if it did not form, or 11 Oz HH, Nicholson SS, Al-­ Bagdadi FK and Zeman DH.
cerebellar abiotrophy if it has undergone postnatal Cerebellar disease in an adult cow (grazing Lolium perenne).
Canadian Vet J 1986; 27(1): 13–16.
degeneration. In utero destruction of cerebellar tissue 12 Knox B, Askaa J, Basse A, et al. Congenital ataxia and tremor
by toxins and particularly viruses such as Akabane, with cerebellar hypoplasia in piglets borne by sows treated with
bovine viral diarrhea, and swine fever results in Neguvon vet. (metrifonate, trichlorfon) during pregnancy.
Nord Vet Med 1978; 30(12): 538–545.
acquired, congenital, nongenetic, cerebellar syn- 13 Bölske G, Kronevi T and Lindgren NO. Congenital tremor in
dromes. Determining the cerebellum to whole brain pigs in Sweden. A case report. Nord Vet Med 1978; 30(12):
weight ratio or cerebellar quotient (CQ) can assist in 534–537.
14 Cho DY and Leipold HW. Congenital defects of the bovine
documenting a relative small size of the cerebellum and central nervous system. Vet Bull 1977; 47: 489–504.
has been determined to be 0.725 in cattle (n = 8) and 15 Cho DY and Leipold HW. Arnold-­Chiari malformation and
0.841 in horses (n = 131).21,22 Thus, a CQ of <0.7 helps associated anomalies in calves. Acta Neuropathol Berl 1977;
39(2): 129–133.
confirm selective smallness of the cerebellum on imag- 16 Saunders LZ, Sweet JD, Martin SM, Fox FH and Fincher MG.
ing or at postmortem examination,12,13,23–25 although Hereditary congenital ataxia in Jersey calves. Cornell Vet 1952;
control figures for specific groups of similar age-­and 42(4): 559–591.
17 Cudd TA, Mayhew IG and Cottrill CM. Agenesis of the corpus
breed-­matched animals preferably should be used, and callosum with cerebellar vermian hypoplasia in a foal resem-
volumetric imaging techniques allow for such meas- bling the Dandy-­Walker syndrome: pre-­mortem diagnosis by
urements to be made in vivo.26 clinical evaluation and CT scanning. Equine Vet J 1989; 21(5):
378–381.
18 Fraser H. Two dissimilar types of cerebellar disorder in the
References horse. Vet Rec 1966; 78(18): 608–612.
19 Van Bogaert L and Innes JRM. Cerebellar disorders in lambs. A
1 Holliday TA. Clinical signs of acute and chronic experimental study in animal neuropathology with some comments on
lesions of the cerebellum. Vet Sci Comm 1979/80; 3: 259–278. ovine neuroanatomy. Arch Pathol 1950; 50: 36–62.
2 Bourke CA. Cerebellar degeneration in goats grazing Solanum 20 Wheat JD and Kennedy PC. Cerebellar hypoplasia and its
cinereum (Narrawa burr). Aust Vet J 1997; 75(5): 363–365. sequela in a horse. J Am Vet Med Assoc 1957; 131(6):
3 Cook WH and Stavraky GW. A cerebellar component of convul- 291–293.
sive manifestations. AMA Arch Neurol Psychiatry 1952; 68(6): 21 Ballarin C, Povinelli M, Granato A, et al. The brain of the
741–754. domestic Bos taurus: weight, encephalization and cerebellar
4 Kidd AR, Done JT, Wrathall AE, Pampiglione G and Sweasey D. quotients, and comparison with other domestic and wild cetar-
A new genetically-­determined congenital nervous disorder in tiodactyla. PLoS One 2016; 11(4): e0154580.
pigs. Br Vet J 1986; 142(3): 275–285. 22 Cozzi B, Povinelli M, Ballarin C and Granato A. The brain of
5 Beatty MT, Leipold HW, Cash W and De Bowes R. Cerebellar the horse: weight and cephalization quotients. Brain Behav
disease in Arabian horses. 31st Ann Conv Amer Assoc Equine Evol 2014; 83(1): 9–16.
Pract 1985; 31: 241–255. 23 Mayhew IG. Neurological and neuropathological observations
6 Cavalleri JM, Metzger J, Hellige M, et al. Morphometric mag- on the equine neonate. Equine Vet J Suppl 1988(5): 28–33.
netic resonance imaging and genetic testing in cerebellar abio- 24 Scott FW, Kahrs RF, De Lahunta A, et al. Virus induced con-
trophy in Arabian horses. BMC Vet Res 2013; 9: 105. genital anomalies of the bovine fetus. I. Cerebellar degeneration
7 Glass EN, De Lahunta A and Jackson C. Brain abscess in a goat. (hypoplasia), ocular lesions and fetal mummification following
Cornell Vet 1993; 83(4): 275–282. experimental infection with bovine viral diarrhea-­mucosal dis-
8 Gordon PJ and Dennis R. Magnetic resonance imaging for the ease virus. Cornell Vet 1973; 63(4): 536–560.
ante mortem diagnosis of cerebellar hypoplasia in a Holstein 25 Done JT. The congenital tremor syndrome in pigs. Vet Annual
calf. Vet Rec 1995; 137(26): 671–672. 1975; 15: 98–102.
9 Testoni S, Dalla Pria A and Gentile A. Imaging diagnosis – 26 Katalin F, Borbala L, Rita G, et al. The volumetric evaluation of
­cerebellar displacement and spina bifida in a calf. Vet Radiol the canine cerebellum by using magnetic resonance imaging.
Ultrasound 2010; 51(2): 162–164. Magyar Allatorvosok Lapja 2013; 135(11): 675–684.
 23
Tetraparesis, paraparesis, and ataxia of
the limbs: spinal cord diseases

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
176 Large animal neurology

wobbler with the disease cervical vertebral malfor-

Patients with syndromes of tetraparesis, paraparesis, and mation and malarticulation. The term wobbler can
ataxia of the limbs resulting from lesions in the spinal cord, be applied to other ungulates with syndromes con-
spinal nerve roots and ganglia, and neural plexuses and sistent with spinal cord disease.
nerves of the limbs are often referred to as wobblers. With a mild or even moderate cervical spinal cord
Thus, this is a generic term defining neither the precise lesion in an adult cow or horse, especially when
site(s) of lesion(s) nor the cause of the disease. chronic, signs of ataxia and weakness may be evident
in the pelvic limbs only, especially if the patient is
uncooperative. In this situation, and with no evidence
If following the neurologic evaluation, vestibular and of brainstem or cerebellar disease, it is safest to con-
cerebellar involvement can be ruled out in a wobbler clude that the patient has a lesion or lesions between
case showing ataxia and weakness of the limbs then the and including C1 and S3. On the other hand, scrutiny
clinician must attempt to differentiate among the of the gait and posture and of postural responses in the
remaining disorders producing degrees of tetraparesis, limbs, along with a search for localizing findings, are
paraparesis, and episodic weakness to arrive at a diag- often productive. As a rule, large, heavy patients with
nosis. With brainstem diseases, there are usually signs spinal cord disease that sit with the hindlimbs col-
such as somnolence and cranial nerve functional lapsed and the forelimbs extended and supporting
abnormalities. Patients having either static, episodic, or weight for several minutes in that posture most likely
exercise-­associated signs consistent with diffuse weak- have a lesion caudal to T2 (Figure 23.1). By being able
ness due to final motor neuron lesions and neuromus- to accurately define the site of the lesion, the clinician
cular diseases may also have evidence of cranial nerve can reduce the number of possible diseases to be con-
dysfunction but should remain bright and alert and sidered and thus can better direct the ancillary testing
should not demonstrate ataxia (Chapter 24). However, that is available. Ruminants with paresis and particu-
with profound weakness, it can be very difficult to larly painful conditions affecting the more distal tho-
determine the presence or absence of ataxia (subcon- racic limbs will spend prolonged periods upright and
scious proprioceptive) and positional (conscious pro- weight-­bearing on their knees. However, such a pos-
prioceptive) deficits, particularly if the patient is heavy ture is very foreign to horses, and even with thoracic
and very reluctant to move. limb weakness they can position themselves with
Several diseases and syndromes are not emphasized the forelimbs extended and locked for support (see
here because of their parochial or rare nature, or Figure 2.13). This compares with marked extensor
because of their uncertain clinical and neurological weakness in only the pelvic limbs when a crouched
significance. However, the interested reader can refer posture with the pelvic limbs held forward is adopted
to such examples as progressive ataxia of Charolais in all large animal species (Figures 23.2 and 23.3B).
cattle,1 compressive cervical myelopathy in young Degrees of paraparesis and pelvic limb ataxia are
Texel and Beltex sheep,2 degenerative disk disease,3–6 often seen in large animals, although frequently in
ovine cervical vertebral stenosis,7 bovine knuckler mild cases it is difficult to determine whether the
syndrome,8 congenital ataxia in artificially bred calves,9 thoracic limbs are involved (Figure 23.1). In such
a rigid lamb syndrome in Dorper lambs in Rhodesia,10 cases, a scrutiny of the gait and a search for localizing
a suspected inherited neuromuscular disease in Dorset findings are often productive. It can be diagnostically
Down sheep in New Zealand,11 bovine paralysis in helpful to test for cutaneous sensation, cutaneous
Zebu cattle in Cuba,12 spider syndrome in Suffolk reflexes, and spinal reflexes and postural reactions on
sheep,13 segmental axonopathy (Murrurindi disease) all small patients less than ~100 kg. It is more diffi-
in Australian sheep,14 and particular snakebite cult to test classical spinal reflexes, and for postural
­neurointoxications. These and others are presented in reactions in adult cattle, horses and pigs, and the only
Part III and in general references.15–28 consistently useful spinal reflexes of the limbs are the
Spinal cord disease is common in large animals, flexor reflexes and the patellar reflex, the remainder
especially in young of all species and in adult horses. being of little consistent diagnostic utility in heavy
A horse showing variations of ataxia and weakness is large animals. Full hopping responses and hemi-
called a wobbler,29 and this should be used as a walking are easily performed in smaller, lighter
generic term, not defining the cause of the syndrome. patients, and adequate performance of these indicates
Notwithstanding, some folk equate the term equine overall function of sensorimotor pathways controlling­
 Tetraparesis, paraparesis, and ataxia of the limbs: spinal cord diseases 177

(A) (B)

Figure 23.1 Heavy patients that dog-­sit such as this donkey (A) usually have a neuromuscular lesion caudal to T2, with occasional exceptions. Thus, the
Toggenburg doe (B) does have a lesion caudal to T2, but with a head tilt—­and other signs of vestibular disease—­must have another lesion, likely involving
the medullary vestibular centers. Both actually have helminth parasites in their CNS tissue: a S. vulgaris larva migrating through the T-L spinal cord of
the donkey and multiple P. tenuis larvae wandering through the spinal cord and brainstem of the doe.

i­ nitiation of movement and maintaining locomotion.

Modified hopping with one forelimb held up is a use-
ful postural reaction to test large adult animals par-
ticularly horses. Thus, with large patients, the
clinician relies particularly on critical evaluation of
gait and posture to assist in initially localizing spinal
cord lesions (Figure 23.3). Grading of gait abnormal-
ities, testing local cervical, cervicofacial, and cutane-
ous trunci reflexes, testing for clearly defined
alterations to cutaneous sensation and sweating
(horse), and performing the laryngeal adductor
response test are of considerable help in this regard.
All these tests are discussed in the neurologic exami-
nation section in Chapter 2.
When evaluating outbreaks of animals affected
with prominent gait abnormalities suspected as being
ataxia and weakness, consideration must be given to
infectious and toxic disorders. Such a clinical situa-
Figure 23.2 The position adopted by this horse suffering from EPM tion is when multiple horses are alert but recumbent
typifies final motor neuron weakness to the pelvic limbs. The thoracic
limbs are shifting weight to maintain a suitable stance and to allow the
with others walking very weakly and some even
patient to move normally. Lowering of the pelvis and flexion of proximal found dead. Thoughts turn immediately to the viral
joints in the pelvic limbs with the feet placed cranially (crouched posture) diseases such as due to EHV-­1, but botulism and
indicate extensor weakness, likely L3–4 gray matter and femoral weakness. other causes of diffuse weakness (Chapter 24) also
Flexion of the digits indicates digital extensor weakness, likely L5–6 gray need consideration.
matter and peroneal weakness. Obviously, such explanations assume
that the horse postured for characteristically prolonged periods, and it did
In relating a spinal cord segment to a specific ver-
not have other evidence of bilateral femoral and sciatic nerve or lumbosacral tebra, we need to recall that there are eight cervical
plexus involvement. segments and only seven cervical vertebrae. Also,
178 Large animal neurology

(A)

(B)

Figure 23.3 Marked tetraparesis (A) and marked paraparesis (B) in adult cattle are characterized here by a case of diffuse degenerative myeloencephalopathy
in a young Watusi bull (A) and multifocal, lumbosacral, epidural lymphosarcoma in a Holstein dairy cow (B). With central motor pathway lesions and weakness in
all four limbs in adult cattle, a normal weight distribution and a normal method of rising from recumbency do appear to create greater difficulty in weight support
in thoracic limbs (A) compared to similar forms of tetraparesis in smaller patients and in other species. As in the horse with EPM in Figure 23.2, this cow shows
pelvic limb extensor weakness that could be caused by a lesion between T2 and S2. However, as the flexed posture was maintained and the cow stood over on its
fetlocks, a final motor neuronal lesion in the femoral and sciatic outflow was suspected. The major masses of epidural lymphoid tumor tissue were at the level of
the L4 and the L6 spinal segments and nerve rootlets.

cows, sheep, goats, and horses most commonly have hopeless outlook for return of function arise. A CSF
six lumbar vertebrae, pigs have seven, and donkeys sample may best be taken at the lumbosacral space
have five. The spinal cord usually ends at vertebral from patients with this syndrome because the fluid
level S1–2, but in pigs it ends at S3. sampled is frequently closest to the lesion. If this is
It behooves the large animal clinician to complete unsuccessful, it is worth trying at L5–6, especially in
a thorough neurologic workup as early as possible in lambs, kids and calves, and at L6–7 in piglets.
the course of all neurologic syndromes. This is Caring for a heavy and recumbent large animal
particularly so as more is known about various requires very good facilities and dedicated nursing
spinal cord diseases, and more advanced medical attention.30–32 Because of the considerable concern for
and surgical therapeutic regimens become available. life-­threatening complications and the high prevalence
Ancillary aids, such as neuroradiology, advanced of S. neurona protozoal myeloencephalitis—­at least in
computerized imaging techniques, electrodiagnostic horses coming from the Americas—­many clinicians use
testing, and spinal fluid analysis, can be of tremen- glucocorticosteroids sparingly in the treatment of wob-
dous help in developing a useful plan for treatment blers and tetraplegic horses. Unfortunately, caring for
when performed early in the course of disease, before such patients is frustrating, time-­consuming, expensive,
permanent neurologic signs and the consequent and fraught with ­ complications. Notwithstanding
 Tetraparesis, paraparesis, and ataxia of the limbs: spinal cord diseases 179

these factors, remarkable recoveries are recorded par- is c­haracterized in Figure 23.4 that depicts the typ-
ticularly with some of the inflammatory and traumatic ical primary and secondary lesions seen in wob-
insults to the spinal cord. bler horses suffering from a single focal
Lastly, an understanding of primary lesions as compressive lesion due to cervical vertebral mal-
well as secondary Wallerian-­like neuronal fiber formation (A), from a diffuse neuroaxonal disor-
degenerative changes (refer to Chapter 4) is para- der, equine degenerative myeloencephalopathy
mount to the interpretation of pathologic reports (B), and from a multifocal disease, equine proto-
of patients s­ uffering from spinal cord disease. This zoal myeloencephalitis (C).

cranial to lesion
site of lesion
caudal to lesion

(A) (B)

(C)

Figure 23.4 Diagrams of the lesions seen in some of the most common diseases affecting the spinal cord of horses resulting in wobbler syndrome.
Darkened areas indicate sites of various lesions.

A. Cervical vertebral malformation (and trauma). There is (usually) a single, focal, cervical, pressure-­induced lesion affecting gray and especially white
matter. Secondary, Wallerian-­like, white matter fiber degeneration is present in sensory pathways cranial, and motor pathways caudal, to the lesion
(stippling).
B. Equine degenerative myeloencephalopathy with no focal lesion. Degeneration of central sensory and motor white matter tracts (stippling) throughout
the spinal cord, particularly in the superficial lateral (sensory) and ventromedial (motor) pathways of the thoracic segments. Selective gray matter degen-
eration (neuroaxonal dystrophy) in caudal medullary, cranial cervical, and thoracic regions (black nuclear areas).
C. Equine protozoal myeloencephalitis. Asymmetric, multifocal, nonsuppurative inflammatory lesions affecting gray and white matter in the brain and
particularly the spinal cord with scattered, irregular secondary Wallerian-like fiber degeneration.
180 Large animal neurology

References 17 Summers BA, Cummings JF and de Lahunta A. Veterinary

Neuropathology. Mosby, St. Louis, M.O. 1995; 527.
1 Duchesne A, Vaiman A, Frah M, et al. Progressive ataxia of 18 Maxie GM. The Nervous System. Volume 1, Chapter 3 in Jubb,
Charolais cattle highlights a role of KIF1C in sustainable mye- Kennedy & Palmer’s Pathology of Domestic Animals 5th ed.
lination. PLoS Genet 2018; 14(8): e1007550. Saunders, St. Louis, MO. 2007.
2 Penny C, Macrae A, Hagen R, et al. Compressive cervical mye- 19 Windsor P, Kessell A and Finnie J. Review of neurological dis-
lopathy in young Texel and Beltex sheep. J Vet Int Med 2007; eases of ruminant livestock in Australia. VI: postnatal bovine,
21(2): 322–327. and ovine and caprine, neurogenetic disorders. Aus Vet J 2011;
3 Foss RR, Gentzky RM, Riedesel EA and Graham C. Cervical 89(11): 432–438.
intervertebral disc protrusion in two horses. Case report. Can 20 Finnie J, Windsor P and Kessell A. Neurological diseases of
Vet J 1983; 24(6): 188–191. ruminant livestock in Australia. I: general neurological exami-
4 Rooney JR. The vertebral column, in Biomechanics of Lameness nation, necropsy procedures and neurological manifestations
in the Horse. Williams & Wilkins, Baltimore. 1969; 90–253. of systemic disease, trauma and neoplasia. Aust Vet J 2011;
5 Bergmann W, Bergknut N, Veraa S, et al. Intervertebral disc 89(7): 243–246.
degeneration in warmblood horses: morphology, grading, and 21 Finnie JW, Windsor PA and Kessell AE. Neurological diseases
distribution of lesions. Vet Pathol 2018; 55(3): 442–452. of ruminant livestock in Australia. II: toxic disorders and
6 Lapointe JM and Summers BA. Intervertebral disk disease nutritional deficiencies. Aust Vet J 2011; 89(7): 247–253.
with spinal cord penetration in a Yucatan pig. Vet Pathol 2012; 22 Kessell A, Finnie J and Windsor P. Neurological diseases of
49(6): 1054–1056. ruminant livestock in Australia. III: bacterial and protozoal
7 Palmer AC, Kelly WR and Ryde PS. Stenosis of the cervical infections. Aust Vet J 2011; 89(8): 289–296.
vertebral canal in a yearling ram. Vet Rec 1981; 109(3): 53–55. 23 Kessell A, Finnie J and Windsor P. Neurological diseases of
8 Howard JR. Bovine “knuckler” syndrome; nervous system ruminant livestock in Australia. IV: viral infections. Aust Vet J
degeneration. Proc 18th World Vet Congress Mexico. 1971: 2011; 89(9): 331–337.
176–180. 24 Windsor P, Kessell A and Finnie J. Neurological diseases of
9 McClintock AE and O’Neil JA. A possible case of inherited ruminant livestock in Australia. V: congenital neurogenetic
abnormalities in the central nervous system of calves by an AI disorders of cattle. Aust Vet J 2011; 89(10): 394–401.
sire. Vet Rec 1974; 94(17): 382–383. 25 Rech R and Barros C. Neurologic diseases in horses. Vet Clin
10 Rudert CP, Lawrence JA, Foggin C and Barlow RM. A rigid North Am Equine Pract 2015; 31(2): 281–306.
lamb syndrome in sheep in Rhodesia. Vet Rec 1978; 102(17): 26 Scott PR, Penny CD and Macrae A. Nervous System Diseases,
374–377. Chapter 6 in Cattle Medicine. 1st ed. CRC Press, Florida. 2011:
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33(10): 172–173. CRC Press, Florida. 2018.
12 Torano ME, Oplistil M and Gomes A. Aetiology, therapy and 28 Scott PR. Neurologic Diseases, Chapter 8 in Sheep Medicine.
prevention of the syndrome called “bovine paralysis” in Zebu 2nd ed. CRC Press, Florida. 2015: 187–230.
cattle in Cuba. Acta Vet Brno 1975; 44: 197–202. 29 Alcott CJ. Evaluation of ataxia in the horse. Equine Vet Educ
13 Rook JS, Spaulding K, Coe P, et al. The spider syndrome: a 2017; 29(11): 629–636.
report on one purebred flock. Comp Cont Ed Pract Vet 1986; 30 Poulton PJ, Vizard AL, Anderson GA and Pyman MF. High-­
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 24
Diffuse weakness

Syndromes of static, exercise-­associated, and episodic involvement is important in the diagnosis of these
diffuse weakness result from those diseases that disorders. Clinically, widespread, symmetrical, and
diffusely affect components of the final motor neurons diffuse weakness of limbs and other body parts
notably diffuse CNS alpha motor neurons, peripheral characterize these diseases (Figure 24.1). Consequently,
somatic spinal and cranial nerves, neuromuscular degrees of paraparesis and tetraparesis leading to
junctions, and muscles, and combinations thereof. recumbency are most often seen. The rapid develop-
Thus, the demonstration of such final motor neuron ment of muscle atrophy, elevated circulating muscle

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
182 Large animal neurology

resulting atrophy and fibrous contracture of muscles

with subsequent rapid fixation of joints.1 These rigid
joint contractures occur very rapidly in the fetus in its
flaccid state or in its restricted environment.
Floppy or flaccid, recumbent neonatal animals are
seen wherein the reflexes are poor, and they improve
rapidly with nursing care to become normal. It is most
(A) improbable that the later-term fetus in these cases was
hypotonic and immobile or else arthrogryposis would
set in rapidly. The few that have been evaluated
at postmortem examination have not had morbid
CNS or PNS lesions on light microscopy. Intestinal
dysbacteriosis is the likely cause of the increased
­
plasma d-­lactate concentration in acquired floppy kid
­syndrome in 4 to 14-­day-­old goat kids.2,3 Alkalinizing
fluid therapy can resolve that syndrome.
Botulism, the most commonly suspected and
diagnosed cause of diffuse somatic weakness in large
animals, results in flaccid tetraparesis to tetraplegia
(B) often accompanied by degrees of oral and pharyngeal
dysphagia. The patient often will tremble more with
Figure 24.1 This tetraplegic neonatal lamb (A) demonstrates poor limb weakness when forced to move or when one limb is
and neck tone when lifted and promoted to extend and weight support (B). lifted, and particularly just before becoming recum-
The presence of poor tone on limb and neck manipulation and almost are-
bent. Weak, silent palpebral reflexes, relatively silent
flexia confirmed flaccid paralysis in all limbs, an indication of a diffuse final
motor neuronal lesion rather than a single cervical lesion. Indeed, there was chewing movements, and prolonged eating times can
widespread neuronal chromatolysis in the caudal brainstem and particu- be early signs of cranial nerve involvement.
larly the spinal cord gray matter suggestive of an inherited, toxic, or nutri- Most cases of equine motor neuron disease suffer
tional disorder such as copper deficiency, which was never proven. weight loss while maintaining a good appetite that
precedes the onset of weakness and trembling by
enzyme activities, and electromyographic evidence several weeks (Figure 24.2). Like many diseases that
of final motor neuron, peripheral nerve and muscle produce diffuse somatic weakness in heavy patients,
involvement are variable but important diagnostic
markers. A few of these processes can also involve
diffuse final motor neuron stimulation, notably in the
early stage of those diseases, with subsequent stiffness
and muscle contraction adding to and complicating
the clinical syndrome of weakness. These syndromes
are to be distinguished from acute collapse associated
with seizures, sleep disorders and syncope wherein
there is altered mentation, and other signs relating to
forebrain and/or brainstem involvement.
It should be recalled here that in heavy patients
that are recumbent for any reason, spinal reflexes
can be notoriously difficult to detect consistently.
Notwithstanding this, patients with marked, diffuse Figure 24.2 A clinical diagnosis of equine motor neuron disease (EMND)
neuromuscular weakness, surprisingly, may still have was made on this teenage horse that also had lesions consistent with a
tone in the limbs and have intact—­though certainly not lipoid retinopathy (Verhulst et al.5). Predominant signs developed after the
horse had been confined to a box for many months and included low head
hyperactive—­spinal reflexes. Interestingly, any process
carriage, hind feet placed well forward, and loss of muscle mass over proxi-
that causes decreased movement in utero, especially mal limb, shoulder and gluteal regions. This was despite a good appetite
diseases affecting any part of the final motor neuron and ad lib. hay. In addition, the horse showed prominent tremor of proximal
unit, can result in arthrogryposis at birth because of limb muscles and spent a lot of time lying down.
 Diffuse weakness 183

affected horses adopt a characteristic stance with all many muscles to accompany the somatic weakness
four feet close together as if to equilibrate weight resulting in involuntary recumbency, possibly with
distribution to all limbs and frequently have an hypoactive spinal reflexes. This syndrome is like
abnormally low head carriage. Significantly, horses several equine cases seen with steroid-­responsive,
affected with motor neuron disease move better exercise-­associated, myasthenic syndrome, believed
than they stand presumably because motor neurons to represent acquired, immune-­associated, postsyn-
controlling type-­1 postural muscle are affected in aptic myasthenia gravis. And, a myasthenia gravis-­
preference to those innervating type-­ 2, exercise-­ like syndrome does occur in cattle.4
related muscle. The stance and the muscle trembling Of final note here is that sometimes a horse with
are very similar to that seen in equine grass sickness West Nile virus infection will remain bright and alert
and in botulism. but paralyzed in lateral recumbency due to the ventral
Usually, as a result of exercise, Quarter Horses horn poliomyelitis, also documented in people.6,7
affected by a severe attack of hyperkalemic periodic Although not likely to be misdiagnosed as a neuro-
paralysis can have prominent trembling and tetany of logic disease, there is a syndrome associated with

(A) (B)

(C) (D)

Figure 24.3 An abrupt onset of apparent, temporary tetraparesis, paraparesis, or paresis of thoracic limbs can be seen in animals suffering various severe
skin conditions including sunburn (especially in white pigs), external parasites, and dermatophilosis. A group of 5-­month-­old lambs suffered severe dorsal
dermatophilosis. Many lambs began showing intermittent unusual posturing and movement as shown in (A) and (B). The diffuse, severe extent (C) and
full thickness nature (D) of the dermatophilosis was evident on postmortem evaluation. Source: Images courtesy of C.P. Champion et al.9
184 Large animal neurology

s­unburn in pigs that can be so baffling as to warrant References

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tions including external parasites, photosensitivity, and ita in a thoroughbred foal. Vet Pathol 1984; 21(2): 187–192.
dermatophilosis (Figure 24.3).8,9 Affected pale-­skinned 2 Bleul U, Fassbind N, Ghielmetti G, et al. Quantitative analysis
of fecal flora in goat kids with and without floppy kid syn-
pigs and sheep with little wool on the dorsum which drome. J Vet Intern Med 2013; 27(5): 1283–1286.
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20(4): 1003–1008.
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mate blistering may initially be overlooked but can be drome in a Hereford heifer. J Vet Intern Med 2008; 22(1): 231–233.
severe especially with any concurrent dermatophilosis 5 Verhulst D, Barnett KC and Mayhew IG. Equine motor neuron
disease and retinal degeneration. Eq Vet Edu 2001; 13(2): 59–67.
Other diseases that warrant inclusion in the 6 Kramer LD, Li J and Shi PY. West Nile virus. Lancet Neurol
­differential diagnosis of an acquired, diffuse, somatic 2007; 6(2): 171–181.
myasthenic syndrome are tick paralysis,10 elapid snake 7 Gyure KA. West Nile virus infections. J Neuropathol Exp
Neurol 2009; 68(10): 1053–1060.
envenomation,11 and a generalized poly­radiculoneuritis 8 Allworth MB, West DM and Bruère AN. Ovine dermatophilo-
that does not selectively target cranial and sacro- sis in young sheep associated with the grazing of Brassica spp.
caudal nerve roots in parti­cular. Widespread, immune-­ crops. N Z Vet J 1985; 33(12): 210–212.
9 Champion CP, Bycroft K, Castillo Alcala F and Collett MG.
associated polyradi­culoneuritis with a typical acute Postural and gait abnormalities in a group of Romney lambs
onset of flaccid tetraparesis and tetraplegia does due to pain induced by severe chronic cutaneous dermat-
not seem to occur often in large animals, although ophilosis. N Z Vet J 2021; 1–13.
10 Serra Freire NM. Tick paralysis in Brazil. Trop Anim Health
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been reported,13 and congenital neospora-­induced envenomation in horses: 52 cases (2006–2016). Equine Vet J
2018; 50(2): 196–201.
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Undiagnosed cases of generalized weakness with- Barre syndrome. Neurology 1988; 38(3): 375–378.
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and others have been euthanized with no CNS lesions induced congenital myelitis and polyradiculoneuritis in a one-­
month-­old Holstein calf. Can Vet J 1994; 35(10): 653–654.
detected to explain the syndrome. Chemical-­induced 15 Votion D-­ M and Serteyn D. Equine atypical myopathy: a
neuromuscular blockade would seem to be a reason- review. Vet J 2008; 178(2): 185–190.
able explanation, though the putative agent(s) have 16 Finno CJ, Valberg SJ, Wunschmann A and Murphy MJ. Seasonal
pasture myopathy in horses in the midwestern United States: 14
not been defined. Other cases have been associated cases (1998–2005). J Am Vet Medl Assoc 2006; 229(7): 1134–1141.
with megaesophagus, raising the possibility of gener- 17 Valberg SJ. Muscle conditions affecting sport horses. Vet Clin
alized polymyositis or delayed organophosphate tox- North Am Equine Pract 2018; 34(2): 253–276.
18 Bradley R. Skeletal muscle in health and disease. In Pract 1981;
icity for example being involved. 3(2): 5–13.
Per acute, severe myopathies such as clostridial 19 Cardinet III GH and Holliday TA. Neuromuscular disease of
myositis in ruminants and atypical myopathy in domestic animals: a summary of muscle biopsies from 159
cases. Ann NY Acad Sci 1979; 317: 290–313.
horses15,16 result in recumbency and sudden death. 20 Hodgson DR. Diseases of Muscle. In Equine Medicine and
For a review of syndromes accompanying myopa- Surgery, Collahan PT, Mayhew IG, Merritt AM, Moore JN,
thies in large animals, the reader is also directed to Editors. Volume 1. Mosby, St Louis, MO. 1999; 1482–1496.
21 Piercy RJ and Rivero JL. Muscle Disorders of Equine Athletes.
other general veterinary medical resources.17–26 Chapter 7 in Equine Sports Medicine and Surgery, 2nd edn.
Heavy, recumbent patients affected with final Hinchcliff KW, Kaneps AJ, Geor RJ, Editors. Saunders,
motor neuron—­as opposed to myopathic—­paralytic Philadelphia, PA. 2014: 109–144.
22 Valentine BA. Skeletal Muscle, chapter 15 in Pathologic Basis of
diseases have relatively flaccid muscles and tend not Veterinary Disease. Sixth Edition. Moseby, St. Louis, MO.
to struggle as much as those with hypertonic paral- 2017: 908–953.e1.
ysis associated with tetany and with myelopathies. 23 Nollet H and Deprez P. Hereditary skeletal and muscle diseases
in the horse: a review. Vet Q 2005; 27(2): 65–75.
For this reason, they are somewhat easier to manip- 24 Aleman M. A review of equine muscle disorders.
ulate and to nurse while tetraplegic than those with Neuromuscular Disorders. 2008; 18(4): 277–287.
tetanus and those with cervical spinal cord lesions 25 Freestone JF and Carlson GR. Muscle disorders in the horse: a
retrospective study. Equine Vet J 1991; 23(2): 86–90.
(see also notes on handling recumbent large animals 26 Goedegebuure SA. Spontaneous primary myopathies in
in Chapter 23). domestic mammals: a review. Vet Q 1987; 9(2): 155–171.
 25
Paresis and paralysis of one limb:
monoparesis

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
186 Large animal neurology

The term monoplegia can be used to describe the syn-

dromes that result from lesions in the ventral gray mat-
ter and nerve roots of the brachial and lumbosacral
plexuses, and peripheral nerves and muscles of the
limbs (Figure 25.1). It goes without saying that the most
frequent causes of an animal not using a limb to stand
and walk on are orthopedic, particularly due to injury.
The clinical syndromes accompanying specific limb
nerve lesions are introduced in Chapter 2. On occa-
sion, a lesion involving just thoracolumbar white
matter on one side results in degrees of ataxia, weak-
ness, and dysmetria in only one pelvic limb. Even less
commonly, a cervical (C1–T2) lesion involving white
matter tracts only can result in monoparesis and
ataxia of one thoracic limb with no definitive evi-
dence of the ipsilesional pelvic limb being compro-
mised. This syndrome has been identified in cases of
listeriosis in sheep and S. neurona myelitis in horses.
Monoparesis and monoplegia is a common problem Figure 25.1 Sheep, goats, and pigs with lameness or with weakness of
in large animals with trauma being the most frequent one thoracic limb will totally carry the forelimb and will rest by supporting
known or suspected cause1 (Figures 25.1–25.4). Vague weight on their carpi. This ewe has traumatic brachial plexus injury and ina-
and unusual lameness occurs frequently in large ani- bility to bear weight on the left thoracic limb; soiled carpus indicates that it
has been kneeling to graze.
mals and can be very difficult to evaluate and distin-
guish from neurologic disorders (Figure 25.5).2 It
should be recalled that musculoskeletal diseases are far
It is indeed almost impossible to pass a hypodermic needle
more common than primary neurologic diseases such
into a peripheral nerve that is not held fixed or is against a
that when there is indecision in making a diagnosis,
solid structure such as bone. Thus, although any neurapraxia
common and especially treatable musculoskeletal dis-
can occur immediately from such compounds as procaine in
eases should be ruled out first. In horses, S. neurona
procaine penicillin, any axonotmesis that occurs following
protozoal myelitis can produce selective gray matter
an injection usually takes some hours to days to occur after
lesions that cause such signs and can mimic syndromes
necrosis and inflammation have been induced.
of peripheral nerve disease3 (Figures 25.6 and 25.7).

(A) (B) (C) (D)

Figure 25.2 This young Jersey calf (A–C) and month-­old Thoroughbred foal (D) were both treated with various systemic drugs for illnesses and later
presented for poor protraction and knuckling of one pelvic limb—­right in the calf and left in the foal. An upright positioning and atrophy of the leg
muscles resulted. The calf’s condition improved sufficiently for return to the herd but signs in the foal progressed, and at necropsy examination an empy-
ema was found starting in the deep gluteal region and spreading around the head of the femur, following the sciatic nerve. Sciatic monoparesis most
often occurs in younger patients and is most often due to the misplacement of irritant intramuscular injections in the rump and thigh muscles.
 Paresis and paralysis of one limb: monoparesis 187

(A) (B)

Figure 25.3 This newborn calf (A) was born after an assisted delivery having been involved in a dystocia due to fetal/pelvic malproportion (a hip lock).
The calf could only just support weight on the pelvic limbs on day one (A), had marked extensor weakness and no patellar reflexes. Atrophy of the
quadriceps muscles developed, worse on the right than left (B), and there were needle electromyographic changes consistent with denervation in just
quadriceps muscles. A very satisfactory recovery resulted in many weeks.

(B)

(A) (C)

Figure 25.4 Brachial injury is most caused by trauma forcing the scapula(e) against the ribs causing compression of the nerve roots, plexus and nerves,
and blood vessels, all comprising the brachial neurovascular complex. This results in poor thoracic limb function and often degrees of muscle atrophy as
shown (A–C). If there is simply neurapraxia, then full function can return in hours to a couple of weeks. With degrees of axonotmesis, function will not
return completely with some atrophy remaining. Signs can improve markedly but may take up to a year or so to stabilize. Radial functional loss and triceps
and extensor carpi radialis muscle atrophy are often the most striking aspect of this injury. But additional, selective, forearm and arm atrophy, and
electromyographic evidence of denervation of other muscles often indicates a more widespread lesion. Accompanying this there so often is suprascapular
denervation atrophy of shoulder muscles (Sweeney) as seen here. Because the suprascapular nerve is so exposed and vulnerable to pressure-­induced
damage as it runs around the cranial border of the scapula, it is usually assumed that this component of the syndrome is a separate lesion, with its own
criteria for repair, or not.
188 Large animal neurology

(A) (B) (C)

Figure 25.5 Examples of non-­neurologic disorders that need to be considered with apparent hypometric limb movements include rupture of the peroneus
tertius in a horse (A), a cattle beast with patellar fixation (B), and a sheep with severe proximal limb (elbow) arthritis and almost no limb flexion (C).

(A) (B)

Figure 25.6 Selective and marked muscle atrophy is the hallmark of final motor neuron disorders. In large animals with long hair coats and fleeces,
such atrophy can be difficult to detect. Also, any lameness can rapidly result in proximal limb atrophy of shoulder and gluteal regions. However, middle
gluteal muscle atrophy to the extent seen here (A) with no overt crippling lameness is almost certainly L6 final motor neuron or cranial gluteal nerve
disease. This also could well be the result of selective myopathy. In this instance it was most likely due to lumbar myelitis associated with S. neurona in
a horse in the UK that originated from Argentina. Likewise, the selective, unilateral quadriceps femoris atrophy (B) in a North American horse was due to
a selective L5–6 ventral gray horn lesion caused by S. neurona detected at postmortem examination.

Acute and specific, distal ulnar, musculocutane- precise zones of skin insensitivity that occur consist-
ous, and median nerve paralyses do not for the most ently with selective limb nerve ablations are referred
part result in well-­defined and permanent gait abnor- to as autonomous zones and have been identified in
malities, detectable muscle atrophy, and particularly the limbs of horses.9–11 These relatively small zones
analgesic zones as are seen in small animals.4–8 The are shown in Figure 2.15 and should be evaluated
 Paresis and paralysis of one limb: monoparesis 189

(B)

(A) (C)

Figure 25.7 Marked atrophy of proximal limb muscles (A) can occur without any identifiable ataxia and weakness being evident at a walk. This New
Zealand bred Thoroughbred ex-­racehorse residing in the UK suffered atrophy of the muscles of the right hind limb as outlined (A and B). This occurred
over a 3–4-­month period without any prominent gait or postural change or any identifiable sensory deficits present. The horse was seronegative for
antibodies to S. neurona. To explain the marked and selective muscle atrophy shown (B and C), the lesion must be L6–S2 ventral gray horn or proximal
cranial and caudal gluteal nerves as they pass over the dorsolateral sacrosciatic ligament. LL: longissimus lumborum; GM, GS, GP: gluteus medius, super-
ficialis, profundus; ST: semitendinosus; BF: biceps femoris. Source: Image courtesy of Amanda O’Gorman.

using a two-­ step, cutaneous pinch technique, as postures and movements, and a further caution here is
described in the neurologic examination (Chapter 2). that bilateral severe forelimb injuries can mimic such
Single suprascapular, musculocutaneous, median, ungainly postures and movements, also discussed as
and ulnar nerve sections can also result in little if brachial paresis and paralysis in Chapter 26.
any permanent gait abnormality.8 Horner syndrome,
associated with brachial plexus lesions, and focal
areas of sweating due to local loss of the sympathetic Video sequences replayed in slow-motion can be most
supply to skin in the horse can be findings that are useful for observing some forms of monomelic gait
helpful in localizing a lesion. Repeated, careful, docu- abnormalities, as well as movement disorders, during
mented neurologic examinations and repeated EMG the process of differentiating musculoskeletal from
studies are most helpful in evaluating these cases of neurologic disorders.
final motor neuron syndromes. It is worth iterating
that at least in adult (tall) large animals, in practice it
can be 2 weeks or more before denervation potentials Of interest here is the sidewinder syndrome seen
are consistently demonstrated by needle EMG study when the pelvic limbs and caudal body remain to
following known peripheral motor nerve injury, one side or the other while the cranial body and tho-
possibly a simple effect of axonal length. racic limbs move straightforward. Such gait can be
The functional and morphologic categories of referred to as ‘crab walking’ and ‘having two tracks,’
neurapraxia, axonotmesis, and neurotmesis and the and can be associated with many causes of very
process of Wallerian-­like neuroaxonal degeneration asymmetric spinal cord, nerve root, and orthopedic
and regeneration are pertinent to understanding disorders including vertebral fracture, fractured pel-
diseases of peripheral nerves and are further discussed vis, fibrocartilaginous embolic myelopathy, equine
in Chapters 2 and 4. protozoal myelitis, and ruptured round ligament of
Bilateral prominent pelvic limb extensor (femoral) the head of femur.12
paresis causes the patient to stand with all pelvic limb
joints flexed and only able to support weight with assis-
tance to posture with the flexed limbs acting as props, References
when placed well forward under the trunk. Paraparesis 1 Furr M. Disorders of the peripheral nervous system. In Equine
and paraplegia are further discussed in Chapter 23. Neurology, Furr M, Reed S, Editors. Blackwell Publishing,
Ames, IO: 2008; 329–336.
Bilateral thoracic limb extensor paralysis with relatively 2 Dyson SJ. Unexplained forelimb lameness possibly associated
normal pelvic limb function results in some ungainly with radiculopathy. Equine Vet Educ 2018; 32(S10): 92–103.
190 Large animal neurology

3 Furr M. Equine protozoal myeloencephalitis. In Equine 7 Vaughan LC. Peripheral nerve injuries: an experimental study
Neurology, Furr M and Reed S, Editors. Blackwell Publishing, in cattle. Vet Rec 1964; 76: 1293–1304.
Ames, IO. 2008; 197–212. 8 Henry RW. Gait alterations in the equine pectoral limb produced
4 Hahn CN, Mayhew IG and MacKay RJ. The nervous system (Ch by neurectomies. PhD Thesis, Ohio State University. 1976.
11). In Equine Medicine and Surgery, Collahan PT, Mayhew IG, 9 Blythe LL. Neurologic examination of the horse. Vet Clin
Merritt AM and Moore JM, Editors. Vol 1. 55th ed. Mosby-­Year North Am Equine Pract 1987; 3(2): 255–281.
Book Inc., St Louis, MO. 1999; 863–996. 10 Blythe LL. Autonomous zones for the limbs of horses. Pers
5 Diesem CD, Hunter MA and Rankin JS. The effects on equine Comm 1988.
gait produced by neurectomies of the major nerves of the pelvic 11 Blythe LL and Kitchell RL. Electrophysiologic studies of the tho-
limb. Anat Histol Embryol 1985; 14: 82–83. racic limb of the horse. Am J Vet Res 1982; 43(9): 1511–1524.
6 Dyce KM, Sack WO and Wensing CJG. Textbook of Veterinary 12 Paulussen E, Versnaeyen H, Deneut K, Chiers K and van Loon G.
Anatomy. WB Saunders, Philadelphia, PA. 1987; 542–95, Sidewinder syndrome associated with partial rupture of the liga-
697–728. mentum capitis ossis femoris. Vet Rec Case Rep 2018; 6(1): e000505.
 26
Bilateral brachial paresis to paralysis

Bilateral thoracic limb extensor (brachial) paresis smaller ruminants (Figure 26.1) ultimately results
to paralysis with relatively normal pelvic limb in the affected patient weight-­b earing mostly on
function results in some ungainly postures and pelvic limbs such that the thoracic limbs are
movements, varied due to species and weight of ­p assively flung forward during locomotion as a
patient. Such prominent paresis to paralysis in kangaroo without weight-­ b earing to any great

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
192 Large animal neurology

extent. Occasionally, such patients, especially goats, port weight with the extended thoracic limbs act-
learn to walk on predominantly the pelvic limbs. ing as props and the sternum close to the ground.
This has occurred with listeric myelitis and with This has occurred due to bilateral brachial plexus
bilateral brachial compression in sheep tightly compression associated with external trauma and
confined in metabolism cages. Piglets and espe- with the neuromyopathy that can follow general
cially pigs suffering from selenium toxicity with anesthesia. Bilateral cervicothoracic ventral gray
thoracic limb paralysis use their snout to help sup- column lesions due to S. neurona and West Nile
port weight and to move forward. Heavy cattle and virus poliomyelitis also have resulted in this syn-
particularly heavy horses with prominent brachial drome (Figure 26.2C). Acutely, such affected heavy
final motor neuron disease and even bilateral patients may collapse over on the thoracic limbs to
structural limb problems including fractures nose-­dive, and this syndrome bears resemblance to
involving just the thoracic limbs can, with some that caused by the dopamine antagonism com-
maneuvering, posture crouched, with the thoracic pounds (Chapter 34).
limbs extended as if bowing in prayer (Figure 26.2). Also pertinent here are the ill-­defined thoracic
Using neck and pectoral girdle muscles and any limb forelimb lameness cases that do not appear to
remaining limb extensor muscle function, they can have an orthopedic lesion as the cause but have some
quickly learn with assistance to fling both thoracic evidence of neurologic disease possibly associated
limbs forward together to advance and again sup- with radiculopathy.1

(A) (B)

Figure 26.1 A weaned black-­face lamb (A) suddenly developed ataxia and tetraparesis with evidence of mixed leukocytic meningitis. Reflexes were
poor in the thoracic limbs and when made to trot it would stumble on the thoracic limbs to almost somersault and would posture and jump on the pelvic
limbs as a kangaroo. This likely represents another example of the syndromes caused by C6–T2 final motor neuron disease. The lamb was treated for listeri-
osis and the signs were ameliorated greatly. The ram shown here (B) also acted like those sheep suffering from the syndrome referred to as kangaroo
gait. It had compression of the cranial thoracic spinal cord and C8–T2 nerve roots producing marked thoracic limb extensor weakness and was very slightly
weak in the pelvic limbs. When moving it would leap forward with both forelimbs off the ground.
 Bilateral brachial paresis to paralysis 193

Figure 26.2 Lesions involving only final motor

neurons at C6–T2 gray matter, particularly at C8–T1,
result in weakness in the thoracic limbs that can
result in this unusual syndrome referred to as a
praying posture (A and C). This particularly occurs
when the thoracic limb final motor neuron weak-
ness is greater than any pelvic limb central motor
pathway weakness from associated white matter
damage at C6–T2. Thus, such a syndrome can occur (A)
with bilateral brachial plexus trauma, thoracic myo-
pathy, and myelopathies such as those caused by
WNV, metazoa, and especially S. neurona. The
latter was the cause in case 1 (A, B and C) and in (B)
case 2 (D), with the lesion at the C8 segment from
case 1 shown in C. An unusual aspect of this case
was sweating over the cervicothoracic region, but
the absence of sweating over the brachial (C6–T2)
dermatomes as shown in B. Sweating often implies
sympathetic decentralization of the skin with
vasodilation, so that the demarcated absence of
sweating at the lesion site subsequently suggests
that there is localized, regional vasoconstriction, per-
haps due to selective sympathetic overstimulation. (D) (C)

Reference
1 Dyson SJ. Unexplained forelimb lameness possibly associated
with radiculopathy. Equine Vet Educ 2018; 32(S10): 92–103.
 27
Urinary bladder distention, dilated
rectum and anus, and atonic tail: cauda
equina syndrome

This syndrome results from lesions involving sacro- nerve roots supplying the lumbosacral plexus for the
caudal spinal cord segments, spinal nerve rootlets and pelvic limbs. Clinically, it consists of all degrees of
roots of the cauda equina, sacral plexus and peripheral hypotonia, hypalgesia and hyporeflexia of the tail, anus
nerves to the bladder, rectum, anus, tail, and perineum. and perineal region, degrees of urinary bladder paresis,
It is often present without any major gait abnormality and rectal and anal dilatation. A zone of hyperesthesia
because of a minimal involvement of the lumbosacral may surround a well-­demarcated zone of analgesia of

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Urinary bladder distention, dilated rectum and anus, and atonic tail: cauda equina syndrome 195

the perianal skin and can be due to inflammation of Surra.1 Degrees of paralysis of the penis, bladder, and
nerve fibers at the edge of a lesion and to sprouting of pelvic limbs can occur but the generalized signs of
sensory axons attempting repair. This is a common these diseases are more distinctive.
problem and most frequently results from fractures of Clinical signs for this syndrome usually include
the sacrum of horses and crushed tail head in cattle. retention of feces and urine, loss of tone of tail and
Recumbent large animals that have been assisted to anus, and analgesia of the tail and perineum. Abnor­
stand by grasping or tying the tail can have poor tail mality in the pelvic limb gait and muscle wasting are
and anal function. Paraparetic and paraplegic heavy less often seen. The most common cause is a fracture of
animals and immediate postpartum patients that S2, this being much more common than polyneuritis
receive multiple rectal examinations can have poor equi and the miscellaneous myelitides (Figure 27.1).
tone and movement of the tail and anus. Such patients Congenital syndromes related to dysfunction of the
may also have some degree of urinary and fecal cauda equina are usually associated with caudal
retention without necessarily having sacrocaudal vertebral anomalies (Figure 27.2).
segment or nerve lesions, partly due to the lack of Analysis of CSF collected from the lumbosacral
opportunity to posture and strain appropriately. Thus, space can be a useful ancillary aid in diagnosing the
distinguishing final motor neuron paralysis of the cause of this syndrome. This is partly because the CSF
bladder, tail, and anus from central motor neuron sample is likely to be collected from close to the site of
weakness with urinary retention, and from tail and any lesion and thus more likely to reflect associated
anal contusion due to recumbency or ‘dog-­sitting,’ is changes in cytologic analysis and protein content, and
difficult, particularly in heavy recumbent horses. even possibly in immunologic and PCR test results.
When evaluating horses with urinary incontinence Needle electromyography has been useful in deter-
only, consideration must be given to cauda equina mining the extent of muscle denervation and can assist
syndrome and to urinary tract and reproductive organ in monitoring the progress of a disease process, some-
diseases. Included in these diseases would be trypano- times indicating that reinnervation is occurring.
somiasis known variously as Dourine, Nagana, and Measuring conduction velocity across the cauda

(B)

Figure 27.1 Mild to moderate signs of involve- (A)

ment of the sacrocaudal spinal cord segments
resulting in sensory and voluntary and reflex motor
loss of function (A) of the tail anus and perineum
can result from causes such as EHV1 myelopathy,
rabies, WNV myelitis, and helminthiasis. This case
resulted from myelitis suspected as being caused
by S. neurona with signs improving considerably
associated with antiprotozoal therapy. Less than
total loss of function from such diseases indicates
that not all the sensory and final motor neurons
in the gray matter of the S1–Ca segments are
destroyed, as was the case with a migrating hel-
minth causing a hemorrhagic, necrotic myelitis
seen in another case (B). Complete loss of function
of this region is more commonly due to fracture of
S2 destroying all the S2–Ca nerve roots and results
in degrees of urinary and fecal incontinence, uri-
nary bladder overflow (C and D), and subsequent
(C) (D)
scalding of the perineum (D).
196 Large animal neurology

equina has been undertaken in standing horses and

under general anesthesia and can be considered for
evaluating the progress of a disease process. Also, the
measurement of intravesicular and urethral pressure
profiles could well be useful in monitoring horses with
urinary incontinence.2
In considering the differential diagnosis for this
syndrome, the following diseases warrant considera-
tion. Fracture S2 (Figure 27.1 and 27.3) and crushed tail
head3 (Figure 27.4) are probably the commonest cause
and careful palpation and ultrasonographic examination
externally and per rectum are necessary to support the
diagnosis. At least in cattle, the distal cutaneous branch
of the pudendal nerve and the pelvic nerve may be sus-
ceptible to physical and chemical damage from drugs
such as ivermectin plus closantel injected in the region of
the ischiorectal fossa causing urine retention and urinary
(A) bladder rupture.4 In horses, polyneuritis equi should be
considered though it is rare. Evidence of a mixed non-
suppurative inflammatory response on lumbosacral CSF
analysis is supportive for this process. Signs of ataxia and
paraparesis frequently accompany mild to moderate
degrees of urinary incontinence and tail and perineal
hypalgesia and hypotonia with EHV1 myeloencepha-
lopathy, and xanthochromia of CSF without pleocytosis
(B) is often present. Both West Nile virus and S. neurona
can produce degrees of a cauda equina syndrome,
Figure 27.2 Dysfunctional tail, perineum, and sometimes urinary bladder although usually there are other signs to indicate a mul-
and rectum can result from congenital malformations of the sacrocaudal
vertebrae and associated spinal segments. This foal was born with a wry
tifocal or diffuse encephalomyelitis is present. In endemic
tail, a soft fluctuant swelling over the sacral dorsal midline (star), and a areas, rabies virus can result in these signs, probably
deformed anus and vulva (A). There was a degree of urinary and fecal more so if the bite is on a pelvic limb or the tail region.
incontinence present. This was associated with bifid sacral vertebral spines Toxicity due to the ingestion of Sorghum spp., such as
and myelodysplasia of the sacrocaudal spinal cord segments (B) including Sudan, Sorghum, and Johnson grass, is associated with
hydromyelia (arrowhead) and myelomeningocele (arrows). The latter filled
the soft subcutaneous swelling seen and felt on the midline.
ataxia often ­accompanied by mild to moderate urinary

(A) (B)

Figure 27.3 In horses, the most frequent cause of marked and of total loss of function of the structures innervated by the sacrocaudal segments and
nerves—­cauda equina syndrome (A)—­is fracture of S2 vertebra (B).
 Urinary bladder distention, dilated rectum and anus, and atonic tail: cauda equina syndrome 197

flicking the tail excessively.7 Unfortunately, many such

horses also have evidence of variable anal, rectal,
urinary bladder and even pelvic limb paresis, and
perineal hypalgesia to analgesia.7–9 Presumed cauda
equina neuroma formation and axonal sprouting
account for later effects such as marked perineal pruri-
tus and allodynia.
Animals with even a prominent cauda equina syn-
drome can be maintained with nursing care, fecal
softeners, and attention to emptying the rectum
and urinary bladder (Figure 27.1D). Affected patients
often get cystitis with mineral and purulent concre-
tions accumulating in the bladder. Urinary pooling
in the cranial vagina and even in the uterus may become
a significant problem that compromises reproductive
capability. This is compounded by poor innervation
of the caudal reproductive tract so that the reproduc-
tive soundness of such affected mares is dubious at
best. Stallions having even minor residual signs of
sacral involvement have been rendered impotent
because of incomplete erections and have become
Figure 27.4 Crushed tail head syndrome shown here affects cattle and sterile because of urospermia.
results from injuries received during being mounted by other cattle and
possibly when falling backward onto the sacrum and tail. Some deformity
may be evident to the caudal and or sacral vertebrae as was the case with
References
this patient. Neurologic signs relate to combinations of cauda equina 1 Levine ND. Veterinary Protozoology. Iowa State University
deficits of sensory and motor loss of function to the tail, anus, perineum Press, Ames. 1985; 30–37.
(shown), rectum and bladder, and less so to the pelvic limbs. The latter 2 Ronen N. Measurements of urethral pressure profiles in the
takes the form of sciatic, particularly tibial nerve dysfunction consisting of male horse. Equine Vet J 1994; 26(1): 55–58.
some pelvic limb ataxia and postural abnormality seen as the hock flexed 3 Watson C and Penny C. Crushed tail head syndrome in cattle.
Vet Rec 2003; 152(17): 542–543.
and the fetlock knuckled while the foot remains flat on the ground when
4 Castillo-­Alcala F, Brown S, Crawshaw T, et al. Urine retention in
standing. cattle putatively associated with injection of an ivermectin and
closantel anthelmintic formulation into the ischiorectal fossa. N Z
bladder paralysis and less often by perineal hypalgesia.5,6 Vet J 2019; 67(3): 148–154.
5 Varshrey JP, Gupta AK and Yadav MP. Occurrence of ataxia-­
Also, rare cases of verminous myelitis (Figure 27.1B) and cystitis syndrome in horses fed on Sorghum vulgare in India.
neoplasms such as melanoma, hemangiosarcoma, and Indian Vet J 1996; 73(9): 985–986.
lymphosarcoma can be considered in a full differential 6 Bardley GA, Metcalf HC, Reggiardo C, et al. Sorghum spp. neu-
rotoxicity in sheep. Aust Vet J 1995; 72(12): 467.
diagnosis list. 7 Lowder M, Bridges E, Gutierrez A and Padmore C. Tail blocking
A dangerous and unethical tail alteration procedure in a Quarter Horse. Equine pract 1991; 13(6): 17–19.
is tail blocking, which has been defined as “paralyzing 8 Stewart R, Reed S and Weisbrode S. Complications associated
with alcohol tail-­blocks in three horses. Prog Vet Neurol 1990;
the tail to cause it to hang limply.” This practice is 1(4): 476–480.
illicitly performed by caudal epidural and paraverte- 9 Hepworth-Warren KL. Tail Alterations: An Unnecessary and
bral ethanol injection on horses competing in Western Dangerous Procedure. Equine Health Update: Purdue University
CVM. 2015; 17(1): 1–6. https://vet.purdue.edu/search.php?
riding disciplines, such as pleasure and reining classes, q=Tail%20Alterations#gsc.tab=0&gsc.q=Tail%20Alterations&
where horses are penalized for wringing, raising, or gsc.page=1
 28
Pruritus, self-­mutilation, headshaking,
complex regional pain syndrome,
and miscellaneous distressing disorders

Syndromes involving itching, self-­mutilation, head- cord white matter, dorsal gray columns, dorsal root
shaking, and regional hyperresponsiveness, as well as ganglia, dorsal nerve roots, and sensory peripheral
several related miscellaneous disorders, are not terri- nerves. In some cases, such as ruminant nervous
bly common but do appear to be distressing to affected ketosis, a metabolic derangement is assumed to
patients. Lesions associated with these syndromes account for the signs. In others with widespread
have been found in—­or suspected to be in—­a wide lesions such as suppurative meningitis, polyradicu-
spectrum of diffuse and focal sites in the brain, spinal loganglioneuritis, rabies, pseudorabies, and bovine

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
Pruritus, self-­mutilation, headshaking, complex regional pain syndrome, and miscellaneous distressing disorders 199

spongiform encephalopathy, the exact site of the cases have followed localized injury and can be
lesions associated with the hyperesthetic component calmed by temporarily desensitizing the region,
of signs is ill-­determined, and in others still no molec- although permanent neurectomy may not resolve the
ular or structural abnormality has been detected. problem and has made such a syndrome worse.
These are not common problems in large animals; Considerations for pathogenesis include deviant
however, when experienced they can be spectacular, behavior, focal seizures, myelitis, radiculitis, neuritis,
frightening, and distressing to the observer. In the and undetected sources of pain such as enterolith and
context of these problems, it is assumed that there is hormone imbalance.13 Breeding stallions require
itching, self-­mutilation, or tail chasing etcetera without continued, hard exercise as part of their manage-
overt evidence of other problems like dermatologic ment, which can be overlooked. This may be of some
disease such as mange and pediculosis, a generalized significance if the syndrome is one of stereotypic
disease process such as equine multisystemic eosino- behavior stemming from boredom and the release of
philic epitheliotropic disease,1,2 hairy vetch toxicity3 or endogenous opioids afforded by performing the
scrapie,4 or a more generalized or specific neurologic activity.
disease with signs such as seizures or paralysis. Even One aged pony mare showing allodynia and spon-
without such other overt conditions, the clinician taneous and inducible pruritus involving the perineal
must still rule out dermatologic disorders and com- region, which spread up to involve the caudal half of
plete a careful neurologic evaluation. Examples of the body over many months and for the pony to
enigmatic conditions of this type such as intense heat-­ became completely unmanageable and dangerous,
reflex pruritus5 and venous air embolism-­ induced was found to have neuronal loss and astrogliosis
pruritus6,7 are recorded. Sometimes a local intense of the thoraco–lumbo–sacro–caudal dorsal gray
pruritus develops immediately or within hours of an ­columns (Rexed laminae I and II).
intramuscular injection being given, and intense itch- If this is a profound form of stereotypic behavior,
ing has followed routine use of epidural morphine then as with other similar syndromes including
during an orthopedic procedure under general anes- cribbing and weaving, physical punishment and
thesia in a horse.8 Some cases of problematic pruritus obstruction to performing the actions may induce
in horses have responded to the use of anticonvulsant more profound deviant behavior if the animal
drugs (e.g., phenytoin 6–12,mg/kg, BID; gabapentin remains in the same environment.13,22 Thus, the best
20–50 mg/kg, BID).9–12 approach is to alter the environment, feeding prac-
Adult horses with self-­mutilation syndrome can tices, breeding management, exercise program, and
be quite intimidating if not downright dangerous13 social contacts as appropriate to replace the vice
(Figure 28.1). This syndrome often involves mature, with normal activity. In this regard, animal com-
light breed, stallions,14–17 although mares and geldings panionship with a goat, donkey, old barren mare, or
are afflicted.18 The onset may follow a major change in placid gelding has been useful in reducing self-­
environment, exercise program, or breeding regimen mutilation.16,17 Castration has been relatively suc-
such as returning to stud from racing, being laid up cessful in preventing fighting among horses.23
because of lameness, or being taken into a new herd. Certainly, castration will be discussed and can be
Cutaneous lacerations with pieces of flesh missing are tried in cases of self-­mutilation syndrome, but it has
seen, particularly in the pectoral, flank, stifle, and not always been successful; the general environment
thigh regions. Results of routine neurologic workups and management of the animal must be altered to
are essentially unremarkable, and dermatologic causes expect a change in behavior.
of pruritus must be ruled out.5,19 The horse shows Many drug regimens have been tried16,18,24,25 with
spells of looking at its flank, squealing, grunting, spin- little success, and nonpharmacological management
ning, running in circles, kicking, and biting at its body, should also be tried.13,26 Sedative drugs might exac-
but usually can be distracted by human interaction erbate signs, although weekly to monthly doses of
such as with a whip. One gets the impression that the some unlicensed, long-­term sedatives such as reser-
patient does not want to hurt itself; if it did so desire, it pine (1 mg IM or 4 mg PO) or fluphenazine enan-
could completely devour the forelimbs. thate or decanoate (50 mg IM) have been used. The
Forms of localized bilateral, asymmetric, and uni- owner should be cautioned that apparent untoward
lateral pruritus can be baffling to unravel and mostly behavioral reactions have been seen in horses treated
remain idiopathic, even though many causes are to with such drugs (see fluphenazine dyskinesia,
be considered, at least in humans.20,21 Some such Chapter 34). Signs have included spinning in circles,
200 Large animal neurology

(A)

(B) (C)

Figure 28.1 Self-­mutilation syndrome in horses (A) is an enigmatic problem that may well have a neurohormonal basis, but almost certainly does not
represent a consistent morbid neurologic lesion. Nonetheless, it can be a very impressive with the patient damaging itself considerably (close-­up views,
B and C). There do not appear to be triggering tactile stimuli to the clinical signs in comparison to those with suspected paresthesia and complex regional
pain syndrome when the affected area is incessantly attacked or is consistently protected from certain contact stimuli.

adopting a stargazing or a praying posture for management, and possibly short-­term pharmacologic
­prolonged periods, snapping at imaginary flies, and approaches are undertaken.
total distraction and somnolence. Narcotic agonist– Recurrent and chronic pain syndromes with and
antagonist drugs have been used to alter various without demonstrable morbid causes are incredibly
unacceptable behavior in man and animals. These common in human populations.29 Those with no
have been said to be effective in suppressing stereo- structural cause associated do appear to occur in ani-
typic behavior such as tail chasing in the dog,27 and mals, and chronic nerve ligation in animals is used as a
in horses demonstrating crib biting,24 and have been model for neuropathic pain studies.30,31 Complex
tried in self-­mutilation cases.25 Whether or not such regional pain syndrome in humans is a debilitating
regimens of treatment could benefit cases of self-­ clinical pattern of signs falling within the spectrum of
mutilation is not known. Various progestins have neuropathic pain disorders, characterized by a chronic,
been used successfully to obviate aggressive and severe, burning pain sensation and having other
hypersexual behavior in horses.28 Some regimens strict diagnostic criteria.32,33 These are usually ulti-
include 0.4 mg/kg progesterone in oil, IM, daily; mately identified by an area of intense allodynia (pain
0.044 mg/kg altrenogest PO, daily; 60–80 mg response to nonpainful stimuli), hyperalgesia (increased
megestrol acetate PO, per horse, daily; and 2000 mg responsiveness to painful stimuli), objective evidence of
repositol progesterone, IM, per horse, weekly. Finally, local autonomic dysregulation (vasomotor disturbance,
to prevent large wounds from developing special increased or decreased skin temperature, sweating
chain muzzles, or better still, a fixed surcingle-­to-­ abnormalities, and edema), and dermal changes (e.g.,
halter pole (Figure 28.2) may need to be resorted to hyperpigmentation, altered hair growth, and inflam-
when this syndrome is severe, while environmental, matory skin lesions). Many cases can be traced to
Pruritus, self-­mutilation, headshaking, complex regional pain syndrome, and miscellaneous distressing disorders 201

gabapentin, phenothiazine drugs, anticonvulsant drugs,

and others31,32,36,42,43 have been used in attempts to control
signs in patients diagnosed with complex regional
pain syndrome and pain-­associated myelodysplasia.
Currently, there is a lot of interest in the use of cannabi-
noid drugs in treating epilepsy and intractable pain in
humans and animals. Cannabidiol at a dose of 0.5 mg/kg
BID, PO, reducing to 0.33 mg/kg SID, PO, appeared to
be effective in abating signs of marked regional allodynia
for several months in a 4-­year-­old Quarter Horse mare.44
Occasional episodes of bizarre, violent, and aggres-
sive behavior, particularly in horses, for which there
is often no underlying neurologic explanation, are
reported by large animal clients. Certainly, the pos-
Figure 28.2 To prevent a horse self-­mutilating, a fixed surcingle-­to-­ sibility that these are related to transitional estrus or
halter pole can be constructed. A rope is threaded through a rigid polyvi- to isolated seizures does exist. A few unusual findings
nyl chloride pipe running from a surcingle strap to the halter. The rope has
a quick-­release snap on each end that attaches to rings on the surcingle
that have been thought to explain such occurrences
and halter. The patient cannot spin either way but can comfortably graze include fright by the sight or smell of an offending
and lift the head up and down without inconveniencing the horse, even animal or object, stinging nettle, fire ants, earth-
at pasture. quakes, thunder, stray voltage, colic and insects, or
objects in the external auditory canal.45–47
A few adult beef and dairy cattle that frantically lick
­revious history or evidence of previous local or
p and chew on objects to the point of self-­inflicted mouth
regional tissue injury. The spectrum of clinical presen- trauma have been investigated and were found to have
tations is exemplified by the various historical terms neither evidence of extant ketoacidosis, hypomagne-
used to describe this debilitating syndrome including semia and hypocalcemia, nor any neuropathologic
reflex sympathetic dystrophy, causalgia, algodystro- lesions accounting for the syndrome. Some affected
phy, Sudeck atrophy, and post-­traumatic vasomotor cattle in one beef herd recovered spontaneously, beg-
syndrome.33–35 Cases of complex regional pain syn- ging the question of unrevealed ketosis and lipidosis.
drome have been reported in horses (Figure 28.3)36 in Headshaking in horses is a common48 and enigmatic
which the localized profound allodynia has been so syndrome that is best described as the horse acting as
debilitating as to prompt decisions for euthanasia. if a bee has flown up its nose. Considerable empirical
Interestingly, sometimes following a perineural anes- literature exists on this syndrome, but little new has
thetic block that is performed in the limb of a horse, been defined on the syndrome since clinical descrip-
there is a regional strip of reflex vasodilation and tions in the 19th century.50 Clinical signs and empirical
sweating proximal and distal to the injection site. The observations on this syndrome are well described.49–56
regional distribution of this sympathetic response out- Whether any or all cases of idiopathic headshaking
side the resulting analgesic area is like that seen around in horses are associated with a trigeminal neuralgia
the trigger point of horses having complex regional or neuritis, or not, is still quite questionable.49,57–60
pain syndrome. The syndrome has also been diag- However, there is some electrophysiological evidence
nosed in an adult cow following trauma, multiple surgi- that the trigeminal nerve may be dysfunctional,61,62
cal procedures, and eventual amputation of one digit.37 and this has resulted in the syndrome being also
In cases where regional allodynia, pruritus, or
hyperesthesia are investigated, the possibility of forms
of myelodysplasia, especially syringomyelia, should
be considered. The syndrome of Chiari-­like malfor-
“As the head is twitched, there is generally
mation with associated pain and syringomyelia in
considerable motion of the muzzle, the upper
Cavalier King Charles spaniels is well recognized,38,39
lip being moved as though irritated, and if a
and cases of regional pain and allodynia associated
convenient obstacle is near, the lip is rubbed in
with myelodysplasia are reported in horses.40,41
a hurried and quite intense way as though to
Most of the drug regimens mentioned above includ-
dislodge an insect.”50
ing glucocorticosteroids, opioids, NSAIDs, reserpine,
202 Large animal neurology

(B)

(A)

(C)
Figure 28.3 This 11-­year-­old Thoroughbred gelding (A) was presented with a 6-­year history of allodynia, hyperalgesia, hyperthermia, and variable
hyperhidrosis affecting a well-­demarcated region corresponding to cutaneous dermatomes C3–5 on the right side of the neck. The horse frequently rubbed
this area against objects and attempted to scratch it with the right hind foot. Apparent distress caused by allodynia increased when the horse was ridden
particularly when the reins brushed against the affected region. Alopecia and hyperpigmentation were present in the C6 cutaneous dermatome. Local
anesthetic infiltration and attempted surgical extirpation of the C5 vertebral nerve were partly effective in relieving the pain, and a tentative diagnosis of
complex regional pain syndrome was made.36 Sometimes, selective sympathetic decentralization results in regions of sweating (Chapter 29) in association
with evidence of pain and/or pruritus indicating that the autonomic system is also involved in some cases. The next patient here (B) shows regional
sweating restricted to the C5–7 dermatomes on the right side. With time, such areas show hair coat changes as was the case with case (A). The other case
shown (C) developed out-­of-­character, spontaneous avoidance behavior by lifting its forelimbs in turn, flagging its tail, tossing its head, stomping its feet,
and compulsively walking its box whenever approached such that loose bedding could not be used. NSAID, opioid analgesia, and α-­2 agonist drug heavy
sedation was to no avail in controlling this behavior. This activity that was very like that displayed by the previous case (A) was likely a form of compulsive
behavior (see Chapter 5) as there were no trigger points to initiate it.

referred to as trigeminally mediated (sic) headshak- Some cases may well be akin to the syndrome in
ing.48,58,63 Many conditions likely can act as trigger humans known as photic sneezing—­a.k.a. Autosomal
factors for the syndrome,64–68 but no definitive mor- dominant Compelling HelioOphthalmic Outburst
bid neural lesions have been consistently identified.57 (ACHOO).53,56,69,70 The headshaking and face rubbing
Pruritus, self-­mutilation, headshaking, complex regional pain syndrome, and miscellaneous distressing disorders 203

syndrome that can follow damage to the trigeminal nerve foundly distressing to the patient and cause self-­
branches resulting from tumors and from head surgery inflicted lesions is not to be questioned. No attempt
is usually quite fulminant, and unlike the case with typi- is made here to cover such stereotypic or obsessive
cal headshakers, the allodynia can be profound.71,72 and compulsive behavioral disorders or all forms of
A plethora of treatments including antihistamines, abnormal behavior for which there almost certainly is
corticosteroids, applying a small net to cover the nos- no morbid disease of the nervous system (also see
trils and infraorbital neurectomy have been tried for Chapter 5). A discussion of this aspect of veterinary
decades.49,50,53,55,59,60,73 Also, results of sclerosis of the studies is outside the scope of this text, and readers
posterior ethmoidal branch of the trigeminal nerve are referred to expert authorities on the subjects of
on headshaking have not always proved successful ethology, and animal behavior science and medi-
with some unfortunate patients described as frantic cine.15,16,18,23,89–99 Notwithstanding, if an animal with an
and violent postoperatively since the procedure was acquired aggressive problem is euthanized, then thor-
first attempted.60 Recently, uncontrolled trials using ough scrutiny of the CNS should be undertaken. The
relatively noninvasive percutaneous electrical nerve main reasons for this are the possibility of rabies or
stimulation58 and electroacupuncture74 may offer of a spongiform encephalopathy, and for obscure but
therapy to better ameliorate this perplexing, and definitive neuropathologic lesions in regions such as
almost certainly distressing, syndrome. the frontal cortex and limbic system, which have at
Patients, especially mature horses, are frequently least been detected in the brains of aggressive dogs.100
presented with a little or with considerable evidence of Finally no inherited sensory neuropathies causing
painful neck or back problems. Most are evaluated by self-­mutilation with or without nociceptive deficits101,102
lay practitioners, and when all reasonable and quack appear to have been recognized in large animals.
attempts at curing these patients have failed, they often
are presented for veterinary orthopedic and neurologic
evaluation. Only rarely has there been proof that such
patients have spinal nerve root (intervertebral neuro- References
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62 Aleman M, Rhodes D, Williams DC, Guedes A and Madigan Accuracy of ultrasound-­guided intra-­articular injection of
JE. Sensory evoked potentials of the trigeminal nerve for the cervical facet joints in horses: a cadaveric study. Equine Vet J
diagnosis of idiopathic headshaking in a horse. J Vet Intern 2003; 35(7): 657–661.
Med 2014; 28(1): 250–253. 85 Laflin SL, Steyn PF, VanMetre DC, Uhrig JL and Callan RJ.
63 Wilmink S, Warren-­Smith CM and Roberts VL. Validation of Evaluation and treatment of decreased libido associated with
the accuracy of needle placement as used in diagnostic local painful lumbar lesions in two bulls. J Am Vet Med Assoc
analgesia of the maxillary nerve for investigation of trigeminally 2004; 224(4): 533, 565–570.
mediated headshaking in horses. Vet Rec 2015; 176(6): 148. 86 Cousty M, Firidolfi C, Geffroy O and David F. Comparison of
64 Stephenson R. An unusual case of headshaking caused by a medial and lateral ultrasound-­guided approaches for periar-
premaxillary bone cyst. Equine Vet Educ 2005; 17(2): 79–82. ticular injection of the thoracolumbar intervertebral facet
65 McGorum BC and Dixon PM. Vasomotor rhinitis with head- joints in horses. Vet Surg 2011; 40(4): 494–499.
shaking in a pony. Equine Vet J 1990; 22(3): 220–222. 87 Girodroux M, Dyson S and Murray R. Osteoarthritis of the
66 Mair TS. Headshaking associated with Trombicula autumnalis lar- thoracolumbar synovial intervertebral articulations: clinical
val infestation in two horses. Equine Vet J 1994; 26(3): 244–245. and radiographic features in 77 horses with poor performance
67 Moore LA, Johnson PJ, Messer NT, et al. Management of head- and back pain. Equine Vet J 2009; 41(2): 130–138.
shaking in three horses by treatment for protozoal myeloen- 88 Liotta A, Sandersen C, Couvreur T and Bolen G. Technique,
cephalitis. Vet Rec 1997; 141(11): 264–267. difficulty, and accuracy of computed tomography-­ guided
68 Kold SE, Ostblom LC and Philipsen HP. Headshaking caused by a translaminar and transforaminal lumbosacral epidural and
maxillary osteoma in a horse. Equine Vet J 1982; 14(2): 167–169. intraarticular lumbar facet joint injections in dogs. Vet Radiol
69 Dean L. ACHOO syndrome. In Medical Genetics Summaries, Ultrasound 2016; 57(2): 191–198.
[Internet]. Pratt VM, Scott SA, Pirmohamed M, et al., editors. 89 McGreevy P. Equine Behavior. Saunders, Edinburgh. 2012;
Bethesda, MD. National Center for Biotechnology Information 378.
(US). 2015. Available from: https://www.ncbi.nlm.nih.gov/ 90 Waring W. Horse Behavior. 2nd ed. William Andrew,
books/NBK109193/ Norwich, NY. 2002; 456.
70 Whitman BW and Packer RJ. The photic sneeze reflex: litera- 91 Houpt KA. Domestic Animal Behavior for Veterinarians and
ture review and discussion. Neurology 1993; 43(5): 868–871. Animal Scientists. 6th ed. Wiley-­Blackwell, Hoboken, NJ.
71 Gilsenan WF, Getman LM, Parente EJ and Johnson AL. 2018; 448.
Headshaking in 5 horses after paranasal sinus surgery. Vet Surg 92 McAfee LM, Mills DS and Cooper JJ. The use of mirrors for
2014; 43(6): 678–684. the control of stereotypic weaving behaviour in the stabled
72 Fenner MF, Verwilghen D, Townsend N, et al. Paranasal sinus horse. Appl Anim Behav Sci 2002; 78(2–4): 159–173.
cysts in the horse: complications related to their presence and 93 McGreevy PD, Cripps PJ, French NP, Green LE and Nicol CJ.
surgical treatment in 37 cases. Equine Vet J 2018; 51(1): 57–63. Management factors associated with stereotypic and redi-
73 Tutt JFD. Headshaking in horses. Vet Rec 1946; 58: 372. rected behaviour in the thoroughbred horse. Equine Vet J
74 Devereux S. Electroacupuncture as an additional treatment 1995; 27(2): 86–91.
for headshaking in six horses. Equine Vet Educ 2019; 31(3): 94 McGreevy PD, French NP and Nicol CJ. The prevalence of
137–146. abnormal behaviours in dressage, eventing and endurance
75 Dyson SJ. Lesions of the equine neck resulting in lameness or horses in relation to stabling. Vet Rec 1995; 137(2): 36–37.
poor performance. Vet Clin North Am Equine Pract 2011; 27(3): 95 McGreevy PD, Richardson JD, Nicol CJ and Lane JG.
417–437. Radiographic and endoscopic study of horses performing an
76 Garcia-­Lopez JM. Neck, Back, and Pelvic Pain in Sport Horses. oral based stereotypy. Equine Vet J 1995; 27(2): 92–95.
Vet Clin North Am Equine Pract 2018; 34(2): 235–251. 96 Price EO. Farm animal behavior. Vet Clin North Am Food
77 Dommerholt J, Finnegan M, Hooks T and Chou LW. A critical Animal Pract 1987; 3: 217–481.
overview of the current myofascial pain literature – October 97 Overall K. Manual of Clinical Behavioral Medicine for Dogs
2017. J Bodyw Mov Ther 2017; 21(4): 902–913. and Cats-E-Book. St. Louis, MO. Elsevier Health Sciences.
78 Quiroz-­Rothe E, Novales M, Aguilera-­Tejero E and Rivero JL. 2013; 815.
Polysaccharide storage myopathy in the M. longissimus lum- 98 Broom DM. Broom and Fraser’s Domestic Animal Behaviour
borum of showjumpers and dressage horses with back pain. and Welfare. 6th ed. Cabi. 2015: 512.
Equine Vet J 2002; 34(2): 171–176. 99 Houpt KA. New perspectives on equine stereotypic behavior.
79 Licka T and Peham C. An objective method for evaluating the Equine Vet Educ 1995; 27(2): 82–83.
flexibility of the back of standing horses. Equine Vet J 1998; 100 Caldwell DS and Little PB. Aggression in dogs and associated
30(5): 412–415. neuropathology. Can Vet J 1980; 21(5): 152–154.
80 Haussler KK and Erb HN. Pressure algometry for the detection 101 Forman OP, Hitti RJ, Pettitt L, et al. An inversion disrupting
of induced back pain in horses: a preliminary study. Equine FAM134B is associated with sensory neuropathy in the bor-
Vet J 2006; 38(1): 76–81. der collie dog breed. G3 Genes, Genomes, Genetics. 2016;
81 Wijnberg ID, Back W, de Jong M, et al. The role of electromyo- 6(9): 2687–2692.
graphy in clinical diagnosis of neuromuscular locomotor 102 Amengual-­Batle P, Rusbridge C, Jose-­Lopez R, et al. Two
problems in the horse. Equine Vet J 2004; 36(8): 718–722. mixed breed dogs with sensory neuropathy are homozygous
82 Wijnberg ID, Back W and Van der Kolk JH. The use of electromyo- for an inversion disrupting FAM134B previously identified in
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 29
Autonomic nervous system dysfunction

Horner syndrome (Figure 29.1) is the most fre- decreased secretions from the muzzle occurs in cattle.
quently documented form of autonomic dysfunc- Damage to peripheral nerves and vessels in horses
tion recognized in large animals and is discussed does result in regional and dermatomal segments
fully in Chapter 10. Although vasodilation accom- of hyperhidrosis when cutaneous sympathetic fib-
panies sympathetic denervation of skin in all large ers are also affected (Figure 29.2). Following some
animals, sweating occurs only in horses1 whereas perineural anesthetic blocks in the limbs of horses,

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Autonomic nervous system dysfunction 207

there is a regional strip of reflex vasodilation and

sweating proximal and distal to the injection site Symmetric and diffuse dysautonomias such as
that likely represents local sympathetic decentrali- equine grass sickness can result in irregular and
zation. The regional distribution of this sympathetic fluctuant areas of sweating and nonsweating pre-
response outside the resulting analgesic area is like sumably related to the loss of regulation of para-
the aura of hyperesthesia and allodynia seen around sympathetic and sympathetic control of superficial
the trigger point of horses having complex regional blood flow. Interestingly, any process that allows
pain syndrome (Chapter 28). Although well-­ increased peripheral blood flow, such as sympa-
demarcated sweating may not be apparent with all thetic skin denervation, makes for a more attrac-
sympathetic lesions in horses in cold climates, the tive envi­ronment for lice and other ectoparasites.
hyperemia and vasodilation are usually readily
apparent, and with time so are localized skin and Adrenergic agents have powerful sudomotor effects
hair coat changes similar to that seen in chronic and this can be semiquantitated.9 The antithesis of this
grass sickness survivors.2 In very chronic cases, this is the enigmatic and possibly genetically linked syn-
consists of erect hair fibers, a seborrhea, and pig- drome of anhidrosis in horses residing in hot and
mentation. The vast spectrum of clinical signs and humid climates which appears to be the result of unre-
pathologic findings that can be seen in cases of gen- sponsiveness (overstimulation?) of equine sweat
eralized dysautonomia are well described for equine glands to adrenergic command.10,11 A similar effect of
grass sickness (Figure 29.3).3–6 Topical α1-­adrenergic the lack of responsiveness of sweat glands to adrener-
agonists can be diagnostically useful to confirm the gic stimulus appears to be produced by agents such as
induced drug hypersensitivity occurring with sym- macrolide antibiotics12 that are commonly used in
pathetic denervation.7,8 foals and sometimes result in hyperthermia.

(A) (B) (C)

Figure 29.1 Horner syndrome (see also Chapter 10) with prominent facial sweating is clearly evidence of loss of sympathetic innervation to the left
head in this first case (A). As the neural lesion was distal to the guttural pouch, sweating stops at the level of C1–2 (arrowhead). More proximal lesions
along the cervical sympathetic trunk result in sweating occurring further down the neck. Another case of guttural pouch disease causing Horner syndrome
on the right side (B) also shows how well demarcated the sweating on the head usually is. Spinal cord lesions from the brachial intumescence (C6–T2)
caudally can result in sweating on the ipsilesional side of the body with the cranial border of sweating almost at the level of the lesion. This horse (C) had
asymmetric ataxia and tetraparesis with sweating of the caudal neck, thoracic limb, trunk, and hindlimb on one side.
208 Large animal neurology

Figure 29.2 Proximal limb perineural local anesthetic injections some-

times result in variable linear regions of local sweating that dissipate in
minutes to hours as the local anesthetic action abates. Two separate
examples of such patches of sweating after tibial nerve perineural injec-
tions are shown in (A) and (B) with the sites used for skin penetration
indicated (blue rectangles). That this is due to the local blockade of
sympathetic fibers passing with the neurovascular bundles of the major
limb nerve branches innervating blood vessels in the areas demarcated
by sweating, is the most likely explanation. However, that this does not
occur every time a successful perineural block is undertaken and that
the sweating usually projects well proximal to the injection site (B) is
interesting. Likely, there is variation in the final path for peripheral sym-
pathetic fibers when they pass with blood vessels and nerves to tar-
geted terminal blood vessels, and this re-­emphasizes just how far away
from sites of injection local anesthetic solution can migrate along fascial
(A) (B)
planes.

(A) (B)

(C) (D)

Figure 29.3 Components of the syndromes presented with cases of equine grass sickness represent autonomic and pseudosomatic dysfunction. Thus,
many subacute (A) and chronic (B) cases of grass sickness will posture as if generally weak with all four limbs close together. They can also show weight
shifting from one limb to another and muscle trembling, to lose muscle bulk quite fast, all very similar to cases of botulism and of EMND. In contrast,
such cases of equine grass sickness do not generally lie down excessively, and when they do, they have been noted to continue to tremble. Also, there is
minimal EMG and pathological evidence of widespread and marked final motor neuron disease to account for this apparent weakened state. Consideration
is thus given to the possibility that inanition and autonomic failure with poor thermoregulation are major factors in this cluster of signs. Undoubtedly,
swelling and chromatolysis of final motor neuronal cell bodies in ventral gray matter (C; yellow arrows) compared with normal neuronal cell bodies (white
­arrowheads), and in cranial nerve nuclei, is a prominent feature of acute and subacute cases, though whether all these reactive neurons go on to die does
not seem to be determined. Degrees of gastrointestinal hypofunction predominate in the syndromes, and evidence of large colon stasis with secondary
impaction and inspissated, dark mucus covering ingesta is a hallmark of the postmortem findings (D).
 Autonomic nervous system dysfunction 209

References 7 Hahn CN and Mayhew IG. Phenylephrine eyedrops as a diag-

nostic test in equine grass sickness. Vet Rec 2000; 147(21):
1 Jenkinson DM, Elder HY and Bovell DL. Equine sweating and 603–606.
anhidrosis Part 1: equine sweating. Vet Dermatol 2006; 17(6): 8 Hahn CN and Mayhew IG. Studies on the experimental induction
361–392. of ptosis in horses. Vet J 2000; 160(3): 220–224.
2 Doxey DL, Milne EM, Ellison J and Curry PJ. Long-­term pros- 9 MacKay RJ. Quantitative intradermal terbutaline sweat test in
pects for horses with grass sickness (dysautonomia). Vet Rec horses. Equine Vet J 2008; 40(5): 518–520.
1998; 142(9): 207–209. 10 Jenkinson DM, Elder HY and Bovell DL. Equine sweating
3 McGorum BC and Pirie RS. Equine Dysautonomia. Vet Clin and anhidrosis Part 2: anhidrosis. Vet Dermatol 2007; 18(1):
North Am Equine Pract 2018; 34(1): 113–125. 2–11.
4 McCarthy HE, Proudman CJ and French NP. Epidemiology of 11 Johnson EB, Mackay RJ and Hernandez JA. An epidemiologic
equine grass sickness: a literature review (1909–1999). Vet Rec study of anhidrosis in horses in Florida. J Am Vet Med Assoc
2001; 149(10): 293–300. 2010; 236(10): 1091–1097.
5 Cottrell DF, McGorum BC and Pearson GT. The neurology and 12 Stieler AL, Sanchez LC, Mallicote MF, et al. Macrolide-­induced
enterology of equine grass sickness: a review of basic mecha- hyperthermia in foals: role of impaired sweat responses. Equine
nisms. Neurogastroenterol Mot 1999; 11: 79–92. Vet J 2016; 48(5): 590–594.
6 Doxey DL, Milne EM, Gilmour JS and Pogson DM. Clinical and
biochemical features of grass sickness (equine dysautonomia).
Equine Vet J 1991; 23(5): 360–364.
 30
Vertebral and paravertebral problems:
stiff neck and sore back

Patients, especially mature horses, are frequently ing these patients has failed, they often are presented
presented with degrees of evidence of the problems for veterinary orthopedic and neurologic evalua­
referred to as neck pain and sore back (Figures 30.1 tions.1–3 Some cases of acquired torticollis will be due
and 30.2). Most are evaluated by lay practitioners, to soft tissue damage in the neck, but the possibility
and when all complementary therapy aimed at cur­ of spinal cord disease must still be entertained

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Vertebral and paravertebral problems: stiff neck and sore back 211

(Figures 30.1 and 30.3).4 Only rarely has there been

proof that such patients have spinal nerve root dis­ Wherever the meningeal worm of white-­tailed deer
ease, but they often can have evidence of a painful (Parelaphostrongylus tenuis) occurs, this specific
process most particularly forms of cervical and thora­ parasite, in its selective meanderings through dorsal
columbar discospondylosis (Chapter 33) and degen­ cervicothoracic gray matter, must be considered as a
erative intervertebral osteoarthritis.5 Regarding likely cause of nontraumatic cervical torticollis.
cervical intervertebral neurovascular bundle com­
pression, it should be recalled that, especially for
the caudal cervical region, the ventrolateral-­directed The use of ultrasound-­guided injection of dor­
intervertebral orifices can be poorly defined on lat­ sal articular process joints and adjacent periar­
eral radiographs and articular processes need to be ticular tissues with many agents has become
very, very enlarged to compromise its contained common practice in treating back and especially
neurovascular bundle. Many cases undoubtedly have neck problems, at least in horses,22,27 and can give
various forms of painful vertebral and paravertebral considerable short-­term pain relief. A word of
problems including tendonitis, arthritis (Figure 30.4), caution however is reasonable. Many cervical ver­
myofascial fibrosis, and similar abnormalities. These tebral and articular process fractures are not
conditions require objective evaluation6–12 before clearly visible on plain lateral radiographs and can
empirical and directed systemic and local treatments produce minimal scintigraphic definition. Thus,
can be entertained.13–19 Certainly, newer imaging with the possibility of a fracture being present in a
techniques can be useful in attempting to interpret case of neck pain in a horse, considerable caution
the clinical significance of common vertebral column should be used in deciding to inject analgesic and
anatomic variations, and of age-­related and wear and anti-­inflammatory ­compounds with the possibil­
tear degenerative changes.14,20–26 ity of the fracture then becoming unstable. The

(A) (B)

Figure 30.1 Determining the real presence and relevance of apparent back pain and assigning such to any neurologic syndrome is problematic
and subjective. Shown in (A) for example is a young horse that suffered trauma to the atlantooccipital region and became ataxic and tetraparetic.
The exaggerated lordotic and sinking stance adopted in response to mild pressure applied to the dorsum was interpreted as being due to the ataxia
and central motor pathway weakness interfering with the normal response to such stimuli. On the other hand, horses with evidence of severe but
chronic myopathy such as the bay gelding in (B) can respond excessively to manipulation of the lumbar dorsum. However, it is all the other clinical
findings rather than such a response to palpation that must be used in forming a diagnosis. The elevated serum CK activity and exacerbation of
apparent lumbar hyper-­responsiveness to digital manipulation as shown increased with exercise.
212 Large animal neurology

(A) (B)

(C) (D)

Figure 30.2 Reluctance to fully bend or move the neck (A), deviations of the cervical vertebral column, and unusual positioning and movement
of the head, neck and thoracic limbs can all reflect cervical pain and can all occur without signs of spinal cord compression. Apart from soft tissue
conditions such as a wire in the neck, these syndromes may occur acutely with fracture (B), luxation (C), and fusion (D) of cervical vertebrae. The
horse in (A) had degenerative joint disease involving the C6-­7 and C7–T1 articulations and reluctantly postured as shown to eat from the ground.
Such a posture may also occur with rare, painful sternal disorders. Acute fractures of C3–4 articular processes (B) (white arrow), resulted in severe
degenerative joint disease and subsequent cervical spinal cord compression many months later. True subluxation of adjacent vertebrae, being align-
ment beyond the maximal range of joint movement, does not often occur in adult large animals without fractures being present but it is present
here (C) in a polo mare at C6–7 (black arrow). The base of the mare’s neck appeared unusual at its attachment to the thorax and the mare was
lame on both thoracic limbs without any limb lesions being found after a full orthopedic evaluation. Acquired, complete fusion of vertebral arches
and articular processes does not often occur without damage and fusion of the vertebral bodies (D). This aged horse had a history of a fall as a
young horse and at the time had no neurologic abnormalities. The dorsal fusion of C5 and C6 is complete and modeled as to appear as a primary
malformation (white arrowheads).

same can be said for vertebral manipulation, particu­ reader is referred to some selected literature
larly when undertaken under general anesthesia28 on syndromes involving neck pain and back
when catastrophic consequences are possible. The problems.6,10–12,15,16,18,19,29–43
 (A) (B)

Figure 30.3 This Thoroughbred mare (A) and Nubian doe (B) both suffered from acquired, fixed, cervical torticollis. This means that there was
lateral curvature of the neck in more than one direction, as depicted here by the red lines, and the neck could not be straightened onto the median
plane. Additionally, following the initiating fall, the mare constantly held the neck and head low and was unable or unwilling to raise it to feed from
an elevated site. In the acute stage of acquired cervical torticollis, with or without evidence of ataxia and tetraparesis and when the neck is not
fixed in its abnormal position, forms of myelopathy should be considered as possible causes.

(A)

(B) (C)

Figure 30.4 In some cases, there is compelling evidence that there truly is back pain causing unusual gait and postural signs. Thus, this teenage
riding pony began refusing jumps and would posture abnormally with constant flexing of the pelvic and even thoracic limbs at rest (A) and espe-
cially when a rider was in the saddle. Signs initially improved in response to NSAID therapy. Somewhat indiscriminate local anesthetic injections
into the paravertebral soft tissues temporarily alleviated some of the postural abnormalities. Thoracolumbar radiographs (B) did give evidence of
intervertebral arthritis (arrows) that on postmortem examination was represented by modeling of the caudal thoracic and cranial lumbar dorsal
articular processes (C) with accompanying synovial proliferation.
214 Large animal neurology

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20 Didierlaurent D, Contremoulins V, Denoix JM and Audigie F. pain and their clinical significance. Ann Cong Europ vet diag
Scintigraphic pattern of uptake of 99mTechnetium by the cervi­ imaging. Vet Radiol Ultrasound 2019; 61: 110.
cal vertebrae of sound horses. Vet Rec 2009; 164(26): 809–813. 43 Veraa S, de Graaf K, Wijnberg ID, et al. Caudal cervical vertebral
21 Withers JM, Voute LC, Hammond G and Lischer CJ. morphological variation is not associated with clinical signs in
Radiographic anatomy of the articular process joints of the Warmblood horses. Equine Vet J 2020; 52(2): 219–224.
 Part III
Mechanisms and Specific Diseases
Chapter 31 Congenital, familial, Chapter 35 Nutritional diseases 481
and genetic disorders217
Chapter 36 Metabolic diseases 503
Chapter 32 Infectious, inflammatory,
and immune diseases 292 Chapter 37 Neoplasms and other tumors 521

Chapter 33 Physical, chemical, Chapter 38 Multifactorial and idiopathic

and thermal causes373 disorders532

Chapter 34 Toxic diseases 412

 31
Congenital, familial, and genetic disorders

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
218 Large animal neurology

Diseaseɸ Page Central and peripheral axonopathy in

Rouge-­des-­pres (Maine Anjou) calves 240
Citrullinemia219
Progressive myelopathy in cattle 240
Maple syrup urine disease 219
Spinal muscular atrophy 240
Status spongiosus of white matter in
Motor neuron disease in Romney lambs 241
newborn Gelbvieh-­cross calves 220
Shaker calf syndrome 241
Cerebellar hypoplasia 220
Neurofibrillary degeneration 241
Lissencephaly with cerebellar hypoplasia
Myofibrillar hypoplasia in piglets
in Churra sheep 221
(congenital adductor weakness) 241
Cerebellar abiotrophy 221
Progressive paresis in Angora goats 242
Bovine familial convulsions and ataxia 222
Occipitoatlantoaxial malformations (OAAM) 242
Ovine cerebellar cortical degeneration
Cervicothoracic subluxation in sheep 243
(daft lamb disease) 223
Bovine complex vertebral malformation 243
Dandy–Walker syndrome 223
Congenital chondrodystrophy in
Arnold–Chiari malformation 223
beef cattle 244
Miscellaneous cerebellar degenerative
Myelodysplasia and congenital vertebral
disorders223
malformations244
Congenital myoclonia (neuraxial edema) of
Optic nerve hypoplasia 246
Hereford calves 224
Congenital stationary night
Congenital myoclonus in peruvian paso
blindness—nyctalopia246
foals and Merino lambs 224
Congenital sensorineural deafness 247
Lavender foal syndrome; tetany syndrome
Bilateral convergent strabismus and
in Arabian foals; coat color dilution
exophthalmos247
lethal227
Divergent strabismus 248
Spinal dysmyelination in crossbred American
Juvenile pendular nystagmus 248
Brown Swiss and in Braunvieh calves 227
Congenital flaccid mandible in newborn
Congenital tremor syndrome 227
calves and lambs 248
Encephalopathy in neonatal Swaledale
Spastic syndrome of adult cattle 248
lambs229
Spastic paresis of calves 249
Miscellaneous forebrain malformations 230
Familial neuropathy of Gelbvieh cattle 250
Familial epilepsy in cattle 230
Congenital hypomyelination sensory
Benign epilepsy of foals 230
neuropathy251
Narcolepsy with cataplexy 231
Hindlimb spasticity in piglets 251
Narcolepsy without cataplexy 232
Arthrogryposis251
Sporadic idiopathic (essential, primary)
The myotonias 253
hypersomnia in adult patients 232
Myotonia congenita 254
Hydrocephalus232
Myotonic dystrophy and myotonic
Hydranencephaly233
myopathy255
Limousin cattle encephalopathy 233
Nonmyotonic congenital and familial
Simmental cattle encephalomyelopathy 233
muscular dystrophies and myopathies 256
Encephalomyelopathy of Angus calves 234
Hyperkalemic periodic paralysis in horses 257
Romney sheep spongiform
Congenital myasthenic syndromes 258
leukoencephalomyelopathy234
Porcine stress syndrome and malignant
Lysosomal storage diseases 234
hyperthermia258
Portosystemic vascular anomalies 235
Equine glycogen storage metabolic
Neuroaxonal dystrophy 235
myopathies259
Familial ataxia in Merino Sheep 238
Mitochondrial myopathy 260
Progressive ataxia of Charolais cattle 238
Equine familial isolated hypoparathyroidism 261
Bovine progressive degenerative
References261
myeloencephalopathy (weaver syndrome) 238
Degenerative axonopathy in Tyrolean In the general order of: Brain and diffuse CNS; Spinal cord;
ɸ

gray calves (Demetz syndrome) 238 Peripheral nerve; Neuromuscular junction; Muscle
 Congenital, familial, and genetic disorders 219

These diseases are incorporated together in this As with other chapters, the diseases are ordered such
chapter because there is a proven, suspected or pos- that the predominant region(s) involved follow a­ natomic
sible relationship with the patients’ genotype, even if sites from those involving the diffuse brain, then the
in utero insults can be responsible for some of the forebrain, brainstem, cerebellum, spinal cord and PNS,
syndromes. and, finally, neuromuscular and muscular sites.

A selection of international animal genetics diagnostic laboratories (accessed September 2021) is given in the
table below.
Company URL

Animal DNA Diagnostics https://www.animaldnadiagnostics.co.uk/

Animal Genetics Inc. https://www.animalgenetics.us/Home.shtml
Center for Animal Genetics & Generatio https://generatio.de/en/services
Genetic Testing at Gluck http://getgluck.ca.uky.edu/
Genetic Visions - ST https://www.geneticvisions.com/services/services-new.aspx?language=english
Laboklin http://www.laboklin.co.uk/laboklin/GeneticDiseases.jsp
SLU Animal Breeding & Genetics https://www.slu.se/en/departments/animalgenetics/about-the-department/hgenlabeng/
UC Davis, Veterinary Genetics https://www.vgl.ucdavis.edu/services/index.php
VetGen Services https://www.vetgen.com/equine.html
Zoetis Services LLC https://www.zoetisus.com/animal-genetics/dairy/index.aspx

the frequency of the citrullinemia gene to 0.23%8 to

Citrullinemia 2.27%.2 Moreover, introduction of a vector expressing
Aminoaciduria is an acutely fatal, neurologic disorder arginosuccinate synthase into affected calves has
affecting Holstein–Friesian calves at 1–7 days of age. resulted in the transduction of hepatocytes, partial
Affected calves are normal at birth, but develop dull- correction of the enzyme defect, and clinical improve-
ness, facial twitching, blindness, head pressing, aimless ment in the affected calves’ clinical signs.9,10
walking, tremor, stupor, seizures, and opisthotonus,
resulting particularly from hyperammonemia. They Maple syrup urine disease
usually die within several hours to 4 or 5 days from the
onset of signs. Diffuse cerebrospinal edema is evident Maple syrup urine disease is another aminoaciduria
as fine, spongy neuropil, with astrocytic swelling and that affects newborn calves of the Polled Shorthorn
some neuronal degeneration p ­resent on histologic and Polled Hereford breeds.1,11,12 They are bright,
examination.1,2 It is caused by a point mutation in the alert and active at birth, and then show signs of pro-
gene coding for arginosuccinate synthetase (AS) gressive dullness, ataxia, difficulty rising, and pad-
resulting in a deficiency of this urea cycle enzyme. The dling of the limbs at 1–3 days, terminally in lateral
absence of AS causes elevated plasma citrulline con- recumbency with opisthotonus and are dead by
centrations (2.25 ± 1.64 mmol/L; normal 0.19 ± 1 week of age. The urine may smell like burnt sugar.13–16
0.07 mmol/L), elevated CSF citrulline concentrations Branched-­chain amino acids, valine, isoleucine, and
(1.72 ± 0.88 mmol/L; normal 0.0005 ± 0.0001 mmol/L), leucine, accumulate in body fluids because of a heter-
and lowered plasma arginine concentration (0.04 ± ogenous molecular defect in affected breeds resulting
0.02 mmol/L; normal 0.06 ± 0.02 mmol/L), with mas- in a deficiency of mitochondrial branched-­chain α-­
sively elevated blood ammonia concentrations but keto acid dehydrogenase activity.9,14–16 Vacuolation
without elevated serum argininosuccinic acid concen- (status spongiosus) becomes severe and widespread
tration or plasma liver enzyme activity in affected in the white matter of the optic pathways, cerebellum
calves.3–5 Identification of elevated citrulline concen- and cerebrum, and in the gray matter of the brain-
tration in prenatal amniotic fluid can identify affected stem and spinal cord in affected calves.13,17
calves in utero.6 The progenitor bull for most cases has The disease is an autosomal recessive disorder due
been identified,2,5 and the identification of the mutant to mutations in one of the genes coding for the
DNA sequence in body fluid and tissue samples can branched-­chain α-­keto acid dehydrogenase (BCKD)
be used in diagnosis of the disease.7 Screening for complex.9,18–20 Identification of, and not breeding
the genetic defect in breeding bulls has reduced from, carrier heterozygote animals has resulted in a
220 Large animal neurology

reduction of the frequency of the phenotype.16,17 cerebellar cortex were reduced. In Hereford calves
Earlier reports of a lethal syndrome in Hereford that are usually recumbent from birth, at least one
calves21 may have been maple syrup urine disease. disease is believed to be the result of an autosomal
There is very good evidence that hyperornith- recessive trait, which results in combinations of
inemia, hyperammonemia, and homocitrullinuria hydrocephalus, polymicrogyria, stenosis of the
occurred in several Morgan weanling foals showing mesencephalic aqueduct, and severe cerebellar cor-
progressive, variable somnolence, circling, and tical maldevelopment. Cataracts, retinal dysplasia
seizures.22 with detachment, and myopathy are also seen.
Signs of cerebellar dysfunction are stable from
Status spongiosus of white matter birth and are usually accompanied by cerebral or
other signs.24,25 Inherited cerebellar hypoplasia in
in newborn Gelbvieh-­cross calves
Shorthorn26 and Illawarra Shorthorn and Shorthorn
A distinctive neurological syndrome was identified cross27 calves occurred in Australia at an annual
in newborn male and female calves in a stabilized prevalence of 1% of newborns, but up to 8% on
Gelbvieh × Red Angus crossbred herd. Affected severely affected farms.26 Signs of hypometric,
calves were born full term, had constant whole-­body wide-­based ataxia, and head tremor were seen at
tremors when stimulated, and remained in lateral birth and remained stable. A marked scarcity of
recumbency until death or euthanasia at several days cells in the granular and Purkinje cell ­layers and
of age.20 There was diffuse, moderately severe, bilat- thinning of the molecular layer were identified.27
erally symmetrical, status spongiosus with Alzheimer Ayrshire, Angus, and unknown breeds of calves
type-­II cells throughout the white matter of the brain. also have been suspected of having hereditary cere-
No myelin deficits were evident though vacuoles bellar hypoplasia. The mode of inheritance of most of
were due to cleaved myelin sheaths. Neither recog- these congenital cerebellar hypoplasia syndromes is
nized mutation of branched-­chain α-­keto acid dehy- thought to be autosomal recessive.28
drogenase complex was identified making this A reproducible, congenital, cerebellar maldevelop­
disorder distinct from maple syrup urine disease. A ment—­ presumed to be genetically determined—­
genetic defect and the action of an in utero insult, occurred as an outbreak in several litters of Wessex
such as a toxin or virus, could be considered in the Saddleback × Large White piglets.29 Piglets were
etiology. ­unable to stand at first and showed perverse limb
movements. With time they were able to walk with sig-
nificant dysmetria, at which time body tremor was
Cerebellar hypoplasia
seen. Depletion of granular and Purkinje cells and
Signs of cerebellar dysfunction are evident when the Purkinje axonal swellings were present in the cerebel-
affected newborn animal begins to move and walk. lum of affected piglets.
Signs are nonprogressive and indeed, unlike cere- Permanent recumbency associated with severe
bellar abiotrophy (degeneration), may abate with cerebellar hypoplasia has been seen in a 6-­day-­old
time. By far the most common detected and sus- Thoroughbred colt.30 Also, profound jerky and dys-
pected causes of congenital cerebellar hypoplasia in metric though strong movements characterized a
ruminants and pigs, often associated with other congenital syndrome in two Paso Fino foals, which
defects such as hydranencephaly and arthrogrypo- were unable to sit sternal or to stand, even after a
sis, are viral infections of the developing fetus (see month of nursing care in one foal (IGM, pers. obs.).
Infectious, Inflammatory, and Immune diseases, Wide floppy movements of the head and trembling
Chapter 32). Additionally, several toxins including eyeball movements were also present. Both foals had
organophosphates, again acting in utero, can be cerebellar hypoplasia (cerebellum <6% total brain;
associated with cerebellar disease in offspring. normal >8.5%) and depopulation and degeneration
The first description of bovine hereditary cere- of cells in the granular and cerebellar pyramidal
bellar hypoplasia was in Hereford calves.23 Affected (Purkinje) layers.
calves were recumbent and exhibited stiff thrashing Defective or delayed development of the cerebel-
movements of the limbs. Opisthotonus and tremor lum with no documented lesions has been seen in
were also mentioned. The cerebellums were small neonatal cerebellar syndromes in cattle31 and in
in size, and cell numbers in all layers of the foals.32 In the latter cases, signs were not seen until a
 Congenital, familial, and genetic disorders 221

few days of age and waned by a few weeks of age, compromised expression of the candidate gene MutY
­suggesting an acquired disorder may be more likely. homolog (MUTYH), with perhaps more than one
abnormal variant.50
Lissencephaly with cerebellar hypoplasia Signs are typical of diffuse, symmetric, cerebellar
disease. A base wide stance and hypermetric or hypo-
in Churra sheep metric ataxia may be prominent, although some
A syndrome of lissencephaly with cerebellar hypo- affected animals show a hypometric gait at a walk
plasia has occurred in Spanish Churra milking sheep that becomes hypermetric at faster gaits. As with
that are born showing recumbency, an inability to many neurologic diseases that result in abnormal gait
walk unassisted and muscular rigidity.33 There is in large animals, affected animals may pace at a walk
almost total lissencephaly with marked cerebellar (two-­beat walk). No weakness occurs. Severely
hypoplasia, and a deletion in the gene encoding ree- affected animals—­particularly piglets—­may use their
lin (RELN) has been identified and is considered a noses to assist in posturing. A head bob, intention
strong positional and functional candidate defect as tremor, and especially an absent menace response
reelin plays critical roles in neuronal migration and with intact vision and normal pupillary light and
layer formation.34 dazzle reflexes can be found.
The term abiotrophy is derived from Greek:
a = absence; bios = life; trophic = nourishment. There
Cerebellar abiotrophy is a presumed deficiency of a vital, trophic substance
These clinical syndromes, for the most part, are not in cells (cerebellar neurons in this instance), which
congenital. Affected animals have a normal gait for a results in the degeneration and depletion of cerebel-
period postnatally and then demonstrate a syndrome lar pyramidal (Purkinje) and granular cells that may
related to progressive cerebellar degeneration.25,35,36 be regarded as premature apoptosis.51 Ultimately, the
Arabian, Arabian cross and Gotland pony foals of cerebellum usually becomes small and less than circa
either sex are affected, usually between 1 and 8% of total brain weight.31,38,46,52.
6 months of age, rarely at birth.37–40 Oldenburg41 and Histologically (Figure 31.1), evidence of degenera-
Eriskay Pony foals and juvenile mixed-­breed goat tive Purkinje and granular cells and swollen Purkinje
kids42 are usually 1–2 months old when the signs first axons (torpedoes) may be prominent.25 Because of
occur. Affected Yorkshire piglets are usually great histologic variations in Holstein calves,43,44,52
3–12 weeks old,25 and Holstein calves are either Yorkshire piglets,25 and Merino sheep, 3,36 more than
affected at birth43 or are 3–8 months old44 when signs one form of cerebellar abiotrophy may exist in these
are noticed. Affected Charolais45 and Wiltshire46 breeds. In Merino sheep, a thalamic–cerebellar neu-
lambs show progressive cerebellar signs from 1 to ropathy (sic) suspected to be genetic has been
2 months of age, but Merino sheep are 3–6 years described36 accompanied by more diffuse cerebellar,
old3,36 at the onset of signs. These all are believed to brainstem, and spinal cord signs and lesions.
be cases of cerebellar abiotrophy wherein there is an Unusual findings of focal mineralization with mild
inherited metabolic defect in cerebellar pyramidal gliosis in the rostral thalamus53 and axonal swellings
(Purkinje) cells causing a delayed cell dysfunction in the habenular nucleus49 of affected Arabian foals
and death. may represent similar vulnerability of these thalamic
Usually, a progressive dysmetric gait abnormality neurons to the inherent insult/deficit affecting
with head tremor occurs, but the progression of signs ­cerebellar neurons. It may also reflect trans-­synaptic
varies. In Yorkshire piglets and Oldenburg foals, pro- neuronal degeneration.
gression is abrupt, whereas in Arabian foals and in Based on the signalment, history, and neurologic
Charolais and Wiltshire lambs, signs may progress examination, a presumptive diagnosis can be made.
insidiously. The incidence of disease has been Several clinicopathologic findings have been
recorded as 1.2% in Gotland ponies,38 but as high as described in a group of six affected Arabian foals
5–8% in families of Arabian horses.47,48 One or more which may assist in diagnosing cerebellar abiotrophy
founding sires have been identified in the Arabian in that breed.53 The CSF protein content was elevated
horse disease,49 and an autosomal recessive mode of to 2.04, 2.07, and 2.68 g/L in 3 of 6 foals and the
inheritance is shown or suspected in most breeds. CSF-­CK activity was elevated to 62 and 21 U/L in 2 of
The disease in Arabian foals is associated with 4 foals. The EEGs of all 6 were abnormal, showing
222 Large animal neurology

Bovine familial convulsions and ataxia

Aberdeen Angus and Angus cross calves with this
disorder are affected at birth or by a few months of
age.36,59,60 Many Polled Hereford cross calves of a sim-
ilar age61,62 and one 9-­month-­old Charolais calf 63 are
reported to be affected by a similar if not identical
disorder. This disease has been classified as a cerebel-
lar cortical atrophy or abiotrophy, but the presence of
paroxysmal events interpreted as convulsions makes
it notably different.
(A)
After being born recumbent and unable to rise,
calves demonstrate one or several convulsive episodes
usually in the first few days of life. After standing, or
when first observed at days to weeks of age, a wide-­
base posture, ataxia, and a mild intention tremor are
seen in calves that survive several of these episodes.
Signs abate, and by 12–15 months the convulsive
­episodes rarely occur such that by 2 years of age survi-
vors are clinically normal.61,64 Up to 30% of the calves
in a herd may be affected.61,64
This disorder is seen as waxing and waning signs
of cerebellar disease. At times, the extensor tone
(B)
and opisthotonus is so strong that the animal falls to
the ground in an apparent convulsive episode, but
Figure 31.1 Clinical syndromes resulting from various types of cerebel-
lar degeneration and abiotrophy can be congenital or delayed, and with rest it becomes ambulatory again. The dura-
­progressive, static, or improving. There is evidence of degeneration of tion of such paroxysmal recumbency may be up to
particularly cerebellar pyramidal (Purkinje) cells (A) in these tissues from 10 h.61 These convulsive episodes may be true cere-
a Holstein calf with delayed cerebellar abiotrophy showing depletion of bral seizures, but more closely resemble paroxysmal
soma and contracture and vacuolation (open arrows) of pyramidal cells
exacerbations of cerebellar signs, so-­called cerebel-
when compared with the normal pyramidal cell layer (open stars) in a
control calf brain (B). lar fits. Several factors that corroborate this state-
ment are as follows: the relationship to excitement
and induced movement; the ease with which the
episode can be aborted by positioning the calf
prominent synchrony and abrupt frequency changes upright and calming it; the absence of signs of auto-
compared to unaffected horses. The use of morpho- nomic involvement; the absence of lethargy and
metric MR imaging may assist in making a clinical blindness, even after prolonged episodes lasting
diagnosis.42,54 several hours; and the absence of abnormalities on
A genotypic test for cerebellar abiotrophy in the EEG tracings.59,64 Also, during these episodes, two
Arabian breed is available,55 although the affected affected Angus/Holstein crossbred calves were
genotype has been identified in a few unaffected found to be easy to attract to a human’s presence
Arabian horses, likely attributable to downstream and could suck on offered fingers.
modifying genetic cofactors.56 Similar or identical In summary, prolonged paroxysmal events are
mutations have also been identified in a Danish Sport dominant clinical signs in the first 2–3 months,
Horse, Bashkir Curly horses, Trakehner horses and thereafter cerebellar ataxia becomes prominent and
Welsh Ponies, all with confirmed Arabian ancestry.57 can resolve.
The outlook is grave for moderately to severely There are fusiform, spheroidal, or argyrophilic
affected animals, although some calves with late swellings found on Purkinje cell axons.65 Early in the
onset and mild signs can recover to an acceptable disease, these may be difficult to detect. Unaffected
state43 and some affected sheep and ponies have parents of affected calves may have similar changes.
­survived for many years.3,38,58 Recovered calves have fully resolved lesions.
 Congenital, familial, and genetic disorders 223

The disease may be inherited as an autosomal Although the clinical syndrome can be quite
dominant gene with incomplete penetrance.64 There distinctive, differentiation from Border disease,
­
is no specific treatment, and although affected calves hydrocephalus, and swayback requires histologic
may have to be destroyed, many survive and can be examination.69 Indeed, the interpretation of the
salvaged. In the UK, the disease has been controlled cause of loss of cerebellar cortical neurons and of
by gradual elimination of affected lines of Aberdeen gliosis as being a genetic defect is problematic as
Angus cattle.65 variable and intermittent hypoxia, as well as other
insults in fetal and term lambs can result in prefer-
Ovine cerebellar cortical degeneration ential changes in these groups of cells.70,71
(daft lamb disease)
Dandy–Walker syndrome
This rare disease, or group of diseases, occurred in
many breeds of newborn lambs in the UK and Congenital agenesis of the caudal cerebellar vermis
Canada.66 Affected lambs with daft lamb disease type (central lobe) and cystic dilation of the caudal
A (DLD-­A) have great difficulty rising, and only ­ventricular system has been seen in a lamb,72 a kid,73
some can walk with wide-­based, ataxic movement. several calves,28,74,75 and a Quarter Horse and a
They may wander, circle, and stagger. Head tremor Thoroughbred foal.76–78 All of these cases can be lik-
and wide swinging head movements may be seen, ened to the Dandy–Walker syndrome in children in
and most stand and sit with the head and neck hyper- which there are often other midline malformations.79
extended to the point that the poll reaches the with- In some calves and foals, there was also agenesis of
ers. Usually, they are bright and can suckle but most the corpus callosum that can often accompany this
die if considerable nursing care is not offered. pathologic syndrome in other species. Affected
The syndrome of profound cervical lordosis as ­animals can be incapacitated at birth,76 while others
seen in such cortical cerebellar lesions as described in have survived up to 6 months with signs mostly
DLD can be difficult to distinguish from the same ­referable to the cerebellar hypoplasia.72,74,77
head and neck posture seen with marked forebrain
disease such as polioencephalomalacia. In the latter, Arnold–Chiari malformation
there can also be limb extensor rigidity, but this is not
always seen. Differentiation requires scrutiny for A maldeveloped cerebellum with elongated cerebel-
other evidence of cerebral verses cerebellar deficits. lar tonsils protruding through the foramen magnum
The clinical syndrome may be related to the neu- is part of the Arnold–Chiari malformation seen in
ropathologic lesions described in DLD-­A.66 In this human infants and in calves of many breeds. Many
form, cerebellar Purkinje cell degeneration and cases reported in large animals are stillborn, but, with
Bergmann glial proliferation occur. However, sug- survival, signs associated with other malformations—­
gestions of weakness, patellar hyperreflexia, blind- especially hydrocephalus and spina bifida—­ often
ness, and deafness make purely cerebellar disease overshadow signs of cerebellar disease.80–84
unlikely. Also, in what is claimed to be an identical
syndrome (DLD-­B), patients have been described as Miscellaneous cerebellar degenerative
having no histologic cerebellar lesions.67 Indeed, the
characteristic head and neck posture (stargazing)
disorders
with the dorsum of the head often resting on the It can be difficult to distinguish genetic, toxic, and
withers, but even decreased tone in the neck muscles infectious causes of selective neurologic disorders
and wide swinging movements of the head, are most such as cerebellar degeneration.85–87
reminiscent of bilateral vestibular disease.67 Further Mature, medium-­wool Merino sheep demonstrat-
confounding factors are the indications of skeletal ing dysmetric, wide-­based ataxia, head tremor, loss
fragility67 and myopathy,68 at least in DLD-­B. of balance, and paresis have had cerebello-­thalamic
The disease has been likened to familial convul- neuronal degeneration and more diffuse Wallerian-­
sions and ataxia in calves,63 and is thought to be like fiber degeneration in brainstem and spinal cord.
inherited as an autosomal recessive trait.66,67 This can be distinguished from four other potential
However, environmental factors have not fully been abiotrophies of Australian Merino sheep and is likely
excluded from the pathogenesis of the syndromes. hereditary.36,88
224 Large animal neurology

A more necrotic degenerative disease involving the congenital reflex myoclonus in two Merino cross
­
olives and lateral cuneate nuclei as well as Purkinje lambs from South Africa, but there were no histo-
cell degeneration resulted in progressive ataxia and pathologic lesions detected.99 Whether these discrep-
head tremor in a juvenile American Miniature ancies reflect phenotypic variations of one or more
Horse.89 Two distant relatives probably were also genetic disease(s), or a genetic disease and one or
affected, thus a genetic basis was suspected. more acquired (in utero) disease(s), is unclear.
At least the congenital myoclonia in Polled
Hereford calves appears to be an autosomal recessive,
Congenital myoclonia (neuraxial edema) inherited disorder.92,100 The molecular substrate for
of Hereford calves this disease appears to be a nonsense mutation in the
Newborn Horned Hereford, Polled Hereford, and gene for the α-­1 subunit of the inhibitory glycine
Hereford cross calves are affected with a rather typi- receptor that leads to a reduction in spinal cord
cal syndrome of congenital myoclonia.90,91 When rec- ­glycine receptor levels by 80–90%, also resulting in
ognized, other cases will have previously occurred in overexpression of cerebral γ-­aminobutyric acid
the herd. Inability to stand and hyperesthesia when receptor function.101,102
being handled are immediately evident signs. The There is no treatment for this stable or progressive
gestational period is shortened to a mean of 274 days disorder, and the hyperesthesia and spontaneous and
compared with 284 days for unaffected calves.90 stimulus-­initiated myoclonic jerks do not respond to
Affected calves are bright and alert but remain routine doses of many muscle relaxant and anticon-
recumbent from birth. Muscle tremor may be pre- vulsant drugs.90,100 Affected calves should be
sent, but whole body, repetitive and widespread, destroyed, and the sire and dam should not be used
muscle contractions (myoclonia) and rigidity (myo- for breeding stock.
tonia) can be prominent. Periods of such tetanic
muscle spasms of all four limbs and the neck and In clinical practice, we come across cases in young
head, along with temporary apnea, are initiated by cattle involving various neurologic syndromes for
­
voluntary effort, by handling the calf, and especially which we are suspicious of an inherited basis and we
by tapping the calf on the tip of the nose. After initia- try to make sense of the disparate references to such
tion of whole-­body muscular spasms, it takes several disorders in order to advise a client appropriately. We
seconds to a minute for the calf to relax, although it have thus curated Table 31.1 to include the common
never achieves total relaxation. Muscle tremor ceases clinical syndromes in young cattle that are covered in
with longer periods of rest. Amazingly, suckling does this chapter to help us distinguish those that have rec-
not initiate rigidity and there usually is no dystocia. ognized genetic basis and those for which a definitive
Nystagmus or jerky eye movements may be seen. The genetic cause is suspected but wanting. This is not
frequently found hip joint lesions92 appear to be encyclopedic and excludes the primary cerebellar dis-
mechanical damage associated with the sustained eases, storage diseases, epilepsy, narcolepsy, and the
and intermittent muscle contractions. morbid brain and spinal malformations that are
Degrees of vacuolation of the brainstem and spinal ­covered elsewhere in this chapter.
cord are frequently found at postmortem examina-
tion.91 Such status spongiosus (incorrectly inter-
preted as neuraxial edema) may be prominent in Congenital myoclonus in Peruvian Paso
white matter as has been reported most often from
California93 and the UK.91 It also may be present in
foals and Merino lambs
gray and white matter in affected Horned Hereford94 Three young Peruvian Paso horses were affected with
and Polled Hereford91 calves. Degrees of hypomyeli- congenital myoclonus and demonstrated hyper-­
nogenesis have also been reported.91 In many cases, responsiveness to tactile and auditory stimuli that
notably those reported from Australia, no consistent resulted in inexhaustible, diffuse, myoclonic contrac-
CNS lesions are found.90,92,95 tions. All three foals could be assisted to stand and would
Other syndromes, such as “Doddler” calves,96 walk,135 and one had a “bunny hopping” gait when forced
degenerative axonopathy,97 selective cerebellar degen- to move.136 As with the Polled Hereford calves with myo-
eration,98 and congenital spongiosus in Gelbvieh clonia congenita (that could not stand and walk), there
calves (below), may also represent this disease. was a deficit in the inhibitory spinal cord glycine recep-
An identical clinical syndrome was reported as tor levels but only to 40–60% of control levels.
Table 31.1 Congenital, familial, and genetic disorders in calves with commonly occurring neurologic syndromes‡

Disease Alternate name Breeds Age at onset Initial signs Progress Cause Lesions Comments Selected
(Human disease ) references
Citrullinemia Holstein–Friesian 1–7 days Forebrain Rapid Mutation in gene Spongy neuropil, Hyperammonemia 1, 2
tremors coding urea cycle astrocytic swelling,
enzyme neuronal
degeneration
Maple syrup urine disease Organic acidemia Polled Shorthorn 1–7 days Forebrain Rapid Mutation in genes Widespread status Build-­up of isoleucine, 1, 11, 12, 36
and Polled coding branch spongiosus leucine, valine
Hereford breeds chain α-­keto acid
dehydrogenase
(BCKD)
Status Spongiosus of white Gelbvieh × Red Newborn Whole body tremor on Rapid Possibly genetic Status spongiosus In utero insults not ruled 20
matter Angus stimulation Alzheimer type-­II cells out
Congenital myoclonia Neuraxial Edema Horned Hereford, Newborn Recumbent Slow Mutation in α-­1 No consistent CNS Signs relate to 90, 91, 101,
Polled Hereford, Tremors subunit of glycine lesions overexpression of 102
Hereford cross myoclonia receptor GABA function
myotonia, tetany on
stimulation
Doddler calves Texas Hereford Newborn Severe clonic and tonic Static Lethal autosomal None consistent Possibly congenital 96
muscle spasms recessive mutation myoclonia
Ataxic eyeballs
Degenerative axonopathy Holstein–Friesian Newborn Opisthotonus head Some improvement Presumed inherited Widespread Syndrome variable 97, 103
tremor, nystagmus, Wallerian-­type
blindness? Especially neuronal fiber
when stimulated. degeneration
Spinal dysmyelination Hereditary spastic Crossbred American Newborn Recumbency Static Mutation in SPAST Defective myelination SPAST codes spastin 104–107
paraplegia Brown Swiss, opisthotonus body gene axonal degeneration protein
Braunvieh tremor astrocytosis
Congenital tremor Jittery Calves Jersey Newborn Tremor of limbs and Usually recumbent Recessive sex-­linked Marked 108
Shorthorn usually head, ataxia at birth, but hereditary trait hypomyelination +/-­ 109
Can improve over Axonal loss +/-­
Angus-­Shorthorn 110
weeks–months Cerebellar hypoplasia
Gelbvieh/Red Angus 20
Holstein Friesian 111
Many 28
Limousin cattle (Subacute Necrotizing Limousin and 1 month + Hypermetric ataxia Slow; few months Likely mitochondrial Cavitating necrosis Survive <4 months 36, 112, 113
encephalopathy Encephalopathy; Limousin-­X Blindness DNA mutation – optic chiasm and
Leigh Disease) Aggressiveness as for Leigh cerebellar peduncles
Disease Diffuse CNS fiber
degeneration
 Simmental cattle (Subacute necrotizing Simmental and 5–12 months Hypermetric ataxia Rapid; few weeks Likely mitochondrial Necrotic lesions in Ultimate recumbency 36, 114, 115
encephalomyelopathy encephalopathy; Simmental-­X Weakness DNA mutation – brainstem and
Leigh disease) as for Leigh spinal cord gray
disease matter
Progressive ataxia of Charolais 6+ months Weakness Slow; 6–24 months Single nucleotide Demyelination Recumbent by 24 months 116–118
charolais cattle Ataxia polymorphism in Pale eosinophilic Unusual ataxic urination
the coding region plaques especially in
of the KIF1C gene cerebellar peduncles
and medulla
oblongata
Bovine progressive Weaver Syndrome Brown Swiss 6+ months Weakness Slow; 3–4 years Likely nonsynonymous Neuronal fiber Possibly in US Watusi 119–121
degenerative Ataxia SNP in PNPLA8 degeneration cattle
myeloencephalopathy gene spheroids
Purkinje cell degeneration
Degenerative axonopathy Demetz Syndrome Tyrolean Gray 4–6 weeks Weakness Slow; months Potential bovine Spinal and PNS neuronal Recumbent by 12 months 122, 123
(Charcot-­Marie-­ Ataxia MFN2 gene fiber degeneration Very like Charcot-­Marie-­
Tooth disease) mutation Tooth disease-­2A2
(CMT2A2)
Central and peripheral Syndrome des veaux Rouge-­des-­pres 2–6 weeks Weakness Moderate; Single nucleotide Spinal neuronal fiber Paraplegia predominates 124, 125
axonopathy tourneurs (Turning (Maine Anjou) Ataxia 1–3 months polymorphism in degeneration
calves syndrome) the SLC25A46 Spheroids
gene
Progressive spinal Murray Gray Newborn to Weakness Variable; Suspected to be Neuronal fiber 126, 127
myelopathy months Ataxia weeks–months genetic degeneration
Chromatolytic neurons
Holstein × Gir 3 months Dysmetric ataxia Rapid; 1 month Spinal neuronal fiber Thoracic limbs worse 128
degeneration
Spinal muscular atrophy American Brown 1–8 weeks Weakness Rapid; weeks Bovine FVT1 gene Nonapoptotic final Bronchpneumonia 129, 130
Swiss-­X Recumbency mutation is strong motor neuron Resemblance to SMA-­1 in
Danish Red candidate degeneration humans but not same 106
gene defects
Holstein–Friesian 131, 132

Shaker calf syndrome Horned Hereford Newborn Generalized tremor Possible temporary Suspected to be Neurofilament Inanition 133
Difficulty rising remission genetic accumulation in Pneumonia
Weak gait, aphonia Progressive over CNS, PNS, ANS
weeks (motor) neurons
Neurofibrillary Afrikaner cattle Young stock Tetraparesis to Variable Unknown Spinal neurofibrillary May well be acquired 134
degeneration tetraplegia accumulation and
Weak neck neuronal fiber
degeneration
‡
Not including cerebellar, epileptic, sleep, storage, and morbid malformation disorders.
 Congenital, familial, and genetic disorders 227

A very similar syndrome to the myoclonia seen in Congenital tremor syndrome

Hereford calves also occurred in two newborn Merina-­
cross lambs in South Africa. They were unable to stand Newborn piglets, lambs, occasionally calves, and
but could support some body weight and could suckle rarely foals are affected by the Congenital Tremor
with assistance. No lesions were detected on routine Syndrome. It is hereditary in Saddleback (UK) and
histopathologic examination performed at 2 weeks of Landrace pigs,143 in Jersey,108 Shorthorn109 and
age.99 Angus-­Shorthorn110 calves, and possibly Quarter
Horse foals.144 At birth or shortly after, degrees of
tremor of the limbs and usually the head are seen.
Lavender foal syndrome, tetany syndrome Some affected animals appear more ataxic than oth-
in Arabian foals, and coat color dilution ers. Signs are usually not progressive, and animals
lethal may improve, even to a normal state, over several
weeks to months. Physical examination is unre-
Newborn Egyptian Arabian foals with unusual coat markable unless the neonate is a “runt” or it cannot
color can be bright but recumbent from birth and nurse, then cachexia will occur. Lambs have a hairy
demonstrate episodes of tetanic muscle contrac- fleece and difficulty gaining weight.145 Grayness to
tions with opisthotonus and paddling limb move- the coat has been seen in Holstein calves in associa-
ments both spontaneously and in response to tion with this syndrome.
tactile stimuli such as testing limb reflexes.137,138 Fine to jerky tremor, usually of the limbs, trunk
The coat has striking iridescent silver to pale laven- and head are seen in affected animals. They may have
der color, hence the name lavender foal syn- a base-­wide stance and a hypometric or rocking-­
drome.139 There are no neuropathologic lesions to horse gait. Such signs of cerebellar ataxia can be so
account for the syndrome,137 thus a genetic neuro- severe that affected neonates cannot stand unas-
chemical defect, such as a glycine receptor gene sisted.108 Ataxia is present, but usually without weak-
dysfunction, is suspected. A single base pair dele- ness. The tremor can often be enhanced with
tion in the MYO5A gene has been found responsi- excitement and movement and usually abates with
ble for lavender foal syndrome with an allele rest and sleep. Shaking Piglets146 and Dancing Pig
frequency of 1.62% for Arabian horses from Disease147 are hackneyed but descriptive terms used
Europe.140 Another study found 10.3% of Egyptian in pigs, as are Hairy Shaker Disease in lambs148 and
Arabian horses, and 1.8% of non-­Egyptian Arabian Jittery Calves.108
horses were identified as carriers.141 The syndrome of congenital tremor, most particu-
larly in pigs, consists of varying degrees of cerebellar
Spinal dysmyelination in crossbred American and spinal cord white matter signs and lesions; however,
Brown Swiss and in Braunvieh calves sometimes no histologic abnormalities are present.
Table 31.2 summarizes the clinical, pathologic, and
Numerous reports define an autosomal recessive
biochemical characteristics of these syndromes,
disease of congenital recumbency with limb exten-
which have been studied in most detail in pigs.149,150
sion, moderate opisthotonos, and degrees of body
Hog cholera/swine fever, is caused by a Pestivirus,
tremor, occurring in Braunvieh (Swiss brown) and
and is well known to cause congenital tremor in pig-
American Brown Swiss cattle as well as in several
lets that may be accompanied by additional systemic
European cattle breeds upgraded with American
and nervous syndromes, especially cerebellar dis-
Brown Swiss lines.104 Signs are the result of deficient
ease.150–152 Usually variations of cerebellar hypoplasia
and defective myelination and lesser degrees of con-
and cerebrospinal hypomyelinogenesis (Type-­A CT
current axonal degeneration and astrocytosis, par-
in pigs) are found at necropsy.
ticularly involving the dorsal, dorsolateral, and
Other viruses including atypical porcine pestivi-
sulcomarginal spinal cord funiculi.105–107 The gene
rus, porcine circovirus-­ 2, and possibly porcine
responsible for bovine spinal dysmyelination resides
teschovirus are now recognized as common causes of
on bovine chromosome 11142 and has been defined
CT.146,147,153–156 Type-­AV congenital tremor associated
as a mutation in the SPAST gene, making it similar
with in utero organophosphate exposure may be
to one form of the human disorder hereditary spas-
more frequent than initially thought.153,154,157,158
tic paraplegia.104
Table 31.2 Diagnostic characteristics of the common diseases resulting in congenital tremor syndrome in pigs

Type and cause*

A-­I A-­II A-­III A-­IV A-­V B

Hog cholera Other viruses** Genetic, Genetic, Chemical, Unknown
sex-­linked recessive autosomal e.g., trichlorfon
recessive

Field observations
Proportion of litters affected High High Low Low High Variable
% piglets affected in litter 40% 80% 25% 25% 90% Variable
Mortality Medium-­high Low High High High Variable
Gender Both Both Male Both Both Both
Breed of dam Any Any Landrace Saddleback Any Any
Recurrence with rebreeding No No Yes Yes Yes ?
Duration of outbreak <4 months <4 months Indefinite Indefinite Variable ?
Macroscopic observations
Cerebellum:whole brain (≤0.08 = abnormal) ↓ ~ ~ ~ ↓ ?
Spinal cord size (weight) ↓ ~ ↓ ↓ ↓ ?
Microscopic observations (CNS)
Myelin deficiency + + + + + ?
Myelin aplasia (partial) −­ −­ −­ −­ −­ ?
Oligodendrocytes swollen + + −­ −­ −­ ?
Oligodendrocytes reduced ~ ~ + ~ ~ ?
Neurochemistry (spinal cord)
Total DNA ↓ ~ ↓ ↓ ↓ Variable
Whole lipid/g ↓ ↓ ↓ ↓ ↓ Variable
Cerebrosides/g ↓ ↓ ↓ ↓ ↓ Variable
Lipid hexose:phosphorous ratio ↓ ↓ ↓ ↓ ~ Variable
Cholesterol esters reflecting demyelination + + −­ + −­ ?
Serology
Maternal antibodies to virus + + −­ −­ −­ −­

Notes: + present; −­absent; ~ not significantly changed; ↓ decreased; ? unknown.

* Type-­A = a form of congenital tremor with defined pathological characters and known etiology; Type-­B = a form of congenital tremor as yet inadequately characterized and/or of unknown etiology.
** At least atypical porcine pestivirus and porcine circovirus-­2, possibly porcine teschovirus.
Originally reprinted by permission from Bradley and Done149 and modified from Done et al.150 and Mayhew.151
Source: Modified from Bradley and Done149
 Congenital, familial, and genetic disorders 229

Confirmation of the diseases in pigs can be by Diffuse status spongiosus throughout the white
histology and histochemistry of myelin lipids (see matter of the brain has been seen in a congenital
Table 31.1). There is no treatment, but many ani- tremor syndrome with peripheral blindness in a
mals recover with time. Considerations of genetic stabilized herd of Gelbvieh/Red Angus crossbred
influences, infectious agents, and organophos- cattle. The areas of myelin vacuolation were accom-
phates should be made clear to the owner. Future panied by Alzheimer type II astrogliosis. Lesions
identification of precise genetic markers present were most prominent in the reticular formation,
in purely genetic forms of this syndrome will medial longitudinal fasciculus, cerebellar pedun-
make diagnosis and control more accurate and cles, optic tracts, internal capsule, and several gray
useful. matter areas.20
One distinct syndrome in Pietrain piglets involved Affected calves of many breeds showing congeni-
high-­frequency (~15 Hz) tremor that occurred only tal tremor have had varying degrees of hypomyeli-
while the newborn piglets were standing and resolved nogenesis and cerebellar hypoplasia.28 The same
with sternal and lateral recumbency along with general lesions were present in two captive Eland
­difficulty walking.159 This probably inherited condi- Antelope and two sibling Santa Gertrudis calves
tion was referred to as Campus Syndrome, and showing degrees of congenital tremor and cerebellar
although likely to be inherited there is no evidence of dysmetria.
electromyographic or pathologic neural or muscular Several other descriptions of congenital clinico-
lesions present to account for the syndrome, making pathologic syndromes in newborn calves, lambs, and
it a model for orthostatic tremor in humans.160 Some goats are documented, some associated with central
authors relate the syndrome of splayleg in piglets to and/or peripheral myelin and/or axonal lesions and
congenital tremor, but this syndrome is likely a dis- with and without tremor as the principal sign.97,110,167–171
tinct inherited disease.161,162 Most probably, these represent several different dis-
Border Disease, also referred to as Hairy Shaker eases with acquired and inherited etiologies.97,111,172,173
Disease, was originally identified in lambs from the
Scottish–English border and is a form of hypomyeli-
nogenesis associated with in utero infection with a Encephalopathy in neonatal Swaledale
Border disease virus, a Pestivirus that shares some
lambs
antigens with classical swine fever virus and bovine
viral diarrhea virus (BVDV).163 Clinical expression of This interesting syndrome is a presumptive breed-­
Border disease virus infection in a flock of sheep related condition identified in hill breeds includ-
includes barren ewes, abortions, stillbirths and birth ing, but not exclusively, Swaledale lambs.174,175
of small, and weak lambs. Individual affected lambs Lambs with this disease are normal at birth, but
can show tremor, abnormal body conformation, and rapidly become dull and develop seizures to suc-
hairy fleeces (so-­called hairy-­shaker or fuzzy lambs). cumb by 3–14 days of age. There are symmetrical
Infection of fetuses can result in persistently infected lesions of marked neuropil rarefaction, capillary
lambs that are viremic, antibody negative, and con- proliferation, and astrocyte necrosis or depletion,
stantly excrete virus, being a potent source of often with relative preservation of neurons.
infection.163 Adjacent white matter shows vacuolation and vari-
Holstein–Friesian calves with congenital tremor able astrocyte activation. These lesions are promi-
and occasional tetany, degrees of incoordination, nent in the tegmentum, olives, and thalamus. The
absent menace response (without blindness), and clinical presentation is quite distinctive with clini-
nystagmus have been found to be persistently cal signs of head tremor, trismus, and stiffness,
infected with BVDV in an outbreak in Holland164,165 progressing to seizures and commencing between 3
and UK.166 Signs varied in severity, and in some and 21 days of age. There are clinicopathologic
calves the syndrome tended to improve. similarities of this disorder with Leigh’s syndrome
Histologically, there is hypomyelination in the cen- in human infants that is associated with several
tral nervous system, most severe in calves that genetic defects in mitochondrial oxidative phos-
remained recumbent.166 phorylation chain enzymes.
230 Large animal neurology

Miscellaneous forebrain malformations some calves. This would make a purely genetic form
of epilepsy somewhat questionable; however, this
Many congenital and inherited brain malformations may have been a form of benign adolescent epilepsy
occur that involve the forebrain. These are well as seen in Arabian foals (below). A description of
described in calves.28 Certainly, several in utero familial epilepsy occurring in certain Swedish Red
neurotropic virus infections, including Akabane,
­ cattle185 lacks clinicopathologic and genetic detail to
Aino, bluetongue, bovine viral diarrhea, and draw conclusion as to the cause.186
Schmallenberg viruses, often have resulted in epizo-
otics of neonatal neurologic syndromes relating to
induced forebrain malformations in ruminants.86,176 Benign epilepsy of foals
Stillbirths and syndromes of somnolence, behavio- Young growing foals up to 12 months old may be
ral changes, blindness, and failure to thrive fre- afflicted with this condition, particularly Arabian
quently occur. Great variability in the severity of the foals of Egyptian lineage.187,188 These foals abruptly
clinical syndrome may accompany the same mor- become recumbent and thrash violently. Usually, this
phologic defect, such as agenesis of the corpus cal- occurs on more than one occasion, although epi-
losum. The latter anomaly occurred along with sodes may not be seen. A frequent complaint of the
polymicrogyria in 23 of 345 (7%) Murray Gray client is that the foal has a head injury with no expla-
dominant × Aberdeen Angus calves over a period of nation as to the origin. Corneal ulcers with soil
6 years.177 impacted in the conjunctival sac and lacerations of
Five calves and one sheep with cranial menin- the lips, gums, or knees can also be original problems
gocele are reported from Iran,178 and in three cases detected. Concurrent adolescent diseases such as
the cephalic sac containing meninges was surgically pneumonia, arthritis, or diarrhea are sometimes
resected and the calves recovered well. present.
Holoprosencephaly, with undivided, hypoplastic Seizures may not be subsequently confirmed in
cerebral hemispheres and associated flattened skull, the early stages of the syndrome, particularly if the
may be common in Border Leicester lambs179 and has foal is taken into a different environment for hospi-
been reported in a Hereford calf.180 Semilobar holo- talization. Temporary somnolence, loss of affinity for
prosencephaly was diagnosed in a 6-­ month-­ old the dam, loss of suckle reflex, aimless wandering, and
Morgan filly that demonstrated many subtle behavio- particularly amaurosis can often be present in the
ral signs including fearlessness, hyperactivity, and postictal period. Because seizures all tend to occur
abnormal chewing.181 And another equine case with a more frequently during quiet periods, 24-­h video
similar malformation was euthanized shortly after recording can be useful to capture typical paroxysms
birth.182 Anencephaly (absence of major portions of for review.
the prosencephalon) has been seen in an aborted Efforts must be made to rule out identifiable causes
miniature donkey183 and in live newborn calves that of seizures that can include head trauma, meningitis,
move limbs and neck but are unable to rise. Various protozoal myeloencephalitis, and electrolyte abnor-
other congenital monstrosities with a variety of cra- malities, the latter especially in sick foals.189–191
nial and encephalic defects have been seen and must A similar neonatal and adolescent syndrome
be euthanized. occurs in children.192–194 The syndrome in foals
appears to be more frequent in adolescent Arabian
foals and possibly reflects a relatively low seizure
Familial epilepsy in cattle
threshold present during development. Indeed, the
Seizures characterized by lowering of the head, young brain is intrinsically hyperexcitable, and
tongue chewing, foaming at the mouth and collapse because of ongoing ­ontogeny and primary exposure
occurred in certain Brown Swiss calves beginning by to a vast array of environmental stimuli and toxins it
6 months of age.184 Attacks were often prompted by is more prone than the adult brain to initiating and
undue excitement. Although the disease was pur- propagating seizure discharges. This would allow
ported to have an autosomal dominant mode of for the expression of seizures in response to many
inheritance, there was a positive and repeated “temporary” developmental (genetic), toxic, infec-
response to IV calcium borogluconate, at least in tious, metabolic and physical cerebral perturbations.
 Congenital, familial, and genetic disorders 231

Currently, numerous channelopathies are associ- onset, excessive daytime sleepiness, sleep-­ onset
ated with predisposition to a variety of human epi- (hypnagogic) hallucinations, and paroxysmal sleep
lepsies, and in childhood several are directly related attacks with rapid eye movements (narcolepsy).
to protein defects in K+ channels, Na+ channels, Patients with NT-­1 are also distinguished by exhibit-
and nicotinic-­acetylcholine receptors.195 To compli- ing paroxysmal, profound, or complete loss of mus-
cate the search for genetic basis of each epileptic cle tone and reflexes (cataplexy), and it is caused by
syndrome, exemplified in children, mutations of the a marked reduction in neurons in the hypothalamus
same gene may cause both encephalopathic and that produce orexins (hypocretins), which are
relatively benign epilepsy. Thus, a clear phenotypic wakefulness-­associated neuropeptides. Most NT-­1
analysis of each disorder is vital to further under- patients carry the specific human leukocyte antigen
standing of these disorders. (HLA) allele HLA-­DQB1*06:02, but genetic varia-
Guidelines for anticonvulsant therapy are out- tions at multiple loci are associated with the disease.
lined in Chapter 6. Also, any underlying disease Except for c­ataplexy, NT-­2 has most of the same
must be attended to. As in children,192,193,196 the deci- symptoms as NT1 and it is also a complex disorder,
sion of whether or not to institute maintenance but its underlying genetic architecture is poorly
anticonvulsant therapy can be difficult to make understood.
because some foals totally recover from temporary Narcolepsy with Cataplexy has been seen in
epilepsy without treatment, particularly when the Suffolk foals (“fainting foals”),201 Miniature Horse
seizures do not generalize with the foal remaining foals,202 Morgan foals (MacKay, pers. obs.), Fell
standing. However, several foals that have not had ponies, Icelandic foals,203 Lipizzaner horses,204 in
their seizures controlled well to begin with, have Shetland and Welsh pony and Appaloosa foals, and
gone on to develop intractable epilepsy. At post- possibly in a crossbred lamb205 and in bulls.206,207
mortem examination, some of these foals have had These cases are possibly analogous to inherited
hippocampal, dorsal thalamic, laminar cerebrocor- narcolepsy with cataplexy (NT-­1) in humans and
tical, and cerebellar Purkinje cell neuronal necrosis. dogs.208–211 The typical syndrome in foals tends to
Such lesions are most probably the result of pro- develop into a stable pattern of sleepiness and
longed, repeated, generalized seizures, but also may recumbency, depending on the environmental
act as seizure foci themselves; a vicious cycle can stimuli, and persists for life. Between typical cata-
thus result. Therefore, it is reasonable to consider plectic attacks, there are no neurologic abnormali-
using maintenance anticonvulsant therapy if multi- ties. An attack may progress from buckling at the
ple, generalized seizures have occurred over several knees without falling to sudden and total collapse
days. One to three months is a reasonable period of and areflexia, usually with the maintenance of
anticonvulsant therapy, and it has been successfully some eye and facial responses and normal cardi-
utilized in many cases. During this period when sei- orespiratory function. Each recumbent episode
zures are controlled, the drug (phenobarbital, KBr, may last up to hours if the foal is totally undis-
etc.) dosage may be held the same as the foal grows, turbed, but the patient can usually be aroused from
thus initiating slow drug withdrawal over 2 or this state with varying degrees of difficulty and can
3 months. An affected foal, effectively treated, does regain its footing quietly and rapidly. To conform
not appear to have any greater chance of having sei- with the criteria for diagnosis of this disorder in
zures as an adult than any other foal. humans,212 a clinical diagnosis of narcolepsy with
cataplexy in animals is best substantiated by
observing rapid eye movements and demonstrating
Narcolepsy with cataplexy the absence of spinal reflexes during repeated epi-
Paroxysms of collapse and an apparent somnolent sodes of inappropriate recumbency, along with
state can be caused by many known and undefined excessive ­daytime somnolence.
causes.197 The specific syndrome of sleeping for Deep, rapid-­eye-­movement sleep, with its associ-
excessively long periods however has been called ated atonic, areflexic state, occurs at inappropriate
narcolepsy and in people it is categorized as times with no morphologic lesion to account for
Narcolepsy Type-­1 (NT-­1) and Type-­2 (NT-­2).198–200 this sleep dysrhythmia. As with human NT-­1, a
Both are characterized by juvenile to young adult biochemical and/or cytological defect is probably
232 Large animal neurology

operative in the brainstem sleep-wake Sporadic idiopathic (essential, primary)

centers.213,214 Various neuropeptides such as hypo- hypersomnia in adult patients
cretins (orexins) that are associated with sleep
and arousal states occur in hypothalamic and other Excessive daytime sleepiness accompanied by sleep
sleep-­projecting, brainstem nuclear regions. attacks occurring while the patient is standing and at
Indeed, abnormal levels and activities of hypocre- inappropriate times, and usually not accompanied by
tins or their receptors, and possibly other neuro- profound loss of muscle tone (cataplexy) nor rapid
peptides, occur in various sleep disorders both in eye movements, occurs reasonably commonly in
situ and in CSF. Detection of abnormal expression adult to aged large animals of many breeds. The syn-
and activity of such neurotransmitters can assist in drome is best considered multifactorial in etiology
defining subtypes of genetically associated and and is covered in Chapter 38.
acquired narcolepsy.215,216 That such protein abnor-
malities are defined does not rule out environmen- Hydrocephalus
tal and other acquired influences acting to effect
individual disease states in this multifactorial dis- Broadly speaking, hydrocephalus refers to increased
ease.199,200,209–211 The presence of transferable and CSF volume within the cranium. Because an increased
functional autoantibody in human cases of narco- volume of the subarachnoid space (so-­called external
lepsy with cataplexy,217 the lack of response to hydrocephalus) is very rare,229 and in many cases is
­systemic and intrathecal hypocretin in cases caused likely a false postmortem observation, the term here
by receptor defects,218 and clinical improvement refers to the enlargement of the ventricular system
over time in the disease in some dogs219 make within the brain with any resulting cavity being lined
defining the etiopathogenesis of the equine disor- by an ependymal cell layer; the spinal equivalent for
der still more problematic. this being hydromyelia. This relatively common con-
Long-­term therapy is probably unpractical, although genital brain defect occurs in all species and can be a
short-­
term responsiveness to imipramine202,220,221 in rare inherited trait in cattle and in Belgian, Friesian
horses and some effectiveness of other drugs in humans and Standardbred horses. Or it can be an isolated
and dogs222–227 allow for a few options in therapy of this occurrence in all species, often accompanying other
syndrome in large animals. midline malformations.230–238 It accompanies numer-
ous diseases that result in pre-­or postnatal loss of
brain tissue, when it is rightly referred to as hydro-
Narcolepsy without cataplexy cephalus ex vacuo, or with obstruction of the aque-
Juvenile onset, persistent, excessive daytime sleepi- ductal drainage of CSF when there may or may not be
ness, with paroxysmal sleep attacks (sometimes ventricular hypertension.236,239–244
with rapid eye movements detectable – narcolepsy), Hydrocephalus occurring alone in cattle is divided
but not accompanied by complete loss of muscle into Types I to VI based on breed, inheritance, and
tone and reflexes (cataplexy), have also been seen in nature of the pathologic lesions.238 In Friesian horses
Warmblood, Icelandic, and Thoroughbred foals. and at least one Belgian foal, congenital hydrocepha-
This is analogous to the same syndrome in humans lus has been associated with a nonsense mutation of
(narcolepsy without cataplexy; NT-­2) and dogs in the B3GALNT2 gene occurring with an estimated
which there is a familial basis but in which the role allele frequency in the Friesian horse population of
of genotype and/or immune response is also ques- 0.085.232–234
tioned.199,200,210,211 These foals intermittently remain Clinical signs in all species can be very subtle even
standing in a trance-­like state or stagger around, with minimal cerebral mantle remaining but usually
occasionally falling to injure their knees or face. include degrees of failure to thrive, somnolence and
Future neurochemical and genetic studies will be aimless activity, poor suck reflex, poor swallowing,
necessary to determine whether this is truly a and central blindness. Other signs can accompany
genetic disorder, and if and how it differs from nar- any additional lesions present in individual disease
colepsy with cataplexy and from idiopathic hyper- types.238 In association with the deformed forehead
somnia.198-200, 223 Management of this syndrome is as associated with marked congenital hydrocephalus, a
for narcolepsy with cataplexy.228 ventrolateral deviation of the eyeballs can also occur.
 Congenital, familial, and genetic disorders 233

Presumably, this is the result of a change in shape and regions in the brains of month-­old Limousin and
position of the bony orbits. Normal eyeball move- Limousin-­cross calves with a progressive, fatal neu-
ments can occur. Prominent doming of the forehead rologic syndrome have been described in the UK
of the fetus may result in dystocia.231 and Australia.36,112,253 Progressive signs of hypermet-
Intrauterine infection of ruminant fetuses by many ric ataxia, particularly involving the thoracic limbs,
viruses such as pestiviruses, reoviruses, and espe- are first seen, followed by evidence of peripheral
cially bunyaviruses, during the susceptible periods of blindness, staggering, and aggressiveness accompa-
development around gestation days 60–180, readily nied by weight loss. Affected calves do not survive
causes malformations in the central nervous system, past 4 months. Signs are attributable to necrosis and
especially in the brain. The brain lesions occurring cavitation particularly of the optic chiasm and mid-
with in utero infection with BVDV, Schmallenberg dle cerebellar peduncles, with myelin destruction in
virus (SBV), bluetongue virus (BTV), Akabane virus the internal capsule, thalamus, and midbrain, as well
(AKAV), Aino virus (AV), and Main Drain virus as modest vacuolation and Wallerian-­like neuronal
(MDV) typically consist of hydranencephaly, poren- fiber degeneration in the spinal cord white matter.
cephaly, hydrocephalus ex vacuo, and cerebellar Glial cell destruction appears to be part of the pri-
hypoplasia. With SBV, AKAV, AV, and MDV mary morphologic lesion. Of striking neuropatho-
­infections, these brain lesions may be associated with logic interest was the presence of large numbers of
malformation of the axial and appendicular skeleton peripheral Schwann cells contacting and attempting
particularly arthrogryposis.176,236,245–248 remyelination of demyelinated CNS axons in chronic
The newer diagnostic techniques of CT, MR, and vacuolating lesions in the cerebellar peduncles.112
ultrasound imaging, as well as plain radiography, all Although toxicities must be considered in the
can contribute to defining the degree and nature of pathogenesis, this disease warrants comparison with
hydrocephalus.229231,241,249 Heroic surgical ventriculo- subacute necrotizing encephalopathy (Leigh disease)
peritoneal shunting has been attempted in a foal.250 of human infants that is associated with a large num-
ber of genetic mutations in mitochondrial DNA.113
Hydranencephaly
In distinction to hydrocephalus, hydranencephaly Simmental cattle encephalomyelopathy
refers to the presence of fluid-­filled cavities within About the same time that the Limousin cattle enceph-
the brain which are lined with astrocytic processes alopathy was described, a similar clinicopathologic
and not by ependymal cells, the spinal equivalent syndrome in Simmental and Simmental-­cross calves
here being syringomyelia. Hydranencephaly, often in New Zealand and Australia was reported.36,103 The
accompanied by a secondary hydrocephalus ex affected calves showed rapidly progressive weakness
vacuo, may be more common than hydrocephalus and ataxia resulting from widespread discrete multi-
alone in large animals, particularly in calves. As dis- focal destructive lesions in brainstem and spinal cord
cussed under hydrocephalus in ruminants, hydra- gray matter. Early signs of swaying and dragging the
nencephaly and other induced brain malformations hind feet in 5–12-­ month-­ old calves rapidly pro-
are frequently associated with transplacental infec- gressed over several weeks to prominent pelvic limb
tion with pestiviruses, reoviruses, bunyaviruses, and hypermetric ataxia and tetraparesis with marked
other in utero infections.176,236,240,245–248,251,252 Signs weight loss and ultimate recumbency. In a report of a
resulting from any accompanying congenital cerebel- larger number of cases from North America,114 the
lar dysfunction and from arthrogryposis usually clinical syndrome was corroborated with some evi-
predominate the clinical syndromes, but variable
­ dence of hyperexcitability being noted and recum-
somnolence and central blindness may be evident bency occurring in an average of 6 weeks from the
because of the hydranencephaly. onset of signs. Thoracic and pelvic limb reflexes were
said to be intact. Sudden death was occasionally
reported.
Limousin cattle encephalopathy Underlying consistent lesions comprise necrosis
Widespread, bilaterally symmetric, degenerative, and poliomalacia in the olivary nuclei and ventral
and destructive lesions in various white matter thoracic gray columns.103,114,115,254,255 Other gray
234 Large animal neurology

matter areas that can be affected include basal nuclei, reported in New Zealand Romney sheep,258,259
mesencephalon, and pons. Of note in comparing although it appears to be a primary myelin disorder.
this disorder with the Limousin cattle encephalopa- Two-­to three-­ month-­ old lambs showed rapidly
thy was the absence of lesions in cerebral white mat- progressive, flaccid (sic) paraparesis to paraplegia
ter and cerebellar peduncles, and especially in optic over a week or so and had widespread, severe vacu-
nerves and chiasm. Destructive foci result in even- olation and myelin loss particularly in the cerebellar
tual loss of neuronal cell bodies, and all glial ele- peduncles, ­central cerebellar white matter and dor-
ments although neuronal soma and axons initially solateral spinocerebellar tracts in the caudal brain-
seem to be spared. stem, and in dorsomedial and ventromedial spinal
Some proof for there being mitochondrial altera- cord funiculi where it was most severe in the tho-
tions in this disease has been put forward.113 Although racic and lumbar segments. An inherited cause was
there is good evidence that this is an inherited disor- postulated.
der, it is yet to be shown that Simmental cattle
encephalomyelopathy is an inherited mitochondrial
Lysosomal storage diseases
disease akin to Leigh disease in children.113 The find-
ings of elevated tissue concentrations of aluminum These rare diseases result from an inborn error or
and deficient hepatic copper and manganese concen- acquired defect in a metabolic enzyme pathway,
trations in two affected calves raise the issue of the often reflected by the accumulation of undigested
role of micronutrients in this and related animal and polymeric molecular substrates within the lysoso-
human neurodegenerative disorders.254 Certainly, mal system of cells in various tissues of the body,
mitochondrial disturbances may account for altered particularly in the nervous system.260–266 The onset of
metal ion metabolism, but there is some evidence for neurologic signs of most of these diseases is either at
at least manganese, iron, copper, and zinc, metal-­ birth or is heralded by mild signs of ill thrift and
mediated mitochondrial dysfunction being linked to separation from other animals. Behavioral changes
neurodegeneration.256 such as aimless wandering, seizures, and aggressive-
ness are common signs along with evidence of cen-
tral and peripheral blindness (Figure 31.2). Many of
Encephalomyelopathy of Angus calves
these are excellent models for the human counter-
A more fulminant syndrome than that in Limousin parts and understanding the pathogenesis of neu-
and in Simmental cattle was caused by a multifocal, ronal dysfunction and cell loss contributes to
symmetrical, necrotizing encephalomyelopathy that mastering the devastating human neurodegenera-
occurred in ~1% of calves born in one purebred tive diseases.260,267 Genetic probes are available for
Angus herd in Australia.36,257 Signs of ataxia, nystag- many of these inherited diseases, and when the
mus, and strabismus at 2–6 weeks progressed within genetics pattern is clear it is usually represented by
4–7 days of onset to recumbency, hyperesthesia, an autosomal recessive mode of inheritance. Testing
tonic spasms, and seizures. Bilaterally symmetric for abnormal protein expression usually in blood
lesions were present in olivary, dorsal vagal and lat- sampling, followed by a nonbreeding/slaughter pol-
eral cuneate nuclei, and sometimes in substantia icy, has usefully reduced the frequency of the pheno-
nigra, cerebellar peduncles and spinal cord gray mat- type in breed populations.264,266 The precise mutation
ter. Lesions were characterized by dissolution of the for some of these disorders has been identified.268
neuropil but with relative sparing of neurons, and Other syndromes await full investigation as to
with minimal vascular and glial response. As for the whether or not they are even an inborn error or are
Limousin and Simmental cattle encephalomyelopa- an acquired defect in a metabolic enzymic path-
thy, a mitochondrial disorder akin to Leigh disease in way.269 The toxin-­induced lysosomal storage diseases
humans113 is suspected but not shown. allow further understanding of metabolic pathways
involved in the acquired and in the inherited disor-
ders, and give some insight into the genotypic–phe-
Romney sheep spongiform
notypic interactions allowing for some explanation
leukoencephalomyelopathy for individual susceptibility to such toxicities.270
A disease that warranted some comparison with the Many large animal storage diseases are great models
Simmental and Limousin disorders has been for their human counterparts. Rather than detail
 Congenital, familial, and genetic disorders 235

Figure 31.2 Many inherited disorders have an onset of clinical signs sometime after birth and are progressive. Such is the case with the form of ceroid
lipofuscinosis seen in South Hampshire sheep. These ~18-­month-­old patients have had signs of ill thrift, blindness, behavioral changes, and mild general-
ized seizures over many months. Shown here is the tendency to wander aimlessly to the right (sheep 1) and left (sheep 2) and to bump into objects
(sheep 3). They would spontaneously and with tactile stimuli often demonstrate mild generalized seizures consisting of stopping any locomotion, facial,
jaw, and head tremor and teeth chattering, all lasting 2–20 s.

characteristics of all large animal lysosomal storage and Romney, Coopworth and Perendale sheep in
diseases, important examples of these disorders are New Zealand258,338,339 have a similar syndrome of pro-
given in Table 31.3. gressive ataxia, sometimes leading to recumbency.
Affected Romney lambs have an interesting way of
urinating wherein they adopt a much crouched pos-
Portosystemic vascular anomalies
ture for a prolonged time before and after voiding
Congenital anomalies in portal circulation can result urine.340 This may well be due to the combination of
in failure of the liver to adequately complete its vital extensor weakness and pelvic proprioceptive func-
metabolic and detoxifying tasks with eventual tional deficit. Widespread neuroaxonal dystrophy is
­systemic signs of liver failure such as ill-­thrift and prominent in lateral cuneate and thoracic nuclei,
variable signs of hepatoencephalopathy.327–329 These along with neuronal fiber degeneration in spinal cord
congenital defects have been documented at least in white matter. An inherited basis to these cases is also
the foal, pig, and calf with intermittent drowsiness, suspected. A congenital form of ovine neuroaxonal
bizarre behavior, and seizures.329–333 Some attempts at dystrophy with peripheral axonal involvement is also
surgical correction of portosystemic shunts after recorded in crossbred Merino sheep in Australia.341
confirmation of the nature of the particular anomaly And two pathogenic variants in ovine PLA2G6 gene
have been successful.332–335 causing a novel form of neuroaxonal dystrophy in
Swaledale sheep has recently been determined.342
A single case of neuroaxonal dystrophy, very simi-
Neuroaxonal dystrophy lar to the New Zealand sheep disorder, has been seen
A syndrome of worsening ataxia and paraparesis pro- in an Angus heifer.343
gressing to tetraparesis and ataxia affects 1–6-­month-­old The disease equine degenerative myeloencephalop-
Suffolk lambs in the USA.336 It is associated with accu- athy344–346 does appear to be the same as, but perhaps
mulations of spheroids (dystrophic, swollen axons) in a more advanced form of, equine neuroaxonal dystro-
certain brainstem and spinal cord gray matter nuclei. It phy, and both clinicopathologic syndromes are asso-
is familial and probably inherited. ciated with an induced vitamin E-­deficient state that
Up to 10% of lambs from weaning till 18 months may well have a genetic basis;345,347–352 both disorders
old in certain families of Merino sheep in Australia337 are discussed in Chapter 35.
Table 31.3 Details of major lysosomal storage diseases of large animals

Disease Colloquial name Breed Syndrome Onset of signs Course References

GM-­1 gangliosidosis GM1 Type-­1 Friesian cattle Depression Birth 6–8 months 271
Ataxia
Recumbency
GM1 Type-­2 Coopworth sheep Ataxia 1 month 3 months 272
Romney sheep Recumbency
GM1 Type-­2 Suffolk sheep Ataxia 4 months 2–8 weeks 273, 274
Blindness
Recumbency
GM-­2 gangliosidosis Tay-­Sachs disease Yorkshire pigs Hypermetria 3 months 4–6 months 275
Sandhoff disease Weakness
AB Variant
GM-­3 gangliosidosis Type-­3 G(M1) gangliosidosis Romney sheep Unknown Adult ? 276
(lesions in corpus striatum)
Galactocerebrosidosis Globoid cell leukodystrophy Polled Dorset sheep Ataxia Young mature 18 months+ 277–279
Krabbe disease Merino sheep Muscle tremors
Recumbency
α-­Mannosidosis (genetic) Alpha mannosidosis Aberdeen Angus cattle Aggressiveness Birth–few months Few months 264, 280
(MAN2B1) Cerebellar ataxia
Murray Gray cattle Aggressiveness Birth–few months Few months 264, 280
Cerebellar ataxia
Galloway cattle Aggressiveness Birth–few months Few months 265, 281
Cerebellar ataxia
α-­Mannosidosis (toxic) Locoism Herbivores Ataxia Variable Variable 282–285
Swainsona, Oxytropus, Ipomoea, Behavioral changes
Turbina, Sida, Astragalus* spp.
β-­Mannosidosis Beta mannosidosis (MANBA) Anglo Nubian goats Recumbency Birth Days 36, 286–289
Head tremor
Salers cattle Recumbency Birth Days 290–292
Head tremor
Mucopolysaccharidosis–IIID Sanfilippo syndrome Nubian goats Systemic signs Birth Days 293, 294
Weakness
Glycogen Storage –II
#
GSD II Beef Shorthorn cattle Tetraparesis 3 months 1–2 years 295–297
Pompe disease Heart failure
Brahman cattle Muscular weakness Few months 6–9 months 298–301
Hypometria
Corriedale sheep Ataxia 6 months 10 months 259
Lethargy
Sudden death
Glycogen Storage–V McArdle disease Charolais cattle Exercise intolerance Few weeks–months Months–years 302–305
Neuronal Ceroid Lipofuscinosis NCL-­CLN6 South Hampshire Sheepф Blindness Early adult 12–30 months 260, 306–308
(NCL)‡ Wandering (3 months)
Mild focal seizures
NCL Rambouillet sheep Blindness 4 months 1–2 years 309, 310
Star-­gazing
Ataxia
NCL-­CLN5 Borderdale sheep Blindness 15 months 2+ years 260, 311
Circling
NCL-­CLN6 Merino sheep Blindness 7 months 27 months 312, 313
Behavioral changes
Seizures
NCL Beefmaster cattle Blindness 12 months 18 months 314
Circling
Coma
NCL-­CLN5 Devon cattle Blindness 12 months 2–4 years 315
Weakness
NCL Holstein cattle Blindness Adult Unknown 316
NCL Nubian Goats Stiffness 4 months 2–4 years 317, 318
Tremor
Ataxia
NCL Icelandic X Peruvian Paso foals Trunk and limb ataxia 6 months 18 months 319
Blindness

* The indolizidine alkaloid swainsonine inhibits Golgi α-­mannosidase as well as lysosomal α-­mannosidase.
#
Not including the primarily myopathic glycogen storage disorders320–324 and Fanconi–Bickel syndrome in original Braunvieh and German Fleckvieh cattle.325
ф
Figure 31.2.
‡
For nomenclature see Mole and Cotman.326
Sources: Adapted from Tarnopolsky320; Mickelson and Valberg321; Ward et al.322; Valberg et al.323; Gil et al.324; Joller, Stettler et al.325; Mole and Cotman326
238 Large animal neurology

Finally, the age-­related accumulation of neu- of preservation of the structural integrity and func-
roaxonal spheroids, as well as ceroid/lipofuscin tion of myelin.117 Along with this effect, there
and vascular-­associated mineral deposits, through- appears to be a trend for better muscular develop-
out the aging CNS, is well documented, particu- ment in heterozygous carriers, p ­ ossibly explaining
larly in certain caudal brainstem nuclear regions. a selection pressure accounting for a high fre-
This process may or may not be related to geno- quency (13%) of the allele in the French Charolais
type and particularly to cumulative oxidative breed.
damage.353
Bovine progressive degenerative
Familial ataxia in Merino sheep myeloencephalopathy (Weaver syndrome)
Clinically and pathologically distinguishing the Affected Brown Swiss calves of either sex are
possibly genetic diseases affecting Merino sheep in 5–8 months old at onset of paraparesis, ataxia, and
Australia can be problematic.88,279 These diseases, dysmetria involving the pelvic limbs far more than
that include neuroaxonal dystrophy, segmental the thoracic limbs. An insidious progression of
axonopathy,354,355 degenerative thoracic myelopa- signs over many months is usually expected. Some
thy,356 cerebellar abiotrophy,3 and thalamic-­ muscle wasting may become evident over the hind
cerebellar degeneration,88 must be distinguished quarters, although there is no evidence of final
from many other, likely more common, toxic, meta- motor neuron involvement.119,363,364 There is
bolic, and infectious disorders, resulting in progres- Wallerian-­like neuronal fiber degeneration seen
sive ataxia. To that end, the reader is referred to diffusely in the spinal cord, with swollen axons
Table 31.4. (spheroids) present in spinal white matter, in some
brainstem nuclei, and in the cerebellar granular
Progressive ataxia of Charolais cattle layer and there can be loss and/or degeneration of
cerebellar Purkinje cells.364 The ­ disease is seen
Originally reported from the UK in the mid-­ throughout North America119,364 and Europe.365
1970s,116,357,358 Progressive Ataxia of Charolais Cattle Interestingly, there is a positive association between
has been recognized worldwide.117,118,359–362 Affected the disease and milk production.366 The disease is
cattle of both sexes are usually 6–24 months old at inherited and associated with a nonsynonymous
the onset of signs. Initially, there can be difficulty SNP in the PNPLA8 gene as a candidate causal
rising and dragging of the toes seen on walking, pro- mutation.120,121 A similar clinicopathologic syn-
gressing to ­ stiffness and ataxia and paraparesis, drome has been seen in members of a closed herd of
finally leading to recumbency in 6–24 months. Watusi cattle (IGM, pers. obs.).
Affected cattle, especially females, may urinate with
frequent short spurts. Nystagmus and fine, whole-­ Degenerative axonopathy in Tyrolean
body tremor have been mentioned.360
There are quite classical though subtle histologic
gray calves (Demetz syndrome)
lesions involving white matter in the brain and spi- Progressive ataxia and paraparesis occurs in Tyrolean
nal cord with demyelination and production of Gray calves originally from Tyrol in Austria and
multifocal, acellular, pale eosinophilic plaques South Tyrol in Italy.122 Starting at the age of 4–6 weeks,
prominent in the cerebellar peduncles and medulla signs of paraparesis progress to involve all four limbs
oblongata.116,361 Defective oligodendroglia can be with severe ataxia and weakness most pronounced in
detected ultrastructurally and the plaques appear the pelvic limbs, leading to recumbency before a year
to represent redundant, proliferated, oligodendro- of age. Of some clinical importance is the fact that
glial processes at paranodal sites.357,362 Line breed- postural reactions were normal in the thoracic limbs
ing has been associated with a frequency of 10% in and decreased to absent in the pelvic limbs. Spinal
one UK herd.118 The disease is inherited and associ- reflexes of the thoracic limbs were normal but were
ated with a single nucleotide polymorphism in the decreased in pelvic limbs and the cutaneous trunci
coding region of the KIF1C gene. The mutation responses were absent. Symmetric Wallerian-­ like
leads to a functional knockout resulting in a failure neuronal fiber degeneration is prominent in the
Table 31.4 A guide to differentiating five familial diseases resulting in progressive ataxia in Australian Merino sheep (excluding storage diseases)

Clinicopathologic characteristic Disease

Neuroaxonal dystrophy Segmental axonopathy Degenerative thoracic myelopathy Cerebellar abiotrophy Thalamic–cerebellar degeneration

Clinical features
Wool type Medium Fine Medium Fine Medium
Age at onset 4 months 12 months 5 months 3 years 2 years
Spinal ataxia + + + + +
Hypermetric ataxia − −­ −­ + +
Weakness + + + −­ +
Falling over −­ −­ −­ + +
Head tremor −­ −­ −­ + +
Pathologic lesions
Thalamus gray −­ −­ −­ −­ +
white −­ + −­ −­ +
Midbrain gray −­ −­ −­ −­ −­
white + −­ −­ −­ −­
Pons gray −­ −­ −­ −­ −­
white −­ + −­ −­ +
Medulla oblongata gray −­ + −­ −­ −­
white + + −­ −­ +
Cerebellum gray −­ −­ −­ + +
white + + −­ + +
Spinal cord gray + −­ −­ −­ −­
white + + + −­ +

+ = present.
−­= absent.
Sources: Modified from Harper et al.3; Bourke et al.88; Jolly et al.266; Harper and Morton337; Bourke279; Hartley and Loomis355; Harper et al.356
240 Large animal neurology

dorsolateral and sulcomarginal spinal funiculi and in ­ isease.128 These calves were normal until 3 months
d
at least the femoral nerve, and swollen and chroma- of age when they demonstrated prominent dysmetric
tolytic neuronal cell bodies can be found in the red ataxia in the thoracic limbs and mild signs in the pel-
nuclei and in brainstem and spinal motor regions. A vic limbs resulting in recumbency within a month.
mutation in the bovine MFN2 gene has been detected Symmetrical, Wallerian-­like neuronal fiber degener-
that may account for the genetic defect.123 This dis- ation in the spinal cord was most prominent in the
ease is very like Charcot-­Marie-­Tooth disease-­2A2 spinocerebellar tracts and ventral funiculi.
(CMT2A2) in humans. Other cases of apparent degenerative myelopathy
may be focal or multifocal acquired lesions that can
Central and peripheral axonopathy be very difficult to define pathologically, particularly
when very chronic.167,367
in Rouge-­des-­pres (Maine Anjou) calves
Affected calves of both gender show signs at
Spinal muscular atrophy
1–4 months of age and the ataxia and paraparesis
progresses quite rapidly to paraplegia and tetraple- Bovine spinal muscular atrophy is a progressively
gia. This has been referred to as Syndrome des lethal, inherited disease described first in offspring of
veaux tourneurs (Turning calve syndrome) because American Brown Swiss bulls crossed with several
of a propensity for the affected calves to turn European breeds.105,106,129,368–370 It bears strong resem-
around and pivot on the pelvic limbs before falling blance to spinal muscular atrophy SMA-­ 1 in
down. This clinical syndrome (turning) in calves humans.371 A remarkably similar, if not identical, dis-
relates to marked pelvic limb neuromuscular defi- ease is also reported from Spain in Holstein–Friesian
cits with minimal or no thoracic limb deficits, such calves.131 Beginning at birth to 8 weeks, usually at
as can be seen with severe thoracic spinal cord 3–4 weeks old, affected calves begin to show pelvic
injury. Wallerian-­like neuronal fiber degeneration limb weakness progressing to sternal recumbency
occurs in peripheral nerves and in dorsolateral, lat- with thoracic and pelvic limbs resting cranial and lat-
eral, and ventromedial spinal white matter along eral, by 5–12 weeks of age.129,131,368 Some degree of
with spheroid formation particularly seen in lateral limb arthrogryposis can be present at birth indicat-
vestibular and in thoracic nuclei.124 This disease ing reduced motor function in utero.370 Testing patel-
resulted from a single nucleotide polymorphism lar reflexes tends to produce abduction, but poor
in the coding region of the SLC25A46 gene, lead- extension and pelvic limb flexor reflexes are poor.
ing to an apparently damaging amino acid Pelvic and thoracic limb muscle atrophy is evident.
substitution.125 Some calves have difficulty swallowing and breath-
ing, and most develop bronchopneumonia even
though no overt deficits in cranial nerve function are
Progressive myelopathy in cattle
reported. Sensorium and sensation remain intact.
Pelvic limb ataxia and paraparesis beginning at birth, Results of routine analysis of CSF are normal, and
and usually progressing to severe tetraparesis, has needle electromyographic examination reveals fibril-
been primarily seen in beef cattle of the Murray Gray lation potentials and positive sharp waves consistent
breed in Western Australia.126 The syndrome is asso- with muscle denervation.131
ciated with fiber degeneration and probably a degree The clinical syndrome results from progressive,
of demyelination in spinal cord white matter and is nonapoptotic131,132 final motor neuron degeneration
often severe in peripheral, subpial zones. Also, neu- and loss in spinal cord ventral horns, more prominent
ronal chromatolysis occurs in several gray matter in the lumbosacral intumescence than the cervicotho-
nuclear regions of the brainstem and spinal cord. racic intumescence.106,129,131,368,370 Wallerian-­like fiber
Lesions are reminiscent of enzootic ataxia of red deer degeneration is evident in nerves. Neuronophagia
and swayback in sheep. The exact etiology is not ending up with empty neuronal beds and glial nodules
known, but the role of heredity, nutrient deficiencies, is evident. Remaining neuronal cell bodies often show
and environmental toxins has been discussed. chromatolysis and appear as ghost cells, containing
A similar disease is reported in two Murray Gray accumulations of 200 kD neurofilaments. Although in
cattle in New Zealand.127 Also, Holstein × Gir calves the Brown Swiss lineage there is pathologic evidence
in Brazil have been affected by a very similar of mild central motor neuron involvement in the form
 Congenital, familial, and genetic disorders 241

of descending white matter tract fiber degeneration,372 eration have been present. Neurofilamentous accu-
this is not seen in the Holstein–Friesian calves.131 mulation is a prominent component of enzootic
A mutation described in the bovine FVT1 gene is a ataxia/swayback in goats, sheep, and deer. Whether
strong candidate for causing bovine spinal muscular these syndromes are familial or are related to copper
atrophy and should allow for efficient selection pres- deficiency or other nutritional or toxic disorders is
sures against the disease to be used in cattle.130,373 not known at present.

Motor neuron disease in Romney lambs Myofibrillar hypoplasia in piglets

Inbred open-­ faced, New Zealand Romney lambs (congenital adductor weakness)
with this disease were normal for the first week of life Myofibrillar hypoplasia is an enormous congenital
then suffered progressive weakness over the next few problem in swine production worldwide with an esti-
weeks. Poor axial and appendicular muscle tone, mated 0.4% of all piglets born in the UK, particularly
flexor hyporeflexia, and medial strabismus were also those from sows raised on concrete, showing inabil-
noted.258,374–376 Loss and degeneration of final motor ity to stand on the pelvic limbs because of adductor
neuronal cell bodies with spheroid formation in weakness, so-­called spreadleg syndrome or splayleg
brainstem and ventral gray columns of the spinal syndrome.380–383 This occurs more in male than female
cord along with secondary Wallerian-­like fiber degen- piglets and is familial.384 Thoracic limbs can also be
eration in peripheral nerves and denervation muscle affected such that if the patients were puppies they
atrophy were recorded. This disease is related to a would be labeled as “swimmers.” The piglets risk
missense mutation in the sheep ATP/GTP-­binding starvation and ~50% die, but if nourished, the pelvic
protein-­1 (AGTPBP1) gene.377 limbs will strengthen and return to function as well
as their litter mates, after about a week.380,385
Although there is no evidence of overt myopathy
Shaker calf syndrome
in limb muscles at the light microscopic level,380 there
This rare neurodegenerative disorder occurs in new- is evidence of myofiber hypoplasia at birth with
born Horned Hereford calves of both sexes. Calves myofiber size improving over the first week of life
are born normally but cannot stand. Within several along with the clinical improvement.386,387 One
hours of birth, they develop fine generalized tremor detailed neuropathologic study of affected piglets381
involving the head, body, and tail, which is exagger- showed that there was reduction of axonal diameter
ated by spontaneous activity or by handling the and myelin sheath thickness of the nerve fibers
calves. With assistance, affected calves may stand and innervating the adductors of the affected limbs, and
suck, but become fatigued easily. Progressive stiffness there was deficient myelination of lumbar spinal
and ataxia are evident, particularly in the hindlimbs. white matter descending central motor neuron fibers
One calf survived for 3 months with continual at birth. More advanced myelination was then pre-
tremor, hyperesthesia, and aphonia.133 There is an sent by 12 days of age. Interestingly, delayed
excessive accumulation of neurofilamentous material myelination—­that can resolve—­of ascending as well
in motor neurons in the central, peripheral, and as descending spinal cord tracts is associated with
autonomic nervous systems. The disease is inherited congenital tremor syndrome in piglets (see above).
and is lethal. It may model some neurodegenerative Electromyographic conduction studies failed to
motor neuron diseases affecting man. record consistently defective electrical behavior of
limb muscle in affected compared with control pig-
lets.388 The conclusion drawn by those authors was
Neurofibrillary degeneration that congenital myofibrillar hypoplasia is not primar-
Syndromes of tetraparesis progressing to tetraplegia, ily a myasthenic syndrome, but that excitation–con-
sometimes with evidence of a weak neck with the traction coupling and/or the contractile mechanism
head held low, have occasionally been seen in young itself are primarily affected.
stock. Affected animals have included Yorkshire pig- Considerable work has been performed to unravel
lets,378 Afrikaner cattle,134 and Zebra foals.379 the likely genetic component to this disease with sev-
Widespread neurofibrillary accumulations within eral candidate genes being targeted but not fully
neurons and degrees of spinal neuronal fiber degen- defined.383,389–391 Nutritional deficiency, possibly of
242 Large animal neurology

methionine and choline, may be an associated cause

as supplementation with these essential amino acids
reduces the frequency of the disease.381 Also, when
pyrimethamine (a competitive inhibitor of dihydro-
folate reductase) was fed to 10 pregnant minipigs on
days 11–22 of gestation, 20 of 22 piglets were born
with splayleg—­along with a high rate of stillbirths.
This compared with 1 of 18 piglets in the control
group having splayleg.392 In contrast to the naturally
occurring disease, piglets with induced splayleg did
not have any greater diminution in myofiber size
than controls. These findings along with the fact that
whole, large litters of piglets can be affected indicate
that this is a multifactorial disease with prominent
(A)
genetic/environment interactions playing in to the
etiology.

Progressive paresis in Angora goats

Three closely related Angora goat kids developed
progressive spastic ataxia and paresis at 4 months of
age and at necropsy examination at 6 months of age
had prominent intracytoplasmic vacuoles in large
neurons in the midbrain, caudal brainstem and ven-
tral horns of the spinal cord along with moderate
Wallerian-­like fiber degeneration in the caudal brain-
stem and spinal cord white matter and peripheral
nerves. A genetic basis was deemed possible. That
this was not an infectious spongiform encephalomy-
elopathy (i.e., scrapie) was mainly based on the young (B)
age of the affected kids.393
Figure 31.3 OAAM would be one of the most encountered, nonlethal,
congenital cervical vertebral anomalies in large animals. Although reliable
Occipitoatlantoaxial malformations for diagnosis, radiographs of immature craniovertebral regions can be
somewhat problematic to interpret. Shown here (A) is a lateral radio-
These disorders are uncommon in large animals graph of a neonatal, ataxic calf with fusion of the atlas to the occiput, a
(Figure 31.3). Arabian foals, newborn to several hypoplastic dens (d) and ventral luxation of the axis relative to the body
months of age, have been diagnosed as having of the atlas (a). The comparative postmortem specimen (B) shows the
affected region with the lamina of the atlas and arch and spine of the axis
occipitoatlantoaxial malformation (OAAM) per-
(dashed outlines) removed.
haps more often than other groups of large ani-
mals.394–397 Isolated cases occur in young horses of
other breeds.398 Calves, particularly of the Holstein of abnormal head and neck posturing.395,400,410
breed,399–401 sheep,397,402,403 and a goat404 have been Occasionally, no neurologic signs are present, just
found with similar malformations. Asymmetric restricted movement of the neck.397,404 An extended
fusion of the atlas to the occiput with or without neck posture is often seen and a malformed atlas
primary malformation of the axis or ventral luxa- and axis with restricted movement can often be
tion of the dens is a separate malformation.400,405–407 palpated. Scoliosis may be present. In most Arabian
Sheep with occipital condylar dysplasia may also be foals, and in Holstein calves, a peg-­like remnant of
included in this broad category.408,409 the wings of the atlas may be palpable. Reduced
Affected animals can be born dead, be ataxic at flexion at the atlantooccipital junction and a click-
birth, or show progressive ataxia and tetraparesis as ing sound as the animal moves its head or when the
weanling or yearling animals with varying degrees head is manipulated may be detected. Facial
 Congenital, familial, and genetic disorders 243

­ alformation, cardiovascular defects, and other

m (kyphosis) of C7 on T1 and extension (lordosis) of C6
congenital problems may be detected in certain on C7, and associated spinal cord compression.424–427
cases.411–413 Paravertebral muscle lesions, either myofiber
Various developmental anomalies of the occiput, hypoplasia with degeneration or overt myonecrosis,
atlas, and axis are present, including atlantooccipital fibrosis, and mineralization, have been recorded and
fusion, hypoplasia of the dens, and additional bony a unifying hypothesis for the diverse neonatal and
pieces (Figure 31.3). There is good clinical evidence adult-­onset clinical syndromes is that an underlying
that the disease is inherited in Arabian horses395,397,414 perinatal myopathy is the precursor lesion. Lambs
and in Holstein cattle,400,401 and a 2.7 kb deletion surviving the perinatal insult develop fibrous con-
between Hoxd4 and Hoxd3 may be associated with tracture of cervical and thoracic paravertebral mus-
the causative genetic defect in most but not all cles with secondary vertebral contractures.424,425,427
Arabian foals with OAAM.412,413 Other of the deform- However, it is reasonable to always consider previous
ities described above and additional individual C-­T trauma as a cause in individual cases.
defects in the craniovertebral region403–405,411,413,415–418 Careful pedigree analysis of 64 Poll Merino lambs
may well not be inherited. Indeed, for many of these affected out of 23,000 born over 16 consecutive years on
cases, a strong argument can be made for peripartum a property in New South Wales supported a genetic basis
or postnatal craniovertebral trauma as being a strong for the disorder with a recessive mode of inheritance.428
contender as a likely cause of the malformation.
The clinical syndromes are distinctive, but the dis-
Bovine complex vertebral malformation
ease must be confirmed with radiographs. In an
Arabian foal, OAAM should not be confused clini- Since 1999, a relatively common, congenital, inher-
cally neither with cervical vertebral malformation ited disease consisting of growth retardation, cervi-
nor with cerebellar abiotrophy. Again, healed atlan- cothoracic vertebral malformation, and symmetric
tooccipital injury can mimic the clinical and radio- arthrogryposis has been recognized as a global prob-
graphic signs of inherited OAAM and must be lem in Holstein cattle.429–435 This is referred to as
considered in individual cases.398,404,405,407,411,415,416,418 Bovine Complex Vertebral Malformation (BCVM)
And, well-­modeled vertebral lesions can be present and is an autosomal recessive disorder due to a muta-
after weeks if not days in neonatal animals. tion in the SLC35A3 gene432,434,436 for which there are
Surgical decompression and fixation can be quite accurate genetic assays.437–441 Probably 80% of
attempted for individual cases,419–423 but affected homozygous affected fetuses are aborted before
Arabian foals and Holstein calves and their parents 260 days gestation, reducing the reported incidence
probably should not be bred from because their mal- in newborn calves, and only a proportion of full-­term
formation is most likely inherited. calves are alive at birth.432,434 The vertebral defects are
characterized by cervicothoracic hemivertebrae,
­scoliosis, misshapen vertebrae, and ankylosis with
Cervicothoracic subluxation in sheep
several additional, nonvertebral defects often pre-
Neonatal lambs and young and adult sheep of s­ everal sent.433,435 Underlying cervicothoracic spinal dysfunc-
breeds with this condition have degrees of cervico- tion likely accounts for reduced in utero movement
thoracic vertebral misalignment and ataxia with and prominent thoracic limb and mild pelvic limb
tetraparesis to recumbency.424–426 At least Suffolk, arthrogryposis. Mutations in the human SLC35A3
Corriedale, Merino, and Columbia breeds in UK, gene are one cause of autism spectrum disorder as
Australia, New Zealand, and USA have been described well as causing epilepsy and arthrogryposis.442
with the disease. International carrier rates for BCVM range from 5
Newborn lambs presented because of difficulty in to 40%, and importantly, the increased intrauterine
lifting their heads and necks to suck or because of mortality leads to repeat breeding and added culling
degrees of ataxia and tetraparesis to recumbency. pressure in affected herds.440,443–447
Sheep several months to 3 years old presented for Because of the wide variation in congenital mal-
degrees of U-­shaped (lordotic) neck or cranial tho- formations described in affected calves, other envi-
racic region, neck rigidity, and evidence of cervico- ronmental causes, including BVDV and neurotropic
thoracic spinal cord disease. All cases have arboviruses, must be considered as contributing to
cervicothoracic subluxation, usually with flexion the resulting phenotypes.430,432,434,448
244 Large animal neurology

Congenital chondrodystrophy in beef

cattle
Congenital Chondrodystrophy has been reported in
both free range and housed beef cattle of many breeds
in Europe, North America, South Africa, New
Zealand, and Australia. Affected calves have been
variously identified as acorn calves, bulldog calves,
congenital joint laxity, dwarfism, congenital spinal
stenosis, and premature synostosis of thoracolumbar
vertebrae.
Up to 100% of calves being affected in some
reports rather rules out genetics as the sole cause
although genetic, infectious, toxic, and nutritional
etiologies are still to be considered.244,449–451
Investigations in Australia have shown that the con-
(A)
dition is associated with drought and with poor qual-
ity maternal nutrition,450,452 prompting a common
hypothesis that the condition results principally from
a maternal nutritional deficiency and may involve a
deficiency of manganese or more possibly zinc.450–453
In addition to the more generalized syndromes of
chondrodysplasia, calves can be found paraplegic at
birth or may present with progressive paraparesis
and ataxia over 1 or 2 months of age all associated
with spinal cord compressions due to thoracolumbar
vertebral canal stenosis resulting from defective ver-
tebral bone and cartilage development. Some calves
have improved with time but not fully recovered.

Myelodysplasia and congenital vertebral (B)

(b)
malformations
Figure 31.4 Congenital neural deformities sometimes are associated
Myelodysplasia has been recorded in all species, with abnormal vertebral and cranial defects. Not necessarily will they be
but most often in calves and consists of various purely genetic and, perhaps surprisingly, may result in a delayed onset of
combinations of spinal dysraphism, syringomyelia, neurologic signs that are progressive. The foal described here developed
hydromyelia, diplomyelia, diastematomyelia, menin- progressive contractural deformities of the thoracic limbs beginning at
gocele, and meningomyelocele, with or without several weeks of age, progressing to difficulty protracting the limbs and
showed an avoidance response when the limbs were manipulated or the
vertebral anomalies including spina bifida, foal tried to move fast. Some response to analgesic medication had been
rachischisis, hemivertebra, block vertebra, butter- obtained, but signs were relentlessly progressive until euthanasia of the
fly vertebra, and transitional vertebra (Figures 31.4 foal at several months of age. There was an unusual midline core defect in
and 31.5).236,339,454–469 the intercentral region of C7 and T1 (A) with a tubular, ventral protrusion
Split spinal cord malformations involving seg- of spinal and meningeal tissue from the C8 spinal cord segment (B; star)
through the bony defect forming a midline cyst in the mediastinum.
ments of spinal cord have been classified as Type-­I Adhesions were evident between the meningeal tissues and the rim of the
(diastematomyelia; two hemicords with separate intercentral vertebral defect that may well have played a role in the clinical
dural coats) and Type-­II (two hemicords with single signs of progressive painful responses to the movement of the vertebral
dural coat) and have been recorded in Hereford, column.
Holstein Friesian, Japanese Black, and Holstein ×
Belgian Blue crossbred calves,470 and in a 9 year old abrupt onset of ataxia and weakness terminating in
Thoroughbred gelding with a Type-­II cervical mal- recumbency, that may or may not have related to the
formation and quite surprisingly with a recent and cervical myelodysplasia.471
 Congenital, familial, and genetic disorders 245

(B)

(A) (C)

Figure 31.5 Sacral myelodysplasia and associated vertebral anomaly occurred in this Holstein calf resulting in a slightly abnormal posture with
hindlimbs placed cranially (A). There was also very mild ataxia and bilaterally-­active pelvic limb movements while moving at a trot or canter (bunny-­
hopping gait). Moderate overflow urinary and fecal incontinence was present, but the calf coped well and grew as expected. A 15 × 1 cm tubular stalk
of skin was attached over the sacrum and lay on the dorsum, ending in a tail-­like structure (A–C; yellow arrows). The myelomeningocele protruded from
the sacral segments into this structure (C; black and white arrowheads). Surgical removal would have been easily accomplished but the neurologic syn-
drome would remain.

Myelodysplasia with palatoschisis has been related bunny-­hopping gait without bilaterally active reflexes
to genetic factors in Charolais and Hereford calves, is most often associated with many, often symmetri-
although the mode of inheritance is unknown.472 In cal, musculoskeletal lesions, including stifle osteo-
most other cases, the cause is usually unknown with chondrosis, hock osteoarthritis, and thoracolumbar
proposed causes including vitamin A and copper pain.
deficiencies, viral infection, or toxic causes such as Congenital kyphosis, lordosis, scoliosis, and torti-
consumption of neuroteratogenic plants, particularly collis are often associated with arthrogryposis in the
lupine.454,456,473 contracted foal and twisted calf syndromes that can
Variations in numbers of thoracic, lumbar, sacral, be inherited but can also result from toxins, infec-
and coccygeal vertebral bodies frequently occur, but tious agents, and even hyperthermia acting in utero
are only rarely associated with spinal cord disease.474,475 to effect such skeletal and nervous system
However, deficient or duplicated cervical vertebrae malformations.236,238,454,467,472,480–486
are rare but have been associated with developmental Outbreaks of various spinal cord and vertebral
ataxia at least in horses.396,476,477 malformations such as spina bifida should indicate
In general, these myelodysplastic disorders are an acquired effect of toxin, infectious agent or other
reported more frequently in several breeds of cattle inciting factor as being a contributing cause of the
but are less common in other species. If not terminal maldevelopment.176,487,488
at the time of birth, or the patient is recumbent, com- Agenesis and dysgenesis of coccygeal vertebrae
binations of ataxia, weakness to recumbency, and and spinal cord segments resulting in “wry tail”
bilaterally active reflexes in the limbs frequently (Figure 26.2), other signs of cauda equine deficits,
occur, sometimes with evidence of pain related to the and sometimes caudal alimentary and urinary tract
site of malformation. Characteristically, affected dysfunction, is a reasonably common defect in cattle
calves238,457,459,478,479 and foals468 have been noted to and occurs in other species. Variable caudal vertebral
have very characteristic, bilaterally synchronous, anomalies have been seen in conjunction with ano-
ambulatory (bunny-­hopping), and reflex movements phthalmia in Japanese Brown cattle.489 Sacrococcygeal
of the pelvic limbs. It needs to be recalled that a spina bifida, myelocele, myelomeningocele, and
246 Large animal neurology

other anomalies have also been seen. In some cases, 1977.506–508 Appaloosa foals and young adult horses
associated cranial anomalies such as hydrocephalus with CSNB have a stable disability that affects
and the Arnold–Chiari malformation accompany vision and performance in restricted light.508–510
such anomalies.236,238,454,467,481,482,490,491 Thus, it can cause stumbling at the end of a trail
Most of the above primitive neural tube defects ride at dusk. Severely affected foals and horses may
with failure of fusion of neural folds result in dorsal also show a dorsal or dorsomedial (rotational) eye
midline defects including cranioschisis, rachischi- deviation, alternating head tilt and nystagmus.
sis (e.g., spina bifida), and various encephalo-­and Daytime visual deficits seen as diminished dazzle
myelo-­meningocele formations (Figure 31.5).25,492 and menace responses and sluggish and incom-
Interesting congenital, ventral midline vertebral, plete pupillary light reflexes can be recorded.509–511
and spinal cord defects have been seen in young As normal neonatal foals have no menace response
foals of various breeds. Signs have usually been for several days, a very early diagnosis will be very
progressive ataxia and paraparesis, some with evi- difficult to make. Even in older foals, other causes
dence of thoracic pain.469,492,493 Meninges and for moderate amaurosis (e.g., postictal effect),
spinal cord tissue have formed ventral cyst-­like head tilt (e.g., otitis interna), and star-­gazing atti-
structures ventrally through a median central tude (e.g., diffuse encephalopathy) can make clini-
defect in one or more cranial thoracic vertebrae cal diagnosis problematic. Additional breeds
(Figure 31.4). Such a defect is likely due to failure of reported to be affected are American Quarter
the notochord to induct appropriate segmental Horse, Thoroughbred, Standardbred, Tennessee
development of the neuroectoderm dorsal to it Walking Horse, and Paso Fino.
early on in embryogenesis. There are no morphologic retinal lesions present,
In straightforward cases of meningocele, with little although the neuroretina is dysfunctional with a pre-
in the way of neurologic deficits, surgical correction sumed defect in neural transmission of the rod pho-
can be undertaken.494 toreceptor synaptic terminal or of bipolar cells.
Typically, in affected Appaloosa horses, the dark-­
As a word of caution, it must be remembered that in adapted ERG response to white light is an absence of
utero and postnatal trauma can result in vertebral the b-­wave and a dominant, depolarizing a-­wave that
deformities that mimic congenital malformations. Thus, increases in amplitude as dark adaptation continues.
some cases of hemivertebra, developmental kyphosco- This a-­wave-­dominated ERG is referred to as a “neg-
liosis, and other deformed vertebrae495–499 could well ative ERG.”509–512
be the result of in utero or postnatal trauma and not Congenital stationary night blindness has been
necessarily represent a genetic defect.409,500 associated with homozygosity for leopard spotting
complex (LP), also known as Appaloosa spotting, at
least in the Appaloosa and Miniature Horse
Optic nerve hypoplasia breeds.510,513 The “Leopard” coat pattern is heterozy-
Degrees of blindness are evident in young animals gous (LP/lp) and unaffected for CSNB, whereas the
with hypoplasia of the optic nerves and the neuro- “Few spot” pattern is homozygous for LP (LP/LP)
retinas,501 although in the absence of globe hypo- and associated with CSNB. The genetic defect is
plasia (microphthalmia)502 this condition is likely caused by a downregulating mutation in the
extremely rare.503,504 As with congenital visual defi- transient receptor potential cation channel, subfam-
cits from any cause, eyeball deviations and abnor- ily M, and member 1 gene (TRPM1).514–516 In addition
mal movements of the eyeballs and head posture to the Appaloosa breed, many other breeds have
can be expected.505 spotting, including Knabstrupper, Noriker, Pony of
the Americas, American Miniature, British Spotted
Congenital stationary night Pony, and Australian Spotted Pony, and have leopard
complex; however, association of CSNB with
blindness—­nyctalopia homozygosity for LP has not yet been documented in
Congenital stationary night blindness (CSNB) is these other breeds.517 A missense mutation in the
characterized by a congenital and nonprogressive metabotropic glutamate receptor 6 (GRM6) gene is
scotopic (low light condition) visual deficit and the likely cause of CSNB in a Tennessee Walking
was first characterized in the Appaloosa breed in Horse that lacked the TRPM1 variant.518
 Congenital, familial, and genetic disorders 247

least some white Paint Horse foals born with enteric

Bellone and co-­workers 514,519 have made two fascinat- aganglionosis (Lethal White Foal Syndrome) are
ing observations in their studies of equine CSNB. First, born deaf.531
that the TRPM1 mutation associated with CSNB likely In describing cattle with incomplete albinism and
resulted from the insertion of a long terminal repeat of heterochromic irises in a Hereford herd,532,533 Leipold
an endogenous retrovirus into the gene.515 Second, and Huston indicated that the ranch owner described
that the first genetic evidence for a leopard spotting the white cattle as exhibiting photophobia and some
gene LP of horses in Europe dates back to the deafness, but only behavioral assessment methods
Pleistocene period, to disappear during the Bronze Age were available at the time. A monogenic autosomal
and reappear in the Iron Age, likely representing dominantly inherited syndrome in Fleckvieh cattle
­alternating selective breeding pressures.519 One inter- associated with hypopigmentation, heterochromia
pretation of these findings is that they might help irises, colobomatous eyes, and bilateral total hearing
explain how genetic diversity has been maintained in loss has been reported as the German White Fleckvieh
domestic animals despite selection for specific pheno- syndrome. A missense mutation within the bovine
types at different times. MITF has been reported to be responsible for this
syndrome,534 making it a model of Tietz syndrome in
humans.535
Congenital sensorineural deafness
Sensorineural deafness has been well studied in
Although congenital sensorineural deafness is quite alpacas536 and because of the perceived relationship
common in particular breeds of dog,520–522 it is far less between white coat color (leucism), blue irises, and
frequently recorded in species of large domestic ani- deafness, a study of normal and abnormal BAEP
mals including cattle, horses, and camelids.523 recordings was made of 63 camelids.537 The high fre-
At least 14 American Paint horses with extensive quency (78%) of bilateral sensorineural deafness in
white markings suspected of being deaf from a very llamas and alpacas with pure white coats and blue iris
early age were found to have flat brainstem auditory pigment resulted in a genetic correlation between
evoked potential (BAEP) recordings. All these horses melanocyte maturation and deafness being con-
had extensive head and limb white markings but with cluded for those species.537
variable amounts of white on the neck and trunk, and Profound sensorineural deafness has been
all had blue irises in one or both eyes.524–526 There was reported in white Chinese Rongchang pigs associated
a strong association between a mutation in the with loss of cochlear hair cells and with a deficiency
endothelin receptor type B (EDNRB) gene and deaf- of melanocytes in the stria vascularis of the cochlear
ness in these Paint horses, and also in Paint foals suf- duct.523,538 A mutation in the melanocyte-­ specific
fering from lethal white foal syndrome.517,526 Because promoter of MITF gene that eliminated expression of
melanocytes are present in the inner ear and impor- the MITF-­M isoform was reported in affected pigs.539
tant for audition, mutations in several genes involved This led to early degeneration of the cochlear stria
in melanocyte function cause both deafness and vascularis and profound hearing loss, as well as
white coat markings in horses. This is the case for depigmentation, all of which resemble the typical
EDNRB and frame overo coloring, and for some phenotype of Waardenburg syndrome in humans.540
horses of several breeds (American Paint, Apaloosa,
Franches-­Montagnes and others) with the “splashed Bilateral convergent strabismus
white” or related “macchiato” coat color patterns that
are caused by mutations in 2 genes, microphthalmia-­
and exophthalmos
associated transcription factor (MITF), and paired This disease of cattle has been described since the
box gene 3 (PAX3), that are involved in melanocyte nineteenth century541 as an inherited trait in many
development.527–530 cattle breeds worldwide.542–550 A moderate exophthal-
Thus, congenital (inherited) sensorineural deaf- mos occurs due to the ovoid shape to the globe, and
ness should be considered in horses suspected of some epiphora may also result.542,543 In most cases,
being deaf from an early age, particularly in those the syndrome is not congenital but usually appears in
breeds that have extensive white marking and/or a yearlings or as late as 10 years of age, making herd
propensity for white or blue irises such as Appaloosa, management of the disorder difficult. It usually ends
Paint, Piebald, Skewbald, and Clydesdale breeds. At with a severe visual deficit that is often recorded as a
248 Large animal neurology

change in behavior described as “shy,” “leery,” This condition appears to be stable and has no
“jumpy,” or “wild.” apparent clinical consequences; thus, it should not be
One cytonumeric study on the abducens nuclei taken as evidence of more serious vestibular disease.
and nerves and the extraocular muscles in black and On the other hand, most humans with childhood
white cattle in Germany that had bilateral convergent nystagmus and no overt blindness have various other
strabismus and exophthalmos (BCSE) revealed a visual and oculomotor disturbances.562,563 The older
paucity of abducens neurons and hypoplasia of the term Congenital Nystagmus has been replaced by
retractor oculi and lateral rectus muscles.547 Some Infantile Nystagmus for humans, particularly as the
evidence for a myopathic lesion of extraocular mus- onset is usually at weeks to months of age.562,563 This
cles has also been discussed.542,543,551,552 umbrella term encompasses many phenotypic forms
The exact mode of inheritance for BCSE has not of inherited nystagmus in children, for which there
been determined, but at least in German Brown cattle are more than 100 candidate genes recorded.564
affected by BCSE there has been an SNP association
with the disease for two candidate genes located on Congenital flaccid mandible in newborn
BTA5 (PLXNC1) and BTA18 (RDH13) so that it is
likely that these genes, or nearby mutations, could be
calves and lambs
responsible for BCSE in that breed.542,553–555 Several Usually following anterior presentation, dystocia,
different candidate gene mutations are associated and assisted delivery, a calf or lamb may have a flac-
with BCSE in Holstein cattle so there is obvious cid mandible. Some recover completely. It is assumed
genetic heterogeneity regarding the inheritance of that a neuromyopathy associated with degrees of
the syndrome among cattle.556 edema of the head usually accompanies the syn-
drome. However, one newborn calf that was seen
with masticatory muscle atrophy and a flaccid man-
Divergent strabismus
dible at a few days of age had a degenerative myopa-
Unilateral545 and bilateral557 divergent strabismus thy consistent with white muscle disease involving
may also be an inherited defect in Highland and the masseter muscles.
Holstein cattle. In the former report of two affected
Highland steers,545 the insertion of lateral rectus mus-
cle was displaced 40° ventral to normal; and the cattle Spastic syndrome of adult cattle
had “crop ears.” Known for almost 80 years,565,566 spastic syndrome
(Figure 21.6b) is also referred to as Barn Cramps,
Crampiness, Stretches, Krämpfigkeit, Periodic Spasticity,
Juvenile pendular nystagmus and Standing Disease, among others, and occurs in
The term pendular or oscillatory nystagmus refers to adult cattle, worldwide.567–573 As the clinical syndrome
rapid (>>1 Hz), involuntary eye saccades with speed consists of spontaneous and reflex, fluctuating hyper-
equal in both directions. About 1 in 200 Holstein and tonia of predominantly extensor pelvic limb and
Jersey dairy cows was found to be afflicted with pen- thoracolumbar musculature, and not knowing the
dular nystagmus with no other evident signs. The pathogenesis of the disorder, the terms spasmodic syn-
nystagmus most often was vertical, but in some cases drome of cattle (syndrome spasmodique des bovins567)
it was horizontal or rotary, and in one case it was uni- and spasmodic extensor hypertonus seem to be more
lateral.558 Some cattle are affected at birth. The same, preferred terms. It is recorded as more frequent in
presumably inherited, syndrome has also been seen 3–7-­year-­old Holstein and Guernsey bulls in North
in Ayrshire, Guernsey, and Holstein cattle.559,560 America,573 although it occurs in a wide range of dairy
Up to 20% of lambs from two Scottish Blackface and beef cattle, particularly in large-­framed, heavy
flocks were found to have degrees of pendular nystag- mature cattle that reach middle age.570,574,575 A
mus. In some adult affected sheep, there was an asym- 2-­year-­old, large-­framed, 140 kg blue-­faced Leicester
metry to the saccades of nystagmus, referred to as jerk ram has been seen with the same syndrome
nystagmus. Evidence of decreased visual acuity was seen (Figure 21.6c).576
as affected lambs and adult sheep huddling in groups There is an onset of progressive, periodic jerking,
more than normal flock mates while tilting their heads and stiffness and fasciculation of pelvic limb and
when visually fixating on distant or threatening fields.561 thoracolumbar muscles, particularly noted when the
 Congenital, familial, and genetic disorders 249

animal first stands up or becomes excited. Periodic, evaluation of the pelvic limbs. Mephenesin (30–
spontaneous, and reflex excessive contraction of 40 mg/kg, orally, for 2–3 days) may control severe
extensor muscles of the lumbar region and extensor signs for some weeks but has not been consistently
and abductor muscles of the pelvic limbs, which may useful. The syndrome persists for the animal’s life
last many minutes, results in lordosis and in limb and usually progresses.
abduction and caudal extension, both while walking
and particularly while standing still. Trembling of the
Spastic paresis of calves
hindlimbs, which may be violent, is usually seen.
Forelimb and head and neck extensor hypertonic The syndrome of spastic paresis of calves
episodes exaggerate the unusual lordotic posture (Figure 21.6a) has been described since at least
(this motion has been likened to Stringhalt, but is not 1922,581 and is also referred to as Elso Heel, Straight
a flexion movement of the hip, stifle, and hock) and Hock Syndrome, and Contraction of the Archilles
thus more akin to Stiff Horse Syndrome and Shivering Tendon. It frequently occurs in calves of a great vari-
(see Chapter 21). Signs are usually worse when the ety of breeds and is first seen at birth or up to
animal first stands up; they abate during recumbency. 12 months of age. Dams and their affected calves
Movement can be impossible during attacks.570,577 usually have been and are at pasture.582,583 A similar
The cremaster muscles can be involved in the sponta- syndrome may rarely occur in adult cattle584 and in
neous and reflex hypertonia and responsiveness pygmy585 and Nigerian dwarf goat kids.
(Figure 21.6c). While the patient walks, the testicle Contemporary, thorough literature reviews have
on the same side as the contracting (advancing) limb been published581,586,587 without resolution as to the
can be raised, and when the scrotal skin is stimulated cause being agreed.
to induce a cremaster reflex, the ipsilateral hindlimb Affected calves are often first noted to have exces-
can demonstrate the typical extensor tone and mus- sively straight hocks then an awkward, hyperex-
cle cramps. Early on it is difficult to distinguish the tended, usually asymmetric pelvic limb gait. The
syndrome from lumbosacral spondyloarthrosis, hip forelimbs are often straight also. The hocks are
lesions, gonitis, upward patellar fixation, and simply straight and the gastrocnemius and superficial digital
excessively straight hindlimb conformation. With flexor muscles have excessive tone. Most often both
some clinical likeness to equine shivers that may limbs are affected, but one more severely, causing it to
involve cerebellar nuclear neuronal degeneration,578 be held extended behind the calf and to jerk forward
it is reasonable to inquire as to the status of cerebellar without touching the ground at each failed, attempted
integrity in this disorder of cattle. For inexplicable step. In such severe cases, the muscle hypertonia is
reasons, cattle with “crampiness” were accepted for also present in biceps femoris, caudal thigh, quadri-
subsidized slaughter under EU BSE containment ceps, and pelvic limb abductor muscles. Cases have
schemes!579 been classed as three types depending on the clinical
Dysfunction of the myotatic reflex arc (including the syndrome and the muscles deemed to be predomi-
γ-­efferent fibers, muscle spindle, and 1a-­afferent fibers) nantly hypertonic.586 Thus, type-­G is where the gas-
or postural reaction, central motor neuron pathways trocnemius muscle is dominantly contracted with the
may be present although no consistent neural or mus- limb held in caudal extension (Figure 21.6a). Type-­Q
cular pathologic findings have been reported.571 A is when the quadriceps muscles appear to contract the
familial tendency has been observed.567 570,573–575 most causing lumbosacral kyphosis and cranial place-
Pedigree analysis of 892 bulls culled from artificial ment of the limbs, and type-­M is regarded as mixed
breeding establishments strongly indicated that the dis- muscle contraction when the limb(s) are held in
ease was inherited as an autosomal dominant gene with abducted extension. Secondary osteoarthritis occurs
incomplete penetrance,574 and an estimate of heritabil- in hock joints of severely affected limbs.582,583,588
ity of 0.26 has been reported for a population of North Neither needle electromyographic abnormalities
American Holstein cattle affected with spastic syn- nor consistent histologic lesions indicative of neuro-
drome.569 As is ongoing for the inherited spastic para- muscular disease are reported.583,588–590 However, two
plegias in humans, further searching for candidate cases did have patchy, mild, nonsuppurative enceph-
genes would seem reasonable.580 alitis of unknown contribution to the signs.582 Other
It can be necessary to use α-­2 adrenergic agonist sparse and discrepant histologic findings, possibly
sedation to examine affected cattle, especially for the artifactual, have been considered.586
250 Large animal neurology

Using dilute epidural procaine, partial sensory Very few cases spontaneously recover.587
blockade, or using surgical deafferentation of the gas- Gastrocnemius tenotomy is not cosmetic, but it can be
trocnemius muscle, there is a reduction in the degree an effective salvage procedure. Partial or total tibial
of hypertonia or spasticity. Therefore, the pathogenic neurectomy is esthetically pleasing, simple, and >80%
mechanism underlying the syndrome is thought to effective for the type-­G and type-­M forms having pre-
be an overactive myotatic reflex.591–593 Some evidence dominant involvement of the gastrocnemius mus-
that there is an imbalance of serotonergic verses cle.596,601 This is performed on the lateral aspect of the
dopaminergic neurotransmitter activity in spinal stifle between the two heads of the biceps femoris mus-
fluid has been presented.591 There being no CNS or cle.596,602 One solitary worker claims that a lithium salt,
PNS consistent changes found on routine histologic at doses quoted as 20–80 mg/kg/d586,597 and 0.2 mmol/
studies, Chiocchett et al.594 studied the central motor kg/d598 orally for 2–4 weeks, has been curative in about
neurons that likely do control hindlimb somatic 75% of cases if begun early in the course of disease! To
muscles and determined that neurons in the medul- confound this amazing result further, the author also
lary reticular formation and possibly in the red claims that amino acids, manganese and especially
nucleus were smaller in three calves affected by spas- copper potentiate the therapeutic response to the treat-
tic paresis than in unaffected calves. These neuronal ment of spastic paresis with lithium.586,598,599
groups may have an inhibitory action on the final Bovine spastic paresis is a very important neuro-
motor neurons that control hindlimb extension, logic disease of young cattle,603 and future work will
leading to the suggestion that an overactive stretch likely focus on the role of molecular mechanisms
reflex resulted from a lack of inhibitory mechanisms involving motor inhibitory pathways in spinal cord
in the disease. and dorsal root ganglion sites as is being revealed in
The syndrome at times appears to be familial, several other human and animal movement and pos-
although of low heritability, and certain famous sires tural disorders.101,102,604,605 The role of contributory
have been incriminated as genetic carriers. These genetic and nutritional factors must continue to be
include an East Friesland bull, Elso II-­34 (hence the investigated.580,581,586
name Elso Heel), and a Dutch bull, Adema-­197, both
of the Friesland breed.581,582,595 Occurrences of
Familial neuropathy of Gelbvieh cattle
0–100% in calf crops have been seen, and a high inci-
dence (30%) in a closed herd in 1 year with no cases Young calves affected with this condition show inter-
in previous or succeeding years, nor in large numbers mittent but progressive pelvic ataxia and paraparesis
of related calves on other properties, invites study of progressing over several days to 20 months, to end up
environmental influences to a genetic background of recumbent.606,607 Neurologic examinations revealed
susceptibility.587,596 Indeed, it has been said that irrev- limb, cutaneous trunci and anal hyporeflexia and
ocable proof for the heritability of spastic paresis is hypotonia in some cases and loss of deep pain sensa-
not available.581 The role of environmental factors, tion in all four limbs in two cases. Cursory needle
including micronutrients such as magnesium, has EMG examinations in three cases revealed sharp
been raised.597 Not surprisingly, the hypothesis that potentials (sic.).606 Results of detailed neurological
bovine spastic paresis is related to a transmissible examinations would be useful in defining the clinical
spongiform encephalopathy,598 specifically bovine syndrome better. Wallerian-­ like neuronal fiber
spongiform encephalopathy (mad cow disease),599 degeneration was present in dorsal and ventral nerve
has not received any further backing. roots from cervical through sacral segments and in
Clinical diagnosis is based on the typical syn- mixed peripheral nerves, and this extended into the
drome. However, gonitis, generalized arthritis, entry root zones. The trigeminal nerve showed
upward patellar fixation, arthrogryposis, partial marked Wallerian-­like degeneration in the one case
sciatic paresis (Figures 25.2), and congenital laxity in which it was examined.606 Minimal fiber degenera-
and overextension of the hock joints clinically can tion was present in spinal cord and caudal brainstem
be confused with this syndrome and must be ruled white matter. An accompanying glomerulopathy was
out. A very similar if not identical condition in consistently present, and this was considered to pos-
newborn calves in Australia has been suspected to sibly be due to myoglobin nephrosis. The presence of
be due to maternal ingestion of low doses of toxic elevated serum CK activities and multifocal muscle
plants.600 necrosis may result from recumbent episodes or be
 Congenital, familial, and genetic disorders 251

an unusual primary component of this familial unguligrade (plantigrade in bipedal animals such as
disease.606,607 Other young calves with progressive humans) at birth (Figure 31.6). Sometimes the verte-
renal lesions should also be screened for the presence bral column and calvaria is similarly affected with
of neuropathy.608 degrees of torticollis resulting. Malformities of pal-
ate, heart, and other organs can coexist. Clinically,
Congenital hypomyelination sensory there are varying degrees of angular fixation of limb
joints with restricted ranges of motion, muscle atro-
neuropathy phy, and vertebral deviations such as kyphoscoliosis
A quite unique case of congenital hypomyelination (Figure 31.6). Most often flexion fixation, valgus
neuropathy was recorded in a lamb showing ataxia deformity of the thoracic limbs, and extension rigid-
and tremor involving the head and limbs from ity of the pelvic limbs occur. Cerebral signs, such as
birth.170 The clinical syndrome consisted of an inten- severe obtundation and blindness due to hydranen-
tion tremor and hypermetric ataxia with no weak- cephaly, and cerebellar signs associated with cerebel-
ness. There were absent patellar reflexes, normal lar hypoplasia, may be present; these are most
needle electromyographic examination, and absent common in cattle and sheep. Charolais calves usually
evoked muscle action potentials. The lesion was have a cleft palate, and profoundly affected foals and
restricted to marked deficiency of myelin in periph- calves can have associated abdominal herniation or
eral nerves with intact axons. visceral eventration in the form of perosomus
elumbis.614–617
Arthrogryposis is secondary to anything that
Hindlimb spasticity in piglets causes reduced movement of the fetus in utero, such
An outbreak of unilateral hindlimb stiffness, inter- as final motor neuron complex defects,618–620 although
preted as spasticity, was seen in all 61, 2-­week-­old pig- it certainly can be inherited.486,612,621–624 So long as
lets of eight litters born during a 4-­month period in a reduced fetal movement occurs for a reasonable
single piggery. Neuronal chromatolysis and degenera- period in utero, muscle, tendon and ligament tissues
tion of unknown significance was detected in some will contract and quickly cause restricted joint mobil-
CNS regions, but the significance of this finding and ity, viz. arthrogryposis.
the cause of the disorder were not determined.609 Even though it can occur with palatoschisis, arthro-
gryposis is more often not hereditary. However,
Arthrogryposis (Gr: arthron = joint; outbreaks of arthrogryposis with or without
­
hydranencephaly in calves have occurred in Australia,
gryposis = curvature) Japan, North America, and Israel due to in utero fetal
Arthrogryposis multiplex congenita refers to a con- infection with Akabane and many other arboviruses,
genital syndrome wherein the patient has multiple, especially of the family Bunyaviridae.86,176,246,625–630
rigid, curved, or sickle-­shaped joints. This relatively Such viruses affect fetal neurons, especially those in
common syndrome that occurs in all large animal the spinal cord, as well as muscle cells. Thus, some
species, especially in newborn ruminants and piglets, final motor neuron complexes are absent and joints
is also referred to as congenital articular rigidity, have limited mobility, with subsequent rapid onset of
crooked calf syndrome, and contracted foal syn- angular fixations in utero.251 Coxsackievirus-­A2 injected
drome.238,454,465,467,481,482,610 Newborn animals are seen into chick embryos can result in myositis and arthro-
to be affected immediately or when they attempt to gryposis.631 Some emergent diseases, characterized by
stand and walk (Figure 31.6). The contracted foal the devastating Zika virus infection in pregnant
syndrome is more frequently seen in certain breeds women within the last decade, have included infant
such as the Thoroughbred in the US and small draft arthrogryposis in their clinical outcome.632,633
breeds in Europe.610,611 The crooked calf syndrome is Various plant toxins probably account for a majority of
common in beef calves in Western Europe.612 In the cases in ruminants, at least in Western North America.619
western United States and Alaska, it may occur at a Tobacco, sweet pea, locoweed, lupine, poison hemlock,
frequency of 40% on some farms and is most com- and jimsonweed ingestion have been shown to produce
mon in calves from first calf heifers.613 the syndrome in pigs and cattle.480,483,612,624,634 Ingestion of
Affected newborn animals have degrees of limb Sorghum spp. grasses by pregnant cows and mares has
flexor and extensor rigidity, with inability to stand been associated with the disease in offspring.635,636 Up to
252 Large animal neurology

40% of beef calves in some herds in the Western United sent in certain species of lupines.613 This syndrome of
States have been affected at various times. This is associ- crooked calf disease and the similar, frequently occur-
ated with the ingestion of lupines by pregnant cows on ring, calf arthrogryposis seen in Europe612 are both par-
days 40–70 of gestation. The principal toxin here appears ticularly characterized by forelimb involvement
to be the quinolizidine alkaloid, anagyrine, which is pre- (Figure 31.6).

(A) (B)

(C) (D)

Figure 31.6 Syndromes of prominent, congenital, rigid contractures of limb and other joints are referred to as arthrogryposis (syn. sickle joints).
Syndromes range from mild and affecting one set of limbs to being profound and lethal with rigidity of all limbs, trunk, and neck, and often with associ-
ated malformations including kyphoscoliosis and hydrocephalus and hydranencephaly. Any process that reduces or restricts in utero fetal movement likely
can result in arthrogryposis. Often there will be reduced muscle bulk and fibrous replacement causing joint contracture and rigidity, and commonly this
muscle deficiency will be due to final motor neuron involvement. This neonatal calf was born with moderate limb contractures (A), suffered thoracolumbar
torticollis (B) and had asymmetric loss of nerve fibers in ventral branches of thoracic segmental nerves that were replaced by connective tissue remnants
within perineural sheaths (C; filled stars) and associated neurogenic-­type atrophy of multifidus thoracicus muscles (D; filled circles) compared to normal
neonatal equine myocytes (D; filled triangles). These collective findings indicate that an in utero insult such as hyperthermia, toxin, or most likely virus
caused the degeneration of fetal cervico-­thoraco-­lumbar neurons with resultant neurogenic atrophy of some thoracic limb and paravertebral muscle
fibers causing fibrous contractures of thoracic limbs and trunk.
 Congenital, familial, and genetic disorders 253

Arthrogryposis—­ sometimes also referred to as

arachnomelia (spider limbs)—­is inherited in at least The spectrum of clinical scenarios that can be found in
Simmental, Brown Swiss, Holstein–Friesian, Red cases of myotonia are numerous such that any disease
Danish, Hereford, and Aberdeen Angus cattle, with that includes myotonia can be subcategorized based
several candidate gene mutations operative.11,359,637–640 on the following criteria:
These include a CHRNB1 frameshift mutation associ- • Inherited or acquired
ated with arthrogryposis in Red Danish dairy cattle638 • Congenital or delayed
and a causative genomic deletion encompassing the • Localized or systemic
agrin (AGRN) gene in Aberdeen Angus cattle.621 • Primary or associated with other clinicopathologic
Likewise, gene defect markers for the disease have signs
been identified on chromosome-­5 of pig (SSC5) and • Progressive, stable, or improving
sheep (OAR5) in at least Swiss Large White pigs and • Exacerbated by exercise, rest or cold, or not
inbred Suffolk and Salz × Suffolk × Fleischschaf sheep • Myopathic (dystrophic) or not
flocks.641–643 • Associated with myotonic, waxing and waning high
Some affected Charolais calves may have hypo- frequency discharges on electromyography or not
tonic (floppy) muscles, and although a neurogenic
defect is suspected, the abnormal joints may be nor- Vigorous, immediate manipulation, splinting, and sur-
mal, lax, restricted, or fixed,644 and thus this particu- gery are regarded as rewarding in even severely affected
lar variant may not reflect true arthrogryposis. human infants,486,653 but the likelihood of becoming an
The cause of the disease in many cases, including athlete is remote. This would probably hold true with
all cases of contracted foals, is not known. In addition horses also. Combinations of capsulotomy, tenotomy,
to the factors already discussed, it is valid to consider and desmotomy have been extremely successful (>80%)
several alternatives to the pathogenesis of arthro- in salvaging crooked calves in Europe.612
gryposis.486 These include other neuroteratogenic
plants,457 exposure to organophosphates,645 gestational
use of anthelmintics,646,647 hyperthermia during preg- The myotonias
nancy,485,648 and fetal overcrowding or fetal–maternal Usage regarding myotonia and connected clinical
disproportion.610,649 and electrical terms in the veterinary literature has
The possibility that some cases of congenital con- been somewhat confused and confusing.654–661 To
tracted tendons in foals and calves represent mild clarify terminology, the following general statements
degrees of arthrogryposis is an interesting hypothesis.650 are accepted herein based particularly on the
Such a syndrome has been related to the ingestion of American Association of Neuromuscular and
locoweeds by pregnant mares651 and to states of hypo- Electrodiagnostic Medicine (AANEM) 2015 glossary
thyroidism in affected foals.652 of terms (see Table on myotonic terminology).662

Generalizations for characteristics of the clinicopathologic terms related to myotonia.

Term Excessive muscle contractions Electrical (EMG) findings Myopathy

At rest With exercise or Myotonic Complex repetitive

fright discharges discharges

Myotonia congenita Yes At onset; improves Yes No No

Paramyotonia (paradoxical) No Worsens Yes No Yes
Pseudomyotonia No Worsens No No No
Neuromyotonia Yes Yes Yes* Yes* Yes
Myotonic dystrophy Yes Yes/No Yes No Yes

*Neuromyotonic discharges with or without myokymia.

Sources: Based on Vanhaesebrouck et al.654; Zakia et al.656; Phillips and Trivedi658; Lowrie and Garosi659; Hahn and Salajegheh660; AANEM662
254 Large animal neurology

myotonia; myotonic myopathy) (see below). If related

to a specific inherent, muscular, molecular defect,
then the term myotonic dystrophy appears most
appropriate. Typical high-­frequency electrical activ-
ity on needle electromyography that waxes and wanes
in frequency and amplitude, and heard as a revving
motorcycle sound or dive bomber, characterizes elec-
trical myotonic discharges.
The clinical syndrome of neuromyotonia reflects
continuous muscle fiber activity manifested as con-
tinuous muscle rippling and stiffness that is accompa-
nied by electrical neuromyotonic discharges secondary
to continuous muscle activity firing at 100–300 Hz.
These are a form of complex repetitive discharges con-
sisting of repeating complex potentials with regular
frequency and amplitude resembling the sound of a
motorboat or motorcycle that does not wax and wane,
but may change in amplitude, and when doing so
abruptly producing a “ping” sound. Neuromyotonic
discharges are not affected by voluntary activity, sleep,
or anesthesia, but may be interrupted by a local block-
ade of peripheral nerve, the presumed generator of the
Figure 31.7 Animals with myotonic syndromes can have prominent
affected musculature as seen with this foal that also demonstrates typical discharges. Tapping on the nerve provokes neuromyo-
hypersensitivity contraction persisting in the proximal semimembranosus tonia. Often also present is myokymia that is seen as
muscle (arrowhead) following percussion with a rubber reflex hammer. spontaneous rippling muscle contractions reflecting
Such spontaneous and induced contraction is accompanied by trains of spontaneous electrical myokymic potentials that have
high-­frequency, electrical discharges with some abrupt changes in ampli-
rhythmic firing of grouped motor unit action poten-
tude seen and heard with an electromyographic unit, making this syn-
drome perhaps more consistent with neuromyotonia. tials. Typically, the discharges are in groups of 2–10 at
a frequency of 2–60 Hz, with a sound like marching
Myotonia refers clinically to the continued physi- soldiers.
cal and electrical contraction of muscle well after the Electrical pseudomyotonia is another high-­
voluntary effort or the reflex, chemical, mechanical, frequency discharge that tends to wane and to stop
or electrical stimulus has ceased. Such muscle con- and start abruptly, unlike true undulating myotonic
traction can be seen as prominent muscles and par- discharges. Such high-­frequency complex repetitive
ticularly as a visible and palpable knot (not dimple!) discharges are usually accompanied by fibrillation
of firm muscle bundles persisting after such stimuli potentials and positive waves, and such EMG activity
end (Figure 31.7). This sign can be present from birth can also be produced with induced hypocalcemia
and accompanied only by muscular stiffness and and hypomagnesemia.663
minimal or no myopathic histologic change when it
is referred to as myotonia congenita. These forms are
related to various membrane and sarcoplasmic Myotonia congenita
defects in electrolyte conductance and thus mostly Myotonia congenita is a rare disorder of large ani-
can be regarded as muscular ion channel mutations mals.664–666 The best studied large animal example of
or channelopathies. Classical myotonia is shown as myotonia congenita is in the goat, and this will be used
stiffness at rest and at the onset of movement with as the archetypal disease for myotonia congenita. It
improvement during exercise. When the excessive was originally found in an unusual breed of small goat
muscle contractions worsen with exercise, especially afflicted with an autosomal dominant form of congen-
when there are some (nondystrophic) myopathic ital myotonia.666–668 This breed (https://faintinggoat.
lesions present, the syndrome is para(doxical)myoto- com/), colloquially referred to as fainting, stiff-­legged,
nia. Myotonia accompanied by weakness and by vari- nervous, seizuring, or epileptic goats, was popularized
able but prominent myopathic findings can be in the nineteenth century in Tennessee and Texas as
referred to as a myotonic dystrophy (syn. dystrophic amusing and easy to keep farm animals, being
 Congenital, familial, and genetic disorders 255

­ nwilling or unable to jump out of low fenced enclo-

u Diseases referred to as Bovine Pseudomyotonia
sures. In watching videos of the syndrome Best of (PMT) in Chianina cattle and Bovine Congenital
Fainting Goats,669 one might be reassured that at least Muscular Dystonia-­1 (CMD1) in the Belgian Blue
in humans the myotonic contractures are not painful breed are described and are associated with several
as are muscle cramps.660 One of the early descriptions bovine ATP2A gene mutations.679–681 The syndrome is
of the signs shown by these goats is descriptively apt: one of muscle stiffness with falling episodes caused
by exercise or by being startled, and although the dis-
“The animals may appear perfectly normal when orders may be different entities, there is some evi-
they are feeding quietly, but sudden exertion of dence from study of a Dutch Improved Red and
any kind produces the myotonic seizures. The White cross-­breed heifer calf682 that they all are the
muscles of the flexors and extensors of the limbs same disease and associated with a missense muta-
are rigidly contracted and stand out beneath the tion in the ATP2A1 gene encoding the SERCA1 pro-
skin. After a few seconds the rigidity passes off, tein (p.Arg559Cys).
and, after one or two failures, the animal regains
its feet and can walk away with little disability Myotonic dystrophy and myotonic
beyond a stiffness in the limbs . . .”666
myopathy
Severity of signs wanes with exercise and worsens Clinical myotonia with variable evidence of an
after a period of rest. A mild and a severe form of the accompanying myopathy is reported in the calf672,675
disease are evident.670 Typical high-­frequency, fluctu- but most often in horses.655,661,683–693 Many breeds
ating, myotonic discharges are found on needle EMG have been affected including Thoroughbred,
examination, and these are not abolished by anesthe- Standardbred, Swedish half-­ bred, Appaloosa,
sia, curarization, or denervation.666 This disease is a Arabian and Quarter Horse foals, and in a Welsh
channelopathy resulting from an alanine to proline pony. Heritability has not been proven in any of these
substitution in the C-­terminal residue of the goat cases, although most are affected at birth or in the
skeletal muscle Cl− channel (gClC-­1) gene.667 first few months of life. Variable, usually progressive
A very similar syndrome has been clearly described signs of stiffness and weakness with difficulty rising,
as occurring in Brasilian Murrah water buffalo and hypertrophied then atrophic musculature, as
calves.671 As with the goats, these patients also show well as mild anomalies present in other organs com-
action myotonia, especially after startle, with parox- plete the syndromes described.684 Muscles of the hind
ysms of a tonic hypometric gait at the onset of exer- quarters are most severely affected and are usually
cise and rigidity and periods of temporary prominent. The gait is stiff, especially after resting for
recumbency. Typical for pure myotonia, stiffness was a while. With exceptions, affected animals do not
less visible after exercise, indicating a warm-­up phe- appear to be debilitated by the disorder, although
nomenon. This form of hereditary myotonia in buf- limb and vertebral column deformities occur with
falo was caused by a substitution SNP in exon-­3 associated fibrous muscle contractures. The clinical
(c.396C>T) in the CLCN1 gene. diagnosis of myotonia can be made by seeing and
A mild form of myotonia congenita with appar- feeling a prominent and prolonged muscle contrac-
ently restricted involvement of more distal muscles is tion with localized firm knotting visible and palpable
also recorded in a Friesland calf.672 following mechanical (finger-­flick) percussion.686,690
The inherited form of myotonia is also seen in Clinical diagnosis of myotonia is confirmed by
well-­muscled show lambs in USA,673 in a Spanish needle EMG studies that reveal spontaneous and
flock of Rasa Aragonesa sheep,674 in Shropshire evocable electrical discharges from affected muscle
sheep,675 and in New Forrest Ponies676 in which muta- membranes. Classically in myotonia congenita
tions in Na+ or Cl− conductance channel genes have (above), the high-­ frequency discharges wax and
been defined or suspected to be associated with the wane and metaphorically should be referred to as
syndrome.658,660,677 A more recent addition to this list sounding like a revving motorcycle. As described
is a recessive form of hereditary myotonia associated above, and for clarity, these may be distinguished
with a large genomic deletion in the CLCN1 gene in from the high-­ frequency step-­ like, on/off, high-­
pigs.678 Myotonic syndromes have also been seen in frequency discharges often found in myotonic dys-
horses and in cattle but most or all of these appear to trophy cases; the amplified sound of these discharges
be other than myotonia congenita (see below). best likened to those of WW1 dive bombers. The
256 Large animal neurology

latter might best be called pseudomyotonic or sheep can have markedly restricted movement by
myotonic-­like discharges. These spectacular poten- 12 months of age, and they become crippled and
tials can be stimulated by voluntary movement, nee- mostly recumbent by 2 years of age. Ill thrift, inter-
dle movement, percussion, and chemicals. mittent ruminal tympany, and respiratory difficulty
Significantly, they do not disappear with depolariz- are also reported.695–697
ing or nondepolarizing muscle relaxant drugs666,686 Elevated serum CK activity is not a feature of the
but are abolished by local injection of lidocaine.692 disease but may be present in some advanced cases,
Usually, evidence of final motor neuron disease with especially after forced exercise when compared with
fibrillation potentials and positive sharp waves are control animals. However, clinical myotonia did not
detected between bizarre discharges.685,686 Where develop, and no myotonic or other abnormal dis-
muscle histopathology is reported, there is usually charges were detected in an affected ram on which
evidence of a primary dystrophic histological pattern needle electromyography was performed.697 This
that includes myofibrillar degeneration, sarcoplas- may not have been an exhaustive nor a clinically or
mic masses, ringed fibers, moth-­eaten fibers, fatty pathologically directed electromyographic study,
infiltration, and collagen proliferation. Some muscle thus some abnormalities could well be found.
relaxant drugs can alter the clinical signs, but the pre- Lesions in muscles can be widespread but are con-
sumed muscle membrane defect and hypersensitivity sistently found in vastus intermedius, occasionally
to mechanical, electrical, and chemical stimulation not evident until 6 months of age.698–700 Lesions are
remain. Phenytoin has not been beneficial in treating restricted to type-­I muscle fibers and consist of fiber
horses with myotonia.694 diameter variation, myofibrillar degeneration, multi-
Evidence is available to distinguish several of these ple central nuclei, fiber splitting, and development of
cases from the myotonic dystrophies of humans and peripheral and central sarcoplasmic masses.703 Fiber
other species.655,686–688,692 Thus, probably in all these atrophy, collapse, and replacement by collagen and
cases of myotonia in horses, it is best to currently cat- adipose tissue then occur. Other muscles very com-
egorize them preferably as myotonic myopathy until monly found with lesions are soleus, medial head of
molecular disruptions to dystrophin and other mus- triceps, and anconeus.
cle proteins are determined. Only then can such a Breeding experiments have demonstrated an auto-
disease be referred to as muscular dystrophy with somal recessive mode of inheritance,698 but the pres-
myotonia or simply myotonic dystrophy. ence of both C-­terminal and D-­terminal dystrophin
in dystrophic fibers as well as in control sheep
Nonmyotonic congenital and familial myofibers differentiates this muscular dystrophy
from other common inherited muscular dystrophies
muscular dystrophies and myopathies in other species such as Duchenne and Becker types
Ovine Muscular Dystrophy is a very well delineated in humans and the mdx model in mice.699–701 There
inherited myopathy of Merino sheep in Australia.695–702 has been uncertainty as to whether this disease is a
Many earlier reports of ovine muscular dystrophy true nonmyotonic muscular dystrophy673 (see above)
undoubtedly referred to nutritional myopathy. Signs or a congenital myopathy with dystrophic features.
of progressive stiffness in the pelvic limbs, thoracic This issue has recently been laid to rest by the identi-
limbs, and then neck begin in 1–2% of 3 weeks to fication in affected sheep, using whole genome
6-­month-­old Merino lambs in affected flocks affected sequencing, of a single base deletion intron 13 in the
with this inherited disorder. Some sheep become type I myofiber-­specific TNNT1 gene (KT218690
crippled by a few years of age, others living to old age c.614 + 1delG) which leads to impaired Ca++-­induced
with minimal clinical signs. Mild gait abnormalities muscle contraction.704 All affected sheep were
involve degrees of symmetrical reduced flexion of the homozygous for this TNNT1 variant. This finding
hock and stifle (i.e., hypometria) and some scuffing allows classification of ovine muscular dystrophy as a
of the toes and a shortened stride while moving, TNNT1 congenital myopathy: Ovine congenital pro-
worse after forced exercise. Signs can progress so the gressive muscular dystrophy.
stifles and hocks become fixed in extension and both An interesting Congenital Myopathy of Beulah
hind toes drag on the ground while the lambs move. Speckled-­face Lambs has also been recorded in pure-
A shortened thoracic limb stride with occasional toe breds.705 Affected lambs were recumbent and “stiff ” at
dragging can also develop. Other severely affected birth, although some could just walk if assisted to rise.
 Congenital, familial, and genetic disorders 257

Partially flexed limbs or hyperextended hocks were ops is one of partial carpal flexion fixations, and a
also evident although as the limb joints had normal crouched posture associated with increased tone in
mobility after death this could not be regarded as back and limb muscles seen while the piglets struggle
arthrogryposis. Myopathic lesions consisted of to keep up with litter mates. Atrophy of type I myofib-
b­asophilic, peripheral, sarcoplasmic rims, and sarco- ers and myofiber caliber variation is most prominent
plasmic hyaline degeneration and vacuolation, and in proximal limb muscles. The disease is suspected to
were most obvious in diaphragmatic, intercostal, be inherited as an autosomal recessive trait.
quadriceps, dorsal cervical, and supraspinatus mus-
cles. There were neither neuropathic lesions nor evi-
dence of a selenium or vitamin E deficient state. A
Hyperkalemic periodic paralysis in horses
familial muscular dystrophy was suspected.
Four Jersey calves, sired by the same bull, were The kalemic channelopathies relating to defective
normal at birth but developed progressive thora- potassium membrane fluxes can be regarded as forms
columbar kyphosis, lumbosacral lordosis, and an of myotonia-­like diseases with clinical features per-
abnormal gait beginning at 3–4 months of age.706 The haps better defined as pseudomyotonia (signs pro-
significant lesion was type II myofiber atrophy in gressive with activity) and electrical activity akin to
lumbar muscles. The disorder is referred to as neuromyotonia662 (see table above).
Kyphosis in Jersey Calves and is suspected to be a form Mainly 2–3-­ year-­
old, male Quarter Horse and
of inherited muscular dystrophy, but biochemical Quarter Horse related breeds have been reported
and genetic testing will be necessary to characterize since 1986 to be affected with Hyperkalemic Periodic
the disease better. Paralysis (HYPP), an autosomal dominant dis-
A skeletal muscle Congenital Myopathy in Braunvieh × ease.711–715 Homozygous animals are more severely
Brown Swiss Calves has been described in six affected than heterozygotes.661 The owner usually
Braunvieh × Brown Swiss calves that showed progres- notices intermittent episodes of muscle trembling
sive weakness leading to recumbency within 2 weeks over the body or face, sometimes with intermittent
of birth.159 There were distinctive myopathic histo- projection of the nictitating membrane, which may
logical findings including the presence of nemaline lead to involuntary recumbency. Other premonitory
rods, proliferated internal nuclei, and intracytoplas- signs include yawning, lowering of the neck, swaying,
mic, homogeneous, mostly crescent-­shaped, periph- and disinterest in food and water. During a mild epi-
eral inclusions consisting of tightly packed, parallel sode, the horse is alert, appears distracted and reluc-
filamentous structures. The lesions did not appear to tant to move, and may stumble as if weak. In a
be related to defects in vimentin or dystrophin expres- fulminant episode fasciculations or muscle tremor,
sion. A hereditary etiology was suspected. particularly involving the flank, shoulders and neck
One further bovine, probably hereditary, muscular and sometimes the face progress to staggering, buck-
dystrophy, occurring in only adult cows of the Meuse-­ ling, marked muscle spasms, and paraplegia, which
Rhine-­ Yssel and Holstein–Friesian breeds, mainly may precede involuntary recumbency. A severe epi-
affected the diaphragm.707,708 The clinical syndrome of sode, perhaps following forced exercise or KCl provo-
Muscular Dystrophy in Adult Meuse-­Rhine-­Yssel and cation, results in severe tremor and tetany of many
Holstein–Friesian Cattle was one of recurrent ruminal muscles with recumbency and sweating. This is fol-
tympany with affected cows being 4–7 years old. As in lowed by a state of flaccidity, possibly with depressed
the Brown Swiss cross calves, the dystrophic myopa- spinal reflexes. Attempts to move the patient result in
thy in these adult cattle included expression of sarco- further tremor and tetany, although the horse remains
plasmic masses and proliferated internal nuclei, but alert. An episode may last several minutes to hours,
the filamentous structures were absent.709 typically less than an hour, with full and usually rapid
The Pietrain breed of pig was introduced because recovery occurring. Between episodes, affected, well-­
of its proximal limb and back muscular hypertrophy. muscled Quarter Horses appear essentially normal.
The Pietrain Creeper Syndrome consists of progres- Most owners notice stridor at some time or other in
sive muscular weakness and intermittent trembling affected horses.716 Exercise and rest following exercise
on the pelvic limbs when standing, beginning at may precipitate episodes that can occur daily or
3 weeks of age, and ending at about 3 months of age monthly, and can be associated with stressors such as
with recumbency.149,710 The unusual gait that devel- transportation, weaning, and anesthesia.711,715,717–719
258 Large animal neurology

The clinical syndrome is distinct but not Congenital myasthenic syndromes

pathognomonic.718 A KCl provocation test can be
used with caution to help make a diagnosis, and nee- The congenital myasthenic syndromes are a diverse
dle electromyographic examination reveals fibrilla- group of diseases resulting in a range of phenotypes
tion potentials and bizarre discharges including involving abnormal neuromuscular transmission, but
myotonic and pseudomyotonic waves in most mus- which are all due to inherited defects at the neuro-
cles.711,715,720 There are no consistent histologic myo- muscular junction.729 A severe congenital myasthenic
pathic findings, although mild sarcolemmal changes syndrome, myasthenia gravis, has been well docu-
are recorded.711 Most often, but not always,721 during mented in Red Brahman calves in South Africa.730,731
a spontaneous or KCl-­provoked attack, hyperkalemia Affected calves are normal at birth and develop rap-
(5.5–9.4 mmol/L) is detectable.715,718 idly progressive muscle weakness at 3–4 weeks of age,
Attacks of tremor and tetany appear to be short-­ and within a week are unable to rise without assis-
lived, although the treatment of horses during attacks tance. If helped to stand, the calves are steady for a
with intravenous fluids containing combinations of minute or so and then abruptly begin to tremble and
Ca++, HCO3–, glucose, and acetazolamide may shake before collapsing back to sternal recumbency. A
shorten an attack. Acetazolamide at 2.2–4.4 mg/kg, decremental MUAP response has been recorded to
BID, orally, hydrochlorothiazide at 0.7 mg/kg, BID, 27 Hz stimulation on evoked EMG recordings. There
orally, and especially phenytoin, 12–15 mg/kg, BID, is short-­lived improvement in strength in response to
orally, appear to have lessened the frequency and acetylcholinesterase inhibitor drugs edrophonium
severity of attacks.711,712,715,718,722 The expense of moni- and pyridostigmine. This is a simple recessive inher-
toring plasma levels of phenytoin is likely to be cost ited form of myasthenia gravis due to a homozygous
prohibitive. General anesthesia can be problematic 20 base pair deletion (470del20) in the gene encoding
but manageable in affected horses.717,723,724 for the bovine ε-­subunit (bovCHRNE) of the acetyl-
This disorder is caused by a missense point choline receptor.732,733 Identification of heterozygous
mutation (cytosine to guanine) of a highly c­onserved carriers of the bovCHRNE-­470del20 mutation indi-
portion of the α-­subunit of the equine adult sodium cates a possible prevalence of 1–2% in Brahman cattle
channel SCN4A gene. This mutation results in phe- in South Africa.731,734
nylalanine to leucine (F1419L) substitution.725 The New insights are being made into the role of muta-
frequency of Quarter Horses positive for the tions in acetylcholine receptors and other post syn-
heterozygote form of the mutation was estimated to aptic receptor proteins resulting in acetylcholine
be 4.4% corresponding to an allelic frequency of deficiency phenotypes.735 Thus, mutations within the
0.02.726 Over a decade later, the carrier rate in 200 acetylcholine receptor genes may result in early clo-
registered Quarter Horses was estimated to be lower sure of the channel, prolonged closure of the channel,
at 1.5% (allele frequency 0.008 ± 0.004), perhaps or a relative deficiency of the channel. Mutations dis-
due to testing and selection pressure, but was 4.5% rupting postsynaptic proteins may affect acetylcho-
(allele frequency 0.025 ± 0.008) in a control cohort line receptor distribution along the postsynaptic
of 180 American Paint horses.727 However, the membrane; and mutations in the genes coding ace-
c­arrier rate for 118 Quarter Horses registered in the tylcholinesterase proteins can result in prolonged
Halter Class was a massive 56.4% (allele frequency acetylcholine receptor over-­activation.729
0.299 ± 0.030). Interestingly, Quarter Horses show Finally, these syndromes must be distinguished
judges appear to favor the muscular phenotype of from the acquired myasthenic syndromes wherein
IMPRESSIVE, the sire that founded the lineage of there are frequently humoral or cellular immune
affected progeny.720 This factor obviously confounds attacks on various neuromuscular junction
attempts at testing for and removing the gene from proteins.736
the equine DNA pool. Finally, the American Quarter
Horse Association requires all breeding stock to be Porcine stress syndrome and malignant
tested for Hyperkalemic Periodic Paralysis as well as hyperthermia
for Glycogen Branching Enzyme Deficiency,
Hereditary Equine Regional Dermal Asthenia, Certain strains of most common breeds of pigs
Malignant Hyperthermia and Polysaccharide Storage including German and Belgian Landrace, Duroc,
Myopathy-­1.728 Large White, Hampshire, Yorkshire, Berkshire,
 Congenital, familial, and genetic disorders 259

Dutch and German Pietrain, and Poland China pigs Equine glycogen storage metabolic
are affected by porcine stress syndrome at rates of myopathies
60–90+%.737,738 On average, about 20% of pigs of
most common breeds were found to be heterozygous Some of the glycogen storage diseases may be
for the ryanodine receptor gene RYR-­1 defect in one regarded as lysosomal storage diseases,320 and the two
study.739 The syndrome of malignant hyperthermia bovine examples, GSD-­II and GSD-­V, are referred to
(MH) that accompanies the clinical porcine stress in Table 31.3.
syndrome is a pharmacogenetic disorder of skeletal The two equine glycogen storage diseases that
muscle that is seen as a hypermetabolic response to have received considerable attention in the last dec-
potent fluorinated volatile anesthetic agents, depo- ade are Equine Polysaccharide Storage Myopathy and
larizing muscle relaxants, and to stressors such as Glycogen-­Branching Enzyme Deficiency. The former
vigorous exercise and heat.740 In humans, there are is an autosomal recessive disorder in Quarter Horse
over 30 variants in the RYR1 gene that are causal for and over 30 breeds worldwide and can result in rather
malignant hyperthermia, and other causal mutations exceptional susceptibility to recurrent exertional
including in the gene encoding calcium voltage-­gated rhabdomyolysis.661,748–757
channel subunit alpha1 (CACNA1S).740 Equine type 1 polysaccharide storage myopathy
Stiffness, hyperventilation, patchy skin vasodila- (PSSM1) is associated with an incompletely pene-
tion, and reluctance to move occur with forced exer- trant, dominantly inherited, missense mutation in
cise in susceptible swine. Sudden death occurs. In the equine glycogen synthase (GYS1) gene, resulting
certain families of susceptible pigs, the syndrome is in enhanced glycogen synthase activity and excessive
associated with pale exudative pork and back muscle glycogen and amylopectate inclusions in
necrosis seen in meat-­processing plants.741,742 muscle.748–750,758,759 At rest, horses with PSSM1 appear
Muscle hyperactivity occurs because of a hypersen- quite normal, but with exercise signs of a short stride
sitive calcium-­release mechanism present in the sarco- length, firm musculature, stiffness, pain, sweating,
plasmic reticulum. Resulting thermogenesis produces and reluctance to move occur. Signs of PSSM1 usu-
hyperthermia and a cascade of metabolic events, ally become evident at 2 or 3 years of age but affected
including lactic acidosis, hypoxemia, and hyperkalemia young foals can have histologic evidence of myopa-
leading to rapid death.737,738 Pigs are affected by the thy, and severe rhabdomyolysis may accompany
result of a single point mutation in the porcine gene for other systemic illness.321,748
skeletal muscle ryanodine receptor (RYR-­1).743 The The syndrome for PSSM1 is evidenced by the pres-
mutation in pigs results in an autosomal recessive ence of the GYS1 mutant and degrees of rhabdomy-
inherited susceptibility to malignant hyperthermia.741 olysis associated with amylase-­resistant, sarcolemmal
Malignant hyperthermia in horses is associated inclusions of acid mucopolysaccharides evident on
with a missense mutation in the equine ryanodine muscle biopsy samples. In distinction, where there
receptor gene identified as MHRYR-­1.738,742,743 The car- are clinical signs of muscle disease but histologic evi-
rier state occurs in less than 1% of Quarter Horses dence of no or mild myopathic changes, then a dis-
and Paint horses,746 although the clinical syndrome tinguishing term such as polysaccharide-­associated
has been seen in Thoroughbred, Appaloosa, and myopathy or type-­2 PSSM (PSSM2) should be used.
Arabian horses and in ponies.744 Afflicted horses can Mild myopathic changes may include proliferated
express the disease while undergoing general anes- and internal sarcolemmal nuclei, with excessive and
thesia with volatile halogenated anesthetic agents. aggregates or cores of sarcoplasmic, mostly amylase-­
Dantrolene sodium at blood concentrations of 2–4 sensitive, polysaccharide (glycogen). Such excess or
μg/mL is said to be protective and therapeutic. In unusual glycogen storage in association with clinico-
horses, an oral dose of 10 mg/kg is required to achieve pathologic myopathic syndromes is far more common
such concentrations for about 2–3 h.747 in most horse breeds that do not have the mutant gly-
Reducing stress during transportation and rou- cogen synthase enzyme.321, 712, 748, 749, 751, 754, 758
tine, calm management practices, along with genetic Histologic examination of a suitably prepared
selection and culling to dilute the prevalence of the biopsy of a Type-­II predominant muscle such as mid-
defective RYR-­1 gene, are the primary means of dle gluteal or semimembranosus,754,760 including
reducing the disease incidence of this welfare-­ study of PAS and PAS-­amylase stained sections, as
sensitive disease.738,739,742 well as appropriate genotyping, is imperative in
260 Large animal neurology

making a diagnosis of PSSM. Interestingly, within allele likely account for ~2.5% of abortions in affected
excessive, amylase-­sensitive polysaccharide accumu- breeds777 and may have caused a delay in recognition
lations in cases of polysaccharide-­associated myopa- of the disease for decades.321,778 Neurologic signs are
thy, there is evidence of abnormal protein degradation nonspecific with generalized weakness, degrees of
occurring in the form of positive ubiquitin somnolence, and correctable flexural limb deformi-
staining.761 ties being a common syndrome. Leucopoenia and
Thus, equine PSSM1 is one cause of recurrent elevated serum activities of muscle enzymes are quite
exertional rhabdomyolysis, and probably glycogen-­ consistent findings, making congenital nutritional
associated myopathy (PSSM2) is as well. Signs of a rhabdomyolysis and steatitis a strong differential
hypometric, short-­stride gait, reluctance to move, diagnosis. Sepsis and other common neonatal ail-
variable thoracolumbar lordotic and kyphotic pos- ments complicate the clinical picture. Affected foals
tures, and several movement aberrations can be seen do not survive much beyond 2 months,323,775,776
in association with these disorders. That recurrent although other forms of metabolic myopathy associ-
exertional rhabdomyolysis is likely a more genotypi- ated with glycogen storage may occur in older
cally complex disease than first appreciated adds patients.324
doubt to the previously accepted theories of typical Muscle biopsy examination reveals the accumula-
Mendelian inheritance.321,762 It does appear however tion of PAS positive globular and crystalline intracel-
that glycogen-­associated myopathy (PSSM2) is not lular masses, which increases with the age of the foal
the cause of most cases of the common postural and as does histologic evidence of mild myopathic
movement disorder known as shivers in draft horse changes. This material contains poorly branched gly-
and many other breeds.757,763–765 cogen and abnormal polysaccharide.322,323,776 Similar,
Because both PSSM1 and PSSM2 likely involve fine intracellular globular inclusions are present in
deranged glucose metabolism, much is discussed older affected foals in gray and white matter in the
about nutritional and managerial control of the clin- CNS. This is prominent in neurons, especially motor
ical syndrome as practiced for such disorders in hum cells, and ependymal cells.776
ans.320,661,693,766–770 The clinical syndromes in Testing hair (follicles) from affected, homozygous
horses can likely be ameliorated in many cases with foals and their unaffected heterozygous parents for
management and dietary modification to include the GBED mutation should assist in formulating
consistent and appropriate levels of exercise768,771 plans aimed at reducing the incidence of this lethal
and progressive introduction of <20% lipid as a equine disease.718
source of energy, along with a reduction of soluble As infdicated above, the American Quarter Horse
carbohydrate content in the animals’ diet.754,766,772 Association requires all breeding stock to be tested
Dantrolene sodium may help in altering membrane for Glycogen Branching Enzyme Deficiency as
Ca++ flux to reduce the outcome of myolysis in these well as for Hyperkalemic Periodic Paralysis,
disorders.773,774 Hereditary Equine Regional Dermal Asthenia,
The other main glycogen storage metabolic myo- Malignant Hyperthermia and Polysaccharide
pathy of equids is Glycogen-­Branching Enzyme Storage Myopathy-­1.728
Deficiency (GBED) that is only recognized in
Quarter Horse and Paint Horse fetuses and new-
Mitochondrial myopathy
born foals. It is caused by the autosomal recessive
inheritance of a nonsense, point mutation in codon Defects of the nucleic or mitochondrial genomes
34 of the GBE1 gene encoding glycogen branching reading for mitochondrial respiratory chain
enzyme. This results in deficiency of measurable enzymes can be transmitted by recessive, dominant,
GBE1 enzyme activity, in spite of abundant GBE1 X-­linked, and mitochondrial inheritance, and can
mRNA in affected foals, severely disrupting glyco- be phenotypically characterized by multisystemic
gen metabolism.322,323,718,775 or organ-­specific dysfunction that can arise at any
The phenotypic expression of GBED disease, first time in life.779,780 They frequently demonstrate a
recognized in 1995,776 varies from fetal death, sudden phenotype that includes a myopathic syndrome,
neonatal death, flexural limb deformity, seizures, car- usually demonstrated best with exercise, and many
diorespiratory dysfunction, and recumbency.323,775,776 will then demonstrate a lactic acidosis.661,711
Abortion of foals homozygous for the mutant GBE1 Although alterations to mitochondrial enzymes
 Congenital, familial, and genetic disorders 261

have been demonstrated in horses prone to 6 Healy P, Dennis J, Rawlinson R and Andersson L.
exertional rhabdomyolysis,781 s­pecific identification Prenatal diagnosis of bovine citrullinaemia. Res
of a very low activity of a mitochondrial enzyme, in Vet Sci 1993; 55(3): 271–274.
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 32
Infectious, inflammatory, and immune
diseases

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Infectious, inflammatory, and immune diseases 293

DiseasePage DiseasePage

Bacterial294 Equine Herpesvirus-­1

Listeriosis294 myeloencephalopathy324
Histophilus somni thromboembolic Transmissible spongiform
meningoencephalitis295 encephalopathies327
Bacterial meningitis and ventriculitis Other agents 329
in young ungulates 296 Equine protozoal myeloencephalitis 329
Brain abscess 297 Trypanosomiasis336
Basilar empyema 300 Additional Protozoal
Suppurative meningitis in adult ungulates 301 meningoencephalomyelitides
Retrobulbar and periorbital cellulitis in ruminants336
and empyema301 Mycotic and amoebic encephalomyelitides 337
Guttural pouch infection 302 Verminous encephalitis and myelitis 338
Bacterial glossitis 303 Nematodes, superfamily
Otitis media and otitis interna 303 Strongyloidea338
Vertebral suppurative arthritis, Nematodes: superfamily
osteomyelitis and discospondylitis 305 Metastrongyloidea338
Ascending bacterial empyema and myelitis Nematodes: superfamily Filaroidea 340
associated with tail docking and tail Nematodes: superfamily
biting Septic aortic thrombosis 308 Panagrolaimoidea340
Septic polymyositis 308 Nematodes: superfamily
Clostridial myositis 308 Habronematoidea341
Streptococcal myositis 309 Cestodes: family Taeniidae 341
Other bacterial causes of myositis 309 Flies: family Oestridae 342
Melioidosis309 Sporadic bovine encephalomyelitis 342
Lyme neuroborreliosis 309 Chlamydia pecorum sporadic bovine
Viral310 encephalomyelitis343
Equine arboviruses 310 Protozoal polymyositis 343
Alphaviruses310 Inflammatory and immune mechanisms 343
West Nile virus 312 Optic neuritis 343
Other encephalitic viruses of equids 314 Granulomatous facial and
Ovine encephalomyelitis virus 314 vestibulocochlear neuropathy in cattle 344
Small ruminant lentiviruses 314 Immune-­mediated myositis 344
Borna disease virus 316 Infarctive purpura hemorrhagica 345
Malignant catarrhal fever 317 Polyneuritis equi 345
Rabies317 Supplementary inflammatory
Picornaviral encephalitis of pigs 319 neurologic disorders 347
Hemagglutinating encephalomyelitis virus 320 Granulomatous meningoencephalitis 347
Porcine rubulavirus 320 Sclerosing panencephalitis 347
Pseudorabies320 Idiopathic eosinophilic
Equine infectious anemia virus 321 meningoencephalitis347
Viral-­induced congenital malformations 321 Granulomas348
Border disease 323 Acquired myasthenia gravis 348
Bovine herpesvirus meningoencephalitis 323 References348
294 Large animal neurology

Bacterial and cornea, and weak jaw closure and deviation

and lowering of the mandible, indicating sensory
Listeriosis and motor dysfunction of the trigeminal nerves,
Neurologic disease produced by pathogenic sero- are common findings (Figure 32.1). Involvement of
types of Listeria monocytogenes, and sometimes other CN VII is indicated by drooping of the ear pinna,
Listeria sp.,1 is common in adult cattle,2–4 sheep,5–7 upper eyelid, nostril, and lip, usually on the same
and goats,8 occasional in camelids,9 but extremely side as the head is tilted to. Other cranial nerves
rare in horses10,11 and buffaloes.12 Listeric abortion frequently showing clinical involvement include
and neonatal and juvenile sepsis are also important IX, X, and XII. Signs related only to spinal cord
disease processes in ruminants, but primary listeric involvement occur rarely.8 Primary purulent oph-
encephalitis infrequently occurs in lambs, kids, thalmitis and particularly secondary exposure ker-
calves, crias, and foals.13–16 Listeriosis is a zoonosis so atitis may further complicate the clinical picture.
that there are public health concerns when the dis- Progressive obtundation associated with spread of
ease occurs, and immunocompromised people infection into the midbrain leads to semicoma and
should avoid contact with suspected cases.17 death as the disease is notoriously fatal without
In listeric encephalitis (Figure 32.1), there is fre- treatment. Significant by absence early in the dis-
quently somnolence and a gradual or sudden onset of ease process are signs of forebrain disease such as
head tilt and circling. Affected animals may isolate seizures, aggressiveness, and blindness, thus distin-
themselves from the rest of the herd or flock. Ocular guishing listeriosis from many other ruminant
and nasal discharge, food remaining in the mouth, encephalitides.
drooling, eye problems, teeth grinding, and bloat can Almost total neurologic deficits relating to cauda
be evident to the owner or handler. equina involvement along with vestibular disease and
On examination, head tilt and turn, circling, and facial paralysis in a working pony was caused by a
paresis and ataxia of all limbs are consistent find- suppurative meningomyelitis from which Listeria
ings. Asymmetric sensory loss from the face, monocytogenes was isolated postmortem.18
particularly identified at the nasal septal mucosa L. monocytogenes is a motile, Gram-­positive bacil-
lus that can live and multiply within macrophages
and other cells. It enters the brainstem in the region
of the trigeminal and facial and possibly other
nerves.5,19 There is good evidence, experimentally
and clinically, that the organism frequently gains
entry to the nervous system via breaks in the tissues
of the head, particularly the face and mouth.20 There
is migration of organisms along cranial nerves, most
especially the trigeminal branches, to the pontomed-
ullary region of the brainstem where meningoen-
cephalitis ensues and spreads. Bacterial infection
occurs in the form of poorly demarcated microab-
(A) (B) scesses and meningitis of the brainstem. The inflam-
matory response transitions from neutrophilic to
Figure 32.1 Clinical evidence of acquired, progressive brainstem disease mononuclear and is even granulomatous or eosino-
in young ruminants warrants a tentative diagnosis of listeriosis being philic at times.20 That retrograde neural migration of
made in most cases. Such was the case in these patients. This 10-­week-­old
organisms is not the only route to the CNS is evident
Holstein calf developed somnolence, inappetence, a right head tilt, and a
flaccid lower jaw (A) as well as right facial weakness and nasal hypalgesia by the fact that encephalitis can result within a very
(not evident here). Analysis of lumbar CSF revealed a mild mononuclear short period after intravenous inoculation of viable
pleocytosis, and the calf recovered to return to the dairy replacement herd Listeria monocytogenes organisms.21
after one dose of glucocorticoids and a 2-­week course of procaine penicil- Feeding of silage, most particularly when it has
lin along with nursing care. The weaned lamb (B) demonstrated ataxia and
not been rendered totally anaerobic during process-
tetraparesis with a wide-base stance along with right head-tilt and
­dysphagia, all indicating asymmetric brainstem lesion(s) consistent with ing, is the singular major risk factor for listeriosis.21–23
listeriosis. The lamb also recovered sufficiently to return to the flock follow- Thus, animals being fed silage, often indoors in win-
ing penicillin therapy and nursing care. ter, that have teeth erupting or are predisposed to
 Infectious, inflammatory, and immune diseases 295

facial and mouth injury by access to coarse straw or proteins that induce a protective immune response
are woody browsers (goats) are overrepresented with may hasten the development of useful effective
the disease. vaccines.32
Cerebrospinal fluid analysis reveals increased num-
bers of large and small mononuclear cells and, espe- Histophilus somni thromboembolic
cially in small ruminants, a proportion of neutrophils, meningoencephalitis
and high (usually >0.4 g/L) protein concentration.4,6,24
One study of CSF analyses from nine affected goats Thromboembolic meningoencephalitis (TEM) is one
and sheep showed a mean protein content of ~2 g/L manifestation of the multisystem infection of cattle
and total nucleated cell count of ~0.2 × 109 /L. with Histophilus somni (prev. Haemophilus som-
Culturing L. monocytogenes from CSF is difficult and nus).33,34 This disease is primarily seen in feedlot cattle
usually unsuccessful but may be easier from an of any age, but usually occurs in the weanling to young
inflamed eye. The sample should be refrigerated for adult stage.35 There is an acute onset of anorexia, stag-
several days prior to culture. Listeria monocytogenes gering, and coma. Death may occur from 2 h to several
can be seen in brain tissue using tissue Gram stains19 days later, and an outbreak of the disease may be her-
and is retrievable from the brainstem following cold alded by finding dead animals. High fevers >42°C are
incubation and culture. Immunohistochemical identi- early found in the disease process. There may be other
fication is a more sensitive way to confirm the dis- signs of H. somni infection such as bronchopneumo-
ease,21,25,26 and more recent quantitative real-time PCR nia or polyarthritis in the patient or in pen mates.
identification can be very sensitive in confirming the The somnolence and apparent blindness character-
presence of listeric protein genes.27 Serotyping, phage istic of the early stages of the disease cause affected
typing, and molecular testing of cultured Listeria animals to become separated from pen mates and
monocytogenes strains can assist in identifying source explain the origin of the commonly used term sleeper
and spread of outbreaks in animals and humans.17,22,28 syndrome. Paralysis, coma, tonic–clonic seizures,
Therapy with penicillin, ampicillin, sulfonamides, opisthotonus, and dysfunction of multiple cranial
tetracyclines or florfenicol for 2–4 weeks, begun nerves may be evident on closer neurologic examina-
while the animal is ambulatory, is often curative; tion. The main differential diagnoses for encephalop-
however few studies have rigorously compared drug athy in feedlot cattle are TEM, polioencephalomalacia,
regimens for efficacy.28 Reported survival rates in lead poisoning, and water intoxication.36
small ruminants and cattle with listeric encephalitis This disease is a septic, thromboembolic, suppura-
are 26 and 70%, respectively.28 Considering results of tive, and necrotic meningoencephalitis predomi-
in vitro antimicrobial sensitivity tests, licensing nantly of cattle.37 H. somni is an important respiratory
requirements for milk and meat withholding times, pathogen involved in the bovine respiratory disease
cost, ease of use, and clinical impression, therapy complex. Dissemination of bacteria into the circula-
using high doses of crystalline penicillin IV, every 6 tion leads to endothelial biofilm formation, expres-
h for the first 24–48 h, continued by procaine peni- sion of tissue factor activity on endothelial surfaces,
cillin G IM, BID, for 14–21 days is a very reasonable, and disruption of intercellular junctions. The net
effective regimen.21,23,29,30 As with primary suppurative effect is intravascular coagulation and thrombosis of
meningitis, the use of one or two anti-­inflammatory small vessels of the brain.38,39 Survival of the organism
doses of corticosteroid compounds at the onset of in lesions may be partly related to its ability to resist
therapy is controversial but often done. Relief of bloat intracellular killing by professional phagocytic cells.40
and administration of fluids, electrolytes and a gastro- Usually, there is low morbidity and high mortality,
intestinal transfaunate, and an energy source into the although devastating outbreaks of TEM with high
rumen are often required.4 The outlook is bad if the morbidity and mortality do still occur.41 Virulence
animal is recumbent and/or cannot swallow, but sur- factors and mechanisms that are well characterized
vival rate is at least 50% if the animal can stand and include membrane lipooligosaccharide, induction of
swallow and is treated appropriately.6,21 apoptosis of host cells, intraphagocytic survival, and
Numerous killed and attenuated L. monocytogenes immunoglobulin Fc-­binding proteins.42 Knowledge
vaccines have been developed, but these are not avail- based on the genomic sequence of H. somni will help
able in some countries and efficacy and economic unravel virulence factors and the precise mechanism
utility data are limited.6,21,31 Identification of listeric of the neurovascular lesions.42,43
296 Large animal neurology

Analysis of CSF reveals many neutrophils, high pigs with Streptococcus suis infection frequently have
protein, and xanthochromia. With a herd problem, vestibular signs because of primary otitis interna.56
the diagnosis should be confirmed by necropsy Histologic meningitis/ventriculitis often occurs
examination. Antibiotics that can be effective ther- with neonatal sepsis in ungulates even in the absence
apy include ceftiofur, penicillin, fluoroquinolones, of overt neurologic signs. It is possible that the
and florfenicol along with NSAID products and meningeal tissues become involved via infected
nursing care.44 Tetracyclines and macrolides have mononuclear cells migrating into the CNS through
become progressively less effective. With the patient normal pathways.57 Specific expression products of
still ambulatory, the outlook is fair to good with pathogenicity-­ associated islands and virulence-­
intensive therapy. The prognosis is bad for recum- associated plasmids of E. coli, including capsular
bent patients, and efforts should be directed to iden- polysaccharides, fimbriae, adhesins, and hemolysins,
tifying disease in contact animals and treating them likely also play roles in the pathogenesis of meningi-
early and even prophylactically.34 Meta-­analysis of tis.58 Pore-­ forming cytolysins such as suilysin on
several oft-­cited studies of preventive efficacy of rela- Streptococcus suis promote meningeal invasion by
tively crude vaccines available since the 1980s indi- injuring epithelial cells of the choroid plexus.59 E. coli
cated that the risk of bovine respiratory disease in and other Enterobacteriaceae including Salmonella
vaccinated cattle was not statistically different than spp. and Klebsiella pneumoniae are the usual causes
that of controls.45 Newer recombinant subunit vac- of neonatal meningitis in calves, lambs, and kids.
cines show early promise.46 However, with a low mor- Streptococcus spp. also frequently cause meningitis
bidity, the economic value of a vaccination program and polyarthritis in calves, lambs, and piglets. Other
targeting TEM must be considered. organisms cultured from neonatal and juvenile ani-
A very similar or identical bacterium, H. somni mals with meningitis and ventriculitis include
(sheep strain; Syn. Histophilus ovis), has been isolated Actinobacillus equuli in foals, Trueperella pyogenes,
from sheep with multiple organ diseases, some show- Staphylococcus, Mannheimia, and Pasteurella spp. in
ing signs of meningoencephalitis with collapse when ruminants, Erysipelothrix rhusiopathiae in piglets,
moving, recumbency, and nystagmus. Septic, and Gram-­negative enterococci in South American
fibrinopurulent, thromboembolic meningoencepha- camelids. Mycoplasma bovis is also an important
litis was confirmed at postmortem examination.47 cause of the disease in calves, and M. mycoides subsp.
mycoides large colony variant causes meningitis in
kids.34,48–51,56,60–65 Other novel Gram-­positive cocci can
Bacterial meningitis and ventriculitis
be involved in epizootics of meningoencephalitis in
in young ungulates
young ruminants.66
This disease is common in neonatal and weanling A complete blood count may reveal neutrophilic
ungulates.33,34,48–52 Primary signs include hyperesthe- leukocytosis, but septic neonates, especially foals,
sia, stiff neck, muscle tremor, somnolence, seizures, frequently have neutropenia. In acute cases, CSF
and blindness. Reasons for inadequate passive trans- has high protein content and increased numbers of
fer of maternal immunoglobulin are important his- cells, predominantly neutrophils, whereas in pro-
torical factors as is a history of or current evidence of tracted and treated cases, mononuclear cells are
prematurity and other illnesses such as enteritis and often prominent.67 Glucose content of CSF meas-
omphalophlebitis. ured on a urinary reagent strip can be negative, a
Often this disease is associated with fever finding which is consistent with the presence of
(40–42°C), but temperature may be normal or sub- inflammatory cells and microbes, although hypo-
normal in neonates. On clinical examination, ompha- glycemia must also be considered as a cause. Blood
lophlebitis, polyarthritis (especially in piglets), cultures are often positive. A sepsis score based on
ophthalmitis, lack of suck reflex, somnolence, audi- predisposing factors and clinical parameters is use-
tory hyperresponsiveness, tactile hyperesthesia over ful in predicting sepsis in critically ill foals and
the entire body and a stiff and extended neck posture calves. Inadequate intake of colostral immunoglob-
are commonly found. Other signs of diffuse brain ulins, i.e., failure of passive antibody transfer, is the
involvement that are frequently seen include aimless primary predisposing factor for neonatal meningi-
wandering, moderate opisthotonus (star-­ gazing), tis, and accurate measurement methods should be
abnormal vocalization, and seizures.34,50,51,53–55 Young employed to address this.48–51,68–72
 Infectious, inflammatory, and immune diseases 297

Two to six weeks of appropriate antimicrobial early phase of meningitis. This effect was thought to
therapy as determined by culture and sensitivity is partly result from improved cerebral perfusion pres-
indicated.48–51 In farm animals, treatment choice sure and an attenuated inflammatory response.78 As
needs to be tempered by the bad prognosis, applica- with empyema in other tissue compartments such as
ble drug-­use regulations, cost, tissue antibiotic resi- with septic peritonitis and arthritis, medical wisdom
dues, and practical issues. In meningitis, the suggests that removing excessive inflammatory debris
blood–brain barrier (BBB) is porous, and most anti- and mediators is a positive approach to the resolution
biotics are likely to get into the CSF and brain paren- of the lesion. Thus, it is perhaps not unexpected that
chyma. However, the organisms are often extremely additional subarachnoid lavage in experimental
pathogenic and resistant to commonly used antibiot- Streptococcus pneumoniae meningitis in lambs
ics. Combinations of an aminoglycoside (usually reduced the extent and severity of suppuration, less-
gentamicin or amikacin) with a beta-­lactam antibi- ening formation of leptomeningeal adhesions, and
otic (penicillin or ampicillin) offer the most potent quelling the degree of brain edema markedly, com-
and broad-­spectrum regimen for initial treatment of pared to antibiotic therapy alone.79 Finally, whether or
neonatal meningitis, although expense and persistent not the use of corticosteroid drugs alters the outcome
tissue residues may make this choice impractical. in septic meningitis in ungulates is not known, but
Third-­ generation cephalosporins, such as soluble many practitioners will use one or two doses in farm
salts of ceftiofur, cefotaxime, and moxalactam, have animals at the beginning of therapy based on the the-
suitably broad-­ spectrum antibacterial activity, but ory that a pulse of bacterial toxins, including LPS, will
are also expensive and their use may be forbidden.53 be released from killed organisms when antibiotic
Potentiated sulfonamides such as trimethoprim-­ treatment begins.55 Such an approach is in line with
sulfamethoxazole and macrolides such as tulathro- evidence in humans wherein a short course (3–7 days)
mycin may be tried, but these drugs have limited and of corticosteroid drug (e.g. 0.2–0.5 mg/kg/d dexa-
diminishing efficacy against Enterobacteriaceae. methasone) beginning at the onset of antimicrobial
Because of its penetration into CSF, florfenicol therapy is beneficial in bacterial meningitis in adults
appears to be a useful choice for meningitis due to and children.80,81
Gram-­positive and nonenteric Gram-­negative bacte- Anticonvulsant drugs (see Chapter 6) and hyper-
ria.73 The fluroquinolone antibiotics are probably tonic solutions of sodium chloride or mannitol (head
quite efficacious, but their use in veterinary medicine trauma, Chapter 33) may be used in economically
should be discouraged. Temporary prophylaxis with valuable patients to control seizures and treat or pre-
penicillin for at-­risk piglets may well be reasonable vent presumed cerebral edema and brain herniations.
practice for S. suis meningitis outbreaks.74 Plasma is The prognosis for survival is bad but does depend
needed if there is hypogammaglobulinemia (i.e., for on how aggressive the affordable therapy and nursing
foals, serum IgG <8 g/L in a hospital setting or <4 g/L care is. Survival rates have been reported at 0%82 to
in the field), and administration of hyperimmune 30%83 for calves, 5% for lambs,55 and 25% for foals
plasma rich in antiendotoxin antibody may improve when a specific organism is isolated and treated
the outcome for septic foals.75 aggressively.84 Chronic CNS and other foci of infec-
Regarding therapy focused on the meningeal tion such as cerebellar meningitis83 and chronic, sep-
inflammation, analgesic, and anti-­ inflammatory tic osteoarthritis may be persistent and difficult to
drugs such as NSAIDs should be administered.48,49 control. Essentially, the prognosis is very guarded,
Lipopolysaccharide (LPS) released from Gram-­ particularly if little or no immunoglobulin transfer
negative bacteria can directly induce suppurative has occurred.
meningitis at least in piglets and calves,76 making the
use of NSAID drugs well indicated in Gram-­negative Brain abscess
meningitis. Another consideration is induction of
core body hypothermia (35–36°C) to attenuate the In addition to listeriosis that is quite common in
early inflammatory response as shown in E. coli-­ ruminants, there are three additional, well-­described
induced meningitis in experimental piglets.77 Using a suppurative intracranial processes identifiable in
similar E. coli model, evidence for reduction in cell adult ungulates that are described here, but they are
membrane disintegration and lipid peroxidation has not common. Considering all species, probably they
been shown by the use of hypertonic saline in the occur in the following order of frequency: (a) brain
298 Large animal neurology

abscess, (b) basilar empyema (pituitary abscess – sic),

and (c) suppurative meningitis. Direct extension of
necrosuppurative processes involving other struc-
tures of the skull, including those associated with
head trauma, dehorning lesions, and otitis media/
interna, also on occasion results in secondary pyo-
granulomatous intracranial lesions. Brain abscessa-
tion is the most common of these processes in horses,
whereas basilar empyema is most common in rumi-
nants and pigs.
It is worth recalling some characteristics of suppu-
rative inflammation and terminology as to how cen- (A)
tral nervous tissues respond to it. Suppurative
processes often create considerable necrosis to which
the CNS is quite prone. Such accumulation of tissue
debris confined within a tissue (the brain) is an
abscess. If that purulent material accumulates
between adjacent tissues such as meningeal layers,
venous plexuses, and brain, or in a (potential) tissue
cavity, it is empyema. Depending on the inciting
agent(s), a necrotic and inflammatory process may
form granulomas without true pockets of liquefied
debris (pus). Also, although astrocytes do respond
readily to inflammation, they do not deposit great (B)
amounts of collagen. Thus, many abscesses within
the CNS are not well demarcated by a gross fibrous Figure 32.2 Slowly progressive lesions involving the forebrain in large
capsule, this being the hallmark of abscessation else- animals can become extremely large with minimal clinical signs appar-
ent. Such was the case with a Trueperella pyogenes abscess of the left
where in the body. Finally, as with any space-­
forebrain in this 9-­month-­old heifer. Over several months the calf, which
occupying process in the CNS, especially within the had continued to grow well, had become quieter than expected and
cranium, tissue adjacent to any of these processes will tended to wander to the left (A). It did have poor menace responses but
be forced away and herniations of brain sections and no other definitive neurologic signs. At postmortem examination, the
lobes can occur with devastating secondary patho- calvarium was opened and is shown from a dorsal view (B), with the
bony orbits to the left (OS and OD) and a removed flap of bone from the
logic and clinical consequences (see Chapter 4).
dorsal calvarium to the right (Calv). A large amount of purulent material
Brain abscesses occur most commonly in mature (P), estimated to be 300 mL, escaped from the left cerebral
cattle, goats, sheep, and horses (Figure 32.2); the most hemisphere.
frequent form reported being those caused by
Streptococcus equi subsp. equi in horses.85 Other organ-
isms isolated from brain abscesses include Enterococcus Corynebacterium pseudotuberculosis may be evident
spp., nonhemolytic Staphylococcus spp., Streptococcus in a flock of sheep or herd of goats in which one
equi subsp. zooepidemicus, and Pseudomonas aerugi- animal has a brain abscess. Evidence of metastatic
nosa from horses86–88 and Corynebacterium pseudotu- suppuration may be observed in horses with stran-
berculosis, Trueperella (Arcanobacterium) pyogenes, gles.85,93,96 Indications of such disease may be evi-
and Fusobacterium spp. from ruminants.89–91 dent on physical examination, although vital signs
Brain abscesses may develop following a localized usually are normal.
or generalized pyogenic disease elsewhere in the Signs of behavioral changes and blindness, which
body, such as lymphadenitis, sinusitis, polyarthritis, frequently fluctuate, are most commonly seen,
omphalophlebitis, traumatic reticuloperitonitis, or although vestibular syndromes or tetraparesis may
pododermatitis. In horses, a history of strangles first be evident. Compulsive circling, a head turn,
with secondary S. equi abscesses forming in the somnolence, unilateral or bilateral, central or periph-
brain, is frequently given.92–95 Evidence of systemic eral blindness, and a slowly performed or overtly
pyogenic disease such as that associated with ataxic gait most often occur.97,98 Focal seizure activity
 Infectious, inflammatory, and immune diseases 299

with disconnection from environment, widened pal- be wise to either forego CSF collection or use the lum-
pebral fissure, dilated pupils and asymmetric facial, bosacral site rather than the cisterna magna or C1-­C2 in
and other muscle twitching may occur. Subtle evi- order to avoid rapid changes in spinal CSF tension and
dence of forebrain disease in the form of slight asym- subsequent brain herniations. Notwithstanding, CSF is
metry of the menace response, nasal mucosal often abnormal with inflammatory cells, frequently of
sensation and thoracic limb hopping responses, mixed cell type with a modest, large mononuclear pleo-
needs to be diligently searched for. A few cases with cytosis and slightly high protein content. However,
cerebellar abscessation demonstrated hypermetric prominent suppurative meningitis may accompany a
ataxia and head tilt as the prominent syndrome.91,99 cerebral abscess.100,102
Papilledema is not frequently documented in Cerebral angiography has been used to define the
horses,100 but is seen in small cattle with cerebral space occupying effect of an abscess in a cow97 and
abscesses.97,101 This difference possibly is that the rela- visual evoked potential and electroencephalographic
tively long optic nerve in adult horses obviates trans- recordings assisted in localizing a Trueperella pyo-
fer of high intracranial pressure to the optic papilla. genes cerebral abscess in a steer.103 However, current
Signs, for the most part, are due to the space-­ high definition imaging techniques including
occupying nature of the abscess rather than the contrast-­enhanced CT (Figure 32.3), MRI, and ultra-
inflammatory response. Brain herniations (see sound techniques can easily define the site and even
Chapter 4) such as the cerebellum moving caudally tissue nature of brain abscesses in large
through the foramen magnum, compressing the animals.86,87,90,92,94,102,104–108
medulla oblongata, can occur and can be lethal. Antimicrobial therapy alone has not been suc-
Abscesses tend to localize within one or both lateral cessful in resolving cerebral abscesses in large ani-
ventricles or, less commonly, the fourth ventricle, and mals. Surgical drainage and appropriate prolonged
perhaps have a similar genesis to bacterial meningi- antimicrobial therapy have been successful and
tis/ventriculitis that follows bacterial seeding of the are recommended.86,94,97,102 Following measure-
choroid plexus (see above). ments taken from CT scan images of cerebral
Unless there are septic foci elsewhere in the body, few abscesses, successful surgical drainage has been
if any hematological indicators of inflammation are evi- achieved with or without ultrasound guidance.94,102
dent. If there are prominent signs of encephalopathy Without surgical drainage and antibiosis, the out-
and increased intracranial pressure is suspected, it may look is hopeless.

(A) (B)

Figure 32.3 A 3-­month-­old cria had minimal signs of forebrain disease and mild mononuclear CSF pleocytosis. A moderately well-­encapsulated abscess
was clearly defined in the left cerebral hemisphere on CT scanning (A, arrowheads) prior to surgical drainage. A pony with the left-­sided pyogranuloma-
tous ependymitis (B); transverse section of deformed forebrain just rostral to thalamus expanding the left lateral ventricle had fluctuating somnolence,
wandering, and had right central blindness that became fulminant when the caudal herniations of the cerebrum followed by the cerebellum subsequently
occurred. Source: CT image courtesy of Dr. Rebecca Packer Purdue University.
300 Large animal neurology

Basilar empyema
Included in this diagnosis are disorders reported clini-
cally and pathologically as pituitary abscess, hypophy-
seal abscess, cavernous sinus syndrome, rete mirabile
abscess, basilar abscess, basilar meningitis, and basilar
empyema.109–114 The majority are associated with local
(skull) or distant traumatic lesions or distant or gener-
alized septic foci. In only a few instances, there is evi-
dence that pituitary seeding and suppuration is a
primary event. In others, there is evidence for basal
(A)
vascular structures surrounding the pituitary gland to
be primarily involved, with clinical signs usually only
seen when septic thrombosis results in a suppurative
and necrotic process (basilar empyema) within the
paired dural venous sinuses of the rostral and/or cau-
dal fossae to involve more distant brain and cranial
nerve structures (Figure 32.4).111,112,114,115
There is often a history of or evidence of processes
such as nose ringing of pigs and bulls, placement of
weaning flaps in calves, dehorning, fighting, foot
abscess, reticuloperitonitis or paranasal sinusitis in (B)
ruminants and sinusitis, dental disease, lymphangi-
tis, endocarditis, and periocular or retrobulbar cel-
lulitis in horses. An associated mucopurulent nasal
discharge is very common.111,116,117
Degrees of obtundation, poor appetite, ataxia, and
an extended head posture are early signs in cattle,
often followed by dysphagia, drooling, blindness, and
other ophthalmic signs. There is bradycardia in possi-
bly half the cases.111,116–118 Horses often present rapidly
progressive obtundation, ataxia, circling and other (C)
compulsive behavior, vestibular signs, dysphagia, oph-
thalmic signs, blindness, and recumbency.114,115 Figure 32.4 Chronic suppurative processes of structures around the
neurocranium can spread to seed the sphenopalatine respiratory
Signs of diencephalon and brainstem involvement sinus(es) and basilar venous system. In this way, basilar empyema (so-­
and cranial nerve lesions are found on neurologic called cavernous sinus syndrome) occurs wherein a suppurative process
examination. Sensory and motor trigeminal involve- surrounds all neurovascular and meningeal structures on the base of the
ment, pupillary dilation and degrees of peripheral brain. This black face ewe (A) was suspected to have such a syndrome
blindness, and eye deviations are most often seen. with signs of somnolence, wandering, slight fever, bradycardia, and
peripheral blindness with dilated pupils, and facial analgesia. The ewe
However, with more caudal spread, often asymmetric improved markedly after one dose of dexamethasone and a week long
signs of facial, vestibular, vagal, and hypoglossal course of trimethoprim - sulfonamide and was to continue on therapy
nerve involvement also appear.111,114–117 for a further course of antimicrobial drugs when returned to the farm. In
Listeriosis is the most significant differential diag- the following busy figures (B and C), the anatomic landmarks of the
nosis in ruminants, although blindness is not usually basilar part of the brain are identified as being involved in such an
empyema. A pony suffered from a septic process around the guttural
seen in that disease. The other bacterial, viral, and pouch (GP) that seeded the sphenopalatine sinus (star, C), pituitary fossa
protozoal encephalitides are also significant diseases (Pit) and sphenoid region (BSp). In B, the olfactory bulbs (Olf) are to the
to consider, and neoplasia has almost mimicked the left of the necrotic left optic nerve (CN-­II) that are adjacent to the pitui-
disease.119,120 As with brain abscesses, focused imag- tary region (Pit) in the middle fossa. The pons (Pons) and pyramids (Pyr)
ing techniques can identify the site and nature of of the brainstem are to the right. The basilar region of the forebrain
including hypothalamus and thalamus, and the midbrain, can be
these lesions.86,87,90,92,94,102,104–108 involved along with cranial nerves II through V with further extension to
By the time that postmortem examinations are CN VII–XII if the empyema spreads to the caudal fossa housing the pons
undertaken, there is usually devastating necropurulent and medulla oblongata. [Eth = ethmoid turnbinate]
 Infectious, inflammatory, and immune diseases 301

damage to multiple basilar structures making it very Fever and malaise do occur and likely precede onset
difficult to determine the route of sepsis to the region. of ataxia and tetraparesis or paraparesis. Asymmetric
A rational explanation would be that three routes of and sometimes fluctuant vestibular signs and facial
introduction of sepsis can occur to this area.112,115,121,122 paresis, neck pain, muscle trembling, blindness, phar-
In ruminants and pigs, orthograde and retrograde yngeal dysphagia, and head-­pressing are also recorded.
seeding via carotid vessels, their rete mirabile, and the Progression to recumbency, seizures, and stupor
venous cavernous sinuses within which these struc- sometimes is very rapid.48,49,102,123,125–128 In adult horses,
tures pass can occur from septic foci in the skull. E. coli and S. zooepidemicus (S. equi subsp. zooepidemi-
Additionally, extension of purulent processes along fas- cus) have been mostly incriminated,3,131 and S. equi (S.
cial (perineural and perivascular) planes can occur equi subsp. equi),132 S. suis, S. pluranimalium,133
from such sites as the guttural pouches and retrobulbar Staphylococcus aureus,126 Actinomyces spp.,100 Borrelia
tissues. Finally, necrosis and erosion of thin walls of burgdorferi,134 and Klebsiella pneumoniae have been
dorsally located paranasal respiratory sinuses, such as rarely incriminated.
the sphenopalatine sinus directly rostroventral to the Some affected horses have hematologic evidence
middle cranial fossa and pituitary gland, allows direct of a systemic inflammatory response, and the analy-
spread of suppurative material to the region.121 sis of CSF usually demonstrates xanthochromia and
Trueperella pyogenes is the organism most isolated predominantly neutrophilic pleocytosis.123 The find-
from ruminants.3,28 A variety of other bacteria have ing of degenerate cells is most consistent with a
been isolated from these lesions, many being oppor- response to a bacterial pathogen, whereas the CSF
tunistic and common pyogenic bacteria. These neutrophilia seen with metazoan (e.g., Halicephalobus
include Streptococcus spp., Actinobacillus equuli, gingivalis) and viral (e.g., Eastern equine encephalitis
Pasteurella spp., and Klebsiella pneumoniae from virus) pathogens more often includes hyperseg-
horses, Mycoplasma sp. from a goat, and Streptococcus mented and nondegenerate neutrophils. A positive
spp., Acinetobacter spp., Pseudomonas spp., and E. bacterial culture from CSF of adult meningitis cases
coli from cattle.3 is not often reported, although was so in 4 out of
Care should be taken in sampling CSF from the 5 equine cases involving S. aureus.126
cisterna magna in cases of basilar empyema because Similar comments are made with respect to ther-
of the possibility of brain tissue herniation. Analysis apy of adult meningitis, as for septic meningitis in
of the fluid may however be normal, indicate a non- young ungulates above. A combination of penicillin
suppurative response, or may be overtly purulent and an aminoglycoside drug, enrofloxacin, ceftio-
with identifiable bacteria present.114,116 fur, trimethoprim/sulfonamide, doxycycline, and
As alluded to above, the outlook is hopeless, and penicillin plus rifampin all have been used in
euthanasia should be strongly considered should reported cases. In the cases involving S. aureus and
there be evidence of the patient suffering. a single case involving Corynebacterium pseudotu-
berculosis biovar. equi, improvement was seen using
chloramphenicol (plus rifampin in one case) with
Suppurative meningitis in adult ungulates
four out of six cases surviving with minimal neuro-
Suspected or confirmed bacterial (septic) meningitis logic deficits.123 Such a 67% success rate is not typi-
in adult ungulates is not common34,48–51,100,123 but must cal of the general literature where fatality rates are
be differentiated from the specific meningoencepha- typically >90%.
litides described above and elsewhere.124 Common variable immunodeficiency,129 and possi-
Primary and contagious forms of bacterial menin- bly other forms of suppressed disease defense mecha-
gitis, as seen in adult (and infant) human patients nisms, may well act as predisposing factors to bacterial
with consistent pathogens and definable epidemio- meningitis in adult horses, when unusual and pro-
logical characteristics, do not seem to occur in adult tracted neurologic syndromes may be expected.
ungulates. Rather, it is a singular event most often
with predisposing circumstances such as a wound or
Retrobulbar and periorbital cellulitis
septic focus near the neuraxis or elsewhere in the
and empyema
body48,49,102,125–128 or, possibly, an immunodeficiency.129
Cryptococcal meningitis does occur with extreme The mechanical pressures and perhaps extraocular
rarity in horses.130 neuromuscular damage associated with retrobulbar
302 Large animal neurology

cellulitis and empyema often result in degrees of nerves. Peripheral injury to other cranial nerves is
proptosis, ophthalmoplegia, and eye deviation.135 not likely without further spread or unusual severity
Such inflammation can originate from foreign bod- of the lesion.
ies, abscessed pharyngeal lymph nodes, and para- Fungal hyphae colonize the guttural pouch, par-
pharyngeal phlegmon due to iatrogenic penetration ticularly in the dorsocaudal region of the medial
of the pharynx and cranial esophagus. In addition, compartment adjacent to the temporohyoid articula-
strabismus and exophthalmos may accompany tion. A variably colored fungal plaque forms, associ-
chronic sinusitis as well as occurring with actinomy- ated with necropurulent inflammation involving the
cosis and actinobacillosis in cattle.136 Such conditions local structures. Small fungal plaques can be seen
can be the forerunner of intracranial suppurative incidentally at postmortem examination. Lesions can
processes as outlined above. involve the internal carotid artery, vagus, glos-
sopharyngeal, and hypoglossal nerves and cranial
cervical sympathetic trunk.151 These ugly lesions can
Guttural pouch infection
be remarkably destructive and infiltrate and destroy
In order of prevalence, the causes of primary guttural the middle and inner ear compartments within the
pouch disease are as follows:137–146 (a) Empyema, most temporal bone and invade the atlas and axis dorsally.
often caused by previous Streptococcus equi subsp. Further extension of the destructive plaque into the
equi infection. (b) Mycosis, caused by Aspergillus spp. carotid artery may explain some other signs such as
colonization. (c) Tympany due to defects in the phar- blindness.152 The factors relating to why specific, nor-
yngeal opening of the eustachian tube. (d) Neoplasia. mally nonpathogenic fungi become established at
(e) Cyst formation. (f) Foreign body. this site and become aggressively invasive are not
Empyema is relatively common in horses of all understood.150 Mycotic lesions were observed after
ages, though neurologic signs accompanying all these inoculation of cultured A. fumigatus conidia into
diseases occur far less frequently. Those diseases that healthy guttural pouches,155 although lesions
occupy space within, or distend, the guttural pouches regressed spontaneously within 28 days.
can frequently be associated with mechanical dys- The predominant fungal pathogens identified in
phagia and dyspnea without there being proof that guttural pouch mycosis are Emericella (Aspergillus)
there is neural involvement. Thus, most of the fol- nidulans and Aspergillus fumigatus. Rarely, related
lowing synopsis relates to guttural pouch mycosis. organisms such as A. niger and A. versicolor occur.140,156
The triad of signs associated with guttural pouch Guttural pouch bacterial catarrh or empyema may
mycosis are ingesta-­tainted nasal discharge, epistaxis accompany Aspergillus spp. infection or occur indepen-
not associated with exercise, and signs of cranial nerve dently and produce mechanical dysphagia. Empyema
dysfunction. Bilateral or unilateral mucopurulent nasal occurs in at least 50% of strangles infections following
discharge, with or without overt epistaxis, are thus fre- rupture of abscessed retropharyngeal lymph nodes into
quent primary complaints made by owners of affected one or both guttural pouches. In fact, there is evidence
horses. Physical examination may reveal filling or ten- that the majority of strangles cases have lesions in the
derness in the area of the guttural pouch, referred to as guttural pouches.142 Chronic empyema ultimately
parotid pain. Combinations of purulent exudate, saliva results in the formation of multiple concretions of stag-
and food, often foul-­smelling, appear at the nostrils. nant cellular debris (commonly but incorrectly referred
Neck stiffness, pharyngeal swelling, abnormal head to as chondroids = resembling cartilage).
posture, colic, and cough may also occur.145–150 The diagnosis is confirmed with guttural pouch
Neurologically there can be varying deficits in endoscopy, radiography, ultrasonography, and cul-
swallowing ability, occasionally with Horner syn- ture. Guttural pouch flushing with large volumes of
drome. Laryngeal and facial hemiparesis, vestibular saline and very dilute povidone–iodine antiseptic
ataxia, nystagmus and eye deviations, hemiatrophy of solution, with or without systemic penicillin ther-
the tongue, and blindness sometimes are pre- apy, usually resolves empyema and catarrh. Strong
sent.139,146–148,150–154 Neurologic signs in guttural pouch irritant solutions must be avoided. Sometimes ven-
disease most often relate to the involvement of vagal tral surgical drainage or fistulation into the pharynx
and glossopharyngeal nerves and the cranial sympa- is required to treat cases of empyema, and endo-
thetic trunk, and less often to involvement of hypo- scopic or surgical removal of formed concretions is
glossal, vestibulocochlear, facial, and trigeminal usually necessary in chronic cases.96,146,157,158
 Infectious, inflammatory, and immune diseases 303

Medical therapy alone to treat guttural pouch myco- Otitis media and otitis interna
sis has usually been unsuccessful, and systemic ther-
The neurologic significance of lesions in the com-
apy using newer antifungal agents can be very
partments of the ear is that part of the facial nerve
expensive. However, several successes are documented
traverses the tympanic cavity of the middle ear, and
using oral itraconazole and topical enilconazole.159
the inner ear houses the peripheral sensory organs of
Surgical removal or cauterization of the fungal lesions
the vestibulocochlear system for the senses of bal-
has been successful, but modern surgical approaches
ance and hearing. Otitis media and interna do not
designed to occlude the internal carotid or other arter-
appear to result in Horner syndrome in ungulates.
ies on both the cardiac and cerebral sides of the
Unlike the case in dogs and cats, there is no evidence
mycotic lesion appear to be more successful than other
that the postganglionic sympathetic nerve fibers
methods.160 In variations of this procedure, platinum
from the cranial cervical ganglion pass through the
coils or nitinol plugs are placed on both sides of the
tympanic part of the temporal bone in these species.
lesion, or the cardiac side of the artery is ligated and
Most likely these fibers course with the internal
the cerebral side is occluded with a balloon-­tipped
carotid artery and its branches to structures of the
catheter or platinum coils/nitinol plugs.146,161Balloon
head, including the eye and cutaneous blood vessels.
catheter occlusion has been performed successfully in
Thus, degrees of facial nerve paralysis occur with
standing horses.162 Overall surgical cures are
middle ear disease, and vestibular dysfunction and
reported.146–150,160,163 Despite evidence for retrograde
hearing deficits occur with inner ear disease. Lesions
arterial blood flow into lesions that have been treated
in one compartment can and do spread to the other
by proximal ligation of the internal carotid artery,
resulting in combinations of signs, and inner ear dis-
some surgeons still prefer to perform simple ligation of
ease can result from, and extend to, the meninges and
the internal carotid artery and other branches of the
medulla oblongata (Figure 32.5). Most often suppu-
carotid artery coursing toward the fungal lesion, usu-
rative otitis media and interna are seen in intensively
ally followed by repeated application of topical anti-
reared young cattle, sheep, and pigs, where there can
fungal agents, and report very good success without
be a high incidence of 20–100% of clinical and sub-
additional hemorrhagic complications in more than
clinical disease.21,56,173–177 Individual cases occur in
80% of cases so treated.164 Postsurgical vascular acci-
ruminants, camelids, and pigs.21,176,178–180 It is rare in
dents may result in signs of cerebral or cerebellar
horses and foals.132,181,182
infarction, optic neuropathy, or brainstem
Otitis externa, rhinitis, pharyngitis, pneumonia,
injury,146,147,165–167 and further hemorrhage can occur
and head trauma can be pathologically significant
over the 2-­week postoperative period. While effective
factors if present in the history. Bottle feeding and
arterial occlusion is often lifesaving, there is no evi-
ingestion of unpasteurized waste milk are risk fac-
dence that the prevention of further bleeding has any
tors in dairy calves. Aural or nasal discharge, evi-
effect on the growth of the responsible mycotic
dence of a stiff neck, cranial cervical pain, or
plaques.168 In fact, the necrogranulomatous lesions,
respiratory disease may be found. Sluggish chewing
fungal colonization, and neurologic signs all can also
may occur due to pain in the temporal region. In
resolve in about 80% of cases, without specific antifun-
addition, signs of concurrent reticuloperitonitis,
gal therapy. This probably relates to yet unknown
foot abscess, sinusitis, or other suppurative process
pathophysiological factors in this unusual fungal dis-
are occasionally present.21,176
ease within this mysterious structure.145,150,169 .
Signs of peripheral vestibular disease include head
tilt, circling, and usually prominent ventral eye devi-
Bacterial glossitis
ation, all occurring on the same side as the lesion.
Bacterial glossitis, or woody tongue, causes degrees Any nystagmus present, either at rest or induced by
of dysphagia associated with tongue swelling and raising the patient’s muzzle or placing the patient in
paresis and is common in cattle at pasture. Most dorsal recumbency, is usually horizontal or arc-­
often it is a pyogranulomatous myositis caused by shaped, with fast phase toward the side opposite the
Actinobacillus lignieresii, but it can be caused by many lesion. The suppurative process of otitis media
organisms.170 It responds well to antibiotics such as impinges on the facial nerve as it traverses the middle
streptomycin and to systemic sodium iodide therapy. ear frequently resulting in paresis of facial muscles on
Occasionally, it occurs in horses.171,172 the affected side. Ptosis is part of facial muscle
304 Large animal neurology

ear through a ruptured tympanic membrane and

thence to the inner ear occurs regularly.21,177 Some of
the important parasites causing such severe otitis are
the mites Sarcoptes scabiei, Raillietia auris and
Dermanyssus avium, the tick Otobius magnini,183,184
nematode larvae of Stephanofilaria zaheeri, free-­
living nematodes Rhabditis bovis, and the blue fly
Chrysomya bezziana. Common ear mites (Psoroptes
cuniculi) rarely cause otitis media and interna in
goats and deer.16,178
(A)
In temperate zones where more intensive farming
is practiced, hematogenous spread and, more com-
monly, ascending infection from common upper and
lower respiratory tract infections are frequently the
routes of infection rather than from otitis externa.185
In pigs, Streptococcus spp., particularly Streptococcus
suis types I and II in suckling and weanling piglets
respectively, are by far the most common causes of
clinical and subclinical suppurative otitis media and
otitis interna.56,186 Other organisms incriminated in
this species include Pasteurella multocida,
Actinobacillus pleuropneumoniae, Trueperella pyo-
(B)
genes, Haemophilus spp., and Mycoplasma hyopneu-
moniae. In ruminants kept under intensive stocking
Figure 32.5 Bacterial and mycoplasmal otitis media and interna are com-
mon in ruminants and swine, much less so in horses, as causes of facial nerve
conditions where calfhood pneumonia and polyar-
paresis and peripheral vestibular disease, respectively. In some regions of the thritis are common, especially in dairy calves,
world, there is a primary bacterial or particularly parasitic otitis externa. Mycoplasma bovis and other Mycoplasma spp. are an
Shown here (A) is the cranial view of a transverse section of the base of the emerging and important cause of suppurative oti-
calvaria through the temporal bones from a calf suffering bacterial otitis tis.16,187–189 Experimental evidence indicates that when
media and interna in the left ear (Lt), having shown both facial and vestibu-
lar signs. The normal external (EE), middle (ME) and internal (IE) cavities can
calves ingest infected milk, M. bovis first colonizes
be seen on the right (Rt) side. Proximity to the medulla oblongata that has pharyngeal tonsils before spreading to the middle ear
been removed (filled star) is evident. A weaned piglet also suffered from via the eustachian tube.190 Also in ruminants, other
suppurative otitis media and interna and responded to a short course of organisms including Pasteurella and Mannheimia
antibiotic treatment. It then abruptly showed an exacerbation of right ves- spp., Streptococcus spp., Staphylococcus spp., T. pyo-
tibular signs with obtundation and difficulty prehending and swallowing
food, and the tongue was noticed to be hanging from the mouth. These
genes, and Corynebacterium pseudotuberculosis are
signs were more consistent with central vestibular and brainstem disease likely to be involved.16,173,174,176,177 Mixed bacterial
that was confirmed on postmortem examination (B); ventral view of whole infections are likely common in chronic otitis media
brain. Purulent material from the ear cavities had ruptured through the inter- and interna in all species. Although uncommon in
nal acoustic meatus on the right side and expanded as a pyogranulomatous foals and rare in horses, Streptococcus spp.,
mass within the meninges, compressing the right ventral medulla oblongata
(arrow). It then expanded through the fourth ventricle dorsal to the medulla
Actinobacillus spp., and C. pseudotuberculosis biovar.
oblongata to protrude from the lateral aperture on the left side (arrow head). equi and Staphylococcus spp. have been isolated from
infected middle and inner ears.191 It has been specu-
lated that the extension of inflammation from the
weakness in ungulates, but Horner syndrome does middle ear to the adjacent temporohyoid joint may
not seem to occur with uncomplicated otitis media lead to osseous proliferation around the joint and
and interna in large animals. development of temporohyoid osteoarthropathy.192
In tropical and subtropical regions, parasitic otitis Although some direct evidence for this association
externa is a major problem in cattle and other domes- was found in a 6-­month-­old foal,193 this theory of
tic animals. Extension of the parasitic and accompa- pathogenesis remains speculative. Extension of gut-
nying purulent and necrotic process into the middle tural pouch mycosis (Aspergillus spp.) to involve the
 Infectious, inflammatory, and immune diseases 305

vestibulocochlear and facial nerves is extremely rare, continued for 2–4 weeks. Residual signs are common
although temporohyoid osteoarthropathy can be in chronic cases. In pigs, and occasionally in calves,
associated with inflammation and compression of death is usual when the disease leads to CNS involve-
these nerves (see Chapter 38). In any species, grass ment. Chronic cases do not do well, and more
awns and neoplasms can be a unique cause of middle detailed imaging studies and accurate identification
and inner ear disease. of the anatomic site, extent, and cause of the lesion
Of neurologic significance is the fact that, in at are required prior to invasive surgical exploration,
least the pig, goat, and calf, the extension of necrotiz- drainage, and debridement of infected and necrotic
ing and proliferative otitis interna centrally through tissues are undertaken.16,179,180,197
the internal acoustic meatus can occur quite readily.
This results in pachymeningitis, leptomeningitis, Vertebral suppurative arthritis,
paramedullary empyema, and localized pyogranu- osteomyelitis and discospondylitis
lomatous encephalitis. Clinical signs include degrees
of somnolence, tetra or hemiparesis, signs referable Vertebrae and their associated structures can be
to central vestibular disease, and the involvement of seeded with pyogenic organisms that produce a variety
other cranial nerves with signs such as facial hypalge- of pathologic lesions to ultimately compress the spinal
sia (Vs), dysphagia (IX, X, XI), vertical nystagmus, cord (Figures 32.6, 32.7, and 32.8). This most
and even paradoxical vestibular syndrome,21,56,175,179,194 frequently begins in colostrum-­ deprived neonates,
thus mimicking listeriosis.195 and it also occurs in conjunction with multifocal
Aural, pharyngeal and guttural pouch endoscopy pyogenic diseases such as those caused by Trueperella
and ultrasonography,185,196 as well as radiographic or pyogenes, Corynebacterium pseudotuberculosis,
CT examination are helpful in confirming a diagno- Rhodococcus equi, and Salmonella Dublin.198–205
sis. Aural discharges can be cultured or tested by PCR By the time clinical signs of vertebral pain and spi-
for the presence of Mycoplasma spp. or other bacte- nal cord compression are recognized, the lesions are
ria. Analysis of CSF, preferably collected from the cis- usually necrotic, proliferative, and extensively suppu-
terna magna, can be used to help determine if there is rated such that the precise site of seeding of organ-
any inflammatory CNS disease.28 isms is unclear (Figures 32.6, 32.7, and 32.8). Thus, a
Ideally, an antimicrobial drug should be chosen plethora of terms, including vertebral abscess, verte-
following culture and sensitivity results. Myringotomy bral body abscess, spinal abscess, pachymeningitis,
and aspiration of the exudate in the middle ear is a spinal empyema, epidural empyema, suppurative
sensible, relatively noninvasive, though overlooked vertebral arthritis, suppurative myelitis, vertebral
procedure in evaluating this condition. In horses and osteomyelitis, and discospondylitis, all have been
probably camelids,180,197 however, this is not an easy used to describe the responsible pathologic pro-
procedure because both species have long, narrow, cess.199–218 The most common necropsy findings are
bony, horizontal ear canals. Traditionally, penicillin, suppurative osteomyelitis and epidural empyema.
ampicillin, or trimethoprim-­ sulfa have been the The most likely initial sites of infection in this pro-
drugs of choice for initial treatment. Because of the cess are the vertebral articular process joint(s), the
emerging and central role of Mycoplasma spp. in the vertebral growth plate, and the intervertebral disc.
pathogenesis of otitis media-­interna of dairy calves Thus, to remove some confusion associated with the
and possibly other species/groups, beta-­lactam anti- use of all these terms, vertebral suppurative osteomy-
biotics are not recommended as sole therapy. elitis and discospondylitis will be used here to best
Furthermore, resistance is an ever-­evolving problem describe the primary disease.
in selecting effective treatments for otitis in rumi- Vertebral suppurative osteomyelitis and discospon-
nants and pigs. Tulathromycin and other newer mac- dylitis are seen most frequently in young ani-
rolides, the quinolone derivatives (where permitted), mals.199,201,202,206,212 Organisms associated with this
florfenicol, and newer compounds such as valnemu- disease in ruminants include the bacteria Pasteurella
lin all are emerging as potentially more useful anti- and Mannheimia spp., T. pyogenes, Corynebacterium
microbial therapies for infectious respiratory disease pseudotuberculosis, Salmonella Dublin, Fusobacterium
in production animals. spp., Staphylococcus spp., Bacteroides spp. and
The outlook is good, perhaps better in calves than Rhodococcus equi, and the fungus Aspergillus spp.207–
other species,16 if treatment begins early and is 209,219
In pigs with osteoarthritis and discospondylitis,
306 Large animal neurology

Figure 32.6 With acquired, progressive ataxia and paresis in (A) (C)
any young ungulate, septic processes involved in compressing
the spinal cord must be the most probable diseases to be
ruled out from a differential diagnosis list. The use of the diag-
nostic term spinal abscess (sic) is not to be condoned.
Most often the initiating foci of axial sepsis appear to be arthritis
of the dorsal intervertebral, and the costovertebral joints, dis-
cospondylitis of the vertebral body, synovitis of a paravertebral
synovial structure such as the atlantal bursa and necrotic celluli-
tis, or osteitis from docking lesions. Such lesions may compress
the spinal cord by direct expansion or quickly spread to the epi-
dural space as an empyema without having a defined fibrous
capsule (i.e., a true abscess is not formed). Such is the case here
with a tetraplegic, 1-­week-­old ram lamb that cannot hold its
head up, suffering from suppurative cellulitis around the cranio-
vertebral region (A). In B can be seen the occiput to the left (Occ)
and cervical spinal cord (SC) exposed by elevating the arches of (B)
the atlas and axis that are surrounded by suppurative matter
(blue stars). Closer inspection of the opened vertebral canal con-
taining the spinal cord, viewed dorsocaudally (C), shows where
the spinal cord was compressed (arrow) by the suppurative
tongue of matter (black star) protruding through the interverte-
bral space into the canal adjacent to the elevated arch of the axis
(Axis). The likely site of seeding for this case of paraxial sepsis
due to Streptococcus sp. was the atlantal bursa. Finally, a
1-­month-­old lamb that had an umbilical abscess became para-
lyzed with intact and hyperactive reflexes in the pelvic limbs.
Compression of the lumbar spinal cord occurred (D) from an epi-
dural, hemorrhagic empyema and pachymeningitis resulting
from extension of suppurative discospondylitis (arrow heads)
(D)
dorsally into the epidural space (green stars).

the organisms recovered have included Trueperella tetraparesis or paraparesis. Sometimes localizing
pyogenes, Staphylococcus spp., Erysipelothrix rhusi- signs of heat, pain, and swelling along the vertebral
opathiae, Actinobacillus pleuropneumoniae and column are found. Areas of cervical or truncal hyper-
Streptococcus spp.208–212 Different organisms have been reflexia, hyporeflexia, and patches of sweating (horse)
isolated in equids including Streptococcus zooepidemi- can also occur. Less often the sacrococcygeal verte-
cus, Salmonella spp., Actinobacillus equuli, Eikenella brae and cauda equina become involved and the syn-
corrodens, and Rhodococcus equi in foals, and drome then relates to paresis, hypalgesia,
Staphylococcus spp., Actinobacillus lignieresii, Brucella and hyporeflexia of the perineal region, tail and anus,
abortus, and Mycobacterium tuberculosis in adult and hypotonia of the penis, urinary bladder and
horses.198,213–217,220,221 Fungal osteomyelitis of vertebrae rectum.225
is rare in large animals.215 Diarrhea, polyarthritis, localized sepsis, tail-­
Reluctance to move, hunched back, stiff limbs, docking abscesses, or intrathoracic or abdominal
neck or back pain, paresis, and ill thrift occur in vari- abscesses can be recognized as being coexisting
ous combinations.199,202–204,207,213,215,216,220–224 Often there problems.199
is sudden reluctance to move or stiffness in one or Suppurative, necrotizing, and sometimes prolifer-
more limbs, the neck or the trunk, usually interpreted ative osteomyelitis, vertebral arthritis and discospon-
as being due to pain, with or without progressive dylitis occur at variable sites in the vertebral column.
 Infectious, inflammatory, and immune diseases 307

(A) (B)

(C) (D)

Figure 32.7 A destructive process (circle) of bacterial discospondyitis is evident here on serial lateral radiographs of the C5–6 region from the early,
acute phase with neck pain (A), through neck rigidity and marked ataxia and tetraparesis (B, C and D) in a young horse. There was strong evidence of
focal chronic active inflammation on blood analyses, and aggressive antimicrobial therapy was used. Although some bacterial organisms were cultured
from blood and urine samples, even at postmortem evaluation evidence for primary bacterial discospondylitis was masked by profound granulomatous
and proliferative lesions. With a degree of authors’ license (JM), it may be concluded that this represented a case of discospondylosis initiated and per-
petuated by sepsis. Source: Courtesy of Derek Knottenbelt, University of Liverpool.

Sometimes there is direct extension from adjacent root involvement as well as to spinal cord compres-
lesions such as paravertebral injection abscesses and sion. It should be noted that because the lumbosacral
intrathoracic abscesses. In ruminants, the lesion usu- spinal cord segments are shifted cranially relative to
ally develops from septic articular process joints with their associated vertebrae, septic processes in verte-
subsequent rupture to form localized paravertebral brae as far cranially as L2 or L3 vertebrae may
and epidural empyemas.202,208,226 With the involve- impinge upon the lumbosacral intumescence.
ment of the brachial intumescence (spinal cord seg- Imaging with radiography, CT or MRI, and needle
ments C6–T2), or the lumbosacral intumescence electromyographic examination are helpful in localiz-
(L4–S2), there will be, in addition to tetra-­and para- ing the site and defining the nature of the dis-
paresis, respectively, final motor neuron signs of ease.199,202–205,213,215,216,222,227,228 Nuclear scintigraphy,216,223
severe flaccid limb weakness and hyporeflexia, ultrasonography,213,224 and infrared thermography have
accompanied by hypalgesia,202–204 likely due to nerve also been helpful. Results of analysis of lumbosacral
308 Large animal neurology

urine cultures can be diagnostically useful in adult

horses.
Therapy mainly consists of prolonged antimicro-
bial therapy, preferably based on culture results214–216,223
and surgical drainage and debridement as appropri-
ate.225,229–231 With recumbency, the outlook must be
regarded as bad unless immediate decompression
can be undertaken and even then the prognosis is not
good although recoveries are recorded.115,202,214,223,232

Ascending bacterial empyema and myelitis

associated with tail docking and tail biting
This disease occurs following laceration to caudal
vertebral structures and secondary cellulitis and
(A)
necrosis.199 Vertebral osteomyelitis and dissemina-
tion of the septic process elsewhere in the body can
occur. More commonly, it is seen in lambs and piglets
following tail docking and in pigs involved with can-
nibalism and tail biting. The lesion usually extends as
a true ascending epidural empyema and necrotic
neuritis and myelitis. Affected animals should be
humanely destroyed.

Septic aortic thrombosis

Diarrhea and E. coli sepsis can be the forerunners of
septic thrombosis of the descending aorta and iliac
arteries with subsequent flaccid paraplegia in neona-
(B) (C) tal or preweaning calves.233,234 Dense and diffuse final
motor neuron deficits with analgesia of the pelvic
Figure 32.8 The early clinical and radiographic changes of infectious limbs, tail, and perineum are terminal findings.
discospondylitis seen here (A) can be very difficult to distinguish from
primary trauma and early discospondylosis. Here (arrows) is shown the
very early radiographic modeling of bone and disc at C5–6 (A and C),
Septic polymyositis
which later progressed to fulminant bacterial discospondylitis. This can be Clostridial myositis
compared with the normal intervertebral site at C4–5 (A and B). Digital
radiography and especially modern diagnostic modalities such as CT
Acute forms of polymyositis often are caused by
imaging are superior in detecting even earlier bone and cartilage changes Clostridium chauvoei (blackleg), less often C. septi-
in diseased vertebrae, but determining the exact cause still can be cum, C. novyi, C. sordelli, and C. perfringens (malig-
problematic. nant edema).235–242 Cattle, sheep, goats, horses, and
swine all are susceptible to these organisms, although
clinical disease is most often seen in young rumi-
CSF may be normal202–204,227 or may show evidence of nants. Usually, sudden deaths signal the beginning of
compression with xanthochromia, slight mononuclear an outbreak. Some animals may be seen with degrees
pleocytosis, and high protein content.115,206,207,215,216,220,221 of mono-­, para-­, or tetraparesis and with painful,
Occasionally, neutrophils predominate but even if swollen muscles, and subcutaneous edema. These
organisms are seen in CSF203,204 the organism can rarely anaerobic organisms grow in sites of mildly bruised
be cultured.207,215 Samples for culture (aerobic and or significantly wounded tissue and produce potent
anaerobic) obtained by direct aspiration from vertebral necrotizing exotoxins. Causative organisms may be
and paravertebral lesions have been useful in identify- identified by characteristic morphology in tissue
ing the organisms and in guiding antimicrobial ther- smears or tissue sections, by immunostaining of tis-
apy. A tuberculin test and Brucella titer and blood and sue exudates or by PCR.242–245
 Infectious, inflammatory, and immune diseases 309

Penicillin is the drug of choice for the treatment of This is a multisystem, acute, or usually chronic and
clostridial myositis, and vaccination schedules are difficult to treat disease. A predominantly lympho-
mandatory in endemic areas. Texts on large animal cytic and monocytic meningoencephalitis and CNS
medicine and on veterinary microbiology should be abscessation occurs in humans and experimentally
consulted for full descriptions of these syndromes. infected animals. Among sporadic cases in animals,
neurologic signs have included circling, blindness,
Streptococcal myositis and seizures in sheep and goats, aggressiveness and
A fulminant myopathy following in days from clini- staggering in cattle, and vestibular and facial nerve
cal strangles has also been reported in horses. There involvement with opisthotonus and violent behavior
is malaise, stiff gait, and firm painful muscles, par- in horses.251,253
ticularly in the paravertebral and gluteal regions,
often progressing to recumbency. A systemic inflam- Lyme neuroborreliosis
matory response with muscle enzyme and myoglobin
release occurs, and mortality is high even with inten- Five species of the spirochete Borrelia burgdorferi
sive antibiotic and anti-­inflammatory therapy and sensu lato complex cause Lyme disease, a poorly
nursing care.246 A severe, acute myonecrosis and defined group of conditions and syndromes of man
macrophage response is seen in muscle samples, and and animals. Lyme disease follows tick-­borne infec-
presumptive Streptococcus equi may be detected by tion and is characterized in man and dogs by a target-­
immunostaining of frozen sections but could not be like skin rash (erythema migrans) initially centered
cultured from myopathic lesions. It was speculated on the site of the tick bite.254 Erythema migrans is
that the disease may be a form of streptococcal toxic apparently not noted in B. burgdorferi-­infected
shock myopathy as well as the direct effect of exotox- horses. Many signs and symptoms have been ascribed
ins produced by circulating S. equi organisms. to Lyme disease of man including flu-­ like signs,
Another severe often fatal myopathy associated with myalgia, polyarthopathy and arthralgia, carditis, skin
strangles in horses is infarctive purpura hemorrhag- disease, headache, neurologic abnormalities, and
ica,247 an immune complex-­mediated disease that is chronic fatigue.254 The disease has long been associ-
associated with hemorrhage and infarction of limb ated with specific geographic areas in northern
muscles. This disease has been likened to Henoch– Europe and in North America and is also reported in
Schönlein arterial vasculitis of humans. the Mediterranean basin, Asia, and South America.254
In North America, there is serologic evidence for
Other bacterial causes of myositis recent and ongoing increases in B. burgdorferi infec-
Multifocal suppurative myonecrosis with infarction tion rates and expansion of geographic ranges in
resulted in widespread muscle masses in a horse with which Lyme disease is endemic.255 Although horses
systemic illness and weakness. Salmonella Infantum with generalized lameness and stiffness living in
was isolated from muscle lesions and liver.248 Other endemic areas are often treated for presumptive
examples of multifocal, nodular, necrotic myositis Lyme disease, the only syndromes in horses that have
have been seen in horses with febrile illness associ- been strongly associated with B. burgdorferi are uvei-
ated with salmonellosis and other severe septic tis, neurologic disease (neuroborreliosis), and cuta-
diseases.237,249 neous pseudolymphoma.255 Rare presumptive cases
of neuroborreliosis have been reported in horses in
North America since 1987256 and in Europe since at
Melioidosis
least 1996,257 and reports have become increasingly
Systemic disease with nervous system involvement frequent over the last two decades.255,258 Two of these
caused by Burkholderia pseudomallei, a Gram-­ cases were in horses with combined variable immu-
negative bacillus, may well be an emerging and re-­ nodeficiency syndrome.134,259
emerging disease in a wide variety of animals and Signs of neuroborreliosis in horses are progressive
man including all domestic animals in tropical and and relate to predominantly lymphohistiocytic and
subtropical regions.250,251 It is hypothesized that neu- plasmacytic perivascular inflammation and neuritis
rologic and other aggressive forms of melioidosis are affecting leptomeninges, cranial and peripheral
associated with strains of B. pseudomallei expressing nerve roots, and nerves and, to a lesser extent, brain
a B. mallei-­like variation in the bimA motility gene.252 and spinal cord. There are combinations of epaxial
310 Large animal neurology

muscle atrophy, hyperesthesia, behavioral abnormal- (VEE) equine encephalitis viruses, and the
ities, cranial nerve dysfunctions (including involve- Flaviviridae that includes West Nile virus.262 An
ment of CN VII, X, and XII,258), limb ataxia, excellent review263 covers surveillance, prevention,
dysphagia, muscle fasciculations, neck stiffness, and and control of the major equine arboviruses, includ-
intermittent respiratory distress related to laryngeal ing the discussion of the likely effects of climate
paralysis. Seizures have been reported.257 Non-­ change on their geographic distributions.
neurologic signs that may be seen include fever, uvei-
tis, joint effusion, cardiac arrhythmia, and weight Alphaviruses
loss.258–260 Cerebrospinal fluid changes, mainly high The causative agents of EEE, WEE, and VEE are New
protein and neutrophilic or lymphocytic pleocytosis, World arboviruses belonging to the genus Alphavirus
were found in 8/13 cases tested in one series.258 of the family Togaviridae.264 Two closely related
Several serologic tests for B. burgdorferi infection are viruses of the Semliki Forest complex, Ross River
commercially available: whole cell IFAT or ELISA virus and Getah virus, infect horses in Australia and
with Western blot confirmation, bead-­ based eastern Asia, respectively. Ross River virus was impli-
multiple-­antigen ELISA (Multiplex), and point-­of-­ cated in more than 100 cases of neurologic disease in
care ELISA kit (C6 SNAP).255 Unfortunately, blood horses during an outbreak of arboviral encephalitis
and CSF titers or concentrations and calculated in 2011 and previously was suspected of causing a
blood:CSF ratios obtained using these tests have poor syndrome of lethargy, muscle soreness, and ataxia in
accuracy and low diagnostic utility in horses with horses in Victoria and South Australia.265,266 Getah
presumptive neuroborreliosis.255,261 In the absence of virus probably is widespread in Japan and SE Asia but
a laboratory gold standard for antemortem diagnosis, is only rarely associated with self-­limiting disease in
presumptive diagnosis currently depends on cau- horses and does not appear to produce signs of
tious use of serologic tests in the context of geo- encephalitis.267
graphic location, compatible clinical signs, and Alphaviral diseases are common in particular
exclusion of competing diagnoses.255 areas and countries of the world, and although these
Antimicrobial treatment of neuroborreliosis in viruses infect a wide variety of species including
horses is based on guidelines for the treatment of humans, they produce clinical encephalomyelitis
human Lyme disease that utilize 2–4-­week courses of most often in horses. Cattle, sheep, New World came-
tetracycline or beta-­ lactam drugs. A reasonable lids, ratite birds, goats, and pigs can get clinical
approach to treatment of horses with neuroborrelio- encephalitis with one or more of these viruses.268
sis is initial treatment with high-­dose penicillin G VEE certainly remains an enzootic and epizootic dis-
(44,000 U/kg IV q6h) or oxytetracycline. If clinical ease threat in central and South America and is
remission is achieved, treatment can be continued regarded by some as a potential biological
with oral minocycline or doxycycline. Some clini- weapon.269–271
cians add metronidazole to the regimen in the belief Clinical signs, which vary in severity with each
that this drug may be active against antibiotic-­ virus, are usually referable at onset to diffuse cerebral
resistant forms of the organism (spheroplasts).255 disease (Figure 32.9), but sometimes signs of spinal
Regardless of the treatment approaches so far used, cord disease predominate. Although horses of any
the outlook for long-­term survival is bad; in fact, only age may become clinically affected, young adult
a single treatment success is reported. horses are most susceptible. The diseases are not
common in suckling foals under 3 months of age.
High fever, prodromal malaise, colic, and ano-
Viral rexia may initially be evident, then there is often an
abrupt onset of progressive somnolence with addi-
Equine arboviruses
tional asymmetric to diffuse brain signs. Head
Under this, general headings are the major causes of pressing and other abnormal behavior, ataxia,
highly infectious equine encephalitides that are blindness, facial paralysis, head tilt, circling, and
arthropod borne and result in large-­scale losses in seizures often become evident. Signs of spinal cord
equid populations worldwide. The two families prin- involvement rarely may occur first, occasionally
cipally involved are the Togaviridae, especially with focal sensory, reflex, and final motor neuron
Eastern (EEE), Western (WEE) and Venezuelan signs.272
 Infectious, inflammatory, and immune diseases 311

(B)

(A) (C)

Figure 32.9 Most cases of EEE (A) are fatal. Thus, in the appropriate clinical setting, finding large numbers of mature nontoxic polymorphonuclear cells
in a CSF sample (B) or detecting a positive serum MAC-ELISA test for the virus warrants a grave prognosis. This horse was febrile and was compulsively
wandering into objects, and although recognized food, it left food in its mouth (A). Occasionally, such fulminant brain lesions as EEE can trigger acute
cardiac dysrhythmias and muscle necrosis (C) referred to as the brain–heart syndrome. In this case of fatal EEE, there were foci of myocardial necrosis (C)
and early mineralization (amorphous purple staining material on H&E in C) within 3 days of onset of neurologic signs.

Birds are reservoir hosts for the American enceph- resulting in diffuse, patchy hemorrhage, which is
alitis viruses, and horses and human beings are seen as congestion and dark staining of the meninges
infected by specialized mosquitoes that are termed and freshly cut brain. In addition, the resulting brain
bridge vectors in that they can feed on both birds and swelling causes occipital and cerebellar herniations
mammals. The timing of horse and human infections under the tentorial process and foramen magnum of
depends on migratory bird life and vector seasons, the occipital bone, respectively, compressing vital
and for EEE virus may be year-­round in southeastern brainstem structures. These movements of brain tis-
USA. sue are associated with terminal events including
These viruses are neurotropic and directly cause dilated pupils (CN III), irregular breathing patterns,
neuronal necrosis throughout the entire CNS, par- cardiac arrhythmias (see Figure 32.9 and Traumatic
ticularly in the cerebrum. In the fulminant syndrome, Brain Injury, Chapter 33), and death. Less severe
which usually occurs with EEE in horses and other and fulminant lesions occur usually with the other
species,268 a prominent neutrophilic infiltrate results alphaviruses.
from tissue necrosis. This is slowly replaced by a less Hemagglutination inhibition (HI), complement
suppurative inflammation if the horse survives. fixation, fluorescent antibody, and virus neutraliza-
Frequently with EEE, massive necrosis and softening tion tests have traditionally been used for serologic
(malacia) occurs, and blood vessels are disrupted, diagnosis.273 The immunoglobulin M antibody
312 Large animal neurology

capture (MAC) enzyme-­ linked immunosorbent vector season. Thus, horses must be vaccinated at
assay (ELISA) is the method of choice for use in least in the early spring and again in summer. Two or
horses with viral encephalomyelitis because titers of more vaccinations per year are also utilized where
greater than 1:400 can distinguish vaccinal (IgG disease is very common. Incomplete primary immu-
only) from viral-­infection-­induced (IgM and IgG) nization of foals is a common cause of vaccination
antibody responses.274,275 The use of RT-­PCR viral failure in adult horses, usually because of the inhibi-
sequence amplification from serum samples may tion of immune responses by maternally derived
well be an accurate, and certainly rapid, means of antibodies. For this reason, it is recommended that
positively identifying the infective viruses.276 Analysis foals of properly vaccinated dams be given three vac-
of CSF shows pleocytosis (Figure 32.9), often initially cine doses, at 6, 7, and 11 months of age.264
neutrophilic, especially with EEE, as well as high pro-
tein and xanthochromia. Occasionally, a prominent West Nile virus
CSF eosinophilic pleocytosis is detected with EEE. West Nile virus (WNV) is a mosquito-­borne virus262
Protein concentration and nucleated cell counts are and is currently recognized to have a greater, and still
typically higher in samples obtained from the atlan- expanding, geographic range than any other known
tooccipital (AO) site than they are in samples from arbovirus.263. It is a member of the Japanese encepha-
lumbosacral taps. The CSF changes are less promi- litis virus serocomplex within the genus Flavivirus
nent with WEE,277 and probably with VEE as well. that also includes Japanese, Kunjin, Murray Valley,
Viral isolation from brain tissue is possible, but it is Usutu,280 and St. Louis encephalitis viruses. The virus
difficult to isolate the virus from CSF. Standard was first isolated from the blood of a woman in
immunohistochemical and PCR techniques278,279 Uganda in 1937 and since then lineage-­1 WNV has
detect virus reliably in formalin-­fixed CNS tissue. been associated with sporadic occurrences and major
outbreaks of neuroinvasive disease, particularly
involving humans and horses, throughout west
Caring for clinically ill patients with these neurotropic viral
Africa, the Mediterranean basin, northern Europe,
diseases is problematic but primarily entails intense nurs-
the Americas, the Caribbean, Australia, and Eastern
ing care, including the treatment of hyperthermia, and
Asia.262,272,281–284 Lineage-­
2 WNV traditionally has
IV fluid therapy and enteric and parenteral nutrition.
caused subclinical infections throughout sub-­Saharan
Africa but, since about 2000, has increasingly caused
Initial treatment should target brain edema and cases and outbreaks of encephalitis in horses and
inflammation. Drugs used for this purpose include humans.285–287 Since 2008, there has been a re-­
DMSO, 1 g/kg as a 10% solution IV, flunixin meglu- emergence of West Nile encephalomyelitis (WNE) in
mine IV at 1.1 mg/kg doses, dexamethasone IV at Europe, caused by both lineage-­1 and lineage-­2 WNV
0.05–0.1 mg/kg daily, and mannitol (IV at 1 g/kg as a with 285 equine cases recorded in EU countries in
20% solution) or hypertonic saline. Dexamethasone 2018.288 Although WNV has not been isolated and
(or equivalent) may need to be continued for several WNV RNA sequences not detected in the UK, cur-
weeks at tapering doses in surviving horses. rent evidence suggests the presence of mosquito spe-
The outlook for survival is very bad for EEE and cies competent for WNV transmission.289,290 In
for VEE with a small percent of clinical cases recov- Australia, the Kunjin strain of WNV emerged in 2011
ering. It is fair to bad for WEE but as with all these to cause an unprecedented outbreak of WNE in at
diseases permanent deficits, particularly poor least 1000 horses.266,291 Over the last 20 years, a mas-
mentation and mild behavioral changes, regularly sive outbreak of lineage-­ 1 WNE in North
persist with survival. Horses suspected of having America283,292–295 has affected tens of thousands of
EEE that have survived often have had some previ- horses with apparent spread to South America.281,282,296
ous exposure to EEE vaccine but with insufficient West Nile virus arrived in New York City in late
protection. August 1999 and by 2006 it had spread to all 48 con-
Mosquito control and immunization have signifi- tiguous states and to South America.297,298 As the
cantly reduced the incidence of these diseases. virus has become endemic in the United States, WNE
However, outbreaks of EEE are still frequent in the incidence in horses has declined dramatically from
southern USA because of the short duration of vac- over 15,000 cases in 2002 to less than 1000 cases per
cine immunity lasting 4–6 months and the long year since 2007. Over the years, this disease has
 Infectious, inflammatory, and immune diseases 313

Reservoir Hosts WEE, VEE, botulism, hepatoencephalopathy, intesti-

nal hyperammonemia, and EHV-­1 myeloencepha-
lopathy. This disease should also be considered in
acute and progressive syndromes involving brain-
stem and spinal cord disease of camelids and other
farm animals in endemic areas.302,303
Dead-end Hosts Analysis of CSF reveals abnormalities in most
(~75%) samples, especially those from the lumbosa-
cral cistern (~90%), with monocytic pleocytosis, high
protein, and xanthochromia predominating.304,305
Several diagnostic tests for the presence of WNV-­
specific antibody and RNA in serum and CSF are
described,284,292,293,295 but IgM antibody capture ELISA
is the immunodiagnostic of choice in both North
America and Europe because it can distinguish anti-
Spread of West Nile Virus body response to WNV infection (IgG and IgM)
from that due to vaccination (IgG only). Microtiter
Figure 32.10 Transmission cycle of west Nile Virus. Possibility of vertical virus neutralization and plaque neutralization tests
transmission within mosquito pool {Nelms et al., 2013, 299} is indicated measure IgG response to either infection or vaccina-
by pink double arrow.
tion and require demonstration of a fourfold or
greater rise in titer between acute and convalescent
become less of a problem because of developing samples.306,307
endemicity and the introduction of effective Many horses appear to begin to recover 3–7 days
vaccines. after neurologic signs are first seen. Attentive nursing
Birds are the reservoir hosts for WNV, and several and supportive care including the judicious early use
species of mosquitoes are vectors for transmission of slinging is of paramount importance. Anti-­
among birds, to mammals, and even between genera- inflammatory medications such as flunixin are used
tions of mosquitoes (Figure 32.10). Multiple cases of empirically, and sedative drugs appear to relieve the
acute deaths in birdlife can herald an outbreak of initial period of hyperresponsiveness. The utility and
WNV in other hosts including horses. Primary signs effectiveness of corticosteroids, DMSO and manni-
in horses are somnolence, transient hyperexcitability, tol, often given in severely affected cases, are
muzzle twitching, and an abrupt onset of progressive unknown. Some horses may require enteric and IV
ataxia with weakness, especially in the pelvic hydrating fluids and possible nutrient support.
limbs.292,293,300,301 Compared to other forms of enceph- In North America, 60–70% of cases survive,
alomyelitis in horses, signs in WNV infection reflect whereas survival rates of 80–90% are more typical in
brainstem and spinal cord involvement rather than Europe and Australia.266,291,308–310 Predictors of sur-
the diffuse cerebral damage that frequently occurs vival are age under 5 years old, predominantly stand-
with EEE and WEE. Other signs are hyperesthesia, ing posture with little weakness and some previous
fasciculations over the neck and trunk, lip or tongue exposure to WNV vaccine.292–294,311 The quality of life
weakness, grinding teeth, blindness, and recumbency for the 60% survivors has been questioned.312 A small
in severe cases. Focal cranial nerve abnormalities, proportion of survivors appeared to have a relapse
often involving CN VII, VIII, or XII, can be present within 2 months of initial signs, and about 20% had
and may be asymmetric. Spinal cord lesions can also sufficient gait or behavioral alterations to interfere
be focal and quite selective such as the unusual syn- with intended use. Thus, possibly as few as 40–50%
drome of repeated episodes of partial collapse of the of horses with WNV in North America will achieve
forequarters and neck reflecting a caudal cervical– full recovery after 6 months.
cranial thoracic gray matter final motor neuron Some discoloration of CNS tissue may be evident
lesion (see Chapter 26) that can also occur with selec- at necropsy examination. Histologic lesions consist
tive lesions in horses with EPM. Differential diagno- of nonsuppurative encephalitis and especially myeli-
ses can vary depending on the country and syndrome tis with a predilection for gray matter. Brainstem
presented but may well include EPM, rabies, EEE, lesions may be more severe in the North American
314 Large animal neurology

cases than in Italian cases.313 Cerebral and cerebellar Both diseases are acquired from pteropid fruit bats
lesions appear to be infrequent. Virus isolation and and spread by infected horses.334 Since 2013, a vac-
detection of RNA sequences in CNS tissue using RT-­ cine which protects against both viruses has been
PCR assay can be regarded as the gold standards for available in Australia.335 The role of the bunyaviruses,
the diagnosis of the disease.293,314 Snowshoe Hare, Main Drain and Bunyamwera,336–338
Disease prevention is by controlling the popula- and equine encephalosis virus, an orbivirus,339 in the
tion of mosquitoes and their exposure to horses, and clinical syndrome of viral-­type encephalomyelitis in
by vaccinating susceptible animals. Reducing horses is unclear.
exposed, stagnant water sources as areas for mos-
quito breeding and judicious use of insecticides and Ovine encephalomyelitis virus
housing horses during dusk and dawn are important
The disease ovine encephalomyelitis or louping ill is
strategies to help achieve the former measure.
caused by a neurotropic virus of the tick-­borne flavi-
Appropriate use of licensed vaccines for horses in
virus lineage262 transmitted by the hard-­back tick
endemic areas is warranted.315 Inactivated whole
Ixodes ricinus. There is a sheep-­tick life cycle with
virus and recombinant subunit vaccines are available
occasional amplification in red grouse in which the
and highly effective. A live chimera vaccine and a
infection is particularly lethal. Louping ill occurs in
DNA vaccine that previously were approved for use
upland areas of the UK and Ireland, and a louping
in the United States have been discontinued or with-
ill-­
like sheep or goat flavivirus encephalitis has
drawn. Passive transfer of WNV-­specific IgG does
occurred in Norway, Spain, Bulgaria, and Turkey.340,341
occur from protected dams to their foals.316 Foals of
It also affects cattle, horses, deer, llamas, and
vaccinated mares should begin vaccination at
pigs.302,342–346
4–6 months of age and should have been given three
Clinical signs vary from transient ataxia to fulmi-
inoculations by 12 months of age. Boosters should be
nant somnolence, recumbency, seizures, and death.
given at least annually and more often in high-­risk
Hyperexcitability, muscle tremor, and ineffective nib-
areas. More frequent vaccination is often recom-
bling can also be early signs. Many affected sheep
mended, but a proportion of horses will have very
bound or leap in a characteristic, louping manner, are
poor anamnestic responses to vaccine.307
ataxic, and their heads flop from side to side. There
are widespread mononuclear infiltrates and destruc-
Other encephalitic viruses of equids tion of neurons, mostly involving brainstem and spi-
nal cord gray matter and cerebellar pyramidal
Another flavivirus,262 Japanese encephalitis virus,
(Purkinje) cells.343,347,348 Scrapie, maedi-­visna, cere-
tends to result in mild generalized illness in horses
bellar disease, and spinal cord disorders are impor-
throughout Asia and in the northern tip of Australia
tant differential diagnoses. Horses may show similar
and has resulted in progressive neurologic signs
signs as well as severe weakness and several seem to
including hyperesthesia, apprehension, and manic
have survived infection and clinical disease.342,349
behavior in horses in Japan and Taiwan due to lym-
phocytic encephalitis.317–321 Rabies has to be a major
Small ruminant lentiviruses
differential diagnosis. Several tick-­transmitted flavi-
viruses including louping ill, Powassan, and tick-­ Lenti or slow viruses are members of the Lentivirus
borne encephalitis viruses have the potential to cause genus of the Retroviridae family. Small ruminant len-
equine encephalitis, but they rarely do so.322–327 tiviruses (SRLV)262 cause multisystemic inflamma-
The recently created Henipavirus genus, family tory disease in goats and sheep. Phylogenetic RNA
Paramyxoviridae, contains two viruses, Hendra and sequence analysis of SRLV gag and pol genes sorts
Nipah, that have caused encephalitis in horses and these viruses into five major groups with at least 20
humans. Since 2008, in the eastern states of Australia, different subtypes. Some strains are species-­specific,
Hendra virus has caused numerous outbreaks of although most can infect both goats and sheep.350,351
fatal, predominantly respiratory disease in horses The prototypic SRLV, caprine-­arthritis-­encephalitis
and humans, sometimes accompanied by signs of (CAEV) and maedi-­visna (MVV), which are classi-
encephalitis.328–330 Nipah virus causes a similar syn- fied into groups A and B, respectively, now appear to
drome of febrile respiratory illness and encephalitis be ubiquitous in sheep-­and goat-­breeding countries
in pigs, humans, and horses in southeast Asia.331–333 throughout most of the world, while viruses from
 Infectious, inflammatory, and immune diseases 315

groups C–E are geographically restricted and rela- or paraparesis, and ultimately to paraplegia or recum-
tively nonpathogenic. The North America version of bency over several months.
MVV is known as ovine progressive pneumonia The clinical syndrome of arthritis in adult animals
virus (OPPV). SRLV cause combinations of intersti- is the most common expression of SRLV infection in
tial pneumonia, polyarthritis, mastitis, and myeloen- goats, followed by neurologic disease in kids, thus the
cephalitis. In sheep, progressive pneumonia is the common disease term used in this species is caprine
predominant manifestation, whereas arthritis is the arthritis-­encephalitis (CAE).354 Often an area or farm
most common form in goats. Neurologic disease, has a high rate of infection (90%) but a low rate of
characterized by demyelinating, nonsuppurative leu- clinical disease (10%).370 Dairy breeds may be more
koencephalomyelitis, is relatively uncommon in both frequently infected because of the practice of feeding
species.302,352–357 pooled colostrum to kids.353 Typically, the neurologic
Although MVV infection of sheep is widespread, syndrome of CAE involves 1–4-­month-­old kids of
associated clinical disease, originally termed maedi-­ many breeds, although it is recognized in a wider age
visna, but also known as zwoegerziekte, la bouhite, range.352,371–374 The dams of affected kids typically are
and Montana sheep disease, is uncommon. young and primiparous. Often, there is more than
Susceptibility to maedi-­ visna is highly variable one kid affected over a period. A history of animals
among breeds; coarse-­wool sheep of breeds such as recently introduced to the herd and adult goats with
Romney and Border Leicester are highly susceptible joint distensions, cachexia, and a hard udder may be
to disease whereas some locally adapted hill breeds offered by the caretaker.352,353,370 Degrees of slightly
are relatively resistant.358 The scientific and political asymmetric, paraparesis to paraplegia are initially
history of maedi-­visna, especially in Europe, makes encountered. This usually progresses to tetraplegia
fascinating reading.359 Dr. Bjőrn Sigurdsson et al. at with hyperactive reflexes, although there may be
the Institute for Experimental Pathology, University hypotonia and hyporeflexia indicative of gray matter
of Iceland, deserve great credit for enlightening us on or nerve rootlet involvement.374 Evidence of multifo-
the concept of a highly contagious, poorly patho- cal disease is helpful in making a presumptive
genic, slowly progressive, demyelinating and inflam- diagnosis. Signs of cerebellar, cranial nerve, and
matory CNS disease.360,361 This disease in Iceland brainstem involvement may be detected in up to 50%
sheep was first described in the 1930s as purra (dry), of cases.374
maedi (dyspnea) and visna (shrinking—­of the ani- Monocyte-­ lineage cells (i.e., monocytes, mac-
mal or possibly of the spinal cord354), and has since rophages, and microglia) become persistently
been eradicated. Progressive pneumonia is now the infected with the retrovirus in the face of circulating
chief manifestation of MVV infection of sheep in and CSF antibodies.364 Infected monocytes, acting as
North America and Western Europe, whereas neuro- “Trojan horses,” carry virus into target organs to pro-
logic signs associated with classical multifocal, non- voke a chronic, prominent, lymphohistiocytic
suppurative, and meningoleukoencephalomyelitis inflammation in lungs, meninges, brain, spinal cord,
are rare,354,362–364 albeit very well described.365,366 mammary glands, and joints.362–364,370 The host
Affected sheep are usually at least 2 years old, mounts a vigorous and sustained, but ultimately inef-
although there is a recent report of an extensive out- fective, immune response against proliferating
break of visna in Spain involving Assaf lambs as SRLV.351,369 Chemokines and proinflammatory, regu-
young as 4 months.367 They develop ataxia and stum- latory and antiviral cytokines generated in the course
bling, progressing to recumbency over several of this response produce impressive inflammation of
months. They usually lose weight, are afebrile, often infected tissues; however, viral mutation and other
have interstitial pneumonia, and rarely also have subversions of antiviral defenses mean SRLV infec-
arthritis and mastitis.354,365,368,369 Initial progressive tion is lifelong.351,375 There is severe granulomatous
neurologic signs can be grouped into those relating perivascular myelitis, especially involving white mat-
to focal, asymmetric thoracolumbar spinal cord ter, nonsuppurative polyarthritis, lymphoprolifera-
white matter and those producing such lesions in the tive pneumonitis, and fibrosing mastitis. Clinically
brainstem. The former often begin as toe dragging, normal CAEV-­infected adult goats and sheep have
tripping and monoparesis, and the latter as vestibular been found with subclinical histopathologic lesions
signs and circling but with normal mentation.368,370 of polyarthritis, pneumonitis, and varying degrees of
Cases progress through degrees of ataxia, tetraparesis encephalomyelitis.
316 Large animal neurology

Prominent (0.1–0.5 × 109 cells/L = 100–500 cells/μL)) the first half of the twentieth century. It is one of six
small mononuclear pleocytosis occurs in CSF early in species and at least 16 subtypes in the genus
the disease course in adult sheep,364 and CSF mononu- Orthobornavirus within the Bornaviridae fam-
clear pleocytosis and high protein are found in about ily.262,381,382 Borna disease is mostly seen as sporadic
half of kids with CAE myeloencephalitis.374 Needle cases of progressive, nonsuppurative meningopoli-
EMG studies may show evidence of mild, multifocal, oencephalomyelitis in sheep and horses in central
final motor neuron disease. Europe but has now has been confirmed or suspected
Specific circulating antibody can first be detected as a rare disease in a wide range of other warm-­
several weeks after infection, but no serologic test is blooded animals, including donkeys, cattle, goats,
considered to be a “gold standard.”351,376 Serum AGID and camelids, in many countries.302,383–388 Alpacas
and ELISA tests are prescribed for international trade. (and, presumably, llamas) appear to be particularly
ELISA are generally more sensitive and AGID more susceptible to Borna disease. In one recent outbreak,
specific, but false-­negative and false-­positive results 11/27 animals (41%) died within a 10-­month period,
occur quite commonly.353,374,377 Virus can be isolated with signs ranging from sudden death to chronic
from buffy coat and CSF mononuclear cells, and con- relapsing disease with death after several months.389
served viral sequences can be detected by RT-­PCR.351 Six additional healthy alpacas were seropositive for
Probably the best field tests for optimal detection of BoDV-­1, suggesting subclinical infection. A similar
SRLV infection are a combination of ELISA and PCR.378 outbreak in 1994 resulted in 30% mortality over
There is no treatment and affected sheep and goats 14 months.390 Experimental infection has reproduced
will die prematurely. The severity of CNS lesions can the disease in many of these species including
be significantly reduced with immunosuppression, horses.391,392 Topical interest has been expressed in
but persistent virus shedding remains.364 Lactogenic BoDV being associated with human neuropsychiat-
and inhaled transfer of free or cell-­associated virus ric disorders with no conclusions reached.302,383 And
are the main routes of vertical and horizontal transfer recently, for the first time, zoonotic spillover infec-
of SRLV, respectively, with inhalation being of impor- tions with Borna disease virus 1 leading to fatal
tance in conditions that force close contact among human encephalitis have been confirmed.397
animals. Schemes that include some or all of the fol- Seroepizootiologic studies indicate that infection
lowing elements are the basis for most control and in animals is widespread, but only occasional animals
eradication programs: minimization of animal den- show neurologic signs. Subclinical encephalitis, tran-
sity, immediate postnatal removal of neonates from sient ataxia, and fever and peracute fatal encephalitis
infected dams to sources of virus-­free pooled colos- all occur. Typical clinical signs in sheep and horses
trum and nurse animals, and repeated clinical and are behavioral along with mentation changes, ataxia,
serological examinations and removal of seropositive asymmetric vestibular signs, and various cranial
animals.352,353,355,359,379,380 A closed-­
flock policy or nerve functional deficits. Compulsive circling, head
introduction of seronegative animals that are quaran- pressing, constant yawning, aggressiveness, sham
tined for 90 days and re-­ tested negative is also chewing, nibbling, dysphagia, hyperesthesia, facial
required. There is no vaccine for SRLV diseases, but muscle fasciculations, trismus, blindness, stupor, and
the identification of genetic markers of resistance to seizures all are described for horses and reflect the
SRLV infection (such as TMEM154 alleles) may allow predominant forebrain and brainstem lesions; signs
future selection of animals that are genetically and lesions of cerebellar and spinal cord involvement
resistant.351,358 are not common.383,384,392 Such syndromes in horses
have resulted in colloquial names for the disease such
as brain fever, hot-­headed disease, and hypersom-
nia.384 The mortality rate is about 80% for horses and
Borna disease virus
50% for sheep.302 Some affected horses develop a
Mammalian 1 orthobornavirus, comprising Borna chronic relapsing form and may become persistently
Disease virus subtypes 1 and 2 (BoDV-­1/2), is the infected carriers.
viral species causing classical Borna disease, so called A modest lymphocytic pleocytosis is often seen in
because of severely fatal epizootics first recognized in CSF during the early stages of the disease. Testing for
cavalry horses in the town of Borna and more widely the presence of serum and CSF antibodies and BoDV
in southern Germany during the late nineteenth and RNA can add to confidence in a clinical diagnosis in
 Infectious, inflammatory, and immune diseases 317

acute disease, but antibody tends not to be present in most common in young adult cattle having some
mild, chronic cases.302,384 association with sheep or deer.302,400–402
Infection is believed to enter via the nasopharyn- Neurologic signs occur 3–10 days after systemic
geal epithelium and trigeminal nerves and likely trav- signs begin. Degrees of febrile illness, panophthalmi-
els via axons to the brain where direct replication tis with peripheral corneal opacity, purulent nasal
occurs in neurons and glial cells, with centrifugal and ocular discharges, exudative dermatitis, and
spread to peripheral nerves and retina. A lympho- lymphadenopathy may be present. There is somno-
cytic, mononuclear polioencephalitis is set up with an lence, blindness, occasional aggressive behavior,
accompanying reactive astrocytosis. The identifica- wandering, seizures, and ultimately recumbency due
tion of eosinophilic, neuronal, intranuclear Joest– to terminal encephalitis occurring in this multisys-
Degen inclusion bodies, especially in the tem disease.302,398
hippocampus, is almost pathognomonic for the dis- Urinalysis may reveal proteinuria because of
ease. Although most clinically affected patients will nephrosis. Skin and lymph node biopsy may show a
produce circulating antibodies, these can develop late necrotizing, fibrinoid vasculitis, which characterizes
or never in some animals. The encephalitis is regarded the lesions present in all organs, including the brain
as representing a vigorous T lymphocyte-­mediated and meninges. Detection of viral DNA in blood and
immune response to the virus.394 Virus isolation, other samples is becoming the method of choice for
immunohistochemical, and in situ RT-­ PCR tech- the diagnosis of sheep-­associated MCF.397
niques are required to confirm the disease.302,383,384 Treatment is palliative. The disease is sporadic and
Controversy still occurs over definitive diagnostic usually fatal, although some long-­term survivors are
criteria for Borna disease.382,395 The high seropreva- reported.403 No vaccine is available for sheep-­
lence of the disease in horses in Europe and the pres- associated MCV; separating cattle from sheep and
ence of many unusual and ill-­ defined neurologic deer is a sensible precaution to help prevent the dis-
syndromes in this species invite irrational clinical ease in cattle.
diagnoses of Borna disease being entertained,384 as
has occurred with equine protozoal myeloencephali-
Rabies
tis due to Sarcocystis neurona in the Americas.
Reverse transcriptase–PCR testing of blood and The genus Lyssavirus in Rhabdoviridae contains the
other body fluids likely will play an increasingly classic rabies virus and at least 14 rabies-­related bat-­
important role, as is now the case for Borna disease associated viruses.262 Strains of classic rabies virus are
(staggering disease) of cats.396 predominantly associated with terrestrial carnivore
species. Rabies is an ancient and dreaded disease that
is rare in developed countries but still highly signifi-
Malignant catarrhal fever
cant because of public health concerns and is fright-
The disease malignant catarrhal fever (MCF) is eningly common and of great economic and
caused by at least six members of the genus Macavirus humanitarian impact in Africa and Asia, and in parts
of the subfamily Gammaherpesvirinae.397 MCF is a of Latin America where unvaccinated domestic dogs
widespread, infrequent, usually sporadic, and often are the norm and where there is mixing of domestic
fatal disease of cattle and other ungulates. It may also and feral dogs and wild carnivore reservoir hosts. A
be seen in outbreak form with affected animals show- few isolated and well-­quarantined countries are free
ing acute diarrhea, rhinitis, ophthalmitis and derma- of the virus. Worldwide, some of the major terrestrial
titis, with terminal angiocentric encephalitis.302,398,399 wildlife reservoir hosts for domestic animal rabies
The disease occurs in two distinct epidemiologic are fox, skunk, raccoon, coyote, raccoon dog, jackal,
forms. Alcelaphine herpesvirus-­1 causes the disease and mongoose.302,404 Infection and death from
in Africa, where subclinical infections in wildebeest hematophagous vampire bat rabies are still common
and other wild ruminants are spread to domestic cat- across much of Latin America as exemplified by a
tle. Ovine herpesvirus-­2 causes subclinical infection recent astounding estimate of 100,000 vampire bat
in sheep worldwide, and the disease is transmitted to rabies-­related cattle deaths per year in Mexico.405
cattle, bison, and deer from sheep and newborn Insect-­and fruit-­eating bats are also reservoirs for
lambs that shed virus postnatally. This form is some- several lyssavirus species, and nonrabies bat lyssavi-
times referred to as sheep-­associated MCF and is ruses have caused fatal human encephalomyelitis in
318 Large animal neurology

South Africa, multiple countries in Europe and aggressive behavior, hyperesthesia, abnormal vocali-
Eurasia, and Australia.406 In Australia, two horses in a zation and other signs of dementia, and drooling,
single paddock suffered rabies-­like clinical signs pre- tenesmus and convulsions. In the brainstem or dumb
sumptively as a result of infection with Australian bat form, somnolence, stupor, opisthotonus, facial hypal-
lyssavirus.407 In the Americas, rabies caused by non- gesia, pharyngeal paralysis, excessive drooling, and
hematophagous bats is relatively uncommon.406 ataxia occur. The spinal cord or paralytic form is
Rabies and other lyssavirus-­associated encepha- characterized by progressive, ascending paralysis,
litides are rare but fatal viral infections of warm-­ initial monoparesis, truncal, limb and perineal
blooded animals in most countries. Programs of hyporeflexia and hypalgesia, priapism, and increased
mandatory vaccination of dogs in the western world urinary frequency and urinary incontinence. Self-­
have greatly reduced the prevalence of rabies in mutilation, often directed to one part of the body and
humans and domestic animals. However, rabies virus sometimes spectacularly gruesome, is seen in the spi-
still circulates among wildlife in enzootic areas, so nal cord form, but may be associated with any initial
there is occasional spillover into domestic large ani- presentation, as well as with vaccine-­associated rabies
mals living in these areas. Because rabies virus is seen in horses. The ascending spinal cord form, pro-
transmissible to man and is fatal, great precautions gressing to brainstem involvement, has also been
must be taken by the veterinarian who examines a seen in the vaccine-­associated disease in horses.413
patient suspected of being rabid.408 Although the clinical signs vary, a few generaliza-
Any age, breed, and sex of warm-­blooded animal tions are worthy of mention. The rabies virus passes
is susceptible to classic rabies. Younger and smaller rapidly along neurons within the nervous system.
domestic large animals, especially when bitten on the Initially, there may be hyperactivity of affected neurons
face as opposed to the distal extremities, appear to be with signs such as hyperesthesia, tremor, straining, and
more susceptible to clinical rabies after a bite from a salivation. Ultimately, the neurons die and signs such as
rabid animal.54,302,409–411 Modified-­live virus vaccine-­ flaccid paralysis, dysphagia, and cutaneous analgesia
induced rabies has occurred in cats, dogs, cattle, and then can be expected. The disease is progressive, but
horses.412,413 the course may be prolonged by corticosteroid ther-
Historically, it may be reported by a caretaker that apy.417 If the patient does not succumb with the early
an animal was bitten by a dog, raccoon, skunk, fox, or signs of furious, dumb, or paralytic rabies listed above,
bat several weeks to months prior to the onset of the virus ultimately spreads through the rest of the
signs, although most rabies cases have no such evi- CNS, causing seizures, coma, and death.
dence and usually bite wounds are healed by onset of As a guide only, frequently occurring neurologic
neurologic signs.302,410 Once signs begin, the clinical signs recorded in large animals dying of rabies, in
course is less than 14 days, usually less than 5 days, approximately decreasing order of frequency
and the animal dies after an average of 3 days of clini- reported, are listed in Table 32.1.54,409–411,413–416,418–422
cal signs.302,411,414 Prodromal colic, lameness, listless- Generally, neurotropic lyssaviruses including
ness, anorexia, and, rarely, hydrophobia, may be rabies virus do not evoke a prominent cellular reac-
recalled by caretakers in large animal cases. Fever tion in the CNS, and the resulting nonsuppurative
may occur independently from the hyperthermia of myeloencephalitis can be very mild in large ani-
seizure activity.410,414,415 mals.418,423,424 When the patient dies spontaneously,
The presenting signs and progressive syndromes often the virus is recoverable from brain and salivary
that can result from rabies virus infection are gland tissue, and characteristic eosinophilic, intracy-
extremely varied and include sudden death. However, toplasmic Negri bodies are often present in neurons.
from a neurologic point of view, it is probably still If an animal is euthanized early in the course of dis-
reasonable to organize them into the classic group- ease, particularly if only signs of spinal cord disease
ings of the signs seen early in the clinical course: the are present, virus and Negri bodies may not be detect-
cerebral or furious form, the brainstem or dumb able in brain tissue54,302,409–411,423 or may be confined to
form, and the spinal cord or paralytic form.54,302,411,416 the spinal cord alone424,425 Thus, premature euthanasia
Almost certainly, these partly relate to the site of a patient that is not unduly suffering may not be
of inoculation into the body and subsequent neu- prudent. This pathologic and diagnostic enigma may
ronal spread of the virus and the body’s response to be more often the case in horses where histologic
it. Forebrain signs (furious form) often include lesions can be found only in spinal cord sections.424
 Infectious, inflammatory, and immune diseases 319

Table 32.1 Commonly reported neurologic signs in large animal rabies cases listed in approximate order of reported frequency of occurrence

Horse Cow Sheep Goat Pig

Aggressiveness Salivation Hyperesthesia Aggressiveness Hyperexcitability

Self-­mutilation Aggressiveness Tremors Bleating Aggressiveness
Hyperesthesia Limb paralysis Salivation Salivation Squealing
Limb paralysis Straining Head tilt Hyperactivity Salivation
Fever Tremors Sexual activity Limb paralysis Seizures
Ataxia Bellowing Pruritus
Seizures Sexual activity Trismus
Opisthotonus

Sources: Based on Green et al.54; Dauda et al.409, Green410; Hudson et al.411; West413; Joyce and Russell414; Reid415; Martell et al.416; Moreira et al.418; Barnard419; Pépin et al.420;
O’Toole et al.421; Kandavel et al.422

If rabies is suspected, caution should be taken in people regarding the disease. Finally, vaccination
performing further diagnostic work; however, the does involve an expense, and the chance of a rare vac-
animal should be treated for other possible nonfatal cine reaction still exists.
diseases. If the patient is stable or improving 10 days
after onset of signs, it almost certainly does not have
Picornaviral encephalitis of pigs
rabies. Handling of rabies suspects postmortem must
accord with local regulations. If permitted, the head Both porcine teschovirus (PTV)429 and encephalomy-
or half-­unfixed and half-­formalin-­fixed brain and ocarditis virus (EMCV) in the genera Teschovirus and
unfixed salivary gland should be sent to a veterinary Cardiovirus, respectively, within the Picornaviridae
diagnostic laboratory designated to handle rabies family cause encephalomyelitis in pigs, particularly
virus-­infected tissue. Direct fluorescent antibody young pigs262. See Table 32.2 for a comparison of the
testing for rabies virus may be performed there, as important viral encephalitides of swine.430
recommended by the World Health Organization. Porcine teschoviral polioencephalomyelitis is
Further immunohistochemical or in situ RT-­PCR caused by a subgroup of pig-­specific teschoviruses,
testing may be performed to identify novel lyssavi- including virulent strains of PTV-­ 1 and PTV-­ 13,
ruses or rabies virus variants associated with particu- referred to as Teschen disease in Europe and Africa,
lar host reservoirs. and seen as the milder Talfan disease probably world-
Palliative treatment and corticosteroid therapy for wide, associated with less virulent PTV-­1, PTV-­2,
other diseases may delay progression of signs but PTV-­3, and PTV-­5. Transmission of virus is predom-
does not affect outcome. Inactivated vaccines are inantly fecal–oral. All ages of pigs may be involved in
licensed by the USDA for use in sheep, cattle and an initial outbreak of PTV-­1 infection, although, in
horses and appear to be quite protective, and off-­ recent years, only small numbers of suckling and
label use in goats, camelids and pigs is common.426,427 weaned piglets are usually affected in an endemic
Thus, an immunologically competent animal that is area. There is a peracute or subacute onset of ascend-
currently vaccinated that is bitten by a rabid animal ing paresis or paralysis, convulsions, and death.
probably will not die of rabies, whereas insufficient Usually, the morbidity rate is high. Signs of general-
and lapsed vaccination protocols are not protec- ized systemic illness may occur. Neurologic signs
tive.411 Postexposure rabies prophylaxis was used in relate to diffuse, spinal cord gray matter disease, such
72 horses, 39 cattle, 3 sheep, 4 goats, and 1 llama sus- as weakness, reflex loss and analgesia, although these
pected of rabies; none developed rabies.428 signs may be masked by acute, diffuse, brain involve-
Postexposure vaccination should only be carried out ment, which produces hypersensitivity and vocaliza-
with regulatory authority approval. tion, teeth grinding, somnolence, seizures, and
Useful prevention strategies include vaccinating recumbency. Older pigs may show prominent ataxia
all domestic dogs and cats, removal of feral dogs and and improve with time, but the disease is fatal in
cats, controlling association of wildlife reservoirs suckling piglets.431,432
with domestic animals, vaccinating wildlife popula- PTVs are neurotropic enteroviruses producing poli-
tions as appropriate and, most particularly, educating oencephalomyelitis with diffuse brain involvement but
320 Large animal neurology

Table 32.2 Syndromes associated with various causes of viral encephalomyelitis (EM) in pigs

Vomiting Neurologic
Disease Group Affected Morbidity (%) Mortality (%) Fever* and diarrhea Signs**

Teschovirus: teschen All 50 <100 + ± ++++

Teschen-­like Nursing-­weanling <30 <100 ± -­ ++
Cardiovirus: encephalomyocarditis Nursing <70 10–100 + -­ +
Coronavirus: hemagglutinating Nursing <100 <100 ± + +++
encephalomyocarditis Growing Low Low -­ ± +
Pseudorabies Nursing-­weanling <100 <100 + + +++
Adult Low Low ± ± ++
Paramyxovirus Nursing Low High + ± ++
Rabies All Low 100 ± -­ ++++
Hog cholera All <100 <100 + + +
African swine fever All <100 <100 + + +

*
Present (+), absent (-­), and sometimes present (±).
**
+ to + + + + indicates increasing likelihood and severity of neurologic signs.
Sources: Adapted from Carter et al.262; Brown430; Taylor 431

having a particular predilection for spinal cord ventral treatment or vaccine. It is diagnosed using serologic
gray columns, viz. poliomyelitis suum. testing, RT-­PCR, and virus isolation.431,435
CSF and EMG studies should be useful in diagno-
sis but do not appear to be recorded in the literature.
Necropsy examination with typical histologic lesions, Porcine rubulavirus
RT-­PCR of blood and tissues, and virus isolation, Porcine rubulavirus262 belongs to the Paramyxoviridae
which is difficult, are the best diagnostic aids. family and causes diffuse, nonsuppurative encephali-
Hemagglutinating encephalomyelitis virus infection, tis of piglets 2–15 days old, characterized by somno-
pseudorabies, rabies, classical swine fever, and lence, ataxia, weakness, and tremor, with seizures
African swine fever are clinically and pathologically and blindness sometimes prominent.436 Mortality
similar (see Table 32.2). may reach 90%. Respiratory signs occur in older pigs.
Live modified and inactivated teschoviral polioen- The disease appears restricted to Mexico.
cephalomyelitis vaccines have been used successfully Panophthalmitis with corneal opacity is an occasion-
in Europe, but with decline in disease, vaccines are ally seen, conspicuous finding that gives rise to the
no longer produced.433 common name for associated disease, “blue eye.”
The cardiovirus262 EMCV affects multiple spe- Gastrointestinal signs and reproductive failure also
cies, including humans. It causes multisystem dis- occur. A killed, oil-­adjuvant vaccine is available in
ease including fulminant neurologic disease in Mexico.
young pigs, probably worldwide.431 Signs of heart
failure usually overshadow those related to enceph-
alitis. The virus is carried by rodents and causes Pseudorabies
sudden death in young pigs but is usually subclini- Since its recognition and description in Hungary
cal in weaned and adult pigs. Vaccines have been early in the twentieth century by Aujeszky, pseu-
patented but are not manufactured because of low dorabies virus (PRV), also known as suid herpesvi-
demand. Rodent control is the key to prevention. rus 1 (SuHV-­1), has become the most studied of the
porcine viruses. It is a neurotropic member of the
Hemagglutinating encephalomyelitis virus genus Varicellovirus262 in the Alphaherpesvirinae
This betacoronavirus262 usually causes chronic vom- subfamily and occurs almost worldwide. PRV pri-
iting and wasting disease in neonatal piglets. marily infects swine, causing sporadic cases in
Encephalomyelitis with hyperesthesia, paraparesis, developed countries and outbreaks, which are occa-
difficulty swallowing, tremor, convulsions and death sionally devastating, in developing countries.
sometimes occurs, and this acute syndrome has been Endemic infection of wild and feral pig populations
referred to as Ontario disease.434 There is no in many countries complicates eradication efforts.
 Infectious, inflammatory, and immune diseases 321

PRV produces fulminant encephalitis in piglets and tests that differentiate infected from vaccinated ani-
milder syndromes and poor performance in older mals (DIVA) has been highly effective in eliminating
pigs; prominence of neurologic signs is inversely PRV from commercial herds. Variant PRV that are
proportional to age. Many mammals, including all vaccine resistant are becoming prevalent in some
domestic large animals and, rarely, humans, are sus- areas. Quarantine measures and separation from
ceptible and most often show signs of an acutely wild pig populations combined with serologic and
progressive, fatal encephalomyelitis including PCR testing with culling subclinical animals most
marked localized pruritus or “mad itch”.302,431,437,438 often continue to be the basis for effective eradication
In piglets, following fever and acute malaise, neu- programs.302,431,446–448
rologic signs comprise ataxia, blindness, aimless wan-
dering, recumbency, paddling, and death.437 Mortality Equine infectious anemia virus
rates in neurologic piglets are very high, with death in
This retrovirus263 is closely related to the small rumi-
24–72 h. In comparison, signs in adult pigs usually
nant lentiviruses and can on rare occasions produce a
comprise fever with respiratory signs and incoordina-
lymphohistiocytic, periventricular leukoencephalitis
tion, more prominent signs of encephalitis being
in adult horses with or without typical weight loss and
transient or nonexistent.302,431,437,439
anemia. A granulomatous ependymitis, meningitis,
Pruritus is seen in other species, with violent lick-
and leukoencephalomyelitis with lymphoreticular
ing, chewing, and rubbing of the face, limbs, or trunk.
proliferation complicated on occasion by hydrocepha-
Maniacal behavior frequently develops with death
lus can occur after acute infection up to 3 years later.
occurring in 1–2 days.302,431,440,441
Occasionally, signs of ataxia and weakness are seen
Outbreaks of pseudorabies still occur in nonpor-
that relate only to spinal cord involvement, but usually
cine farm stock, often but not always associated with
chronic and intermittent or progressive behavioral
direct or indirect contact with pigs.302,431,440,442 Almost
changes, leading to dementia, hyperesthesia, circling
20% of one sheep flock housed next to pigs demon-
and blindness, occur.449–452 It has been shown that
strated encephalitic signs and most had intense pru-
brain lesions are directly associated with lentivirus
ritus. Generalized tremors and ataxia accompanied
infected cells, likely macrophages and microglial cells,
frantic behavior with frenzied nibbling at patches of
and that active viral replication occurs in them.451
wool and skin, at sites suspected to be injuries sus-
tained from recent shearing and probable sites for
Viral-­induced congenital malformations
virus penetration.440
The disease appears to be rare in horses443 although The discipline of large animal neurology greatly bene-
well documented and experimentally transmitted. fited from seminal observations and experiments made
Following febrile illness, affected horses have shown by colleagues in the 1960s when they confirmed the
trembling, lowered head posture, sham chewing and etiologic role of the pestivirus bovine viral diarrhea
drinking, licking and chewing at objects, intermittent (BVD) virus in causing cerebellar hypoplasia when
mania, and recumbency. Analysis of CSF has revealed infecting the bovine fetus during the second trimester
a mild pleocytosis.444,445 of gestation.453–459 Similar plaudits must go to Australian
The virus is highly neurotropic and enters abraded and Japanese groups for clarifying the role of Akabane
skin or the upper respiratory mucosa and spreads to virus, an orthobunyavirus, in inducing multiple con-
the CNS by trans-­synaptic passage and axonal trans- genital malformations, notably arthrogryposis and
port via spinal and cranial nerves. Extensive neu- hydranencephaly, in lambs and calves.460,461
ronal loss with perivascular mononuclear cuffing In addition to these diseases, several other known
and necrosis occurs, and large acidophilic intranu- and unidentified viruses from at least the Flaviviridae,
clear inclusions are seen. Bunyaviridae, and Reoviridae families are known or
A pseudorabies monoclonal antibody has been suspected to cause various congenital neural malfor-
used to reduce death during outbreaks of the disease mations, especially forms of hydranencephaly, cere-
in pigs. No other effective therapy is available. It is bellar hypoplasia, and arthrogryposis in domestic
advisable to remove other livestock from any associa- large animals.61,462–472 An overview of reported con-
tion with affected pigs. Confirmation of the diagno- genital malformations caused by in utero infection by
sis is by viral isolation and in situ PCR. Immunization various viruses occurring in ruminants and pigs is
with gE-­deleted vaccines combined with diagnostic given in Table 32.3.
322 Large animal neurology

Table 32.3 Overview of reported congenital malformations caused by in utero infection with various viruses occurring in ruminants and pigs

Virus

Flaviviridae Bunyaviridae Reoviridae

Neonate of
Malformation species BVD CSF BD WD AKA AINO CACHE RVF SBV OTHER BT CHZ

Hydranencephaly Calf + + ++ ++ + + ++ ++ +
Lamb + ++ + ++ + ++
Kid ++ ++
Piglet
Cerebellar hypoplasia Calf ++ + + + + ++ + +
Lamb + + + + + + ++ +
Kid + + ++
Piglet +
Arthrogryposis Calf ++ + ++ + +
Lamb + + ++ + ++ + +
Kid ++ ++
Piglet

+: present; ++: frequent ant prominent; blank: not recorded or not looked for.
BVD: bovine viral diarrhea; CSF: classical swine fever; BD: Border disease; WD: Wesselbron Disease; AKA: Akabane; AINO: Aino; CACHE: Cache Valley; RVF: Rift Valley fever;
SBV: Schmallenberg; OTHER: other, including La Crosse, San Angelo, Shuni, Main Drain, and unidentified viruses; BT: Bluetongue; CHZ: Chuzan.
Source: Based on Kahrs et al. 453; Wilson et al.473; Nettleton et al.474

If not stillborn, incoordination of limbs and head, Of the viruses listed in Table 32.3, BVD viral infec-
recumbency, or seizures are often the primary prob- tion most consistently results in signs of cerebellar
lem in newborn animals. Combinations of signs of damage.453,473 Signs of cerebellar disease are variable,
hydranencephaly, such as somnolence and blindness, but they are usually symmetric and vary from recum-
and arthrogryposis with its congenital contractures bency with opisthotonus and extensor rigidity of the
occur with some viruses more than others limbs to a mildly hypometric or hypermetric ataxia
(Table 32.3). Signs are first seen when affected ani- and slight head tremor. Abnormal, jerky eye move-
mals try to ambulate, and they may have difficulty ments may be seen. Signs of cerebral disease can be
getting clear of their fetal membranes. In an out- caused by concomitant hydrocephalus, hydranen-
break, abortions, mummified fetuses, birth of weak cephalus, and porencephalic cysts. These cerebral
offspring, and neonatal ill thrift may occur. Usually, lesions frequently occur with fetal Akabane, Aino,
the ataxia remains stable, or the animal may compen- bluetongue, Schmallenberg, and Shuni viral infections
sate for the deficits. Cerebellar signs and arthro- and in utero infections associated with Wesselbron
gryposis predominate in the clinical syndromes, but disease and Rift Valley fever.475,479,480 Piglets exposed in
somnolence and blindness (i.e., dummy syndrome) utero to classical swine fever virus usually show tremor
may be evident because of hydranencephaly. as well as ataxia; this has also occurred in calves
Certain clinical findings often occur when the exposed to BVD in utero (see also Chapter 31).
syndrome is associated with a particular virus. Congenital malformations including cerebellar hypo-
Calves may have ophthalmic lesions with BVD,459 plasia and hydranencephaly, abnormal neurologic
calves and lambs often have arthrogryposis with signs and other problems were seen in >70% of lambs
Akabane, Schmallenberg, Shuni, and Aino born to 1600 Laucane sheep (550 pregnant ewes) that
viruses,475,476 and piglets in particular may be stunted had been inoculated with a modified-­live orf vaccine
(“runts”) by classical swine fever virus. Some out- contaminated with BVD virus.481
breaks of congenital abnormalities in calves due to These viruses, and possibly others, destroy por-
intrauterine infection with BVD virus have included tions of the developing brain457,458,460,470,471,479,480,482–484
animals with whole body tremor associated with dif- The external germinal layer of the bovine cerebellum
fuse hypomyelinogenesis,477,478 and occasionally such is selectively destroyed by BVD virus if it gains access
animals will have abnormal dilution of coat color to the fetus at about 102–183 days of gestation.455–458
(Figure 32.11). Severe destruction of cerebral tissue may result in
 Infectious, inflammatory, and immune diseases 323

evidence453,454 If the ratio of weight of cerebellum to

total brain weight is less than 8%, then cerebellar
hypoplasia is probably present.458,459
There is no therapy, but the various syndromes
usually do not worsen. Cattle with serum-­neutralizing
antibody titers to BVD resist challenge with patho-
genic BVD virus at ~150 days of gestation and do not
(A) produce calves with cerebellar hypoplasia.457,458
Therefore, the use of appropriate vaccines may pre-
vent these syndromes.

Border disease
(B)
Border disease was named for a syndrome in lambs
from the Scottish–English border born with a hairy
fleece, ataxia, short stature, and various skull malfor-
mations. In addition to brain tissue loss and mild con-
genital malformations, there is hypomyelinogenesis
associated with in utero infection with Border disease
(BD) virus, a pestivirus that is antigenically related to
BVD virus (Table 32.3).474 The disease results when
fetal lambs are infected with BD virus early in gesta-
tion. As is the case with calves persistently infected
with BVD virus, such lambs are persistently viremic
(C) but do no mount a neutralizing antibody response.
Indeed, BD viral infection of calves also occurs and is
Figure 32.11 Sometimes in outbreaks of congenital problems in calves difficult to distinguish from BVD viral infection.487 In
associated or suspected to be associated with BVD or other Flaviviridae comparison, it appears that infection of fetal lambs
infection in utero, calves are born unable to rise (A and C). Some may with BD virus later in gestation results in cerebral
have severe tremor and be unable to complete voluntary movements to
stand (A), while others try to stand with very strong effort but because of
cavitation and cerebellar dysplasia (similar to pre-
marked dysmetria (C) they need assistance to stand but may then walk, sumed copper deficiency syndrome), no persistence
with difficulty. The former (A) is strongly suggestive of diffuse hypomyeli- of virus, and a high virus neutralizing antibody
nation and the latter (C) of severe cerebellar deficits. Even less often, response. Infection in late gestation may result in
some affected calves may show a dilution of the coat color (Inset, B), irregular serologic responses and pathologic lesions,
making this syndrome reminiscent of hairy shaker disease in lambs.
possibly dependent on the acquisition of immune
competence by the lamb.488 Experimental evidence
suggests that BD virus-­induced hypomyelination is
hydranencephaly.480–483 Spinal cord ventral gray horn
associated with decreased circulating thyroid hor-
and skeletal muscle lesions can explain the arthro-
mone concentrations due to insidious infection of the
gryposis.482 Many times this clinical syndrome occurs,
thyroid gland by the virus.489
and there is no proof of the nature of the inciting, in
utero agent.485 The degree of cerebellar hypoplasia
Bovine herpesvirus meningoencephalitis
does not always relate to the severity of the clinical
syndrome.459 Bovine herpesviruses in the Alphaherpesvirinae sub-
A positive presuckle viral titer in serum and possi- family of the Herpesviridae, genus Varicellovirus,262
bly in CSF is suggestive but not diagnostic for a par- occur almost worldwide except where eradicated.
ticular cause.453,454,459 Usually, no virus can be detected Bovine herpesvirus 5 (BoHV-­5) is regarded as the neu-
in calves with cerebellar hypoplasia,479,480 although per- rotropic strain that causes highly fatal necrotizing non-
sistent BVD viral infection has been associated with suppurative meningoencephalitis in cattle, especially in
congenital tremor and cerebellar ataxia in calves.486 young calves.301,490 The respiratory virus BoHV-­1 (aka
Confirmation of exposure of the dam to the virus infectious bovine rhinotracheitis virus) is an occasional
d­uring mid-­ gestation is also good circumstantial cause of bovine meningoencephalitis.491
324 Large animal neurology

BoHV-­5 encephalitis is a rare disease of young extremely ubiquitous and responsible for upper res-
calves described worldwide but with a much higher piratory tract infection in young horses and, rarely,
prevalence in Latin America.302,492,493 Individual cases abortion. EHV-­1 also commonly causes respiratory
and sporadic outbreaks are recorded although only disease but, unlike EHV-­ 4, also infects pregnant
isolated cases occur in adult cattle.302,490,494,495 Affected mares to produce syndromes of late-­gestation abor-
cattle present acutely with syndromes of forebrain tion and still-­born or weak neonatal foals. Less com-
dysfunction which include hyperexcitability, ptyal- monly, EHV-­ 1 infection causes overt neurologic
ism, bruxism, head pressing, circling, blindness, and disease, and this is the result of vasculitis with subse-
seizures. In one case, a 3-­year-­old heifer had signs of quent thrombosis and necrosis of CNS tissue.
frenzied licking and attacking parts of the body.496 Neurons and astrocytes are only occasionally positive
Other signs of encephalitis and myelitis were present, for viral antigens.502 It is because the primary inflam-
and the disease was fatal. matory target here is the vascular endothelium, with
BoHV-­ 5 enters the body via upper respiratory secondary ischemic and hemorrhagic infarction of
mucosa and travels intra-­axonally through the olfac- neuropil, that this disease is termed equine herpesvi-
tory and possibly trigeminal nerves to gain access to rus (type 1) myeloencephalopathy (EHM)503–509
rostral portions of the brain where lymphocytic rather than myeloencephalitis (c.f.
necrotizing meningoencephalitis occurs with neuronal BoHV-­5 meningoencephalitis).272,323,504,510
loss and gliosis. Intranuclear, basophilic viral inclusions Definitive association between EHV-­1 and mye-
are evident in neurons and glial cells. Cytotoxic T cells loencephalopathy was first made after the isolation of
are important in clearing whole virus, but incomplete virus from the brain and spinal cord of a horse in
BoHV DNA can remain in the body to later become Norway.511 Similar cases since have been demonstrated
fully expressed and released. Latency, reactivation, to have a worldwide distribution.323,507,508,510,512–519 In
shedding, and transmission are important phases in most instances, the myeloencephalopathy occurs as an
the maintenance of the virus in a population. outbreak, although minor clusters of cases and spo-
Cerebrospinal fluid analysis in cases of BoHV-­5 radic incidences of the disease can also be observed.509
encephalitis reveals mononuclear pleocytosis (up to Very rarely, EHV-­4 has been strongly suspected of
0.2 × 109 cells/L) with ~10% neutrophils and high producing classical EHV myeloencephalopathy.519,520
protein content.497 Sensitive multiplex-­PCR diagnos- Two herpesviruses closely related to EHV-­1, namely
tic techniques and iELISA for use on body fluids and EHV-­8 and EHV-­9, cause fatal encephalitis in various
tissues are available for distinguishing infection with nonequid species and have been shown to infect
BoVH-­1 and BoHV-­5.490,498 horses and/or donkeys.521,522 EHV-­8 was identified in
Inactivated and modified-­ live BoHV-­ 1 virus nasal secretions as the possible cause of severe ataxia
vaccines offer some cross protection against in a 30-­year-­old donkey with pituitary pars intermedia
BoHV-­5 infection.302 Of a cautionary note is the evi- dysfunction.522
dence that such modified-­live vaccine virus has been Contact with EHV-­1 is through inhalation of nasal
associated with encephalomyelitis and death in neo- aerosols from infected horses, or via fomites contam-
natal calves. There is experimental evidence for pro- inated with fluids from an abortion, or in ocular,
tective efficacy of inactivated DIVA marker and nasal, and other respiratory tract secretions.523,524
glycoprotein D subunit vaccines against BoHV-­ 5-­ There is a cell-­associated viremia that, even in the
induced encephalitis.499,500 presence of high circulating antibody, results in
endothelial cells becoming infected. Endothelial
infection incites destructive innate and specific
Equine Herpesvirus-­1 myeloencephalopathy
immune inflammatory responses, which in turn ini-
The Herpesviridae family is divided into three sub- tiate coagulation and widespread arterial micro-
families, alpha, beta, and gamma, on the basis of host thrombosis and hemorrhage of spinal cord neuropil
range, reproductive cycles, in vitro cytopathology triggering onset of clinical signs. Latent viral DNA
and genomic structure. The common equine alpha persists in protected sites such as the sensory neu-
herpesviruses (EHV-­1, EHV-­3, EHV-­4) have a wide rons of trigeminal ganglia and T-­ lymphocytes
host range, short reproductive cycle, and, most in mandibular lymph nodes and undergoes intermit-
importantly, the capacity to establish latent infec- tent episodes of reactivation of infection.525–527
tions.501 Equine herpesvirus type 4 (EHV-­ 4) is Reactivation usually occurs after some stressful event
 Infectious, inflammatory, and immune diseases 325

such as illness, transportation, or management clinical signs of EHM and, with the exception of uri-
change. Although the elements of effective immunity nary incontinence, no difference in clinical disease or
against EHV-­1 are not well understood, they are sug- outcome related to the EHV-­1 genotype.539 It is com-
gested to include both cytotoxic T-­cell and neutral- mon for horses to be latently infected with both vari-
izing antibody responses.514 It can be shown that ants, and there is no evidence that horses latently
EHV-­ 1 evades antibody surveillance by moving infected with the neuropathogenic strain pose a higher
between cells without exposure to extracellular envi- risk of being the source of future EHM outbreaks.505 A
ronments and subverts cell-­mediated immunity by second variant at nucleotide 2254, adenine to cytosine
efficiently infecting and sabotaging the actions of (C2254; allele H752), was recently identified in EHV-1
activated T lymphocytes.514,528 isolated from horses in France. All of the 58 horses in
Horses of any age, sex, or breed are susceptible, this outbreak had signs of respiratory disease; two also
although a breed predilection has been mooted.529 In developed EHM.540 Polymorphism elsewhere in the
some studies, females in general, or mature pregnant genome likely also modulates neurovirulence.
or lactating mares, are most often affected.503,513,530,531 Epizootics have been frequently described in post-
The principal risk factor for the development of EHM foaling mares,323, 513,515,516,541–544 although outbreaks in
is fever, especially the second peak of a biphasic fever.532 adult horses in livery and racing establishments are
The onset of neurologic signs often closely follows the well documented.507,508,510,518,545 Thus, the syndrome
decline from peak temperature. Additional purported has been reported in almost all countries with a large
risk factors in at least some outbreaks were older equine population, and because of epizootics involv-
age,503,531 cooler seasons (all but summer), introduc- ing expensive breeding and performance horses,
tion of horses to a herd,503,533 and inconsistent outbreak-­ EHV-­1 myeloencephalopathy is of major interna-
specific breed susceptibilities.503,514,533 Foals are rarely tional importance. The disease has been suspected to
affected. Mules and donkeys are infected and shed occur in a captive zebra, Equus burchelli,546 and neu-
virus but in the USA apparently do not develop rologic disease with ophthalmitis has occurred as an
EHM.534 In contrast, ­herpes myeloencephalopathy is outbreak in 21 alpacas and one llama.547 The disease
relatively common and highly fatal in donkeys and has been seen after live virus EHV-­1 vaccination with
mules in Ethiopia.535 Frequent (up to four times annu- 400 cases occurring out of 60,000 vaccinates.545,548
ally531,532) and recent531 vaccination against EHV-­1 have In an isolated case or index case of an outbreak, the
been reported as independent risk factors. Stress-­ sudden onset of ataxia or recumbency is characteristic.
associated recrudescence of latent infections and sub- Signs generally are stable after 24 h, though they may
sequent shedding without clinical signs has been fluctuate somewhat. This disease often occurs in out-
difficult to confirm experimentally but undoubtedly is breaks and can be associated with current or recent
important in the initiation of some outbreaks, espe- abortion, respiratory infection, or febrile illness in
cially those occurring after long-­distance transporta- other horses in the herd.518,533 Horses may be febrile at
tion or in closed herds. Experimentally, infected horses presentation, but most are normothermic. Fever, often
may shed virus nasally for 3 weeks or longer after biphasic in profile, is the most consistent premonitory
infection; however, viral shedding was not found sign of neurologic disease, although not all febrile
9 days after onset of clinical signs in 20 horses with horses develop myeloencephalopathy. Some affected
EHM.536 Polymorphism at nucleotide 2254 of the cata- horses and pregnant mares can have prodromal distal
lytic subunit of the viral DNA polymerase gene limb edema, and stallions show scrotal edema.
undoubtedly associates with differences in neuroviru- The severity of clinical signs can range from subtle
lence among EHV-1 variants.537 Viruses with the D752 pelvic limb ataxia and weakness to lateral recumbency
allele (G2254) were found to be 162 times more likely without limb or head movement. Non-­ neurologic
to cause EHM than were viruses with the alternative signs including nasal and ocular discharge, limb
allele N752 (A2254).538 The mechanism for enhanced edema, colic, ocular lesions, and anorexia may also be
neuropathogenicity of D752 partly relates to higher-­ found.503,518,523,532,543,549–553 Turgid bladder distention
order viremia and endothelioitropism in infected without urethral relaxation, sometimes with repeated
horses compared with that in horses infected with N752 erections in males, occurs, particularly in cases of
but is not due to greater neurotropism. In contrast, one mild to moderate severity. Bladder atony and inconti-
retrospective study found there was no difference in nence may also occur along with reflex, sensory, and
frequency of D752 and N752 among 65 horses with motor deficits (including penile paresis) involving the
326 Large animal neurology

perineal region. These signs of cauda equina syn- SID, PO) or heparin (50 IU/kg BID, SC) is advocated
drome strongly indicate sacrococcygeal gray matter for the prevention of the prothrombotic effects of
and, possibly, sensory ganglionic involvement. arteritis,509 but is unlikely to be helpful if begun after
Sensory deficits over the trunk are rarely seen. the onset of neurologic signs.555 The utility of antiviral
Evidence of brain lesions, such as seizures, blindness, drugs such as acyclovir or its prodrug valacyclovir in
stupor, diffuse face, jaw, tongue, and pharyngeal improving the outcome for affected patients has not
weakness, and signs of vestibular involvement occur been well substantiated518,556–558 However, valacyclovir
far less frequently.504,510,513,515,516,518,543,545,549,550,552,554 did significantly reduce severity of neurologic signs
A confident clinical diagnosis can be made at the when begun at the onset of fever and continued for
time of initial examination based on clinical signs, pre- 1–2 weeks.558 It was not effective when given several
vious or current febrile upper respiratory tract disease days later at the time of the second temperature rise;558
or abortions in cohabiting horses, and the presence of thus, if valacyclovir (or related drugs) are to be used as
xanthochromic, hypocellular cerebrospinal fluid. preventatives in at-­risk horses, they should be begun
Cerebrospinal fluid, especially from the LS space, may no later than the time of onset of fever.
have xanthochromia and high protein content (1–4 During outbreaks, the virus appears to spread read-
g/L) reflecting the leakage of blood pigments from ily, and the segregation and isolation of affected horses
vasculitis, but it has few cells.506,518 If EHV-­1 can be is important in containment. Horses that become
identified in nasal secretions and blood, this strongly febrile (including horses with EHM) may nasally shed
corroborates the clinical diagnosis of EHM. virus for more than 14 days536,559 and be the source of
Quantitative PCR testing of nasal swabs and antico- new transmission of EHV-­1 myeloencephalopathy up
agulated blood for EHV-­1-­specific gene sequences is to a week or more from onset of clinical signs. Thus, it
the diagnostic technique of choice.514 Note that horses is recommended that strict isolation protocols remain
infected with the C2254/H752 variant allele were NOT in place for 21 days after evidence of active EHV-­1
detected by current standard A2254G genotyping disease (i.e., febrile animals or new clinical cases)
assays,540 so it is advisable to always include conven- stops.516,560 Maintenance of horses in small groups of
tional glycoprotein B (gB) PCR testing of diagnostic similar disease and exposure status, being especially
samples. Additional samples can be submitted for careful to segregate affected from nonaffected groups,
virus isolation in tissue culture506,545,546 A significant is regarded as judicious, practical, and appropriate
rise in anti-­EHV-­1 viral neutralization, complement containment strategy.513,516,560
fixation, or ELISA antibody titers between acute and Horses that are still able to walk well usually improve
convalescent samples indicates recent virus infec- over a few days to few months and return to neurologic
tion.323 Serologic testing of associative herd animals normalcy. Even recumbent horses have recovered com-
helps define the extent of exposure to virus during the pletely and raced successfully with careful nursing.
outbreak. In addition, histologic evaluation of neural Notwithstanding this, the long-­ term outlook for
tissue from an affected horse will have classic CNS vas- severely affected and long-­term recumbent horses must
culitis and myeloencephalopathy. In situ PCR studies be regarded as bad for performance as well as life.509
on tissues can detect EHV-­1 and differentiate non-­ Vaccines currently used to prevent EHV-­1 respira-
neuropathogenic from neuropathogenic strains. tory and abortion syndromes do not claim to prevent
Probably, it is best to use corticosteroids such as EHM or to prevent EHV-­1 infection generally, and
0.05–0.1 mg/kg dexamethasone, IM, SID, for 1–3 days there is no reliable evidence that they do. A small study
in the acute phase of the disease.293,506,513,543 Good nurs- concluded that modified live virus vaccine provided
ing care with catheterization of the urinary bladder if modest albeit significantly better protection against
necessary is most important for a successful outcome. experimentally induced EHM than did a killed low-­
This may well be best done by inserting a long-­stay antigen vaccine,562 although the duration and robust-
Foley urinary catheter that is attached to the limb or ness of such protection, if any, are not yet clear.
abdomen and urine collected into a sealed collection Vaccination with inactivated “high-­antigen” vaccines,
device. Prophylactic antibiotics should be given to enhanced adjuvant vaccines, or modified live virus
combat the problems associated with cystitis. The use vaccine does have the important effect of reducing
of other drugs such as NSAIDs and DMSO in nonre- nasal shedding and thus potentially limiting the spread
cumbent patients is probably not detrimental and of infection during an outbreak. This rationale has also
may help. Empiric use of acetylsalicylic acid (6 mg/kg been used to justify booster vaccination of at-­risk
 Infectious, inflammatory, and immune diseases 327

horses during an outbreak. Because of persistent later part of last century, the animal TSEs have
evidence-­based concerns about inducing or exacer- become topical and notorious among veterinary
bating EHM by excessive and recent vaccination, how- and human health professionals and in the minds
ever, this practice remains controversial.531,532 In a of the public.
recent promising development, intranasal inoculation Scrapie has been recognized as a distinct disease
of horses with a live deletion mutant vaccine made entity since 1732.262,570,571 The nature and etiology of
from a neuropathogenic EHV-­1 strain was shown to Kuru, a human TSE transmitted by ritual cannibal-
protect horses against EHV-­1 infection by stimulating ism, was elucidated in the 1970s and sCJD has been
production of specific mucosal IgG 4/7.563 If the results known for many years. Bovine spongiform encepha-
of this small experimental study can be replicated in a lopathy (BSE) was recognized in Britain in 1985. It
field trial, the approach offers the prospect of protec- was the astute observation made by William Hadlow,
tion against infection by neuropathogenic strains of a veterinary neuropathologist, in making the connec-
EHV-­1, including use during outbreaks of EHM. tion between Kuru and scrapie that was the first clue
Immunostimulants are sometimes administered as to the etiology of the TSEs.574 Carleton Gajdusek
to horses at risk for EHM based on the theory that received the Nobel Prize in 1976 for his work corre-
immune system activation will prevent viral reactiva- lating Kuru and CJD with animal TSEs, and Stanley
tion or replication,514 but supportive evidence is lack- Prusiner was awarded the Nobel prize in 1997 for his
ing. A history of nutritional supplementation with a discovery of prions in 1982.570,571
product containing zinc protected exposed horses These diseases are generally of low incidence, have
from developing the disease according to a retrospec- prolonged incubation periods, and are uniformly fatal.
tive study of horses involved in the 2011 Ogden, Prions can be detected in several peripheral tissues, par-
Utah, outbreak.531 ticularly those of the lymphoreticular system, and path-
The American Association of Equine Practitioners ological lesions are confined to the nervous system.
(http://www.aaep.org/) and the British Horserace Typical lesions consist of vacuolation and loss of neu-
Betting Levy Board (http://codes.hblb.org.uk/) pub- rons, astrocytosis, and microglial activation. Within
lish biosecurity guidelines for best management prac- infected cells, there is accumulation of misfolded, par-
tices to use in all settings to prevent EHV-­1 infection. tially protease-­resistant prion protein (PrP). The altered
At a minimum, it is prudent to isolate new arrivals to PrP is referred to as scrapie prion protein (PrPSc), named
a property for at least 3 weeks, to not crowd animals for the prototypic TSE agent, and it is formed from host-­
undergoing weaning, vaccinating, deworming and encoded, or constitutive prion protein (PrPC), a normal
castration, as well as mares around foaling time and membrane protein that is highly expressed in nervous
early lactation, and to be cognizant of the risk of using tissues. Demyelination is not a feature of TSEs, and
corticosteroids, especially in late term mares.564 there is no acute inflammatory response evident in the
CNS. Amyloid plaques, being accumulations of PrPSc,
may be present in the brain. Scrapie-­associated fibrils
Transmissible spongiform encephalopathies
(SAF) are structures obtained from detergent extracts of
Prions are proteinaceous infectious particles that infected material and are viewed by electron micros-
cause chronic degenerative, neurological, invaria- copy. SAF are unique to the TSEs and consist at least in
bly fatal diseases of animals and humans referred part of PrPSc. They are resilient structures, and their
to as transmissible spongiform encephalopathies presence can be used to diagnose infection in autolyzed
(TSEs).565–567 The animal TSEs are scrapie, bovine tissue. The TSE agents elicit no detectable acquired
spongiform encephalopathy (BSE), feline spongi- immune response; therefore, there are no serological
form encephalopathy, exotic ungulate encephalop- tests for prion infection. Currently, peripheral lymphoid
athy, transmissible mink encephalopathy, and tissues in membrana nictitans, tonsil, and rectal biopsy
chronic wasting disease of wild and farmed cer- samples are being used to detect scrapie prions in
vids.568 Some members of this family of diseases infected sheep, as part of eradication programs.575 Newly
that affect humans are Kuru, sporadic Creutzfeldt– developed, highly sensitive, functional techniques such
Jakob disease (sCJD), Gerstmann–Sträussler– as the real-­time quaking-­induced conversion assay576
Scheinker syndrome, variably protease-­ sensitive are being used to detect prions in human biological flu-
prionopathy, fatal familial insomnia, and variant ids; however, it is not clear how useful these will be in
CJD (vCJD).33,569–573 With BSE and vCJD in the large animal neurology.
328 Large animal neurology

Classical Scrapie occurs worldwide, although polymorphisms analogous to the Hyper and Drowsy
Australia and New Zealand currently are scrapie-­free strains identified in hamsters.581
and it occurs only rarely in North and South Histopathologically, a spongiform encephalomye-
America.572 The disease is transmitted both from ewe lopathy, with neuronal vacuolation and necrosis,
to lamb and among unrelated sheep. While transpla- and astrogliosis, involves neuronal groups in the
cental infection of lambs is possible, most transmis- brainstem, cerebellum, and spinal cord. Necrosis of
sion probably occurs around the time of parturition cerebellar pyramidal (Purkinje) cells is prominent.
by the oral route. Although the genotype of the host Scrapie can be transmitted experimentally to mice
PRNP gene (and thus the amino acid sequence of and hamsters and can be passaged in these species.
host PrPC protein) plays a major role in susceptibility Even so, the incubation period in mice can be over
to scrapie, it is definitely not simply a genetic dis- 6 months, although one hamster strain has an incu-
ease.577 Indeed, polymorphism among scrapie prions bation period of about 75 days. The use of rodent
likely also plays a role in disease pathogenesis. At bioassays has shown the existence of biological
least 4 different prion strains cause classical scrapie strains of the agent.582 Much has been learned recently
in small ruminants in Europe.578 This is contrast to about the biochemical and genetic properties of the
classical BSE which is caused by a single strain. The agent, but its exact composition and structure remain
various names given to scrapie are somewhat whim- controversial. Of significance to all the TSE agents
sical but apt: Gnubberkrankheit and Traberkrankheit are the partially answered questions: how can a pro-
(Germany), la tremblante and la maladie folle tein agent replicate itself, and how can a protein-­only
(France), rubbers and goggles (England), and cuddy agent account for biological strain variation?
trot, yeuky pine and scrapie (Scotland). Bovine spongiform encephalopathy (BSE; “mad cow
A second TSE of sheep and goats known as atypi- disease”) is characterized by an insidious onset of
cal scrapie was first described in Norway in 1998 and clinical signs in mature (>4 years old) cattle including
has since been found throughout Europe; one case apprehensive behavior, aggressiveness, hyperesthe-
was identified in New Zealand. These cases were spo- sia, and incoordination. The clinical disease is pro-
radic in occurrence and defined as atypical based on gressive and lethal within 1–6 months.583,584 Usually,
clinical presentation, PrPSc structure and tissue dis- there is reduced milk yield and weight loss.
tribution, PRNP genotype, and epidemiology.575 Bradycardia and reduced ruminal activity have also
Clinical ovine scrapie occurs insidiously from 2 been noted. Pruritus is not a prominent feature in
years old onward with a peak at 3–4 years old and is most cases of BSE. The condition is believed to be a
characterized by weight loss, cerebellar ataxia, rest- result of “industrial cannibalism” wherein cattle were
lessness, stargazing, head pressing, bruxism, and fed supplements containing meat and bone meal of
pruritus.579 Pruritus may be evident only as wool on ruminant origin and, in later years, BSE-­infected
fences and tufts of depilated wool in the fleece or can bovine material. The condition was first recognized
be seen as profound wool loss and skin lacerations in the UK in 1985, probably because of cattle infec-
from self-­trauma. A positive “nibble reflex” can be tions beginning early in the 1980s. Cases have
elicited in most cases whereby sheep respond to light occurred in 25 other countries including Ireland,
scratching of the dorsum of the trunk by rapid jaw Switzerland, France, Portugal, Japan, Canada, and
champing with characteristic, lapping tongue, and lip the United States. The incidence is very much higher
movements. A fine head tremor is often present. The in dairy cattle than in beef cattle. There is no evi-
appetite generally remains good until late stages dence of horizontal direct or indirect spread among
when marked weight loss occurs. The clinical course cattle, and virtually no evidence of vertical transmis-
is usually a few weeks to months but can be much sion. BSE has been transmitted to mice in which it
shorter. Selection of sheep for resistance to scrapie closely resembles, but is distinguishable from,
based on PRNP genotyping is an important compo- scrapie.
nent of control and eradication programs. In the UK, The sudden appearance of BSE in the UK may
there is a commercially available genotyping test. have been linked to changes in the early 1980s in the
Scrapie was made a notifiable disease within the EU rendering processes for ruminant offal, particularly
in 1994. Scrapie also occurs in goats where it is asso- cessation of the use of organic solvents, such that the
ciated with two main clinical syndromes, “scratch- changed procedures may have been insufficient to
ing” and “nervous,”580 which may reflect PRNP destroy prion infectivity.585 Rendering practices that
 Infectious, inflammatory, and immune diseases 329

do not inactivate BSE prions have been banned regurgitation with secondary inhalation pneumonia
within the EU, and new guidelines for the inactiva- that is somewhat different to scrapie and BSE in
tion of prions during rendering were introduced. domesticated livestock.
BSE was made a notifiable disease in 1988 with feed-
ing of sheep and cattle products to cattle being
banned, and specified bovine offal that might con- Other agents
tain BSE prions could not be sold for human con- Equine protozoal myeloencephalitis
sumption. The ban on feeding animal protein to
other animals was further broadened and strength- During the 1960s, a novel and interesting neurologic
ened in 1996. Because of the long preclinical incuba- disease was identified by astute veterinary patholo-
tion period (~5 years), annual incidence of BSE gists in Pennsylvania and Kentucky in the eastern
continued to rise until it peaked in 1992. To date, USA and identified as focal myelitis-­encephalitis.592–594
more than 185,000 cases have occurred in the UK, Subsequently, it was referred to as Toxoplasma-­like
but BSE is now rare with 0–5 cases reported encephalomyelitis and reported from several eastern
annually. states.595–598 By 1976, the name used for this fascinat-
In 1996, evidence was reported that BSE might be ing disease with diverse clinical signs was equine pro-
associated with the appearance of a new variant form tozoal myeloencephalitis (EPM), so named because
of CJD in people, vCJD, and this was confirmed in of the presence of the then-­unidentified protozoan
1997.586,587 parasite in the lesions in nervous tissue and the
Atypical cases of BSE have occurred in cattle, some apparent higher frequency of signs referable to spinal
with unusually prominent amyloid plaques and a dif- cord disease than to brain involvement. Despite sub-
ferent molecular signature than classical BSE.588 stantial efforts over the years since, attested to by sev-
These cases have been sporadic, solitary and in geri- eral contemporaneous extensive reviews,599–603 the
atric cows (>10 years), and probably arose spontane- precise disease biology is still not fully understood.
ously in affected individuals rather than as a result of It is known that EPM involves invasion of the
prion infection. equine CNS by protozoa of the phylum Apicomplexa,
During the BSE epizootic in the UK, feed contami- by far the most important of these being Sarcocystis
nated with BSE prions infected captive ruminants neurona.604,605 Some evidence from studies of popula-
such as nyala and gemsbok and domestic and exotic tion genetics of S. neurona isolates shows moderate
cat species causing the TSEs exotic ungulate enceph- genetic diversity within which 13 genotypic strains
alopathy and feline spongiform encephalopathy, have been identified, 2 of which account for most
respectively.584 Sheep and goats can readily be infected infections.606–609 Although Type XIII has been associ-
when given the BSE agent either orally or intracere- ated with severe disease in marine mammals, no such
brally and usually go on to develop a scrapie-­like association between genotype and disease severity
encephalopathy. Surprisingly, there have been no has been made for EPM. Another apicomplexan,
naturally acquired cases reported in sheep and only Neospora hughesi, accounts for a small proportion of
one in a goat.584 clinical cases of EPM.599,610–614 The hosts of N. hughesi
Chronic wasting disease of wild and farmed cervids are unknown, but this organism is distinct from the
(CWD) in North America, Korea, and Scandinavia589 common apicomplexan pathogen, Neospora cani-
has similarities with, and distinct differences to, both num. Interestingly, a single case of protozoal mye-
scrapie and BSE.590 The CWD agent is highly infec- loencephalitis caused by N. caninum has been
tious and has spread rapidly among wild cervids over described in a captive zebra.615
an extensive geographic range (at least 24 states in the Being members of the family Sarcocystidae, both S.
USA and two provinces in Canada567). It has been neurona and N. hughesi have an obligate two-­host life
transmitted intracerebrally, but not orally, to cattle, cycle with a definitive host in which the sexual phase
sheep, and goats.591 The naturally occurring clinical occurs and an intermediate host in which asexual
syndrome in cervid species is likened to end-­stage replication takes place (Figure 32.12). For S. neurona,
scrapie and BSE as early signs usually are missed. the definitive host eats sarcocyst-­infected tissue from
Weight loss, episodic somnolence, teeth grinding, an intermediate host and after sexual reproduction in
sialosis, ataxia, and head tremor all are reported. the small intestine of the definitive host oocysts con-
Perhaps of note is the esophageal dilation and taining two sporocysts form and are passed in the
330 Large animal neurology

Sarcocyst

DEFINITIVE
HOST

Oocyst

INTERMEDIATE
HOSTS

Figure 32.12 Tentative outline for a life cycle of Sarcocystis neurona showing the relationship of the definitive host, the American omnivorous opossum,
putative intermediate hosts, and the horse, acting, it seems, as an apparently dead-­end intermediate host, in which clinical cases of EPM occur.

feces within about 3 weeks from ingestion of the species have been experimentally infected with the
cysts. Following ingestion and excystment of sporo- organism. The horse is generally regarded as an aber-
cysts in an intermediate host, released sporozoites rant intermediate host in which S. neurona only
penetrate the small intestine and pass via the blood develops to precystic stages (i.e., schizonts, merozo-
vascular or lymphatic systems to gain access to vari- ites), but mature sarcocysts have been found in the
ous target tissues in which they undergo several tongue and other striated muscles of a young filly
cycles of asexual reproduction before terminally dif- with neurologic signs of EPM.617 The horse may thus
ferentiating into sarcocysts in striated muscle. With be a rare but true intermediate host.
S. neurona, the definitive hosts are opossum species, EPM is a common cause of many syndromes of
in North America Didelphis virginiana and in central CNS dysfunction in horses that live or have lived in
and South America D. albiventris and possibly D. the Americas.599,600,602,610,618–620 There are a few reports
marsupialis, D. aurita, D. imperfecta and D. perni- of EPM in ponies or mules, suggesting that these
gra.616 There are several natural intermediate hosts equids may be less susceptible to EPM than are
for S. neurona in North America, the more important horses.621–623 With the insidious, and sometimes pro-
probably being the raccoon, striped skunk, nine-­ longed, apparently subclinical state of S. neurona
banded armadillo, and the domestic cat. The sea otter infection in many American horses, and increasing,
and other Pacific marine mammals are also naturally widespread international animal transportation, it is
infected, often fatally. Animals of several other not surprising that serologic evidence of S. neurona
 Infectious, inflammatory, and immune diseases 331

exposure and cases of EPM have been reported to related to the CNS lesions. No consistent involvement
occur in horses imported into other coun- of other body systems has been reported.
tries.602,624–626 In several instances, the onset of EPM Almost any neurologic syndrome of horses can be
has occurred years after the horses departed North produced by EPM. Exquisitely selective focal lesions
America. may involve a single nucleus or tract in the CNS.
The reported prevalence of S. neurona infection as Thus, unilateral facial paralysis, hemiatrophy of the
evidenced by S. neurona antibodies in horses in vari- tongue, unilateral hypermetria, radial paralysis, or
ous locations throughout the United States varies unilateral quadriceps or gluteal muscle atrophy may
from 0 to 89.2%.627,628 Despite the high rate of infec- occur with no other signs of CNS involvement. More
tion by S. neurona, there is probably only about a 1% frequently, syndromes of brainstem or spinal cord
lifetime risk of a horse developing EPM in these disease with asymmetric ataxia and para-­or tetrapa-
areas: estimated from the mean 0.14% 1-­year inci- resis occur. Variable localizing findings of cranial
dence reported in the United States Department of nerve dysfunction and hyporeflexia, hypotonia, mus-
Agriculture NAHMS 1998 survey.629 In a recent sur- cle atrophy, hypalgesia, and selective sweating can be
vey of serum samples from EPM suspects throughout detected. On the other hand, many horses with EPM
the USA, 34% were positive for N. hughesi antibod- are first seen as wobblers with degrees of relatively
ies.630 From uncontrolled studies, it has appeared that symmetric weakness, ataxia, and hypometria in the
EPM was most frequent in young mature thoracic and/or the pelvic limbs indicating spinal
Thoroughbred, Quarter Horse, and Standardbred cord involvement. An unusual syndrome of bilateral
horses at racing, training, and breeding establish- thoracic limb extensor weakness with sparing of pel-
ments. In horses not at racetracks, the frequency vic limb function results from selective gray matter
increased from farm horses to pleasure horses, to off-­ lesions affecting the ventral horn of the brachial intu-
track racing horses, to show and competition horses. mescence (spinal cord segments C6 to T2). This causes
Age groups of 1–5 years and over 13 years are more a characteristic “praying” posture in affected animals
frequently affected and exposure to opossums, heavy (Figure 23.3) and can be seen horses with EPM or
exercise, breeding, transportation, warmer seasons, WNV (above). An archetypal (but improbable) clini-
and high stocking densities are also permissive risk cal case could be envisaged as follows: unilateral left-­
factors. sided gluteal muscle atrophy progresses relentlessly
Undoubtedly, EPM has the widest spectrum of without signs of marked lameness, for several weeks,
possible clinical neurologic signs of any disease in then prominent, progressive, hemiparesis and ataxia
horses. Neurologic syndromes reflect involvement of of the right limbs develops with associated Horner
almost any part of the equine CNS, the underlying syndrome (including ipsilateral sweating over the
lesions represented typically by (multi)focal, necrotic, head and neck) and loss of the entire cutaneous
nonsuppurative meningomyeloencephalitis. A con- trunci reflex, all on the right side. Additional charac-
sequence of the great variety of possible presenta- teristic signs in this unfortunate imaginary horse
tions is that EPM tends to be overdiagnosed.631 could reasonably include unilateral atrophy of chew-
Historically, a mild lameness occurs, which fre- ing muscles and, ultimately, somnolence, seizures,
quently defies localization, or there may be an acute and recumbency. Such a case would indicate local-
onset of ataxia, head tilt, weakness of one or more ized, independent lesions at L6 gray matter (gluteal
limbs or, on occasions, sudden recumbency atrophy), cervicothoracic gray and white matter
(Figure 32.13). Lesions, as evidenced by the associ- (Horner syndrome, cutaneous trunci, ipsilateral limb
ated clinical signs, may be fulminant in hours to days weakness and ataxia, and recumbency), pons includ-
or may remain quiescent for periods of months to ing trigeminal motor nucleus (chewing muscles), and
years with or without therapy. The disease is not forebrain (seizures). There is no other single disease
transmitted from horse to horse, although clusters of that could account for all these signs.
cases are seen on single establishments over periods Other diseases to be considered with cases of EPM
of months to several years. vary considerably, but for the most part depend on
In the naturally occurring disease, there is no con- the anatomic location of the lesion(s). Diffuse cerebral
sistent sign of systemic illness. Physical examination involvement, although not frequently seen, can mimic
may reveal muscle atrophy, sweating, decubitus, con- the equine viral encephalomyelitides particularly
stipation, urine scalding, or other problems indirectly EEE, VEE, and WEE, equine leukoencephalomalacia
332 Large animal neurology

(B)

(A) (C)

Figure 32.13 Many cases of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona have been enlightening in progressing our
understanding of equine clinical neurology. This is because the lesions produced can be combinations of being focal to diffuse, fulminant to chronic,
singular or multiple, and microscopic to massive. Many cases have had thorough postmortem examinations performed giving insight to clinico-­anatomic
correlates and to neural repair, adaptation, and plasticity in large animal clinical neurology. The fulminant, hemorrhagic poliomyelitis in the lumbar ventral
gray columns of a thoroughbred racehorse mare caused by EPM is shown in A. The mare fell during race training and never stood again, requiring eutha-
nasia within 48 h. Another racehorse had signs of symmetric ataxia and tetraparesis resulting in adoption of a praying stance (Figure 26.2 A&D) that was
caused by myelitis at C8 (B). Additionally, the horse developed prominent hypermetric ataxia of only the right pelvic limb that almost certainly resulted
from the separate, acute lesion in the right lateral funiculus centered at T2 (C).

and hepatoencephalopathy. With acute and localized tetanus, Sorghum spp. intoxication, lathyrism,
brainstem involvement, particularly involving stringhalt, fibrotic myopathy, neuritis of the cauda
vestibular dysfunction, WNV, head trauma, equina, and peripheral nerve trauma. Notwithstanding
temporohyoid osteoarthropathy, Lyme the obvious potential for misdiagnosis of EPM, clinical
neuroborreliosis, and verminous migrations need to diagnoses of EPM can be surprisingly accurate. Based
be considered. Cervical vertebral trauma, cervical on 210 cases of neurologic disorders in the horse, both
vertebral malformation/malarticulation (wobbler), a presumptive clinical diagnosis and a definitive (gold-­
vertebral osteomyelitis, various verminous myelitides, standard) pathologic diagnosis were made, and the
equine herpesvirus-­ 1 myeloencephalopathy, and accuracy of clinical diagnosis of EPM was found to be
equine degenerative myeloencephalopathy/ between 81 and 95% depending on the accuracy
neuraxonal dystrophy should be considered in the parameter used.631
diagnosis of cases having just spinal cord involvement. On gross examination of typically large lesions due
Interestingly, with selective CNS involvement, the to EPM, one or more focal areas of pink, brown, or
extraordinarily diverse possible clinical manifestations yellow discoloration can be seen (Figure 32.13), as
of EPM can mimic several other neurologic syndromes well as softening with swelling of the tissue in the
and myopathies. These include rabies, botulism, brainstem and spinal cord. Histologically, necrosis
 Infectious, inflammatory, and immune diseases 333

and inflammation occur in these areas, with mac- the diagnostic assays are based on the yet-­to-­be vali-
rophages, lymphocytes, eosinophils, and sometimes dated principle that horses with EPM have distinctly
multinucleate cells and plasma cells also present. higher serum antibody concentrations than do
With severe necrosis, focal hemorrhage and neutro- exposed subclinically infected horses.639 Because
phil infiltration occur. Merozoites (1–4 μm long), seroprevalence of N. hughesi is relatively low com-
individually or in groups (schizonts), without a well-­ pared to that for S. neurona, a positive serum test has
defined cyst wall, can be seen within or near these a proportionally higher positive predictive value for
lesions.595,597,632 The extent and the severity of the EPM.599 On the other hand, a negative serum test for
meningoencephalomyelitis accompanying EPM vary either organism is strong evidence that the horse is
considerably. Congenital S. neurona infection is rare, not S. neurona-­ or N. hughesi-­infected and thus does
but it is well established that N. hughesi can be trans- not have EPM. The rationale for tests of the second
mitted transplacentally.633–635 type, each of which requires a clean CSF sample, is
Needle electromyography can help localize final that the identification of CNS-­origin antibody is the
motor neuron (gray matter) involvement. With mul- only way at present to discriminate EPM cases from
tifocal sites of denervation revealed by EMG, the merely exposed horses. The most popular tests of
likelihood of EPM as opposed to many, usually uni- each type—­namely, IFAT and snSAG2,4/3 ratios—­
focal or diffuse disorders, becomes more probable. have reported good (i.e., >80%) sensitivity and speci-
Results of routine CSF analysis are usually normal, ficity for diagnosis of EPM among horses with solid
but occasionally there is some degree of xanthochro- postmortem diagnoses.640,641 One drawback of the
mia, with large and small mononuclear cell pleocyto- IFAT is that it is unable to differentiate between anti-
sis and slight or moderate increases in protein bodies against S. neurona and S. fayeri (a relatively
content. Abnormal CSF analysis is most likely when nonpathogenic species).642 One study used samples
the sample is taken from a site close to a large, acute from necropsy-­confirmed EPM-­positive and nega-
lesion and usually normal when there are small, qui- tive cases to specifically compare results of IFAT and
escent, chronic lesions present. Only rarely are eosin- snSAG2,4/3 tests. Accuracy values for serum IFAT,
ophils636 or neutrophils present. serum snSAG2,4/3, IFAT ratio, and snSAG2,4/3 ratio
Antemortem diagnosis of EPM remains challeng- tests were 68, 56, 88, and 97%, respectively.638
ing. Criteria for diagnosis include finding clinical Comparable tests for N. hughesi are also available
signs consistent with EPM, ruling out other differen- commercially (N. hughesi IFAT and nhSAG1 ELISA)
tial diagnoses, positive response to treatment with but have not been fully validated for EPM diagnosis.
anti-­EPM drugs, finding S. neurona–specific antibod- It is clear, on the basis of both flawed concepts and
ies through immunodiagnostic testing, and detecting unsupportive clinical data, that neither CSF Western
S. neurona-­specific DNA in CSF by PCR. As with blot nor serum SAG-­1 ELISA is a reliable diagnostic
other severely necrotic inflammatory diseases, MR test for EPM.643–645 In contrast to the situation with
imaging can be used to assist in defining the location Western blots, snSAG (and presumably IFAT) ratio
of EPM lesions when prominent, but of course such test results are relatively robust in the presence of a
findings are not diagnostic for the cause (see small amount of contaminating blood; however, false
Figure 3.17). Proof of diagnosis postmortem is the positives do occur in cases of moderate or severe
demonstration of protozoa in CNS lesions, often done blood-­brain barrier injury. For samples from horses
with immunohistochemical staining or polymerase with BBB injury (as detected by high CSF albumin
chain reaction. Even when the organism is not seen, concentrations or high albumin quotient values646),
the diagnosis is frequently made presumptively if additional total IgG testing is performed on the
characteristic inflammatory changes are found.631,637,638 serum/CSF sample and a C-­value is calculated.647
Two types of immunodiagnostic tests are available CNS antibody production is indicated by C-­values
for EPM: those that rely on threshold values of serum significantly greater than 1.
S. neurona antibody (indirect fluorescent antibody Although an early report of conventional PCR
test, ELISAs for antibody against various S. neurona testing of CSF for S. neurona suggested that this tech-
surface antigens) and those that purport to detect nique lacked sensitivity for EPM diagnosis,648 results
specific antibody made within the CNS (Western of a recent study indicate that PCR may usefully com-
blot, serum-­to-­CSF antibody ratios, and C-­values).599 plement immunodiagnostic testing.649 In a survey of
Blood samples for serum tests are easily obtained, but 210 CSF samples from horses with neurologic
334 Large animal neurology

disease, 30 had immunodiagnostic evidence for EPM commercial products have been launched.603,633 NTZ
but were negative by quantitative PCR for S. neurona, was withdrawn in 2009. Multicenter studies of SDZ/
25 were positive for S. neurona by quantitative PCR PYR, PNZ, NTZ, and DCZ reported improvement
only, and 13 were both PCR-­positive and had immu- rates of 57.1–61.5% (Tables 32.5 and 32.6).603
nologic evidence of S. neurona infection. The remain- Label directions for dose and duration of FDA-­
ing CSF samples were negative by both techniques. approved drugs should be followed. A loading dose
Horses with a history of antiprotozoal treatment were of 15 mg/kg PNZ (three times the normal dose)
less likely to test positive by PCR (Table 32.4). achieves steady-­state concentrations of PNZ several
days earlier than is the case with conventional dos-
If similar results649 are corroborated, PCR testing of ing.650 Many dosage regimens with permutations
CSF will become a routine part of EPM diagnostic pro- and combinations of these products and the use of
tocols, particularly when applied to acute cases with- pharmacologically similar products occur in clini-
out a history of receiving antiprotozoal drugs. cal practice, although efficacies have not been inves-
tigated. There is experimental support for the
Since 2000, the folate inhibitor combination sul- enhanced antiprotozoal effect of combinations of
fadiazine/pyrimethamine (SDZ/PYR), the triazine PYR with either DCZ or PNZ in the treatment of
coccidiostats ponazuril (PNZ) and diclazuril (DCZ), other coccidian infections,652 so PNZ or DCZ are
and the nitrothiazole nitazoxanide (NTZ) have all sometimes combined with SDZ/PYR. Such treat-
been licensed by the United States Food and Drug ments constitute unapproved and/or extra-­ label
Administration (FDA) for the treatment of EPM, and use, albeit of FDA-­ approved products.

Table 32.4 Comparison of various tests used to assist in the diagnosis of EPM caused by S. neurona

Test format Antigen used Comment Interpretation

Western blot Merozoite lysate None 14.5 kDa

Western blot Merozoite lysate Quantification of CSF IgG based on 17 kDa
serum levels
Western blot Merozoite lysate Preblocking of blot with anti-­s. Cruzi IgG 16 and 30 kDa
IFA Whole merozoites Indirect fluorescent antibody Endpoint titer = last dilution showing whole parasite
fluorescence; titer gives “probability” of EPM
ELISA Recombinant surface antigen SAG1 ELISA Correlates a given titer with likelihood of clinical
disease
IgM -­ELISA Merozoite lysate IgM capture ELISA Likely relates to acute phase (re)infection

Table 32.5 TREATEPM-­1. A selection of drugs and their combinations used for treatment of EPM

Drug Formulation Class Routes Active form Mode of action

TMP TMP-­S tablets, 1.6% for IV (with SMX) Diaminopyrimidine IV, PO TMP DHFR inhibition, ↓folate synthesis
PYR 25 mg tablet, 1.25% suspension (with SDZ) Diaminopyrimidine PO PYR DHFR inhibition, ↓folate synthesis
SDZ TMP-­S, 25% suspension (with PYR) Sulfonamide PO SDZ Competes with PABA, ↓folate synthesis
SMX TMP-­S, 8% for IV (with TMP) Sulfonamide IV, PO SMX Competes with PABA, ↓folate synthesis
TOL 5% suspension Triazinetrione PO TOL, TOL-­so, PNZ# Inhibits respiratory chains in apicoplast,
mitochondrion
PNZ 15% paste Triazinetrione PO PNZ As for TOL
DCZ 0.5% mash, 1.36% pellet, Na+ salt, IV Triazinedione PO, IV DCZ Unknown, possibly as for TOL
formulation
NTZ 32% paste 5-­Nitrothiazole PO TIZ, TIZ-­glu Interference with PFOR; other actions

TMP: trimethoprim; S: sulfonamide; PYR: pyrimethamine; SDZ: sulfadiazine; SMX: sulfamethoxazole; TOL: toltrazuril; so: sulfoxide; PNZ: ponazuril;
DCZ: diclazuril; NTZ: nitazoxanide; TIZ: tizoxanide; glu: glucouronide; DHFR: dihydrofolate reductase; PABA: para-­amino benzoic acid;
PFOR: pyruvate: ferredoxin oxido-­reductase.
#
Note: TOL, TOL-­so and PNZ are the same compounds
Source: Modified from MacKay.603
 Infectious, inflammatory, and immune diseases 335

Table 32.6 TREATEPM-­2: Drugs and combinations approved for treatment of EPM in North America

Dose Duration
Drug Trade name Manufacturer Form mg/kg days Considerations

PNZ Marquis Bayer 15% paste 5 28 Loading dosea, oilb

NTZ Navigator Idexx 32% paste 50 28 Withdrawn 2009
SDZ/PYR ReBalance Phoenix 25%/1% suspension 20/1 90–270 Empty stomachc
DCZ Protazil Schering-­Plough 1.56% pellet 1 28

a
A 3× dose (i.e., 15 mg/kg) on day 1 of treatment.650
b
Addition of ~60 ml corn oil increases absorption.651
c
Should not be administered within 1 h of hay or concentrate feeding.
Source: Modified from MacKay.603

Coadministration with 2 oz corn oil significantly reproductive and neonatal disorders, oral ulcers, and
improves the bioavailability of PNZ.651 bone marrow suppression including leukopenia,
Another drug used commonly as an anticoccidial neutropenia, anemia, and thrombocytopenia in
in calves, decoquinate, was evaluated in horses with decreasing frequency.658–660 Horses treated with SDZ/
presumptive EPM, at dosage of 0.5 mg/kg daily for PYR should be kept on good-­quality green forage
10 days, in combination with the immunomodulator (e.g., alfalfa hay or pasture), which is likely to be rich
levamisole, 1 mg/kg daily.653 Success rates of 93.6 and in folate. There is no advantage to supplementation
89.3% were reported on the basis of improved neuro- with folic acid during treatment, and some evidence
logic gait score at the end of treatment and reversion from other species indicates that this practice could
of serum snSAG1,5,6 titers, respectively. Decoquinate increase the possibility of toxicity.659 Most cases of
was also shown to have potent inhibitory and cidal bone marrow suppression resolve if treatment is sus-
activity in vitro against two different isolates of S. pended for 1–2 weeks. Folic acid (100 mg daily) is
neurona.654,655 If this drug combination continues to appropriate for the treatment of folate deficiency
perform well in wider use, it will obviously become once PYR is discontinued. If signs are severe, treat-
an important treatment option. Drugs belonging to a ment with folinic acid (100 mg IV or PO daily for
novel and promising class of antiprotozoals, known 5 days) is indicated.
as bumped kinase inhibitors,656 which safely target In mild acute cases of EPM (grade 1), additional
apicomplexan calcium-­ dependent protein kinase, therapy is unnecessary. In horses with moderate or
have potent cidal activity against S. neurona in cul- severe signs, nonsteroidal anti-­ inflammatory and
ture and protect gamma interferon knockout mice antioxidant treatment is usually provided for the first
from otherwise lethal doses of S. neurona.657 1 or 2 weeks. If the horse is grade 3 or worse, a corti-
Horses may relapse soon after the initial course of costeroid may be added. Vitamin E is often given
treatment is discontinued or up to several years after throughout the period of antiprotozoal treatment for
improvement or apparent resolution of signs. additional antioxidant effect, with no proof of added
Although there are no data available to guide treat- benefit. Oral administration of vitamin E has been
ment for relapses, it is common practice to change or shown to result in increased concentrations of alpha-­
add antiprotozoal drugs. To prevent future relapses, tocopherol in serum and CSF.661 As a relatively crude
antiprotozoal therapy can be provided prophylacti- way to address putative immunodeficiency and with
cally. Protocols include FDA-­approved formulations the aim of promoting cellular immunity, immune
of SDZ/PYR, 2 days per week at the standard dose, or modulators are sometimes given to horses with EPM.
diclazuril, daily at 0.5 mg/kg. A similar rationale can Based on drug efficacy studies and clinical experi-
be used to treat horses around stressful events that ence, it is reasonable to expect that about 60% of
may predispose to relapses. moderately or severely affected horses will improve
Of the available drugs, only PYR has significant at least one grade of ataxia and limb weakness after
adverse side effects. Toxicity reflects both direct treatment. Only 10–20% of such horses will com-
effects of the drug and inhibition of mammalian pletely recover, and 10–20% of successfully treated
dihydrofolate reductase by PYR, inducing folate defi- horses will suffer at least one relapse. The outlook for
ciency. Signs include convulsions and recumbency, mildly affected horses (grade 1) is considerably
336 Large animal neurology

better, particularly if treatment is begun promptly. as well as other domestic and wild animal species,668
Although there are no published data for the latter and is transmitted by blood-­sucking vectors, espe-
more common class of treated horse, at least 80% of cially horse and stable flies, hematophagous bats
such cases can be expected to improve and at least (Desmodus rotundus) and probably ticks and
50% should recover completely, with low possibility leaches.667
of recurrence. In resurgent outbreaks of Surra in northern Brazil
An inactivated vaccine was marketed under condi- the main clinical signs in affected horses were weight
tional approval by the United States Department of loss, anemia, icterus, ventral edema, pelvic muscle
Agriculture. The conditional license lapsed in March atrophy, weakness, ataxia and frequent falls.667 A case
2008, and the vaccine is no longer available. When demonstrating brainstem disease with vestibular
tested in horses dosed with S. neurona and stressed signs was reported from Israel.669
by transportation, vaccination did not prevent the The basis of the neurologic syndrome in Surra is
development of clinical neurologic signs.50,662. diffuse, mild to severe, lymphoplasmacytic encepha-
Prevention of S. neurona infection may be possible litis affecting both white and grey matter. Swollen
by daily administration of a drug such as DCZ or plasma cells containing cytoplasmic hyaline inclu-
PNZ.663,664 The disadvantage of this approach is that sion bodies (Russell bodies) displacing the nucleus
normal immune responses to the organism may be toward the periphery (Mott cells) can be seen along
prevented. Alternatively, doses of drug can be given with reactive astrogliosis reflecting the sub-­acute to
at intervals to permit division of the protozoal organ- chronic course.667,669,670
ism in the aberrant intermediate host by schizogony, Dourine is a venereal disease of equids throughout
and thus, potentially, immune responses, but prior to South America, Africa and Asia associated with
invasion of nervous tissues. Ponazuril given at 20 mg/ chronic infection by Trypanosoma equiperdum that
kg every 7 days, but not when given every 14 days, results in chronic weight loss, genital swellings,
showed reduction in S. neurona-­specific CSF anti- plaque-­ like, depigmenting skin lesions, and in
body levels in horses challenged with S. neurona spo- peripheral and central neural lesions.671 Moderately
rocysts, suggesting that such a program may be severe lymphocytic, histiocytic polyneuritis occurs,
useful665 particularly involving the sacrocaudal outflow but
Additional precautions against excessive exposure not sparing cranial nerves. Very mild myelitis is
of horses to infective sporocysts are reasonable to described in the caudal regions of the spinal cord, but
instigate. Thus, opossums can be excluded from the majority of these lesions appear to be secondary
premises and all feed, fruit, and organic garbage degeneration of somata and fibers reflecting the
should be kept well contained. Attempts at control- neuritis.672
ling natural intermediate host populations to indi- Chagas disease, or American trypanosomiasis, is
rectly reduce the sporocyst contamination in an area an important tropical human and canine disease in
are of unknown usefulness, but if there is a large non-­Caribbean Latin American countries caused by
intermediate host population in an area, then it may T. cruzi that is transmitted by the kissing bug arthro-
be prudent to keep their numbers under control. pod vector.673 It has been diagnosed in a 10-­year-­old
Products and methods useful for cleaning of areas Texan Quarter Horse following a six month-­history
potentially contaminated with sporocysts have been progressing to marked asymmetric ataxia and para-
described.663 paresis associated with diffuse, patchy lymphocytic,
histiocytic meningomyelitis associated with T. cruzi
protozoan amastigotes.674 This clinicopathologic syn-
Trypanosomiasis
drome mimicked EPM.
At least three species of trypanosomes affecting large
domestic animals are associated with neurologic
Additional Protozoal
syndromes.666
meningoencephalomyelitides in ruminants
Trypanosoma evansi, present in nearly all conti-
nents, is the etiological agent of an important trypa- Sarcocystis spp., Toxoplasma gondii, and Neospora
nosomiasis popularly known in Brazil as Surra, spp. (and possibly related sporozoan parasites) all
Derrengadera and Mal das cadeiras.667 Surra is mainly can produce naturally occurring and experimental
a wasting disease affecting equids, camels and cattle meningoencephalomyelitis in a wide variety of
 Infectious, inflammatory, and immune diseases 337

mammals including ungulates.675–684 Collectively they Mycotic and amoebic encephalomyelitides

are important causes of early fetal loss, abortion,
On rare occasions, opportunistic fungi and amoebae
birth of recumbent, nonviable offspring, and neona-
produce fatal meningoencephalomyelitis in large
tal congenital infections. Transplacentally acquired
animals. Clinical signs are fulminant, and the dis-
encephalomyelitis is often present with all these
eases are fatal.
infections, although from a clinical neurology per-
Of the fungal infections, Aspergillus sp. fungemia
spective it is the neonatal syndrome in calves infected
and necrotic infarctive and angioinvasive meningoen-
with Neospora spp. and young and mature sheep
cephalitis can accompany severe systemic illness, fol-
infected with Sarcocystis spp. that appear to occur
low prolonged antimicrobial and immunosuppressive
more often with recognizable neurologic syndromes,
therapy, or occur in conjunction with hyperadreno-
sometimes as epizootics.684–686
corticism in horses and calves.697–699 Similar infarctive
Calves in which Neospora spp. has been associated
encephalitis can occur with disseminated infection of
with meningoencephalomyelitis can be born with
species of the order Mucorales in cattle and horses700,701
ataxia and weakness of pelvic and thoracic limbs or
and may be characteristic of phaeohyphomycosis in
signs can develop during the first few weeks of life.
horses caused by several species of darkly pigmented
These signs likely represent final motor neuron
fungi.702 Contiguous spread of Aspergillus sp. guttural
lesions as well as some evidence of brainstem
pouch mycosis or Conidiobolus coronatus pharyngeal
involvement.677,679,683,684,687
infection can produce localized meningoencephalitis
More frequently documented are single and multiple
and cause blindness.152 Cerebral infection with the
cases involving young and mature sheep with signs
oomycete Pythium insidiosum may occur as part of a
relating to progressive meningoencephalomyelitis
primary disseminated disease703,704 or in association
caused by Sarcocystis spp. infection. Combinations of
with fungal organisms in cattle and horses.705 Neonatal
progressive, asymmetric ataxia, and paraparesis in
mycotic encephalitis, caused by Mortierella wolfii, has
sheep of all ages, especially fattening lambs, are well
occurred in conjunction with mycotic pneumonia
documented.680–682,688–690 Clinical progression to include
and placentitis in cattle.706 Coccidiodes immitis is a
behavioral signs, such as head pressing and misdirected
pathogenic fungus found in the southwestern United
nibbling, leading to recumbency and seizures also
States that may cause pulmonary infections in horses
occurs.685,691 Merozoites, schizonts, and/or sarcocysts
that have the potential to spread to the CNS.707
may be seen microscopically in CNS tissues. Most times
Cryptococcal infection of the CNS occurs in large
a diagnosis is made with the aid of various serologic and
animals, particularly horses and goats, and is associ-
immunohistologic techniques rather than isolation of
ated with a wide variety of clinical signs relating to
the organism in tissue cultures, but Sarcocystis spp. are
brain and spinal cord locations of the predominantly
most often incriminated. In one report, protozoal mer-
meningeal involvement. Syndromes have included
ozoites of S. capricanis were identified in the CSF of two
progressive ataxia and blindness, stiff gait followed
sheep with protozoal meningoencephalitis.692
by violent behavior, generalized hyperesthesia, asym-
Antiprotozoal therapy, extrapolated from that used for
metric vestibular signs, and deficits relating to
EPM (above), has been used when presumptive diagno-
involvement of the cauda equina.708–714 Mixed inflam-
ses of sarcocystosis have been made.
matory cell, CSF pleocytosis, usually should be pre-
It is possible that transmission across classical spe-
sent, and the presence of cryptococcal organisms in
cies barriers may occur.685 Therefore, all raw meat
CSF is diagnostically significant. Treatment with
and offal from any species should not be fed to dogs
drugs, such as amphotericin B or fluconazole, is fea-
or other carnivores on farms.
sible and has been attempted.130,715
Babesia bovis causes a malaria-­like cerebral syn-
Cattle, sheep, and horses can become infected with
drome that kills quite a few cattle, mostly calves, in
free living amoebae on rare occasions. Usually, this is
Brazil.693 There is sequestration of parasitized erythro-
a fulminant disease course caused by Naegleria
cytes in brain, liver, and kidney capillaries, especially
fowleri and Balamuthia mandrillaris associated with
in the forebrain, with modest pericapillary edema
animals having access to stagnant tepid water. The
being the only consistent morbid lesion with no
portal of entry for the organisms is most often the
encephalitis apparent.694 Neurovirulence appears to be
olfactory mucosa and occasionally via hematogenous
related to the genetic makeup of the particular strains
spread from the lower respiratory tract. Amoebae
of B. bovis causing the cerebral syndrome.695,696
338 Large animal neurology

were identified in the CSF of a cow and a sheep with Nematodes, superfamily Strongyloidea
N. fowleri meningoencephalitis.716 Clinical syn- Verminous myeloencephalitis due to Strongylus vul-
dromes described have been excess salivation, stag- garis arrival and migration through the CNS is a rare
gering and recumbency, ataxia, cranial nerve aberrant event resulting from embolization to the
involvement, weakness, hypermetria, blindness, and CNS of L4 or L5 larvae from verminous thrombi in
seizures.717–721 the left ventricle, proximal aorta, or any of the aortic
branches that supply the brain and spinal cord.722–725
Disintegration of thrombi in these aberrant locations
Verminous encephalitis and myelitis
sends clot fragments and larvae to the CNS. If origi-
For the most part, parasites that spend some of their nating from the carotid vessels, there typically are
life cycle in or close to nervous tissue cause little or acute seizures and recumbency and fluctuating,
no harm in their natural hosts. With aberrant and asymmetrically directed, violent or passive behavior.
unusual helminth and insect parasitic invasion of This is most often what is seen with Strongylus
nervous tissues, there is a peracute onset of an asym- vulgaris-­associated thromboembolism involving
metric neurologic abnormality, which progresses horses. Marked diffuse brain swelling can occur,
rapidly. However, stable periods of days to weeks can resulting in brain herniations and death.725 Many
occur. Usually, degrees of permanent deficit should cases do not show progression of signs, as no parasite
be expected with this group of diseases, but some migration occurs and signs can improve and even
amazing recoveries have been seen when early, resolve. When the thoracolumbar region is involved,
aggressive, anti-­inflammatory, and antiparasitic ther- there is abrupt asymmetric ataxia and paraparesis to
apy has been undertaken. For prevention, the avoid- paraplegia. Signs may change dramatically over time
ance of contact with natural hosts where appropriate or even stop and then restart or spontaneously
and maintenance of routine antiparasitic strategies resolve. A larva may exit the CNS only to re-­enter at
should be considered. Neurologic signs usually a different location and continue its migration.724
reflect tortuous, mostly asymmetric, random migra- Analysis of CSF often shows xanthochromia, high
tions (Strongylus vulgaris, Hypoderma spp., Draschia protein concentration, and increased nucleated cell
megastoma, and Setaria digitata) or diffuse brain or count.722,724,725 Reported differential counts range
spinal cord involvement (Halicephalobus gingivalis). from 70 to 80% neutrophils, 12 to 19% mononuclear
Thus, depending on the number, size, and location of cells, and 1 to 2% eosinophils.
the parasites and the duration of their migration Usually, it must be assumed that a potentially via-
through the brain or spinal cord, a spectrum of signs ble parasite is still present, and anthelmintics and
is possible, ranging from a nonprogressive localizing anti-­inflammatory therapy should be instituted.
neurologic deficit to rapidly fatal, diffuse Without parasite migration, prognosis is fair to
encephalitis. good after the acute seizure episode occurs, provided
The clinical signs result from mechanical tissue brain swelling can be controlled. If the animal sur-
destruction, hemorrhage and inflammation, or a vives, residual signs of fluctuant somnolence, sei-
space-­occupying effect, depending on the parasite. zures, and partial visual dysfunction may persist.
An additional immune-­ associated inflammatory Verminous myeloencephalitis due to S. vulgaris
response may contribute to the pathophysiologic pic- virtually disappeared after the introduction of the
ture (e.g., Angiostrongylus cantonensis). Good diag- macrocyclic lactone anthelmintics in the 1980s; how-
nostic evidence of verminous encephalomyelitis ever, the increasing practice of selective deworming
includes an eosinophilic or neutrophilic pleocytosis may allow the reemergence of large strongyles.726
in CSF with varying numbers of macrophages and In swine, a single Stephanurus dentatus larva usu-
red blood cells. Newer diagnostic imaging and par- ally invades the lumbar spinal cord causing parapare-
ticularly molecular diagnostic testing will play a sis or paraplegia.727,728
greater role in diagnosing and monitoring these dis-
eases in future. Nematodes: superfamily Metastrongyloidea
Examples of helminth and insect parasitic invasion Several nematodes in the family Protostrongylidae are
of nervous tissues of domestic large animals are now important causes of neurologic disease in wild and
considered in several taxonomic groups. domestic ruminants in Europe, Asia, New Zealand
 Infectious, inflammatory, and immune diseases 339

and North America, and likely occur wherever native frequently followed via the dorsal spinal roots and
Eurasian or American cervids coexist with suitable ganglia and spinal meninges.767–769 Also, segmental
terrestrial molluscs that can act as intermediate hosts. sensory deficits and final motor neuron signs, often
There are two genera of these so-­called extrapulmo- observed as nonspecific lameness in one limb, can
nary lungworms affecting the cervids—Elaphostron- occur at this stage.735,739 The process of migration
gylus and Parelaphostrongylus—­that pass through the through spinal meninges and cord and then
host CNS as part of their life cycle. Although they can ­brainstem and forebrain, as well as the progression of
cause neurologic disease in their primary hosts, they accompanying neurologic signs, can halt at any stage.
tend to produce prominent neurologic infections, Spontaneous recoveries do occur, which is the norm
usually nonpatent, in abnormal and aberrant hosts.729– in the primary native host species.739,757,767,768,770
744
Six species are described that are currently perti- Various species of Elaphostrongylus can also invade
nent here: Elaphostrongylus cervi is a parasite of the the vasculature of the head and produce blindness
CNS and skeletal muscle of red deer but also affects and other neurologic signs in various wild rumi-
roe deer and Sika deer; Elaphostrongylus panticola in nants, such as elk and reindeer, and possibly domes-
maral deer; Elaphostrongylus rangiferi in reindeer; E. tic ruminants.771,772
alces in moose; Parelaphostrongylus tenuis, the menin- These migratory nematodes follow amazingly
geal worm of white tailed deer; and P. odocoilei, the selective paths to reach potentially hazardous habitat
muscle worm of mule deer, black tail deer, moose, and in intrameningeal and intramuscular compartments
other wild ungulates in North America. The precise of hosts as exemplified by Parelaphostrongylus tenuis
primary, abnormal, and aberrant host ranges and geo- in some horses751,752,761,773 and alpacas.774 This worm
graphic distributions of these parasites are still being has caused an acute onset of cervical scoliosis that
defined, a task made easier using DNA sequencing was the result of an exquisitely selective unilateral
techniques.744–749 continuous inflammatory lesion of the dorsal gray
Parelaphostrongylus tenuis is a ubiquitous parasite column of the spinal cord on the convex side of the
of white-­tailed deer in the eastern United States (north neck. Cutaneous hypalgesia to analgesia of the neck
of a line through the middle of the states along the and/or thorax and mild unilateral limb ataxia and
Gulf of Mexico750) that produces traumatic and inflam- paresis, all on the side of the lesion, but with no evi-
matory meningomyeloencephalitis in other deer, dence of denervation atrophy in the epaxial muscles,
goats, sheep, and camelids and, less commonly, in cat- was observed in all affected horses. The scoliosis was
tle and horses,751–753 showing syndromes relating to clearly argued to be due to the loss of afferent cervical
asymmetric spinal cord and brainstem involvement. proprioceptive inputs because of the dorsal gray col-
Fatal eosinophilic verminous encephalomyelitis in umn lesions with some white matter involvement
four horses was recently reported from Korea.754 accounting for ataxia and weakness. Even vestibular
Structurally, the worms resembled P. tenuis; however, signs might be predicted with cranial cervical, dorsal
this parasite is not previously known in Korea and the gray matter lesions (see Chapter 19).
usual host, white-­ tailed deer, are not found there. Febrile illness and circulating eosinophilia is
Asymmetric mono-­, para-­, and tetraparesis to paraly- recorded in experimental disease but less frequently
sis occur. Multifocal signs involving both central in naturally acquired forms where the parasite dose
(hypertonic and hypereflexic) and final (flaccid and may be smaller and temporally spread out.757,762,767,768
hyporeflexic) motor neuron paralysis can occur as well A moderate CSF mixed pleocytosis (neutrophils,
as asymmetric cranial nerve signs and occasionally eosinophils, and macrophages) with elevated pro-
signs of cerebellar and cerebral disease.730,751,755–762 tein and sometimes xanthochromia typically is
Elaphostrongylus cervi are ubiquitous where red detected in metastrongyloid nematode myelitis and
deer populations exist, and reindeer and moose can encephalitis cases,730,756,762,764,775 and organisms that
both act as full hosts for both E. rangiferi and E. alces. are occasionally seen in CSF or the anterior cham-
Syndromes resulting from spinal and brain migra- ber of the eye can be identified by morphology and
tions occur in cohabitating sheep and goats, and PCR.749,752,776
probably other domestic ungulates, sometimes in Most of the metastrongyloid nematodes appear to
epizootic proportions.736,763–766 Interestingly, pruritus be sensitive to various anthelmintics such as fenbenda-
can be a prominent sign early in the migratory phase zole and ivermectin, and such therapy has been suc-
of the parasites presumably due to the pathway cessful in nonequids when the cases have been treated
340 Large animal neurology

soon after onset of clinical signs.730,753,756,757,762,765 All of Setaria spp. may cause blindness by migrating into
equine cases so far reported have died or been eutha- the eyes of cattle or horses where they may be found
nized. Horses with scoliosis have not improved with free in the anterior chamber.786 On occasion, prenatal
anthelmintic treatment. Recumbency is a bad prognos- infection with the microfilariae of Setaria spp. has
tic sign. Empiric therapy with NSAID and corticoster- caused abortions or fatal neurologic disorders of new-
oid drugs is probably important. Monthly prophylactic born lambs.787 There can be an aseptic mononuclear
anthelmintic use has been advocated when domestic CSF pleocytosis with eosinophils present.788 A sensi-
ruminants must be exposed to pastures contaminated tive PCR technique can be used on serum samples
by white tail deer and therefore almost certainly to (and on vector arthropods) to detect small fragments
Parelaphostrongylus tenuis larvae.756 of Setaria digitata DNA to assist in clinical diagnosis
Angiostrongylus cantonensis (rat lungworm) is a neu- and in epidemiologic studies.785,789 Several anthelmin-
rotropic parasite in the Angiostrongylidae family with a tics including diethylcarbamazine have been used to
life cycle in rats closely analogous to that of P. tenuis in treat clinical cases and prophylactically, and the mac-
white-­tail deer.777 It is the most common cause of eosin- rocyclic lactones such as ivermectin and moxidectin
ophilic meningitis in humans in Southeast Asia and the likely would be effective in killing the larvae.
Pacific Islands and has spread to Australia, southern Although Onchocera spp. are quite ubiquitous,
United States, and the Caribbean.778,779 Adult worms they rarely result in neurologic disease. An eosino-
reside in pulmonary vasculature of wild rats that philic granuloma associated with a C6–7 intervertebral
become infected by ingesting the infective larva in slugs joint capsule and containing Onchocerca spp. nema-
or snails. Inadvertent ingestion of infected intermediate todes caused progressive cervical spinal cord com-
hosts by atypical hosts such as humans, dogs, and horses pression in an aged mare in North America.790
may lead to aberrant migration in the CNS and the
development of eosinophilic meningoencephalomyeli- Nematodes: superfamily Panagrolaimoidea
tis. Signs of terminal cases in foals have related to migra- Halicephalobus gingivalis is a free-­living microbivo-
tion of larvae in the gray and white matter of the spinal rous nematode that feeds on bacteria in rich organic
cord and caudal brainstem.780,781 Eosinophilic meningi- environments such as decaying vegetation, compost,
tis in humans is treated with corticosteroid drugs or and manure.791 Cases of meningoencephalomyelitis
simply with palliative care as killing large numbers of caused by H. gingivalis occur sporadically worldwide
larvae with anthelmintic drugs can cause a major exac- in equids (including zebras) and occasionally
erbation of meningitis and of clinical signs,778 although humans and cattle.792–798 The nematode opportunis-
additional use of albendazole or mebendazole is proba- tically enters the body through breaks in the mucous
bly indicated.777 However, the lesions in foals were membranes (and possibly skin) of the nose, mouth,
migratory myelitis and encephalitis and should benefit prepuce and mammary gland of horses, and invades
from anthelmintic medication in addition to robust and proliferates locally to cause clinically apparent
anti-­inflammatory therapy. Specific ELISA tests are granulomas.799–804 Such masses can be locally inva-
available for testing of CSF in humans and in dogs.777 sive and destructive, particularly in the jaws, nasal
cavity, and paranasal sinuses.778,805 In one case a foal
Nematodes: superfamily Filaroidea was apparently infected by suckling from its dam
Of the multiple filarial parasites affecting ungulates, who had H. gingivalis mastitis.806 From these super-
several Setaria spp. may invade the CNS, especially the ficial sites, larvae or adults may enter lymphatic or
spinal cord.782–785 Epizootic cerebrospinal nematodia- venous drainage and be distributed hematogenously
sis or kumri (weak back) is a neurologic disorder to various organs and tissues. H. gingivalis has a pro-
affecting goats, sheep, horses, and rarely cattle in many pensity to invade and proliferate in the kidneys,
countries in the Far East causing substantial economic CNS, and eyes, although lesions have also been
losses. This disease is attributed to several Setaria spp., found in long bones, heart, lungs, liver, uterus, tes-
most notably Setaria digitata, all of which are com- tes, lymph nodes, and the walls of the aorta and pul-
monly found in the peritoneal cavity of cattle and buf- monary arteries.804,807–809 The brain is the usual site of
falo and are transmitted by appropriate mosquito CNS infection with lesser involvement of the spinal
vectors. An abrupt onset of subtle to profound ataxia cord or, in one instance, the cauda equina.810 Clinical
and weakness occurs, usually only involving the pelvic signs of H. gingivalis infection of the CNS depend on
limbs and with or without progression of signs. Larvae the location of the lesions and include asymmetric
 Infectious, inflammatory, and immune diseases 341

ataxia, hypermetria in the thoracic limbs, obtunda- even yak, resulting in acute and chronic syndromes,
tion, behavioral changes, compulsive walking, head occurring sometimes as zoonotics819 (Figure 32.14).
pressing, head tilt, circling, nystagmus, recumbency, The disease is of major proportions in sub-­Saharan
convulsions, and coma.793–798,811–813 African agricultural economies where domestic small
Although anthelmintic and anti-­ inflammatory ruminants cograze with wild carnivores.819–829
drugs have and could be used, H. gingivalis menin- The acute disease occurs 2–3 weeks after exposure
goencephalitis is invariably fatal, regardless of treat- and results in acute necrotic and aseptic encepha-
ment; affected horses die or are euthanized within lomeningitis caused by sinuous migration of cestode
several days of onset807,814 Cytology of CSF can be larvae through the brainstem and cerebellum.826,830,831
consistent with an aseptic parasitic meningitis, and A prominent, mixed-­cell type of CSF pleocytosis usu-
Halicephalobus gingivalis larvae may be detected in ally accompanies this form of coenuriasis. If animals
CSF or urine.806,815,816 survive this phase of invasion, which is often subclini-
The disease has been detected in a pair of juvenile cal, then over the next 3–8 months, 1–6 cm diameter,
sibling foals a year apart on the same property reflect- fluid-­filled cysts lined by clusters of scolices form in
ing congenital or transmammary infection or expo- the forebrain and less commonly the cerebellum,
sure to the same saprogenic environment.817 As is the brainstem, and even the spinal cord. Morbidities of
case for other rhabditid nematodes such as 20% are recorded for the naturally occurring acute
Strongyloides spp., evidence for vertical transmission disease with clinical signs such as ataxia, somnolence,
does exist for Halicephalobus gingivalis.806 and blindness.826 The most typical syndrome for the
chronic cerebral form of coenuriasis, also known as
Nematodes: superfamily Habronematoidea gid in sheep and goats in the UK, is inappetence, head
Habronematoids like Draschia megastoma have turn, circling, head pressing, intermittent somno-
invaded brain and possibly spinal cord tissue. One lence, and blindness.823–826,832,833 Closer examination
was quiescent for 6 weeks before remigrating.818 often reveals asymmetric central blindness, nasal and
facial hypalgesia, and limb hopping response and
Cestodes: family Taeniidae positioning deficits. Hypermetric ataxia and excite-
Coenurus cerebralis, the larval stage of Taenia multiceps ment are often recorded for the less commonly seen
of canidae, frequently forms large cysts most particu- cerebellar cysts, and ataxia and paresis to recumbency
larly in the brains of sheep and goats, rarely cattle and reflect brainstem and spinal cord involvement.834

(A) (B)

Figure 32.14 Coenurus cerebralis is the cystic, larval stage in the intermediate host of the tapeworm Taenia multiceps that lives in the small intestine
of canids such as dog, fox, coyote, and jackal. It usually forms in the brain (A) and spinal cord in ungulates especially sheep, and in cats and primates.
Clinical signs depend on the location of the cyst(s) but most often reflect the asymmetric cerebral (yellow arrow) and cerebellar (white arrow) locations.
In the sheep brain shown here (A), there is a midline shift of the left cerebral hemisphere to the right under the falx cerebri. The position of the latter
structure is indicated on the dorsal view of the brain (A) by the green dashes. On transverse sections of the forebrain (B), the extent of one large intrac-
erebral cyst is evident (arrow heads). T. multiceps coenuri (cysts) may contain one to a few hundred protoscolices attached to its wall or floating free with
their characteristic attachment mouthparts visible histologically. Source: Images courtesy of Dr. Caroline Hahn.
342 Large animal neurology

Plain and contrast radiography, CT, and MRI stud- organophosphates contributes to these signs,756,844
ies all can assist in diagnosing encephalitic coenuria- and it is suggested that signs occurring days to weeks
sis in ruminants.833,835,836 following use of such compounds is rather a form of
Surgical removal of C. cerebralis cysts from sheep delayed organophosphate intoxication.
has resulted in excellent recovery rates823,832,833,837 Singular Hypoderma bovis and Hypoderma linea-
Ultrasound guidance may well be an option for local- tum instars can enter through large natural foramina
ization and surgical removal of cysts.826 The use of in horses, such as the foramen magnum, the optic
cysticidal drugs such as albendazole and praziquantel foramen, and occasionally intervertebral foramina845
has improved the prognosis for neurocysticercosis causing fulminant signs of medullary disease, blind-
(Cysticercus cellulosae) in humans and do appear ness and seizures, and ataxia, respectively.
effective for Coenurus cerebralis in ruminants.831,838 Asymmetric brainstem disease results in the most
Abolishing the feeding of raw meat and offal to common syndromes.845,846 Phenylbutazone obviates
domestic dogs as well as routine administration of the systemic and lethal effects of intravenous prepa-
effective cestocidal anthelmintics to them has dra- rations of dead Hypoderma bovis in cattle847 suggest-
matically reduced the incidence of Taenia multiceps ing that NSAID therapy should always be used when
and resultant Coenurus cerebralis infections. treating a case suspected to have Hypoderma spp.
Separating grazing land and fodder for livestock neuromyiasis.
away from wild carnivores is problematic in areas Since the advent of pour-­on and injectable sys-
where wildlife abounds and there is cohabitation temic organophosphate insecticides in the 1950s and
with domestic ruminants. the macrocyclic lactones in the 1980s for systematic
Cysticercus cellulosae is the larval stage of Taenia treatment of cattle, Hypoderma populations have
solium, a large tapeworm in humans, and in some decreased dramatically in the United States and have
countries it occurs commonly in brain and other tis- been eradicated in several European countries so that
sues of pigs. Computed tomography clearly defines intracranial myiasis is now unlikely in developed
this form of neurocysticercosis, and medical therapy countries. Hypoderma diana, a parasite of deer, has
with cestocidal anthelmintics and surgical removal also infested horses and presumably has the potential
are expensive treatment options.831,839 for CNS invasion.848
Hydatid cysts form in the organs of animals and
humans infected worldwide by ingestion of eggs of Sporadic bovine encephalomyelitis
the Echinococcus granulosus tapeworm.840 Although
1–2% of infected humans have cerebral cysts, brain The syndrome of sporadic bovine encephalomyelitis
involvement is very rare or nonexistent in sheep and (SBE) describes scattered cases of bovine progressive,
goats, the usual intermediate hosts.841 We were una- disseminated, acute to chronic, nonsuppurative
ble to find any reports of cerebral hydatidosis in the meningoencephalitis, involving gray matter more
veterinary literature, although there is description of than white matter that have been reported from
ataxia in a horse associated with an extradural many countries.849–852 All ages have been affected, and
hydatid cyst.842 signs have been generally symmetrical and repre-
senting brainstem and forebrain involvement. After
Flies: family Oestridae it was established that Swiss cases of SBE were not
Warble fly or heel fly (Hypoderma spp.) instars may associated with Chlamydia pecorum (aka
be evident on the backs of cattle and horses where Chlamydophila pecorum), the condition in that coun-
this parasite resides, worldwide. In cattle, neuromyia- try was renamed European sporadic bovine encepha-
sis usually results from a single Hypoderma bovis lomyelitis (ESBE).853 It is most probable that there are
instar aberrantly migrating in the spinal cord. several specific causes of this clinicopathologic dis-
Preventative organophosphate therapy may cause ease syndrome of nonchlamydial sporadic bovine
death of epidurally located Hypoderma bovis instars, encephalomyelitis.850,853–856 Astroviruses have been
thereby evoking acute granulomatous inflammatory found in the brains of cattle with ESBE and in cattle
reaction and spinal cord necrosis.756,843 Paraparesis or and a sheep with neurologic disease in Europe and
paraplegia does occur in previously normal cattle north America; however, causality has not been
hours to days following organophosphate treatment. established for these divergent bovine astrovi-
There is debate as to whether the grubcidal action of ruses.857–861 Similarly, there has been evidence for a
 Infectious, inflammatory, and immune diseases 343

paramyxovirus in brain tissues in some cases of thought to be an immunologic inflammatory

ESBE,853,862,863 and preliminary evidence has been response to released Sarcocystis antigens. Clinical
adduced for the possible involvement of obscure signs have included acute recumbency, weakness,
viruses such as parainfluenza virus-­5, bovine poly- muscle tremors, muscle atrophy, difficulty in chew-
omavirus-­2, and bovine herpesvirus-­6.861 ing and swallowing, and swaying upon standing,
with signs worse upon exercising. Loss of extensor
Chlamydia pecorum sporadic bovine reflexes has been consistent with the myopathy in
encephalomyelitis sheep. Elevated serum creatine kinase activity is pre-
sent most often. Sarcocystis cruzi is a rare cause of
Some cases of SBE have been related to infection with
heart failure and death due to severe eosinophilic
Chlamydia pecorum when younger cattle tend to
myocarditis.873 In all cases of suspected sarcocystosis,
have been affected, and there can be isolated cases of
antiprotozoal drugs along with anti-­inflammatory
respiratory diseases, diarrhea, or arthritis occurring
therapy are indicated, with variable clinical responses
in the herd.852,864,865 Occasionally, an outbreak
recorded, at least in equine sarcocystosis.868,872
occurs.866 Inappetence, fever, and somnolence often
In clinically apparent chronic sarcocystosis, whole
precede specific neurologic signs that terminally can
and degenerate sarcocysts are present associated with
result in recumbency, blindness, and opisthotonus.
an aseptic eosinophilic myositis/myocarditis,
Some mildly affected animals recover. The morbidity
whereas the hallmark of acute, experimentally
varies from 5 to 60%, with mortality up to 50%, high-
induced, precystic, disease is the presence of schiz-
est in growing cattle.
onts (multinuclear proliferative stage) in the vascular
Diffuse nonsuppurative meningoencephalitis and
endothelia of many organs.874 Specific Sarcocystis spp.
fibrinous polyserositis caused by C. pecorum are evi-
can be identified by electron microscopy, immunola-
dent on postmortem examination.866 Elementary
beling and transmission procedures, and DNA
bodies may be demonstrated in glial cells and mono-
sequencing techniques.869,870,873
nuclear inflammatory cells in affected brains.
CSF analysis may reveal moderate mononuclear
pleocytosis with high protein concentration. There
Inflammatory and immune mechanisms
are several serologic tests including a complement
fixation test and an indirect hemagglutination test to Optic neuritis
assist with the diagnosis. Isolation of the chlamydial
Optic neuritis or meningoneuritis, unassociated with
agent from brain tissue and identification of genus-­
head injury or other illness, is presumed to occur in
specific chlamydial DNA sequences using PCR
horses that develop acute blindness with dilated
amplification are used to make the postmortem
pupils and some evidence of papilledema. Considering
diagnosis.866
that optic disk swelling is not clearly recognized oph-
Chlamydia spp. are generally sensitive to the tetra-
thalmoscopically with acute traumatic optic neuropa-
cycline and macrolide antimicrobials, and these
thy, and rarely if ever with increased intracranial
drugs are recommended for treatment.
pressure in horses, this syndrome may well be unique
and likely represents optic neuritis when it occurs in a
Protozoal polymyositis
horse, as it certainly does in other species. However,
It has long been considered that disseminated eosin- the possibility of prior head trauma and traumatic
ophilic myositis in ungulates was due to the presence neuropathy must be considered.875 Nonsuppurative
of live and especially dead sarcocysts in muscle. inflammation of the optic nerves or associated menin-
Although usually subclinical, Sarcocystis spp. infec- ges may be seen histologically and may be inferred
tion can cause clinically evident eosinophilic myosi- from MRI.875–877 Idiopathic pachymeningitis was the
tis in cattle, sheep, alpacas and horses.867–872 Severe presumptive cause of transient blindness in a horse.876
myopathy in sheep was associated with Sarcocystis In most cases, the cause is unknown, but possibly
spp. infection and administration of the coccidiostat involves immune-­mediated processes and appears to
monensin,869 and clinical signs were exacerbated respond to corticosteroid therapy.
markedly by high-dose thiabendazole treatment of a Swelling of the optic papilla with exudation can
horse with widespread Sarcocystis fayeri infection.237 occur with associated disease processes,875,878 but such
Exacerbation of signs with anticoccidial drugs is inciting conditions should be well apparent. One case
344 Large animal neurology

of granulomatous optic neuritis, possibly resulting The etiopathogenesis of these syndromes, includ-
from verminous migration, has been reported.879 ing the space-­occupying granulomatous masses on
Suppurative optic neuritis occurred in a 9-­year-­old cranial nerves, has not been determined. It is reason-
Quarter Horse mare because of bacterial endocardi- able to speculate that these cases represent an unusual
tis and Actinobacillus equuli bacteremia880 and has extension from suppurative otitis media and otitis
been associated with Streptococcus equi subsp. equi interna, with partial rupture through the internal
infection.878 Sarcocystis neurona, Borrelia burgdorferi, acoustic meatus and even to sites outside the neuro-
and West Nile virus all theoretically can cause optic cranium.179,882 The possibility of an immune-­
neuritis. associated polyneuritis should also be considered in
With blindness due to optic nerve disease, if no individual cases.
improvement is seen after 2 weeks of corticosteroid
therapy, then the outlook for return of vision is likely Immune-­mediated myositis
to be bad.
Young horses less than 8 years old and aged horses
older than 17 years of Quarter Horse and related
Granulomatous facial and vestibulocochlear
breeds have developed immune-­mediated myositis
neuropathy in cattle
(IMM).885 Cases are sporadic and frequently have a
This unusual syndrome was first reported in Europe history of recent respiratory illness or vaccination
where 15, 2–3-­month-­old calves were affected in 1 (especially strangles vaccination) before developing
year881 and later from South Africa.882 Signs have con- malaise, painful muscles, and stiff gait followed by
sisted of facial paralysis and asymmetric peripheral rapid-­onset, marked, severe muscle atrophy, particu-
vestibular disease. Fever, leukocytosis, and neutro- larly involving the paravertebral and gluteal muscu-
philia were detected in some calves, some of which lature.886,887 Serum activity of muscle enzymes is
had been recently disbudded with caustic soda. increased. Histologically, there are lymphocytic infil-
Nonspecific elevations in CSF protein and cell counts trates both surrounding blood vessels and within
were reported. With and without antibiotic treat- myocytes. Clinical signs, including muscle atrophy,
ment, some calves recovered. The lesions were nod- tend to stabilize and reverse with corticosteroid ther-
ules of pyogranulomatous neuritis followed by apy, but some relapses have occurred upon with-
formation of fibroblastic granulomas involving cra- drawal of the treatment.
nial nerves VII and VIII. In one calf, similar nodular A mutation in the myosin heavy chain 1 gene
lesions were found on the cornual nerve and the skin (E321G MYH1) has been identified which is tightly
around the previously necrotic dehorning site. associated with, and presumably causally related to,
A clinically similar syndrome of bilateral facial paral- the IMM phenotypes of muscle atrophy and lym-
ysis and asymmetric vestibular dysfunction was seen in phocytic myositis.888 The mode of inheritance is not
feedlot cattle in Argentina where 458 out of 5140 ani- certain, but both homozygotes and heterozygotes are
mals on six premises were affected.883 Recoveries susceptible to the development of IMM.
occurred slowly with minimal mortality. There was Homozygotes have more severe, recurrent and per-
gross enlargement of the roots of affected nerves that sistent muscle atrophy. All affected horses could be
was characterized histologically as granulomatous lep- traced back to a single sire within eight genera-
tomeningitis. No infectious agent was identified. tions.888 Interestingly, the E321G MYH1 variant is
Finally, a usually febrile syndrome accompanied also highly associated with nonexertional equine
by mild respiratory illness and referred to as facial rhabdomyolysis (ER) in Quarter Horses, even in
paralysis syndrome—­ colloquially referred to as cases without muscle atrophy or lymphocytic myosi-
“droopy-­eared calf syndrome”—­has been reported in tis.889 There was preliminary evidence that the
New Zealand to occur in dairy calves as mini-­ MYH1 mutation may likewise instigate the immune
outbreaks of 20 or more cases over calving periods.884 response that leads to fatal Streptococcus equi-­
Some cases also show evidence of vestibular disease. associated rhabdomyolysis.242 The authors helpfully
There was minimal evidence of a meningitis, but suggested that the two muscle diseases, IMM and
gross lesions were absent in the examined postmor- nonexertional rhabdomyolysis, that are caused by
tem of the three calves although the state of the inner MYH1 mutation be grouped under the term myosin
ear cavities was not mentioned. heavy chain myopathy (MYHM).889,890
 Infectious, inflammatory, and immune diseases 345

Reported887 and unreported cases of inflammatory

myopathy, with some accompanied by sarcoplasmic
inclusions, occur in horses. Because classical inclu-
sion body myositis of humans is a form of immune-­
mediated myositis, it is reasonable to assume that the
equine cases are a form of equine IMM.888 And finally,
severe myonecrosis with edema and inflammatory
infiltrate is reported in terminally ill horses with
myalgia and influenza confirmed by viral isolation.237
In all these syndromes, an association with
Sarcocystis spp. and Streptococcus spp. must be con-
sidered. Corticosteroid therapy is indicated.

Infarctive purpura hemorrhagica

Horses of any age, usually Quarter Horses, have devel-
oped a fulminant myopathy associated with severe ill-
ness a few weeks after strangles vaccination or infection
with Streptococcus equi subsp. equi and occasionally
with other agents.246,247 This is a form of purpura hem-
orrhagica with immune-­associated infarctive vasculitis
comparable to Henoch–Schönlein purpura in
humans.891 In these cases, there are classical signs of Figure 32.15 Polyneuritis equi (PNE) is likely an immune-­associated
purpura hemorrhagica plus unusually severe and pain- inflammation directed against peripheral myelin particularly that
ful muscle stiffness and swelling with later develop- ensheathing cranial and sacrococaudal nerves. By the time clinical signs
ment of prominent colic signs. Laboratory results are become evident, there is usually a prominent granulomatous inflamma-
tory infiltrate in and around affected nerves. Unusually, this lesion is evi-
typical for purpura hemorrhagica but especially with
dent grossly in this horse affected with PNE having facial nerve (CN VII)
prominent neutrophilia and toxic left shift, hyperglob- paralysis and visible and palpable swelling of the branches of the facial
ulinemia, hypoalbuminemia, and serum creatine nerve (white arrow). Inset shows a low-­power photomicrograph of the
kinase activity greater than 10,000 U/L. Acute coagula- origin of CN VII as it exits the medulla oblongata and becomes a periph-
tive necrosis occurred in several tissues including mus- eral cranial nerve (PNS). There is an obvious tinctorial difference between
myelin produced by oligodendroglia in the CNS and that produced by
cle and gastrointestinal tract associated with acute
Schwann cells in the PNS, with a clear demarcation at the glia limitans
necrotizing and fibrinoid leukocytoclastic vasculitis. (GL). Notice the inflammatory infiltrate (blue staining cells) in the nerve
The prognosis appears grim, although penicillin ther- but not in the central radices of CN VII in the CNS.
apy and particularly prolonged high-­dose corticoster-
oid administration initiated before intestinal infarction
occurs have resulted in a few cures.237,891,892
equina in this widespread neuritis is reflected in the
outdated name cauda equina neuritis. Cranial neuri-
Polyneuritis equi
tis can be prominent, and occasionally neuritis is
The term polyneuritis equi is used to define a disease clinically and pathologically prominent in other
of equids associated with nonsuppurative neuritis demarcated areas of the body.
affecting proximal spinal and cranial sensory and Horses and ponies affected with polyneuritis equi
motor nerve rootlets, nerve roots, and nerves are of many breeds, both sexes, and of a wide age
throughout the body which rapidly progresses to range, although this disease is not reported in foals or
form a chronic, entrapping, proliferative, granuloma- old horses.894–896,902,903 Urinary incontinence and fecal
tous polyneuritis (Figure 32.15).893–896 There are a obstipation, possibly demonstrated as colic, minimal
large number of documented and undocumented straining, rubbing the tail head, and stallion impo-
sporadic cases of polyneuritis equi seen from most tence904 may be reported, and usually there is an
parts of Europe and North America.893–901 abrupt recognition of the signs by the owner.
That there often is a pathologic and clinical predi- Occasionally, the horse is presented for signs of cra-
lection for involvement of the structures of the cauda nial nerve disease—­most noticeably a head tilt. Urine
346 Large animal neurology

scald, fecal retention, and broken tailhead hairs are demonstrated that circulating IgG in affected horses
likely to be found on physical examination. has an affinity for myelin in the cauda equina.911
There frequently is analgesia, atonia, and areflexia However, in a clinical setting the diagnostic utility of
of the tail, anus, perineum, rectum, bladder, and this test is very poor with many false positive
penis, but not involving the prepuce. A ring of hyper- results.912 Notwithstanding, evidence is mounting
sensitivity expressed as allodynia, or painful responses that this disease is an immune-­associated, demyeli-
to physiologic stimuli, is frequently evident surround- nating polyradiculoneuritis. With the neuritogenic,
ing the area of analgesia.893,896,897,902,905 Pelvic limb gait immune-­associated diseases, acute idiopathic poly-
abnormalities are subtle, if present at all. Subtle to radiculoneuritis (Guillain–Barré syndrome) in man
prominent signs of cranial nerve disease, particularly and acute idiopathic polyradiculoneuritis (coon-
involving the facial, vestibular, trigeminal, and hypo- hound paralysis) in dogs, exposure to an exogenous
glossal nerves, are frequently seen and can be asym- factor, such as influenza virus or raccoon saliva,
metric and fluctuating,893,894,896,905 and even progress respectively, may initiate an autoimmune attack on
weeks after the original onset of signs. Occasionally, myelin.893,895,898,911,913 Indeed, a history of recent vacci-
the involvement of nerve roots other than those of the nation or respiratory illness has been frequently
cauda equina, including cranial and other spinal mentioned in cases of polyneuritis equi,895,896,911 but
nerves, is more prominent and clinical syndromes of by no means this is a constant finding.893,897 Thus, the
such cases of polyradiculoneuritis may thus be role of viruses, such as equine adenovirus, which was
expressed as combinations of focal or multifocal mus- isolated from two of three cases sampled911 in the
cle atrophy, pain, pruritus, sweating, and weakness of pathogenesis of the disease, is still not known.
affected body regions.900–902 Clinically, the syndrome is typical if there is cauda
The original lesion appears to be demyelination equina and cranial nerve involvement. A thorough
that quite rapidly evolves into a granulomatous neu- rectal examination, preferably including transrectal
ritis, perineuritis, and pachymeningitis typically ultrasonography and radiography, is helpful to rule
involving the sacrocaudal nerve rootlets and roots of out a fractured sacrum, which is usually by far the
the cauda equina and some cranial nerves. The severe most important differential diagnosis to be excluded.
neural infiltrate can extend out into peripheral nerves Lumbosacral and, occasionally, atlantooccipital CSF
and muscles.893,896 Sometimes there is diffuse involve- may be xanthochromic with moderately elevated
ment of many spinal nerve roots. Histologically, the protein content and prominent mononuclear pleocy-
latter stage is characterized by a severe, chronic, tosis, at least in the chronic stage due to diapedesis
fibrogranulomatous inflammation involving lym- into CSF,893,895,908 but it can be normal on analysis
phocytes, macrophages, eosinophils, fibroblasts, also.902 Denervation potentials in affected muscula-
giant cells, and neutrophils. There are heavy infiltra- ture of the tail and perineum are evident on needle
tions of cytotoxic T cells and macrophages with lesser electromyography. A cauda equina biopsy should
populations of helper T cells, B cells, and plasma provide a morphologic diagnosis, but this has been
cells.906,907 The early lesion strongly resembles very difficult to obtain in the live patient. The diag-
immune-­mediated neuritis with evidence of a demy- nosis was supported in one case by the finding of an
elinating component.893,895,896,898 Histologically, the intense mononuclear neuritis in a biopsy from the
proliferative lesion also affects the peripheral auto- sacrocaudalis dorsalis muscle.906 Thickened sacral
nomic nervous system, possibly by a simple bystander nerves were also imaged by transrectal ultrasonogra-
effect, although recognition of clinical signs resulting phy in this horse.
from this involvement, such as those of Horner With nursing care and attention to bowel and uri-
syndrome, viz., pupillary constriction and focal nary bladder evacuation, horses have been main-
and selective peripheral vasodilation and sweating, tained for up to a year.896 By contrast to patients with
is rare.908 Guillain–Barré syndrome, which usually resolves
Affected horses have been found to have circulat- over months, even without treatment, polyneuritis
ing antibodies against P2-­ myelin protein.909 An equi signs do not improve. Signs may not progress
enzyme-­linked immunosorbent assay using P2 prep- rapidly, but the horse can become unacceptable to
arations from bovine and equine myelin was pur- the owner. Moreover, with dense denervation of the
ported to be useful in identifying horses with this urogenital tract, salvage for breeding purposes is not
disease.910 Also, indirect immunofluorescence has likely to be successful. Systemic antibiotics to treat
 Infectious, inflammatory, and immune diseases 347

cystitis and systemic and subarachnoid corticoster- with this disease.922 Granulomatous meningoen-
oids and systemic immune modulation with other cephalitis (syn. reticulosis) is a well-­recognized dis-
drugs such as gold salts do not appear to alter the ease in dogs, and variants do occur in particular
ultimate disease course. breeds.61 In general, it is accepted that equine idio-
pathic generalized granulomatous disease is a pro-
grammed immune response to chronic environmental
Supplementary inflammatory neurologic
antigens.917,927 On the other hand, with further cyto-
disorders
logic specification, some of the apparently inflamma-
There are numerous pathologic and clinical diseases tory meningoencephalitides may more closely
and syndromes involving inflammation of neural tis- resemble diffuse lymphoma, meningeal sarcoma, or
sue in small animals and humans, and similar pro- microglioma.927,928
cesses likely occur in large animals.61 This fascinating,
enigmatic group of diseases shares characteristics Sclerosing panencephalitis
with other recognized genetic, infectious, immune-­ Sclerosing panencephalitis occurs in at least two spe-
mediated, neoplastic and toxic diseases, and will cific diseases in humans, namely subacute sclerosing
likely be an area of considerable enlightenment in panencephalitis associated with modified measles
future. virus DNA and progressive multifocal leukoenceph-
alopathy associated with a papovavirus. A novel case
Granulomatous meningoencephalitis of sclerosing panencephalitis has been documented
A collection of cases demonstrating disseminated, in a mature horse showing progressive multifocal
multifocal, granulomatous lesions are documented asymmetric signs including blindness, hypermetric
in large animal internal medicine and dermatology ataxia, and multiple asymmetric cranial nerve dys-
literature and are referred to by several terms includ- function over about 12 weeks.929 Lymphocytic
ing idiopathic generalized granulomatous disease, encephalitis, necrosis, demyelination, and prominent
eosinophilic granulomatous disease, equine sar- fibrillary and gemistocytic astrogliosis dominated
coidosis, multisystem granulomatosis, systemic the lesions widespread throughout the neuropil and
granulomatous disease, and equine histiocytic der- meninges of the brain. Although a diffuse astrocy-
matitis; the first term being preferable for many rea- toma could result in some of the cellular characteris-
sons.914–919 In one case of idiopathic systemic tics, it was concluded that this was primarily a
granulomatous disease in an aged mare, there was a panencephalitis. A search for viral DNA in future
multifocal granulomatous meningoencephalitis and cases is warranted and drug-­induced meningoen-
neurologic signs that followed a short period of fever cephalitis also should be considered930.
and abnormal respiratory signs and consisted of
rapid progression of somnolence, head pressing, Idiopathic eosinophilic meningoencephalitis
excitement, seizures, and recumbency.920 Subacute The occurrence of eosinophils within the CNS is
leukoencephalitis and necrosis were accompanied by abnormal. When present, they are usually secondary
necrotizing vasculitis and large perivascular accumu- to infective, toxic, medication-­related, or paraneo-
lations of lymphocytes, macrophages, some neutro- plastic causes of CNS disease.931–933 Among cases of
phils, and multinucleated giant cells. Several other eosinophilic encephalitis wherein comprehensive
very similar isolated cases have been seen in horses diagnostic efforts fail to identify a cause, a rare, spo-
by the authors, with others being documented.61 radically occurring syndrome of idiopathic eosino-
Drawing a likeness between this idiopathic gener- philic meningoencephalitis (idiopathic EMEM) has
alized granulomatous disease in horses to Vicia vil- been identified in several species of animals, includ-
losa (hairy vetch, and fodder vetch) toxicity in cattle ing the horse.931,932,934,935 Case definitions vary but
and horses921–924 is enticing. These plants contain usually include progressive neurologic signs, particu-
numerous phytolectins that bind lymphocytes925 and larly those referable to forebrain dysfunction,
experimental production of acute vetch poisoning in increased numbers of cells in CSF, including any
a cow resulted in systemic granulomatous lesions in number of eosinophils, and exclusion of other possi-
many organs including in the cerebral meninges.926 ble causes of these signs. Histologic findings are those
Also, nonsuppurative, granulomatous leukoencepha- of eosinophilic and granulomatous meningitis over
litis has been detected histologically in one horse the cerebral cortex and cerebellum and, in
348 Large animal neurology

underlying brain parenchyma, variable eosinophilic resulted in dramatic improvement in signs that were
and histiocytic perivascular cuffing, axonal swelling, entirely dose responsive, and several mild relapses
and neuronal degeneration. A 14-­ year-­
old Dutch occurred as the dose of corticosteroid was decreased
Warmblood gelding was euthanized after the acute in two cases. Two of these cases were followed for
onset of manic violent behavior progressing over 24 h over a year after the immunomodulating drug was
to somnolence, head pressing, circling, recumbency, slowly withdrawn, and they remained fully exercise
and seizure-­like episodes.932 CSF nucleated cell count tolerant.937 Indirect measures of the presence of
was moderately high (184 × 106/L; reference range: serum acetylcholine receptor (AChR) antibodies in
<6 × 106/L) and included 3% eosinophils. Histologic two of the patients were negative although one horse
findings were consistent with idiopathic EMEM. had evidence of circulating IgG that bound to normal
Although often cited as an example of bovine idio- equine muscle membranes. These cases of steroid-­
pathic EMEM, an outbreak of fatal eosinophilic men- responsive, exercise-­ associated, myasthenic syn-
ingitis in a group of five Japanese Black cows affected drome could represent acquired, immune-­mediated,
over several weeks likely resulted from exposure to postsynaptic myasthenia gravis. Extremely unusual
unknown toxin(s) in spoiled silage.934 Some affected forms of other myasthenic syndromes, including
dogs with idiopathic EMEM have responded to corti- chronic botulism, could not be completely dis-
costeroid treatment, so the treatment of equine cases counted. Speculative reasons have been given for the
with dexamethasone or equivalent is worth trying. presence of false-­negative serum tests for AChR anti-
bodies in small animals and humans. These include
Granulomas the production of high affinity antibodies that are
As distinct from cholesterinic granulomas that most strongly bound to the muscle membranes and not
frequently arise from the choroid plexus (see circulating, and antibodies directed to additional
Chapter 37), development of singular or multiple, antigens other than those recognized by the testing
apparently aseptic, large granulomas may have a pre- systems used.
dilection for occurring in the choroid plexuses of the
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 33
Physical, chemical, and thermal causes

DiseasePage DiseasePage

Physical injury 374 Temporomandibular luxation in the horse 381

Traumatic brain injury 374 Temporohyoid osteoarthropathy of horses 381
Carotid air embolism 380 Spinal cord and vertebral trauma 383
Traumatic optic neuropathy 380 Acquired scoliosis, lordosis, kyphosis, and
Squeeze-chute accidents in cattle 381 torticollis390

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
374 Large animal neurology

DiseasePage DiseasePage

Intervertebral disc trauma, degeneration, Facial nerve 396

and prolapse390 Cervicothoracic and thoracolumbar
Sacral, sacrocaudal, and caudal vertebral compressive radiculopathy 397
fracture and luxation 391 Postanesthetic myoneuropathy—see
Avulsion of the cauda equina 392 Chapter 38 397
Injury to peripheral nerves 392 Postpartum paralysis; ‘Downer cow syndrome’ 397
Suprascapular nerve 392 Neonatal acquired paralysis syndromes 398
Axillary nerve 394 Fibrotic myopathy 398
Radial nerve 394 Chemical causes 399
Brachial plexus 394 Intracarotid injection 399
Musculocutaneous nerve 394 Paravertebral injection reactions 400
Median and ulnar nerves 394 Caudal epidural ethanol injections  400
Femoral nerve 395 Thermal causes 400
Obturator nerve 395 Dehorning brain injury 400
Sciatic nerve 395 Heat stress and cardiovascular collapse/shock 401
Tibial nerve 396 Lightning strike and electrocution 401
Peroneal nerve 396 Sunburn402
Cranial gluteal nerve 396 References402

Physical injury France indicated that there were 187 cases of trauma
involving the nervous system, of which 139 were
Traumatic brain injury predominantly vertebral and 48 calvarial. Regarding
­
Head trauma occurs in horses of all ages and com- 77 equine racetrack fatalities submitted for postmortem
monly results from direct kicks by other horses, from evaluation recorded over 3 years in Australia, 10 (13%)
running into solid objects and from rearing up and were associated with head or vertebral fractures.5 Finally,
falling over backward and sideways, thereby striking from a survey of 1400 equine postmortem examinations
the poll and side of the skull. The neurologic signs at one pathology service in North America, 21% of cases
resulting from traumatic brain injury (TBI) depend involved neurologic syndromes and 10% of these were
on the site and degree of concussion, contusion, lac- recorded as fracture or hemorrhage.6
eration, and hemorrhage. Obviously, very young ani- As a cause of sudden death in 268 racehorses, CNS
mals have far thinner cranial bones to protect the trauma was diagnosed in 18 out of 143 cases in which
brain than adults. Traumatic brain injury in adult a pathologic diagnosis was made. These included
ruminants and pigs is usually far less common than 11 with cervical vertebral fracture, 3 with CNS hem-
in horses, partly because of their temperaments, the orrhage, 2 with brain trauma associated with skull
relatively slower speeds they attain and the size and fracture, 1 with CNS injury associated with both
strength of their neurocrania. For this reason, much skull and cervical vertebral fracture, and 1 diagnosed
of the following commentary pertains to the horse. with spinal cord trauma associated with cervical ver-
Regarding relative occurrence and survival, of tebral instability.7
450 equine neurologic cases examined at one Australian Road traffic accidents (RTAs) are a major cause of
referral practice, 26% were recorded as traumatic or frac- TBI in small animals but are thankfully far less fre-
ture cases.1 Of these, 40% involved the brain and/or cra- quent in large animals as only scant data is available
nial nerves, and basilar fractures were the most frequent on the proportion of RTAs resulting in TBI in horses.
lesion found. A similar clinical survey in North America Thirty-­four horses hit by motor vehicles and 13 horses
involving 100 referred equine neurologic cases indicated involved in RTAs while being transported were
that 22 were traumatic, 5 of which involved brain and/or included in a study over 22 years from a single equine
cranial nerve damage with 3 surviving.2 Of 448 horse hospital, 1993–2015.8 Of the 34 horses hit by vehicles,
fatalities involving insured horses in France in 1995, 36 5 (~15%) suffered central (TBI; n = 3) or peripheral (n
(8%) were due to neurologic diseases.3 Another report4 = 2) neurologic signs, and only 1 of the 13 involved in
of 4319 equine necropsies over a 20-­year period in an RTA while being transported suffered a TBI.
 Physical, chemical, and thermal causes 375

Table 33.1 Pathologic and clinical classification of traumatic brain injury in animals^

Effect Extent Damage Clinicopathologic effect Comment*

Primary (mechanical) Diffuse Axonal injury Concussion White matter especially

APP expression
Vascular changes Concussion Unregulated vasodilation
Focal Vascular damage Subarachnoid bleed Common
Parenchymal bleed Cerebrum, basal nuclei, rostral brainstem
Epi-­(sub-­) dural bleed Rare when no open fracture
Contusion Open or closed Cerebrum, thalamus, nerve roots
Laceration Penetration Cerebrum, medulla oblongata
Secondary (complications) Diffuse Hypoxic–ischemic Neuronal ischemia, gliosis Excitatory neurotransmitters
Cerebellar granular necrosis
Brain swelling Progressive, global Breakdown BBB, herniations
Focal Hypoxic–ischemic Edema, gliosis Toxic blood and tissue products
Brain swelling Progressive, focal Perilesional, herniations

^
Modified from Finnie and Blumbergs9 and Finnie.10
* APP: amyloid precursor protein; BBB: blood–brain barrier.

Humane experimental studies and summative that result in secondary effects of TBI are hypoten-
works on TBI in animals are illuminating with sion (systolic blood pressure ≤90 mmHg) and hypox-
respect to understanding the effects and conse- emia (PaO2 ≤ 60 mmHg). Oxidative stress, excitotoxic
quences of trauma to nervous tissues in animals.9–15 damage, inflammation, and mitochondrial dysfunc-
Considerable species differences occur concerning tion ensue, leading to hypoxic/ischemic damage,
the effect of focal brain injury,9,13–15 but the overall brain swelling, and increased intracranial pressure.
classification of traumatic brain injury applies to The latter two outcomes then promote distortion,
all models and clinical settings9,16 as outlined in shifts, and herniation of brain tissue (see Chapter 4,
Table 33.1. Figures 4.7, 4.8 and 4.10).
The pathophysiology and sequelae of TBI involve The damage caused by the primary injury is
primary and secondary injuries to the brain.10,17–19 impossible to reverse (Figure 33.1). The events of
Primary injury caused by the initial trauma involves secondary injury however are potentially managea-
the physical impact to brain tissue from acceleration, ble, so therapeutic actions may be addressed to avoid
deceleration, and rotational forces that can result in or minimize the metabolic cascades triggered by the
cranial fractures, brain laceration and contusion, initial injury and decrease the risks of poor neuro-
parenchymal, dural and subarachnoid bleeding, vas- logical outcome and/or death. Thus, clinical com-
cular occlusion (Figure 33.1) and diffuse axonal mentary is warranted on the outline of TBI in
injury.18,20 However, although localized axonal injury Table 33.1. Due to circumstances beyond control,
certainly occurs in naturally occurring TBI in domes- large animal clinicians can only hope to intervene
tic large animals, documentation of diffuse axonal well after primary events have occurred and thus
injury occurring in these species is less certain.10 This only in secondary events that will be well established
point is of clinical importance to us as the effects of within 2–6 h of primary damage. Notwithstanding,
diffuse axonal injury—­ referred to as DAI—­ in although axonal injury is measurable by amyloid pre-
humans is devastating, often leading to a persistent cursor protein (APP) mRNA expression within
vegetative state and severe residual brain impair- 30 min, it is prominent for months after brain injury
ments. Perhaps most of the profound cases of TBI in and there may be means of limiting this effect. In this
our species do not survive long enough for the clini- respect, downregulation of APP expression at least by
cal and histologic signs of DAI to be confirmed. 6 h post-­trauma can be achieved by post-­trauma
Much attention has focused on the significance of cyclosporine-­A administration in a sheep model.21,22
secondary injury from cardiovascular, inflammatory, Such manipulation may thus have a part to play in
and excitotoxic processes resulting in further edema future therapies. Estimation of the likely duration of
formation, increases in intracranial pressure, and concussion (i.e., temporary coma or semicoma) in
reduced cerebral perfusion. The two major factors large animals often is of vital importance to the
376 Large animal neurology

(A) (B) (C)

(D) (E)

Figure 33.1 This 5-­week-­old Quarter Horse filly was found at pasture compulsively turning to the right and walking in circles to the right. The foal
showed no interest in suckling or otherwise interacting with her dam. A single generalized seizure was observed. Additionally, on close examination, a
defective menace response and facial hypalgesia were found, both on the right-­side. The PLR and palpebral reflexes were normal. These signs were
consistent with marked forebrain dysfunction, with some signs localizing to the left side. (A) shows the foal in characteristic posture. (B) is a transverse
CT image using a bone window at the level of the rostral margins of the osseous bullae showing a minimally displaced fracture/separation of the left
calvarium approximately at the parietal-­temporal symphysis (arrow). (C) is a post-­contrast transverse CT image using a brain/soft tissue window at the
level of the temporomandibular joints and middle fossa. There is patchy hypoattenuation of the left cerebrum lateral to the lateral ventricle without obvi-
ous mass effect. In some images, there was contrast enhancement of the medial margin of the lesion. A necropsy was performed 10 d after clinical onset
and (D) & (E) are post-­mortem images of the left-­side of the brain and a transverse section through the mid-­thalamus, respectively. There is a sharply
circumscribed area of discoloration and malacia evident that involved primarily gray matter of parts of the occipital, parietal and temporal lobes. This very
likely is an ischemic lesion resulting from trauma-­related thrombosis of the middle cerebral artery or its branches.

management of head trauma patients. From a neuro- injury must continue and the prognosis may thus
logic point of view, the loss of consciousness is not of change appropriately.
­consequence in and of itself but decisions as to the In large animals, closed head injuries with no cra-
immediate management of the case must be made. nial fractures can result in thalamic and brainstem
Consider a cattle beast hit by a car on a highway and hemorrhages and in subarachnoid bleeding.
the accident case at an equestrian event. With respect Although the latter should be entirely diffuse and not
to these, the extent of (diffuse) axonal injury likely contained, space-­ occupying, locally compressive,
relates directly to the duration of any initial comatose subarachnoid bleeds do occur. Skull fractures result-
state. Studies have indicated that brain injury occur- ing from injury to the occipital region are usually
ring slowly over a relatively long period (20–30 ms), through the occipital, sphenoid, and temporal bones,
such as occurs with complex impact or acceleration particularly their basilar regions. Hemorrhage from
damage with open cranial fractures, tends to result in the venous sinuses often occurs around, and some-
prolonged coma, whereas a short (de)acceleration times into, the medulla oblongata and often there is
time, as might result from a closed head injury fall, bleeding into the middle and inner ear cavities. True
can result in less primary axonal injury.9 If time can subdural (extra-arachnoid) hematomas, which occur
be allowed for concussion to pass, monitoring the frequently in man, are rare or do not occur at all in
patient for improvement or deterioration of signs large animals. However, large hematomas may form
because of the extent of secondary effects of the in the cerebral hemispheres, usually in conjunction
 Physical, chemical, and thermal causes 377

with fractures of the frontal bones, but not necessar- that may progress to recumbency, and death ensues if
ily forming at the site of impact. Injury to the frontal the medulla oblongata is badly compromised. Such
area results in skull fractures that are often com- progression of clinical signs may well be exacerbated
pound, resulting in direct cerebral laceration and by infection via open cranial wounds.27
hemorrhage. With midbrain hemorrhage usually a period of
With severe brain lesions including TBI, the brain– coma ensues, followed by marked somnolence and
heart syndrome (Figure 32.9) can result in cardiac an abnormal gait or tetraplegia. Usually, there is no
arrhythmias, elevated serum activity of heart-­specific blindness or menace deficit, but asymmetric pupils
enzyme MB-­ CK, and elevated cardiac-­ origin tro- with decreased pupillary light reflexes do occur. The
ponin, all due to myocardial necrosis,23,24 and is a pupils may be smaller than normal and pupillary size
cause of sudden death due to heart failure in large ani- often fluctuates. Progression to bilateral pupillary
mals.25 This syndrome has also been seen with other dilation and semicoma or coma warrants a grave
profound intracranial disorders including fulminant prognosis. This syndrome does not occur frequently
eastern equine encephalitis virus infection. Realization in large animals with TBI.
of the great importance of such relationships between Although it is always tempting to include trauma
the brain and the heart over the last few decades have in a differential diagnosis for abruptly observed
resulted in a burgeoning of the study of the brain– onset of specific cerebellar signs, it is really rare for
heart axis, leading to the discipline of neurocardiol- the cerebellum alone to suffer injury from head
ogy. Fascinatingly, the brain–heart syndrome is likely trauma.28,29 This likely is because the caudal fossa is
the explanation for at least some cases of Takotsubo remarkably well protected by the neurocranium,
Syndrome, aka broken heart.26 the cerebellum occupies most of the infratentorial
Clinically, with prominent cerebral injury, there space and the cerebellum is a more fibrous tissue
is a period of coma from which the horse usually than is the forebrain. These factors likely make the
recovers in minutes to hours. Following regaining of cerebellum less liable to effects from acceleration
consciousness, large animal head-­
­ injury patients and deceleration.
usually have degrees of fluctuant signs of somno- Many times, there is direct or circumstantial evi-
lence, dementia, and even violence. Somnolence, dence that head injury has occurred. In its absence,
wandering in circles, usually toward – but not always sometimes the clinician may wish to perform CSF
(Figure 33.1) – the side of the damaged cerebral hem- collection to help confirm a diagnosis of occult
isphere, and occasionally seizures will occur. trauma. However, this must be performed with con-
Characteristically, the patient is blind with intact siderable caution because of the risk that suddenly
pupillary light reflexes and has decreased facial sen- lowering CSF pressure at the cerebromedullary cis-
sation, both on the side opposite the lesion.27 If there tern will precipitate caudal herniation of brain tissue
is local and/or diffuse secondary brain swelling, then because of brain swelling or hematoma formation.
the swollen cerebrum directly compresses the thala- Collection of CSF from the cisterna magna must not
mus, hypothalamus, and piriform lobe. Such cerebral be undertaken when signs of brain herniations, such
swelling, which may be asymmetric, may result in the as dilated pupils, are evident. Lumbosacral CSF col-
occipital lobe herniating caudally under the tento- lection is safer than atlantooccipital collection or col-
rium cerebelli to press on the midbrain (see Figures 4.8 lection at the C1–C2 site in horses under these
and 4.10). This in turn compresses the oculomotor circumstances, but in the immediate post-­trauma
nerves (CNIII) lying between the midbrain and the phase a sample obtained from the LS site frequently
floor of the cranium. Further brain swelling can will not reflect a change in intracranial CSF. Unless
cause the swollen cerebellum to move caudally and base-­line composition analysis is required such as for
the cerebellar tonsil to be forced through the foramen acute antibody titer and if results of CSF analysis are
magnum and ventrally compressing the medulla not likely to alter handling of the case, then CSF col-
oblongata (see Figure 4.8). These movements of brain lection may best be delayed.
tissue result in deepening somnolence, asymmetric Regarding confirmation of a tentative diagnosis of
pupils, dilation of the pupil with depressed pupillary traumatic brain injury, the use of assays for biomark-
light reflex usually on the same side as the lesion, and ers such as ubiquitin C-­terminal hydrolase-­1 and
sometimes eye deviations and other vestibular signs. phosphorylated axonal neurofilament (pNfH) heavy
Affected animals have marked ataxia and weakness chain in CSF and blood may be useful in future.30
378 Large animal neurology

That pHfH is an indicator of CNS neuronal injury Table 33.2 Key steps in an ideal but quite logical scheme for
in horses is demonstrated by recent studies show- immediate consideration in handling patients with acute traumatic brain
(TBI) or spinal cord (SCI) injury.
ing elevated concentrations of the biomarker in
serum and CSF from horses with cervical vertebral 1. Control (drugs) and resuscitate the patient, and protect airway
malformation,31 equine neuraxonal dystrophy/ 2. Immobilize at scene
equine degenerative myeloencephalopathy,31 equine 3. Rapid transport away from danger
4. Airway, breathing, circulation = first aid
motor neuron disease32 and equine protozoal
5. Aim for normotension
myeloencephalitis.32 6. No glucocorticosteroids
It is worth us considering the use of a “severity of 7. Pain control
TBI scale” for large animals to assist in deriving a 8. Imaging assessment if locally available (CT initially best)
semiquantitative prognosis for survival and outcome. 9. Realign/immobilize bone displacements
10. Consider operative decompression early
This has been performed with the well-­ validated
11. Hyperosmolar therapy
Glasgow Coma Scale in people33,34 and the modified 12. Other medications when indicated
Glasgow Coma Scale for dogs.35–38 These scales deter-
mine a total score of 0 lowest, to 18 worst for severity Other traumatic damage such as fractured long bone may necessitate delaying
some steps, and for many practical reasons some steps may be irrelevant.
of TBI (and spontaneous intracranial events) based
Modified from Shank et al.55
on the level of consciousness (0–6), motor activity
(0–6), and brainstem reflexes (0–6). Usually, the
highest grade of severity over the first 24–48 h is used usefully achieved with balanced combinations such
in formulating a prognosis for survival in the first as an α-­2 agonist drug then ketamine, or midazolam–
instance, with an excellent prognosis given for ketamine–xylazine. An idealized schema for decisions
patients having a score of 0 and a high likelihood of to be considered when handling a patient suffering
nonsurvival given for patients with a score of 13–16. TBI is given in Table 33.2.
A decision should be made as to the need for skull Therapeutic intervention into the secondary cas-
radiographs and other imaging.39–53 High-­quality cades of pathologic events outlined above in clinical
digital radiographic images are certainly useful in human neurologic practice is mainly focused on
defining tissue damage accompanying TBI, and these reducing transmembrane calcium influx, blocking
can be worth obtaining at some stage in cases with effects of released proteases and other focal and diffuse
severe or progressive neurologic signs, in cases with inflammatory mediators, downregulation of amyloid
blood discharge from the ears or nostrils, and in precursor protein expression using cyclosporin-­A,21,22
cases with lacerations and fractures of the forehead. and curbing the progress of localized and diffuse brain
However, moving a compromised large animal swelling. Current evidence regarding best therapy for
patient is not usually a necessity in the immediate traumatic brain injury for large animals is lacking,56
post-­traumatic period. If CT is available, then this is but some guidance can surely be taken from experi-
the imaging modality of choice for diagnosis of skull mental and clinical controlled trials in other species to
fractures (Figure 33.1).54 arrive at acceptable guidelines.11,34,57,58
Immediate care of head injury patients begins with In the past, it has been accepted that large animals
attending to preservation of a patent airway, stopping with substantial neurologic signs following cranial
bleeding, and then treating cardiovascular shock. If trauma probably should receive glucocorticosteroid
no other major damage needs to be evaluated, such as treatment44,59,60 and it may be seen as common prac-
fractured long bone, fractured ribs, and ruptured tice still. The most significant report since that time
lung, then therapy for CNS injury may be instituted. on the subject of treatment of traumatic brain injury
For convenience, sedation of a delirious, thrashing is that of the Medical Research Council Randomized
patient is best performed efficiently with minimal Controlled Trial (CRASH, corticosteroid randomiza-
doses of α-­2 agonist drugs. This is despite the theo- tion after significant head injury).61–63 This extensive
retical problems of transient hypertension that may randomized controlled trial involving over 10,000
exacerbate CNS hemorrhage and then respiratory human patients treated within 8 h of head injury with
depression. If seizures are evident, IV diazepam at follow-­up outcome spanning 6 months was stopped
5 mg (foal) to 25–100 mg (horse) doses, repeated prematurely because of results showing increased
according to effect, is useful. Intractable seizures may mortality in corticosteroid-­treated patients. The sup-
necessitate light-­plane general anesthesia that may be ported doctrine from this study was that “. . . corti-
 Physical, chemical, and thermal causes 379

costeroids should not be used routinely in the ondary effects of brain injury as outlined in Table 33.1
treatment of head injury” (Q.E.D.). This recommen- was underwhelming in convincing clinicians to use
dation to not use corticosteroids in the treatment of such compounds as vitamin E, vitamin C, coenzyme
TBI has been accepted by specialists handling large Q, acetylcysteine, glutathione, and lazaroids. Of greater
and small animal head trauma patients.38,50,64 potential is the use of specifically targeted antioxidant
With blood appearing from the ear, nose or mouth, and other therapies still to be validated.75,76
or when there is an obviously fractured cranium, In general, many large animal neurologists are
tetanus prophylaxis and local and short-­term sys- conservative with medical management of brain-­
temic antibiotic treatment such as penicillin should damaged patients.77 Complications of recumbency
be considered as for any other open wound.65,66 The and multidrug therapy, including laminitis, necrotic
use of glucocorticosteroid and NSAID therapy alone cystitis, decubital sores, gastroduodenal ulceration,
in such cases may well invite secondary infection.43,67 nephrosis, and superinfections, are frequently lethal.
Mannitol and hypertonic saline are regarded as Thus, one should not use glucocorticosteroid drugs
useful in reducing increased intracranial pres- routinely and should be very reluctant to use large,
sure.68,69 If a horse remains in a coma or semicoma repeated doses of furosemide, DMSO, and mannitol
and recumbent for say 10 min or longer, or pro- unless the situation is critical.55
gresses toward such a state, then intravenous hyper- There may be a theoretical role for thiamin in
osmolar fluids are indicated. Either 3–5 mL/kg of modifying altered mitochondrial function in TBI;
20% mannitol, or 5 mL/kg of 3% hypertonic saline however, there is no evidence for its efficacy. Indeed,
(=2 mL/kg of 7.2% NaCl; =1 L of 8× normal saline there appears to be only one trial using pretreatment
per 500 kg horse), given IV over 20 min will reduce of experimental rats undergoing TBI with thia-
intracranial pressure and likely reduce brain min—­at a dose equivalent to 200 g to an adult horse—­
edema.68,70,71 If practicable, checking that serum wherein the vitamin possibly protected 2-­oxoglutarate
[Na+] is <155 mEq/L before administering hyper- dehydrogenase and mitochondrial respiration.78
tonic saline is a reasonable precaution to take. This During therapy for TBI patients, there is some dispa-
therapy may be repeated every 6–12 h for 24 h if rate information offered on optimal levels of blood pres-
there is neurologic improvement following its use. sure, blood glucose concentration, O2 and CO2 partial
Controversially, 1.0 g/kg, 10% DMSO in NaCl solu- pressures, and body temperature to aim for. Suffice it
tion or D5W, slowly IV, repeated one to six times in to say that avoiding major deviations from physio-
72 h, appears to be recommended frequently but logic ranges is very reasonable, particularly avoiding
without documented usefulness whatsoever,27,49,59 hypertension, hypotension, hyperglycemia, hypox-
and the drug is not licensed for use in animals by emia, and hypercapnia.79–83 Other interesting avenues
this route of administration. Renal diuretics, such as of study to improve outcome in TBI patients include
furosemide, probably are not as effective as mannitol dietary restriction,84 new drugs58 and stem cells,85,86
or hypertonic saline in the therapy of swollen CNS and as with most interventions there will be optimal
tissue, and although furosemide is used in treating therapeutic time windows57 that may again prove
TBI in horses,49 usually it is not recommended in the rather impractical in large animal clinical settings.
therapy of brain injured human patients.34,72,73 The Surgical debridement and decompressive craniot-
reversible cyclo-­ oxygenase (Cox) inhibitor drugs omy are indicated when bone fragments penetrate the
(NSAIDs) symptomatically appear to be useful in brain from an open skull fracture and also in horses
alleviating somnolence believed to be the result of that clinically deteriorate or fail to respond to medical
pain in these patients. Because these NSAIDs are management.77 Such deterioration, associated with
generally extremely good analgesic agents in horses, hematoma formation and brain edema, progresses
their use is recommended provided the toxic effects until the animal is in a comatose state with dilated,
of gastrointestinal ulceration and renal disease are unresponsive pupils. These signs are related to caudal
considered, especially in dehydrated patients. herniation under the tentorium cerebelli causing com-
With respect to the use of drugs to supposedly con- pression of the midbrain. The procedures for such
trol the pathophysiologic processes of oxidative stress surgical techniques are given elsewhere.42,50,87
and excitotoxicity that may well play a role in ongoing Barring complications, some amazing recoveries
processes following TBI, an extensive review74 of the occur following brain trauma, especially in horses
use of antioxidant drugs to treat both primary and sec- with cerebral damage,27,43,56,77 and survival rates
380 Large animal neurology

for horses referred for traumatic brain injury and Carotid air embolism
peripheral cranial nerve (VIII) injury have been
Small amounts of air must often be aspirated through
reported at 40–60% depending on the type of injury.56
venous needles and catheters without causing any
Post-­traumatic epilepsy is often suspected, especially
untoward recognizable effects. A few dozen cases of
when a compatible brain lesion is found with
jugular catheter-­associated air embolism in horses
advanced imaging techniques.88
are recorded with signs of general irritation to signs
Repeated evaluations, with documentation of
reflecting probable forebrain involvement, with a
signs, cautious fluid, nutrient, metabolic and nursing
mortality of ~20%. Clinical signs that were usually
support, judicious medical therapy, and time, is the
temporary included tachycardia, cardiac arrhythmia,
basis of the successful management of these cases.
tachypnea, muscle fasciculations, agitation, and pru-
Probably, the commonest neurologic syndromes
ritus, but the presence of sweating, blindness, and
resulting from head trauma in horses involve degrees
seizures carried a rather poor prognosis.90,91 Rapid
of vestibular and facial nerve dysfunction as a result
delivery of 500 mL of air IV to an adult horse likely is
of fractures of and hemorrhage into the middle and
lethal, and it may take at least 100–200 mL of air
inner ear cavities, which can also involve the basilar
given slowly IV to result in early signs of discom-
bones and the brainstem (Figure 33.2).2,41,43,44,47,49,50,56,89
fort.91,92 With paradoxical embolism occurring
Signs basically consist of facial paralysis on the same
through air passing the pulmonary circulation, then
side as the lesion, a head tilt toward the side of the
many organs including the brain can suffer from
lesion, and horizontal or rotary nystagmus with
microvascular air infarction. This can be quite pain-
the fast phase away from the side of the lesion.
ful in humans, which may explain some of the syn-
If hemorrhage occurs around or in the medulla
dromes seen in horses. In the absence of inflammatory
oblongata, there are signs of CNS involvement such
(chemical) infarction, the use of glucocorticosteroid
as somnolence, ataxia, and weakness, with additional
drugs is probably best avoided.90
vestibular and other cranial nerve signs. Considerations
of evaluation and management are essentially as for
Traumatic optic neuropathy
temporohyoid osteoarthropathy below.
“Blows upon the head” have been regarded as a cause
of gutta serena (blindness with dilated pupil) since at
least the nineteenth centuary.93 Following head
trauma, usually from rearing and falling over back-
ward and striking the poll on the ground, horses and
foals sustain peri-­and intraorbital injury.94,95 What
frequently accompanies this is optic nerve and retinal
damage that is usually the result of tearing and shear-
ing forces acting in the region of the bony optic canals
and the optic nerves.95–100 This is likely because the
optic nerves are tethered within the optic canals but
more proximally are free to move with the brain dur-
ing sudden head trauma. More rarely, the optic
nerves may be severed at the site of a sphenoidal bone
fracture.101 Peripapillary then generalized retinal
Figure 33.2 A common site for neural damage following blunt head degeneration along with optic nerve atrophy and
trauma in horses is the basilar region including the temporal, occipital,
exposure of the lamina cribrosa become apparent by
and sphenoid bones and surrounding structures. This horse fell over back-
ward striking its occipital protuberance on the ground with subsequent fundic examination usually 2–6 weeks following the
signs of vestibular and facial nerve dysfunction. There was a fracture traumatic event (Figure 33.3). Both partial and asym-
(arrowhead) at the synchondrosis of the basisphenoid (B Sph) and basi- metric lesions do occur, as well as total permanent
occipital (B Occ) bones. Additionally, there was avulsion of the ventral blindness. Histologically, a tearing or compressive-­
rectus muscles of the head (RCV) from their attachment on the basilar
type lesion occurs to the optic nerve(s) within the
bones (curved arrows). This lesion can result in bleeding into and around
the guttural pouches and avulsion of fragments of basilar bone that may bony optic canal, or more frequently, where the nerve
be seen on radiographs. The sphenoidal sinus (Sph S) is indicated for enters the canal about 2–4 cm behind the globe, just
orientation. distal to the optic chiasm. Hemorrhage, then gross
 Physical, chemical, and thermal causes 381

Squeeze-­chute accidents in cattle

Following the use of a neck clamp, or in a squeeze-­
chute during cattle processing, an occasional animal
has been seen to have a lowered and flaccid mandible
or dropped jaw. The tongue protrudes from the front
of the mouth because of its weight, and the animal is
unable to prehend and chew food. Signs may abate in
days to weeks. Fracture of the mandible and luxation
of the temporomandibular joint have not been
detected, although previous luxation of this joint may
play a role in the syndrome, along with degrees of
masseter muscle injury and perhaps trigeminal
(mandibular branch) neurapraxis.

Temporomandibular luxation in the horse

This injury occurs in association with fractures of the
mandible and is reported to occur alone109 and in
Figure 33.3 Head trauma may cause degrees of central and more often association with local septic arthritis.110 Inability to
peripheral blindness. The latter often results from the pendulum effect of prehend and chew food is seen, the mandible may
the brain moving within the calvarium tearing the optic nerves that are protrude, and the teeth cannot be manually apposed.
tethered at their exit from the calvarium into the optic canal. This results in Differentiation needs to be made from temporoman-
degrees of blindness, suppressed menace response, and decreased pupil-
lary light reflex. This young horse was bilaterally blind from such an injury
dibular septic arthritis that can also mimic masseter,
and the optic nerve degeneration resulted in optic atrophy seen here after trigeminal, and temporomandibular injury.111 Even
about 4 weeks as a pallid optic disc, loss of papillary vessels, exposure of with correction of the luxation under anesthesia, the
the lamina cribrosa, and peripapillary retinal degeneration. total resolution of the problem may not occur.
Mandibular condylectomy has been attempted as a
salvage procedure.112
atrophy, neuronal fiber degeneration, and focal
necrosis occur to a variable degree, followed by astro-
Temporohyoid osteoarthropathy of horses
gliosis.100,102 Some reported cases of optic neuritis and
acquired optic degeneration and associated blindness Temporohyoid osteoarthropathy (THO) with prolif-
in horses103–106 most likely represent traumatic optic erative osteopathy involving the temporal bone, tem-
neuropathy. However, the direct effects of severe porohyoid joint, and hyoid bone, mostly in adult
blood loss102,104,106 and intracarotid injections107 can- horses, is reported worldwide.113–120 It can be subclin-
not be excluded totally from etiologic considerations, ical119,121,122 or results in evidence of behavioral altera-
especially when the history is uncertain regarding tions including head shaking, ear rubbing, bit
precise onset of blindness. avoidance and difficulty chewing, or more often of
As the optic nerve is central nervous tissue, neurologic syndromes, notably various combinations
­treatment considerations are as for traumatic brain of facial and vestibulocochlear nerve dysfunc-
injury; the use of glucocorticosteroids is not tion.115,119,123 The disease does seem to be most com-
recommended.102 mon in middle-­aged horses, and most of the cases
Several negative prognostic indicators have been have bilateral disease as determined by endoscopic,
highlighted in traumatic optic neuropathy in peo- electrodiagnostic, and imaging studies, although the
ple108 and may well apply to horses. Thus, if the overt neurologic clinical signs are most often
patient is aged, has lost consciousness, and if vision unilateral.115,119,123–130
does not return within 48 h, the prognosis is bad for The main bones of the hyoid apparatus are the
return of vision. Because of the blindness dampening bilateral stylohyoid and ceratohyoid bones support-
any accommodation to loss of balance, chances of ing the central basihyoid and paired thyrohyoid
recovery from vestibular damage caused by head bones. The main stylohyoid bones articulate with the
trauma when accompanied by blindness are bad. cranium by the temporohyoid joints and the
382 Large animal neurology

basihyoid helps support the tongue base while the that wear and tear of the temporohyoid joint, vigor-
thyrohyoid articulates with the rostral cornu of the ous oral examinations and procedures, as well as
lateral lamina of the thyroid cartilage, thereby sus- head trauma, are responsible for the initiation and
pending the larynx in its craniocervical position. progression of the degenerative osteoarthritis,122
The equine temporohyoid joint is a permanent ultimately leading to subclinical then clinical tem-
synchondrosis that connects the proximal stylohyoid porohyoid osteoarthropathy.
bone to the petrous temporal bone via a bridge of Physical examination findings may include diffi-
tympanohyoid cartilage making this a relatively low culty chewing, pain induction on external palpation
motion joint that appears to dampen the movement of the parotid area, head shaking, and behavioral
of the hyoid apparatus during eating and phonation.122 problems especially when being ridden.119,127,130,136
The rostral surfaces of the temporohyoid joints and Once the joint is fused, sudden forced head jerking,
proximal and mid-­shaft segments of the stylohyoid falling, teeth floating, nasogastric intubation, and
bones are visible on endoscopic examination of the forceful or prolonged vocalization could cause peri-
guttural pouches. Immediately caudomedial to the articular fractures of the petrous temporal bone
temporohyoid joint is the tympanic bulla of the mid- resulting in an abrupt onset of combinations of facial
dle ear, in the dorsal aspect of which runs the facial and vestibular nerve dysfunction. Vestibular signs can
nerve and further dorsomedial still is the inner ear vary from mild head tilt to head tilt and circling with
and end organs of the vestibulocochlear nerve. prominent horizontal nystagmus with the fast phase
The cause of temporohyoid osteoarthropathy is away from the side of the lesion, to recumbency with
unclear although a traumatic origin is quite plausible seizure-­like activity and willingness to only stay on
in most cases.131 Suppurative inflammation second- the affected side. If the facial nerve is damaged, all its
ary to hematogenous otitis media has been suggested branches are usually affected resulting in ipsilateral
as a cause but rarely proven and indeed no evidence ptosis, muzzle deviation away from the side of the
of osteomyelitis appears to be recorded from patho- lesion, and a dropped lower lip and ear on the side of
logic studies (see Otitis Media and Otitis Interna—­ the lesion. Paralysis of the buccinator muscle results
Chapter 32).120,128–130 If suppurative processes initiated in food accumulating within the paralyzed cheek
this disease, it is surprising that affected horses pouch. Postganglionic parasympathetic fibers in the
rarely have clinical signs of otitis externa or facial facial nerve that innervate the main lacrimal gland
paresis well prior to the proliferative osteoarthropa- may also be damaged, with decreased tear produc-
thy that is most often present at the onset of neuro- tion aggravating the lack of eyelid closure to produce
logic signs. However, there are cases of temporohyoid keratoconjunctivitis sicca. Dysphagia that may be due
lesions, and even of hyoid fracture alone,132 where to poor stylohyoid movement and localized hyoid
chronic aural or periaural suppurative drainage from pain rather than being neurological is rarely observed
the region of the middle ear or from the temporo- and for only a few days following any acute fracture.
mandibular or atlantooccipital joints, that secondar- Affected horses may appear quiet and somnolent fol-
ily could induce chronic bony and cartilaginous lowing a fracture, again probably due to pain and
lesions as seen with temporohyoid osteoarthropathy. inflammation associated with the fracture, but occa-
Notwithstanding, the more plausible hypothesis is sionally, and after several days, this has been associ-
that a nonseptic, likely microtraumatic process results ated with septic or nonseptic secondary meningitis.
in an age-­ related, temporohyoid, osteochondral When CSF analysis can be undertaken, the results
degeneration and proliferation,122 leading ultimately usually are normal but on occasion will reflect such
to ankylosing osteoarthropathy.119,127,133,134 Regardless extension to the meninges with xanthochromia and
of the etiology of the osteochondritis, clinical signs increased protein content and, rarely, high inflamma-
can occur from either the osteochondritis/arthritis tory cell count. Occasionally, an affected horse is
itself or from fractures of the adjacent temporal bone febrile which may suggest more sinister, bacterial
and rarely basilar bones, due to partial or complete inflammation.
fusion of the joint. Clinical signs can be induced Endoscopic examination of the guttural pouch is
during passage of a nasogastric tube,119 and there is a probably superior to plain radiographic imaging in
relationship between crib biting and the disease135 confirming the presence of the disease by revealing
with an odds ratio of 8.1 (95% CI 3.5, 18.5).113 For enlargement of the proximal stylohyoid bone due to
these reasons, and to be speculative, it is possible osteoarthritis when compared to the opposite side,
 Physical, chemical, and thermal causes 383

and evidence of hemorrhage around the region of the difficulties in swallowing encountered and to reduce
temporohyoid articulation can be seen. The disease is the possibility of other real and potential complica-
most often bilateral even though almost all cases have tions of this surgery, including healing of the stylohy-
only unilateral signs and the temporohyoid region oid bone,130,131,146 the technique of ceratohyoid
can occasionally appear normal.131,137 ostectomy was proposed and used with success.131,136
Plain lateral and oblique lateral radiographs are not Currently, ceratohyoid ostectomy113 and a basihyoid-­
quite as sensitive a diagnostic tool as endoscopy for ceratohyoid disarticulation technique147 are other
diagnosing the disease,119 although this accuracy may preferred surgical treatments for this disease.
be improved if true ventrodorsal views can be obtained Except with major cranial fractures and if eye
in standing patients, but may require general anesthe- problems cannot be resolved,131 the outlook for sur-
sia. Excellent imaging of the temporohyoid region can vival with residual neurologic deficits is quite
be obtained using computed tomography, and this is good.113,115,116 Of 33 cases of temporohyoid osteoar-
probably the most sensitive and specific means of con- thropathy for which there were longer term follow-­up
firming the diagnosis.125,133,136,138–141 In acute or progres- details,119 20 survived although more than 50% still
sive cases having ill-­ defined endoscopic and plain had evidence of facial nerve deficits and/or vestibular
radiographic imaging findings, gamma scintigraphy dysfunction. Of the 20 survivors, 70% returned to
may be considered as a diagnostic aid. Monitoring previous level of use. One notable survival factor is
brainstem auditory evoked potential recordings is a that possibly 50% of survivors may have degrees of
very noninvasive procedure that can assist in refining bilateral deafness at least as determined by BAEP
the prognosis in individual cases.121,124,142,143 hearing testing.143 Summarily, despite some optimis-
Treatment-­wise, consideration needs to be given to tic suggestions, if full athletic performance without
the reduction of any acute edema and inflammation, neurologic dysfunction is required, then the progno-
attention to keratitis sicca, and reduction of movement sis with or without surgical intervention must be fair
of the hyoid apparatus; the latter meaning avoidance to guarded for these cases.
of forceful nasogastric intubation and of undue mani­
pulation of the tongue.117 Routine doses of NSAIDs Spinal cord and vertebral trauma
should be provided. In the absence of fever and other
systemic inflammatory responses, suppuration, or Trauma is likely the most frequent known or sus-
central neurologic signs, the indications for prolonged pected cause of acquired spinal cord disease in clini-
use of systemic antibiotics are very infrequent and cal large animal practice. Of 450 equine clinical
minimal. However, common practice has favored this neurologic cases reported, a traumatic cause was
poorly indicated use of antimicrobial drugs, and ampi- diagnosed in 26%, and of these, 50% were spinal cord
cillin, ceftiofur, trimethoprim-­sulfonamide, enroflox- cases with the other half being brain, cranial nerve,
acin, and chloramphenicol have frequently been used, and other peripheral nerve involvement.1 Also, in an
perhaps inadvisedly.115,116,123,128–131 extensive survey of 8833 equine necropsies under-
Several cases have improved with the passage of taken in North America, neurologic trauma
time only to show further signs relative to facial and/ accounted for 20% of the cases, of which 14% were
or vestibular nerve dysfunction in a period of a few vertebral fractures particularly involving the cervical
weeks to a few months time. These would seem to be region.148 From a comparative viewpoint, cattle were
ideal candidates for unilateral surgical disunion of more highly represented in a study involving a
the hyoid apparatus.136 The other important consid- selected series of cases of vertebral fractures in
eration in undertaking surgical treatment is as an 39 large animals, followed by horses then small rumi-
attempt to obviate the chance of the neurologically nants.149 Patients up to 12 months of age were more
profound or fatal complication of a severe adjacent frequently injured, and the thoracic vertebrae were
cranial bone fracture,119,133,140,144 which of course could more often affected followed by lumbar, cervical, and
potentially occur during general anesthesia or even then sacral sites. It takes tremendous forces such as
during standing surgery should that approach be falling over a cliff, somersaulting over a jump, or elec-
considered.145 trocution, to fracture the thoracolumbar region in
Initially, surgical disunion of the hyoid apparatus adult horses, cattle, and swine. Acute injury to the
was performed by the removal of a mid-­shaft portion cervical vertebrae in the region of C5–6 (C6–7 spinal
of the stylohyoid bone.144 To reduce the temporary segments) can result in phrenic paralysis, and cervi-
384 Large animal neurology

cal vertebral fracture/instability was the attributed following injury and in the use of ROS-­scavenging
cause of sudden death of racing thoroughbred horses compounds have continued.159–162
in ~5% of 268 cases in one multinational study.7 Injury to the vertebral column and spinal cord
Racehorses likely more often than pleasure-­ridden (Figure 33.4) involves animals of all ages and breeds,
horses suffer lumbar fractures as there were 38 QH particularly those that are easily frightened, those
and 29 TB racehorses reported with such profound with less supporting axial soft tissues, immature
injuries over a 22-­year period in California.150 Some ­skeletons and long necks, and especially those that
fractures were across the endplates and disc at L5–6 can attain high speeds and perform over jumps.149,163,164
when pre-­existing ventral spondylosis may have con- Consequently, young, uncontrolled, athletic horses
tributed to the event. are vulnerable to vertebral and spinal cord damage.1
The pathophysiology of spinal cord injury is very Unique environmental circumstances may predispose
similar to brain damage discussed above. The presence to thoracolumbar injury and vertebral fractures.165
of less complex functional pathways, vascular routes, Iatrogenic vertebral fractures are reported to occur
and tissue planes might seem to make spinal cord more in heifers manually assisted to deliver a first calf,
damage and repair more straightforward, which is not and in these calves fractures are most common in the
the case. Variations in design of experimental studies thoracolumbar vertebrae, especially involving the
and clinical trials have meant that although there is a caudal epiphysis of T13.166 Pathologic fractures are
plethora of hypothetical mediators, mechanisms of, seen in malnourished young stock. Usually, there is a
and therapeutic strategies for, modifying and re-­ sudden onset of reluctance to move, ataxia, or recum-
directing the primary and secondary effects of spinal bency being peracute and nonprogressive, often with
cord injury and repair, there is no general consensus improvement soon evident. With hemorrhage and
for best evidence-­based, practical advice for the ther- instability acutely, and arthritis and callus formation
apy of this devastating process.151–154 One area that has as time progresses, signs of spinal cord compression
attracted considerable interest is the role of reperfu- can begin or can exacerbate days, months, or even
sion in contributing to the secondary events of hypoxic years following initial injury when the original verte-
and ischemic damage following spinal cord injuries bral insult can model to mimic a primary congenital
and its relationship to functional electrical and clinical malformation.167–169 Falls during athletic performance,
recovery. And one final component of spinal trauma rearing and falling over backward, injury occurring
pathophysiology that is of interest regarding possible during breeding or other mounting behaviors, and
promotion of repair is the role of Olig2-­expressing documented thunderstorms are examples of impor-
ependymal cells that can generate mature astrocytes tant historical factors.
and even myelinating oligodendrocytes at the injury The physical examination may be modified so the
site over the course of several weeks.155 clinician first attends to life-­threatening problems
The duration of spinal cord compression rather and does not move the patient excessively as an
than the measures of decreased perfusion appeared unstable fracture may exist.151 Neurologic signs are
to be more directly related to the degree of damage not always present with vertebral damage; whether
and loss of spinal cord function.156,157 In addition, spinal cord compression occurs likely depends on the
a reduction in reperfusion blood flow following underlying diameter of the vertebral canal of the
release of spinal compression that accompanied individual patient.170 The resulting presenting syn-
methylprednisolone pretreatment was associated dromes are very variable and may be complicated by
with a worse clinical and pathologic outcome.158 evidence of concurrent head trauma.171
These two findings suggest that reduced primary The mid-­ thoracic and mid-­ cervical vertebral
perfusion or increased reperfusion alone are not the regions appear to be frequently traumatized in large
major contributor to the degree of secondary damage animals (Figures 33.4 and 33.5).1,60,172 The occipito-­
occurring. Notwithstanding, a conclusion of various cervical region is also a site frequently affected by
studies is that reactive oxygen species and oxidative external injury, with sub-­and full luxations often
stress have a significant role in progression of spinal present,171,173,174 resulting in syndromes of localized
reperfusion injury such that alleviating oxidative pain only, to tetraparesis, to recumbency resulting
stress has been regarded as an effective strategy for (Figure 33.6). Trauma to T3–L6 results in degrees of
treating spinal cord injury, and studies on the role of paraparesis leading to recumbency, and an affected
oxidative stress in perpetuating spinal cord damage animal of any species may sit on its hind quarters
 Physical, chemical, and thermal causes 385

(A) (B)

(C) (D)

Figure 33.4 Neurologic syndromes due to vertebral and spinal cord injury are common in all species, particularly those patients that are small, immature, or are
easily frightened and reach high speeds. Also, it is somewhat saddening that domestication, with its high-­speed vehicles, sport, and pleasure events involving
animals and nutritional and other managemental changes that domestication imposes, likely contributes in a major way to this truism. On the other hand, it takes
tremendous force to damage the well-­protected thoracolumbar spinal cord in a full-­sized horse, cow, or pig; when this happens, there is usually a potentially
unstable fracture present (A). Significantly, this example of thoracic vertebral fracture in a steeplechase racehorse occurred as the horse fell making a jump and it
occurred in the mid to caudal thoracic column where most bending forces are applied with vertebral twisting. Of note are the vascular channels within the cancel-
lous bone (white arrowhead) leading to the medial openings (yellow arrowhead) where the blood from each vertebral centrum drains into the ventral vertebral
venous plexuses situated on the floor of the vertebral canal. Damage to these structures can lead to progressive epidural hemorrhage.
The next image (B) is an example of compressive disc trauma at C2–3 in a ram that had been fighting and butting its pasture mates. Hemorrhagic
necrosis and rupture of the disc (yellow arrow) has occurred with epidural disc material and blood compressing the spinal cord. This is not primary degen-
erative intervertebral disc disease.
Many vertebral fractures in large animals cannot be seen using routine radiographic techniques. Cervical fractures occur more often than thoracolumbar
fractures but even there, undisplaced fractures such as this one (C) involving the base of the left cranial articular process of C5 (red arrowhead), was not
initially evident on lateral radiographs. Other common sites for fractures of cervical vertebrae in horses are also depicted (red bars).
Progressive epidural hemorrhage can occur, resulting in delayed onset and/or progressive clinical signs of spinal cord compression after a traumatic
event. Such was the case here (D) in a horse with acute but progressive tetraparesis and ataxia that sustained a massive epidural hematoma (outlined in
white) compressing the spinal cord (outlined in yellow) within an intact vertebral canal (outlined in light blue). There were no vertebral fractures found and
the left (Lt) and right (Rt) caudal articular processes and the intervertebral disc (IVD) were intact.

with thoracic limbs supporting the body in a so-­ adopt this posture preferentially without there being
called dog-­sitting position. Such a posture is regarded neuromuscular weakness of the pelvic limbs. Of clin-
as more abnormal in ruminants than other species ical significance is the fact that thoracolumbar verte-
due to the normal manner of rising from recum- bral injury resulting only in acute, mild ataxia, and
bency utilizing the pelvic limbs first in those species. paraparesis as opposed to paraplegia is uncommon
However, bulls and rams do seem to sometimes in adult, heavy large animals.2 Considerable force is
386 Large animal neurology

tinence, and mild to moderate gait abnormalities in

the pelvic limbs and caudal rump muscle atrophy.
Degrees of hypalgesia, hypotonia, and hyporeflexia
of the perineum, tail, and anus occur (Figures 27.3
and 33.7).
Diffuse or patchy and localized sweating can
result from adrenaline release and sympathetic den-
ervation (decentralization) respectively, in horses
severely affected by spinal cord injury. Particularly
frightened animals may be frantic as a result of pain
and their inability to stand making neurologic evalu-
ation problematic. However, watching for the degree
of voluntary effort in neck, forelimbs, trunk,
(A) hindlimbs, and even tail can assist in localizing a
lesion.
Spinal shock refers to the state of flaccid paralysis
and areflexia caudal to a thoracolumbar spinal cord
lesion that can accompany paraplegia in mammals
following peracute spinal cord injury.175,176 In dogs,
return of perineal and anal reflex function occurs
first in a few minutes followed by patellar reflexes
and then flexor reflexes within several hours.177
This phenomenon also has been observe in at least
horses but is extremely short lived, probably lasting
no more than many minutes. Notwithstanding,
this must be kept in mind when attending equine
sporting event casualties. It is signs such as persis-
tence of paraplegia, rather than the suspicion of the
presence of spinal shock in the form of apparent
hindlimb areflexia, which should be used to guide
the development of a prognosis. Another immediate
(B) consequence of peracute, severe, usually cranial tho-
racic spinal cord damage, is the Schiff–Sherrington
Figure 33.5 The strength of intervertebral discs and dorsal longitudinal
phenomenon in which there is extensor hypertonus
ligament in horses is attested to by cases in which the dorsal articulations
are no longer supportive and even part of the physeal end plate support is in otherwise functionally normal thoracic limbs.
missing. Such is the case here in this weanling foal that injured its neck This does occur but is infrequently encountered
and suffered cervical stiffness and deformity (A) with no evidence of dam- and short lived, to the extent of a few days, in large
aging the spinal cord. Radiographically (B) there was a luxation of C4–5, animals and is not considered a definitive prognostic
a partial laminectomy sparing a spinal cord catastrophe of the caudal arch
indicator in any species.2,168,178–180 Again, results of
of C4 (white arrow), and a fracture and displacement of the ventral 1/3rd
of the physis of C4 still attached to C5 (curved yellow arrow). These radio- evaluating for persistence of other signs of neurologic
graphic lesions healed with permanent lordotic fixation and fusion at dysfunction will guide an appropriate treatment
C4–5 but minimal clinical deformity. The filly became a useful riding horse. plan and prognosis.
For restraint, it may be necessary to utilize chemical
sedation with α-­2 agonist drugs for example, or to use
required to damage T–L vertebrae in these patients light-­plane general anesthesia to contain a thrashing
and most often, if the spinal cord is compressed at all, patient suspected of suffering from vertebral and spi-
then any associated vertebral fracture is likely to be nal cord injury. If signs are mild, it may be best to do
or to become unstable, and the patient becomes para- nothing but enforce rest.2,181 Certainly, the judicious
plegic and recumbent. use of NSAIDs is appropriate, where it is necessary to
Sacral fractures damaging the S1–Ca neural seg- relieve pain and inflammation. It has often been pro-
ments result in degrees of urinary and fecal incon- posed that in most large animal patients, if neurologic
 Physical, chemical, and thermal causes 387

(A) (B)

(C) (D)

Figure 33.6 The cranio-­cervical region is frequently damaged with neck and head trauma in large animals. Surprisingly, the atlas can be bilaterally
luxated on the occiput without overt fractures being present. Fractures of the dens from the body of the axis usually cause spinal cord compression but
tearing of the strong ligaments of the dens can occur without fractures and can result in combinations of neck stiffness and overt pain on manipulation
with or without ataxia to recumbency. Palpable and audible crepitus can accompany these lesions. This particular horse suffered tearing of the ligaments
of the dens (C and D, yellow arrow), seen on the radiograph (A and B) as separation of the dens dorsal and slightly cranial to the body of the atlas causing
narrowing of the vertebral canal between the dens and the caudal edge of the arch of the atlas. The reference measurement for this distance in normal
weanling foals and yearlings is 29 ± 2 mm (n = 16; min = 26; max = 34) and in this adult horse was approximately 24 mm. The gross postmortem speci-
men of these structures (C and D) shows the degree of separation of the dens from the body of the atlas.

signs resulting from spinal cord injury are moderate or

severe, then they probably should be given glucocorti- ‘To date, there is no accepted, scientifically valid evi-
costeroid drugs such as 0.05–0.25 mg/kg dexametha- dence supporting the use of methylprednisolone or any
sone IV, BID to QID for 48 h unless immediate surgery other medication as a neuroprotective agent following
is considered.44,60 In fact, the evidence for benefit from acute traumatic spinal cord injury.’55
such routine treatment of spinal cord injury in any
species is weak, at best. One strategy for which there Multiple, large, randomized, clinical trials of the
has been some evidence for improvement in morbid- National Acute Spinal Cord Injury Studies185,186 indi-
ity in treating spinal cord injury in humans is high-­ cated that high-­dose, 24-­h infusion of methylpredni-
dose methylprednisolone therapy, begun within 8 solone started within 8 h after an acute closed spinal
and preferably within 3 h after trauma.182–184 This drug cord injury is not a standard treatment nor a guide-
regimen consisted of 30 mg/kg methylprednisolone line for treatment, but is a treatment option for which
sodium succinate IV, followed by an IV infusion of there is very little level II and III evidence.182,187 Given
5–9 mg/kg/h methylprednisolone for 24 h if begun that there certainly are notable side effects of high-­
within 0–3 h of trauma, or for 48 h if begun 3–8 h post-­ dose glucocorticoid therapy in our patients, it is rea-
trauma. Such therapy for large animals is essentially sonable to conclude that there is no usefulness in
impossible. No other regimen of glucocorticoid ther- routinely administering such drugs to large animal
apy has been confirmed to have clinical efficacy. patients suffering spinal cord injury.
388 Large animal neurology

fluids are indicated when clinical signs of spinal dys-

QUESTION: Does the administration of a specific
function are marked or are deteriorating. Either
pharmacologic agent (e.g., methylprednisolone) improve
3–5 mL/kg of 20% mannitol, or 5 mL/kg of 3%
clinical outcomes in patients with thoracic and lumbar
hypertonic saline (=2 mL/kg of 7.2% NaCl; =1 L of 8
fractures and spinal cord injury?
× normal NaCl solution per 500 kg horse), given IV
RECOMMENDATION: There is insufficient evidence
over 20 min will likely reduce spinal cord edema.
to make a recommendation; however, the task force
There is however only little experimental evidence
concluded that the complication profile should be care-
for utility of this form of therapy when given well
fully considered when deciding on the administration
after the traumatic event.191 The same goes for the
of methylprednisolone.
use of diuretics such as furosemide in spinal trauma.
Strength of recommendation: Grade, Insufficient.188
In recumbent horses, the use of such diuretic com-
pounds should be accompanied by means to drain
The use of other drugs to treat large animal spinal the bladder.
cord injury patients is even more empirical.44,151 The Other compounds have been used but their accept-
same comments regarding DMSO, furosemide, and ance as routine therapy for spinal cord damage must
mannitol as were made above for traumatic brain await evaluation by modern assessment protocols
injury can hold. Thus, intravenous hyperosmolar and appropriate controlled clinical trials.192 There is a
plethora of individual publications lauding the use of
a great many antioxidant and neuroprotective thera-
The potassium-­ sparing mild diuretic amiloride may
pies claiming to show protection against the effects of
have benefit in treating spinal trauma via its inhibition
spinal cord injury in experimental models.159,192–200
of proton-­gated ion channels that may promote func-
However, the use of all such compounds to improve
tional oligodendrocyte populations at the site of injury
outcomes in cases of spinal cord injury requires con-
and an improvement in motor functional recovery.189,190
trolled clinal scrutiny.
Antibiotics probably are not required for closed
vertebral fractures or spinal cord trauma, but may be
necessary to treat concurrent wounds, cystitis, and
pneumonitis, especially in recumbent patients.
Finally, although still to be fully investigated, mention
must be made of some of the promising progress
being made in the area of spinal cord repair using cel-
lular transplantation and biomaterial implantation
strategies in clinical cases of spinal cord injury,85,86,201–206
with early studies being undertaken in horses.207

In the final analysis, if a dramatic improvement occurs

in the specific neurologic deficits of a patient with spi-
nal cord trauma following a particular treatment, then
that treatment was probably indicated and considera-
tion should be given to repeating it.

Once an initial neurologic evaluation is complete

and emergency treatment plan decided upon, an
­initial prognosis is frequently requested. The outlook
Figure 33.7 Cattle that sustain trauma to the tail head, usually from must be regarded as being guarded for all recumbent
being ridden by other cattle, can sustain combinations of signs related to large animal spinal cord injury patients.2,181 However,
the cauda equina and a postural and gait abnormality related to sacral much may be gained and little lost if final judgment
segment and nerve root damage. This is usually seen as shown with the
animal standing with the affected limb placed forward and knuckled at
is withheld for one to several hours, provided the
the fetlock with the foot standing flat on the ground. Colloquially, these patient’s suffering can be ameliorated. Considering
animals are referred to as knucklers. the acute phase of experimental spinal cord trauma,
 Physical, chemical, and thermal causes 389

the functional loss is far more profound than that potentials found by electromyography on a patient
expected from the morphologic changes that can be with focal spinal cord trauma would be strong evi-
seen in the spinal cord. Consequently, if continued dence for a multifocal mechanism likely to be one
compression is halted and further damage is pre- other than injury.
vented, the return of functional integrity can be Hematologic, chemical, serologic, and other tests
remarkable, even in patients receiving no immediate can be useful in abbreviating the differential diagnosis
drug. Above all, time and good nursing care are para- of spinal cord trauma cases. However, a hematologic
mount to a successful outcome.208–211 stress pattern, unconjugated hyperbilirubinemia,
Radiographic evaluation is an indispensable diag- azotemia, and chemical and enzymatic evidence of
nostic aid, particularly if decompression and external soft tissue and possibly bone damage all can be
or internal fixation are to be considered.174,212,213 expected in recumbent heavy animals.
Radiography is also useful in detecting chronic oste- Manipulation of misaligned vertebrae is not a
oarthropathy especially at C6–T1, which is present in ­procedure to undertake lightly. However, in selected
some acute, dramatic wobbler cases in which moder- circumstances and to decompress an ongoing com-
ate external injury can precipitate the onset of severe promised spinal cord, this can be successful.222,223
spinal cord compression.214 Particularly for the neck, Mostly these cases will involve subluxation or luxa-
and for all sites in smaller patients, modern imaging tion at the atlantooccipital and atlantoaxial articula-
modalities have greatly improved the precision of tions. Techniques for external fixation using newer,
detecting injury sites and facilitated planning for lightweight casting materials can be useful, especially
surgical decompression and repair.171,215,216 With
­ in smaller patients such as foals, goats, and calves.87,224
­further clinical usage, transcranial magnetic evoked, However, some horses struggle against the presence
multisite potential recordings should assist in defin- of such casts, necessitating their removal.
ing the site and possibly extent of spinal motor tract Selection of patients is vital to any successful surgi-
lesions in large animal vertebral trauma patients.217–221 cal intervention.225 Certainly, some cases of cervical
Transcranial electrical stimulation motor-­ evoked vertebral trauma and fractures with subluxation occur
potential studies may be a feasible alternative to the and heal amazingly well. Thus, the overall clinical pic-
magnetic evoked technique.217 If surgical decompres- ture should be included in any decision as to whether
sion of the spinal cord and vertebral stabilization is surgical intervention is required and one must treat
not a viable option, then moving large awkward the patient and its attendant neurologic problems and
patients should wait until signs are stable so that the not the radiographs.216,226 Surgery is probably to be
chance of further vertebral misalignment is reduced. considered if the patient’s neurologic condition dete-
Collection and analysis of lumbosacral CSF from riorates after appropriate medical therapy, and if
animals that may have suffered spinal cord trauma decompression of the spinal cord with stabilization of
but that show no signs of brain involvement is prob- vertebral body malalignment is feasible227 Surgical
ably safe and sometimes of help in ruling out other texts are available describing these techniques.87,228,229
causes of peracute spinal cord disease such as viral, Particularly in small patients, which are far easier to
verminous, and protozoal myelitis. Firm evidence of manage pre-­and postoperatively, the modification of
subarachnoid hemorrhage may not always be found several of the surgical techniques for decompression
on analysis of CSF in spinal cord trauma cases. In and internal fixation devised for small animals230 is
fact, results of CSF analysis in such animals often are worth considering.87,212,216,226,231–238
normal. Although exceptions are reported,212,237,238 the
Electromyography has not proven to be very prognosis for patients, particularly horses, suffering
much utilized in helping localize the site of subacute from spinal cord trauma associated with luxations or
or chronic spinal cord trauma in large animals. This fractures of the vertebral body, arch, or articular pro-
lack of utility probably reflects both the time cesses is guarded to poor for return to use. Healing of
required to needle-­sample potentially denervated such fractures frequently results in some degree of
muscle fibers and the interference problems vertebral misalignment, sometimes with lordosis,
encountered when needle electromyography is per- kyphosis, scoliosis, or torticollis. Even after apparent
formed in standing patients. Evidence of denerva- healing and resolution of neurologic signs, delayed
tion of muscle only appears a week or two after callus formation and degenerative changes in adja-
damage to the ventral gray matter or spinal nerve cent articulations (the so-­called domino-­effect) can
roots. Prominent multifocal or diffuse denervation result in further spinal cord compression.
390 Large animal neurology

No simple rules can be given for the management accompanied by regional pain has been seen in dogs
of large animal patients suffering from spinal cord and man244 and in suckling foals. These syndromes
trauma, but two points are worthy of emphasis. First, are associated with forms of myelodysplasia such
thorough and repeated neurologic examinations help as hydromyelia and syringomyelia that may be
the clinician arrive at a more accurate prognosis and acquired.244
are paramount in documenting progress of the case. With uncomplicated wryneck, external bracing
Second, no individual medical or surgical therapeu- has worked well when done early during the syn-
tic regimen is more singularly beneficial in healing drome.87 General anesthesia may be needed to rea-
spinal cord injuries than time, and time alone can be lign the neck and apply a cast. Vitamin E and
the most beneficial factor in determining the patient’s selenium therapy should be considered where a
outcome. Hasty decisions to euthanize animals nutritional myopathy is likely.
should not be made, with due consideration given to
pain and suffering of the patient.
Intervertebral disc trauma, degeneration,
and prolapse
Acquired scoliosis, lordosis, kyphosis,
It has for some time been accepted that cervical
and torticollis
intervertebral discs (IVDs) in the horse are usually245
Foals, ponies, goats, calves, and lambs are most often or always246 devoid of a pulpy nucleus, consisting
affected by known and suspected trauma-­associated only of fibrocartilaginous tissue. However, all equine
misalignment of the vertebral column. The deformity IVDs appear to have a grossly and histologically dis-
most often involves the cervical region with degrees cernible proteoglycan-­rich nucleus pulposus distinct
of lateral curvature (scoliosis), extension (lordosis), from a lamellar collagenous annulus fibrosis. There is
flexion (kyphosis), or combinations thereof (torticol- a lack of demarcation between nucleus and annulus
lis). Most often there is a sudden onset of cervical tor- making the equine disc different from that in dogs
ticollis, also referred to as wry neck, whether or not and man.247,248
the animal has a history of trauma or signs of spinal Certainly, degenerative changes consisting of
cord compression. In the acute stage of the disease, nuclear fibrillation, cleft formation, and yellow dis-
the twisted neck sometimes can be straightened, at coloration occur in equine IVDs with age, and are
least to a degree, but later this becomes impossible. most prominent at C5 through T1 compared with
Usually, ataxia or weakness is not present. other regions.248 However, primary chondroid meta-
Radiographs are often not helpful because no bone plasia and hyalinization as seen in IVD degeneration
lesions are initially detected. A few cases show evi- in dogs and humans249–252 are still to be shown in
dence of cervical myopathy, which is based on the horses. The familial intervertebral disc degenerative
examination of muscle biopsy and on serum CK disease as seen in humans appears to have a multifac-
activity and selenium status.239 Many cases are eted cause. Which factors initiate the events in the
assumed to involve traumatic subluxations of verte- degenerative cascade is not clear but most evidence
brae. A high frequency of wryneck occurred over a points to genetic predisposition to an age-­related
few years in a dairy goat herd in Australia,240 which process influenced by mechanical and other environ-
might suggest a nutritional factor. The potential mental factors,252 and the situation in dogs appears to
involvement of Parelaphostrongylus tenuis causing be very similar for both chondrodystrophic and non-
asymmetric dorsal column poliomyelitis and loss of chondrodystrophic dogs.253 That chondroid metapla-
neck proprioception must be considered a cause in sia is yet to be shown as a clear feature, along with the
any herbivore where this and other neurotropic presence of prominent yellow staining that likely rep-
Metastrongyloid helminths exist (see Chapter 32).241,242 resents old hemorrhage, do suggest that repeated
In this regard, flaccid not fixed scoliosis, localized trauma is a major factor in the age-­related, common,
cervical hyporeflexia, no muscle atrophy or electro- degenerative process recorded for equine disc dis-
myographic evidence of final motor neuron involve- ease.245–248 The situation for other species remains not
ment, asymmetric mild ataxia and weakness evaluated.
ipsilateral to the hyporeflexia, and aseptic eosino- At least in horses, fibrocartilage can be forced
philic spinal fluid should be searched for to corrobo- through circumferential collagen of the annulus, dor-
rate such a lesion.243 Progressive, acquired torticollis sally and ventrally, and encroach into the vertebral
 Physical, chemical, and thermal causes 391

canal or ventral vertebral region with or without dally while sacrocaudal luxation will initially com-
signs of compression of the spinal cord or of localized press the caudal roots only. Obviously, with further
pain.247 Cases wherein there has been spinal cord movement of bones and fragments, and subsequent
compression are documented as intervertebral disc hemorrhage following initial injury, signs of involve-
prolapse.254–259 It seems that primary trauma, includ- ment of nerve roots and spinal segments cranial to
ing repeated trauma as age-­related wear-­and-­tear, S2 and to other soft tissue damage do occur.266 Thus,
still remains as the very likely cause in most of these the major syndromes seen depend on the level of
equine cases, making them distinct from the familial, neural damage and are variations of: a) tail paresis;
canine intervertebral disc disease with primary chon- b) tail, anal, rectal, and urinary bladder paresis; c)
droid metaplasia and hyaline degeneration of the such cauda equina syndromes along with gait and
nucleus pulposus resulting in secondary extrusion of posture defects of the pelvic limbs, especially sciatic
abnormal disc material. paresis (Figure 33.7).267,268 Degrees of paresis to
Once fibrocartilage from the disc is traumatically paralysis are accompanied by hypalgesia to analgesia,
forced into the vertebral bony end plates and verte- hyporeflexia to areflexia, and hypotonia to atonia
bral cancellous bone, a cycle of inflammation, granu- around the tail and perineal region (Figure 27.4). In
lation, and further necrosis occurs.254,256 This process the acute stage following trauma, there can be evi-
that most probably is traumatic in genesis likely con- dence of marked pain response evidenced by recum-
tributes to the self-­ perpetuating process of dis- bency, unusual posturing, kicking out, and apparent
cospondylosis in the cervical and thoracolumbar signs of colic.
regions260 as described in Chapter 38 (Figure 38.9). Cases of sacral and caudal vertebral fracture/luxa-
Also, with ageing and wear and tear, discoloration tion most commonly occur in heavy animals falling
and fissure formation are described affecting the cer- over backward onto the rump, in cows in estrus being
vical intervertebral discs, the C5 through T2 discs in ridden by pasture mates, and in calves traumatized
particular,246,248 which is also thought to contribute to by being heavily struck on the caudal rump
the initiation of discospondylosis. (Figure 27.3).267,269,270 Occasionally, the acute onset of
Notwithstanding this discourse on terminology, neurologic signs has occurred in horses days to weeks
on rare occasions soft tissue epidural compression of after the primary sacral fracture occurred. This unu-
the cervical and thoracolumbar spinal cord by fibro- sual pathogenesis has been determined to be caused
cartilage and inflamed tissues with combinations of by temporary but chronic stability of a sacral frac-
ataxia, weakness, and vertebral pain resulting can ture, which becomes unstable with further move-
occur slowly or rapidly.254–258,261–265 These cases are to ment or with the exertion of racing for example.
be evaluated as other forms of spinal cord injury, and With time, and probably related to axonal sprout-
surgical decompression and stabilization can be con- ing and sensory neuroma formation, circumferen-
sidered. The potential for later continuation of the tial perineal regions of hyperesthesia and allodynia
process of discospondylosis (Chapter 38) must be occur, often seen as apparent perineal pruritus.271 In
taken into consideration in arriving at a prognosis. horses, a fractured S2 very consistently occurs
resulting in a dilated rectum with fecal retention
and a paralyzed urinary bladder with urinary over-
Sacral, sacrocaudal, and caudal vertebral
flow, but with little or no gait abnormality being
fracture and luxation
present. In cattle, both sacral and caudal sites of ver-
With trauma to the dorsal sacrocaudal vertebral tebral damage occur as the crushed tail head syn-
region, there are two sites where fracture and l­ uxation drome and abnormal posturing and reluctance to
most often occur. The first sacral vertebral body is move indicate regional pain present at the onset.
well fixed by the very firm lumbosacral articulations Some affected cows have only a flaccidly paralyzed
leaving the remainder of the sacral plateau to act as a tail.270 Others with sacral damage not only show tail,
lever for dorsal forces rendering the S2 body most anus, rectum and urinary bladder involvement, but
liable to fracture (Figure 27.3). The sacrocaudal and also, unlike affected horses, show signs of sciatic,
first intercaudal articulations are the most flexible in especially peroneal nerve involvement with fetlock
this region and are thus more liable to luxate with knuckling,272,273 probably reflecting hemorrhage and
dorsal forces applied. Fractures through S2 initially contusion spreading cranially within the vertebral
result in damage to the cauda equina from S2 cau- canal.
392 Large animal neurology

Signs are generally stable or they improve over Injury to peripheral nerves
weeks to months, and although evidence of regional Readers are referred to Figure 2.15 for areas of cuta-
pain, postural abnormalities and gait abnormalities neous insensitivity, or autonomous zones, likely to be
resolve, residual urinary and fecal retention and encountered with specific and selective peripheral
tail flaccidity can be unacceptable. Occasionally, a nerve injury in the horse.276–278 The discussion below
callus will form and result in delayed and progres- relates to specific peripheral nerves frequently
sive signs. affected by external injury based on selective experi-
Careful palpation of the sacrum through the rec- mental studies and particularly on well-­documented
tum often reveals a fracture site with or without cal- clinicopathologic case material.60,279–287 It should be
lus formation. Repeated rectal examination carried recalled that in practice one often is faced with varia-
out on a flaccid rectum must be performed with cau- tions of these syndromes due to variable degrees of
tion as mucosal tearing can easily result. Also, slight nerve damage and damage to other soft tissue and
asymmetry of the ventral sacrum can be felt in nor- sometimes bone. Generic principles of the manage-
mal horses. Radiographs to include the vertebral ment of peripheral nerve injuries in large animals are
bodies in the area are possible, but they can be difficult discussed in the suprascapular nerve section below.
to undertake and to interpret. This is the case even The more common neurologic syndromes seen in
with good evacuation of the rectum and even with large animals resulting from injury to the thoracic limb
rectally held X-­ray film. Ultrasound examination of reflect suprascapular, axillary, and radial nerve damage,
the sacrum via the rectum can be worth undertaking although many if not most radial paralysis syndromes
to confirm a fracture site, and scintigraphic examina- are likely due to injury to the brachial plexus between
tion can confirm lesion site(s).274 the scapula and the thoracic wall rather than to the
A flaccid tail can be removed for cosmetic and individual nerves that are well protected and difficult to
hygienic reasons.271 The fracture site is usually acces- selectively damage from blunt trauma.
sible from a dorsal approach for exploratory surgery
and removal of any tissues compressing the cauda Suprascapular nerve
equina.271 If surgical decompression and/or stabiliza- This nerve is commonly damaged in horses colliding
tion are to be considered,275 then they probably against objects or other horses and by ill-­fitting neck
should be performed within 3–4 months of trauma to harness in draft animals. This fact partly reflects the
allow time for reinnervation to occur before dener- course the nerve takes around the neck of the scapula
vated structures become degenerate. Conservative about 6–10 cm dorsal to the tubercle. This site is vul-
treatment is usually undertaken, and signs are moni- nerable to direct trauma and is also a region where
tored as with any peripheral nerve disorder. scapular fractures occur.288 The syndrome, with
Without clinical improvement in 6–12 weeks, the ­eventual atrophy of supraspinatus and infraspinatus
prognosis for substantial long-­term improvement is muscles (Figure 33.8), is called Sweeney (syn. swinny =
bad. In horses, as with the less common disease pol- atrophy; Sweeney also is a type of horse-­ collar).
yneuritis equi, genital denervation warrants a Lateral subluxation or slipping of the shoulder upon
guarded prognosis for breeding, especially for weight-­bearing may be seen, and this appears to be
stallions. more common following acute shoulder trauma than
chronic shoulder pressure in draft animals.289 This
lateral shoulder slip can result from a lack of collat-
Avulsion of the cauda equina
eral support to the scapulohumeral joint and can be
This has occurred with heavy cattle and horses being due to paralyzed suprascapular muscles.290 However,
assisted to move or to stand with tail ropes. Excessive there is some evidence that it can also be associated
tail restraint may be a cause in cattle. The clinical with the involvement of additional structures such as
syndrome is complicated by degrees of caudal and the pectoral nerve, the subscapular branch of the
adjacent perineal traumatic cellulitis. The nerve roots axillary nerve, caudal cervical nerve roots, the pecto-
comprising the cauda equina can be stretched or ral, subclavius, and subscapular muscles, and other
torn. If no luxation of the caudal vertebrae occurs, supporting structures of the shoulder.279,291–293 In the
the neural lesion is most likely a neurapraxia with immediate post-­traumatic period, the patient often
degrees of axonotmesis, which has been seen to demonstrates regional pain and reluctance to use the
improve and even resolve with time. forelimb. At this stage, several other acute musculo-
 Physical, chemical, and thermal causes 393

rapid over a few days. Axonotmesis refers to damage to

the delicate axons with sparing of their sturdy Schwann
derived myelin sheaths. Neurotmesis describes
cell-­
local loss of integrity of axons and their myelin sheaths
and does not often occur following blunt trauma with
no penetration of skin. Return of function for the latter
two classes of nerve injury relies on axonal regrowth
that at best can be expected to occur to a distance of
about 300 mm over about 6–12 months before there is
irreversible muscular fibrosis and total functional
failure of the innervated structures. Modest exercise
and physiotherapy are probably conducive to axonal
regrowth, but further damage to malfunctioning joints
and associated soft tissues must be avoided.
Electromyographic examinations are helpful to detect
the involvement of other nerves of the brachial plexus
that may be affected by injury to the pectoral limb
when performed about 2 or preferably 4 weeks after
the traumatic event, thus allowing time for typical
muscle atrophy and spontaneous denervation poten-
tials to develop. Ultrasonographic study of the
region298,299 may allow the identification of present or
potential fibrous entrapment of the nerve. The degree
of any muscle atrophy can be documented serially
Figure 33.8 Known and suspected trauma to the proximal forelimb,
especially in horses, often results in immediate degrees of lameness that by ultrasonography or by needle depth gauge, or by
may resolve quickly or become expressed in degrees of monoparesis to circumferential tape on the more distal limb where
monoplegia. In the absence of musculoskeletal injury, such trauma often appropriate.291 From about 12 weeks postinjury
causes damage to the brachial plexus and/or the suprascapular nerve. onward, if muscle bulk and shoulder abduction are not
These may be due to neurapraxia or degrees of neurapraxia and axonot-
improving then giving consideration to exploring the
mesis for the most part resulting in temporary or more permanent lame-
ness. With suprascapular nerve damage as shown here, some atrophy of site of nerve damage to relieve any entrapment or to
the suprascapular muscles will occur resulting in prominence of the spine perform anastomosis is appropriate.
of the scapula (arrow). Although not present in this case, some lateral With maximal axonal regrowth occurring at about
subluxation of the shoulder joint may occur on weight-­bearing. An addi- 20–30 mm per month, there is probably time for
tional neurologic sign present in this case was analgesia of the areas
­reinnervation of the suprascapular musculature before
marked within the dashed oval indicating damage to the dorsal branches
of the caudal cervical nerve roots at least. irreversible fibrous metaplasia occurs in the muscles.
At the time of exploration and removal of any entrap-
ping tissue, surrounding the nerve with nonirritant,
skeletal diagnoses must be considered including frac- thin, impervious material to help prevent progressive
tured cervical vertebra, scapula, humerus or elbow, adhesion formation is to be considered. Also, the
acute cellulitis and bicipital bursitis, and appropriate removal of a piece of bone from the cranial surface of
critical examinations and testing must be performed the scapula as well as the associated, overlying
in order to exclude these possibilities.294–297 collagenous band has been suggested to relieve
­
The following general principles on the manage- ­tension and pressure on the nerve that may occur
ment of suprascapular nerve trauma can be adapted to ­postoperatively.296,300,301 This procedure has also been
any large animal peripheral nerve injury case. Damage performed successfully in a bucking bull with trau-
to peripheral nerves can be classified clinically and matic suprascapular neuropathy.302 In the long term,
pathologically into three overlapping syndromes. there does not appear to be much difference in the
Neurapraxia can be regarded as concussion of nerve quality of survival in cases treated conservatively ­versus
fibers with no permanent morphologic change. The those undergoing surgical exploration and notch resec-
clinical loss of function can last for up to 2 weeks or tion of the scapula,295,296,303 with 8 out of 11 suprascapu-
more in horses, and the return of function is usually lar damage cases treated conservatively returning to
394 Large animal neurology

previous use in one study.291 Postoperatively, following Brachial plexus

resection of a notch of bone from the scapula, the fatal Most cases of shoulder injury with signs of radial nerve
complication of a fractured scapula occurred during dysfunction are probably caused by compression of
recovery from anesthesia in about 10% of cases.295 In the brachial plexus between the scapula and the thorax
show animals and racehorses, the most rapid and to include particularly the caudal cervical to cranial
cosmetic result may well be mandated so that explor- thoracic nerve roots supplying the radial nerve
ing the area at an earlier time, say 2–6 weeks after (Figure 25.4). Rarely, it may involve caudal cervical to
trauma, without any bone resection, may well be cranial thoracic vertebral hyperextension injury,297 or
justified.295,296,300 fractures of the first ribs, and even rarely be associated
Exercise should be maintained, and physiotherapy with brachial artery thrombosis either spontaneously
such as passive range of motion maneuvers, Faradic or associated with sepsis.312 Brachial plexus injury is
stimulation, and particularly swimming all are likely often accompanied by Sweeney, likely due to a concur-
to be beneficial.304,305 These exercises should not be rent but separate traumatic suprascapular lesion at that
attempted too soon after the time of surgery. nerve’s most vulnerable site over the cranial border of
An understanding of the cellular and molecular the shaft of the scapula. Some selectivity can occur
changes occurring with neurogenic muscle atrophy such that there is also involvement of the origins of
and with muscle regeneration may result in the iden- other nerves from the brachial plexus.290,313,314 In
tification of cell types and of cellular expressed pro- smaller patients, it is possible that there can be true
teins that could act as cell-­and molecule-­ based avulsion of the plexus from its nerve roots, though this
targets for treatment of atrophy while nerve regener- does not appear to be yet documented in big patients.
ation is occurring.306–310 Finally, it is likely that neuro- In such situations, additional signs such as Horner
muscular regeneration rates can be manipulated by syndrome and interference with the cutaneous trunci
such therapy as growth hormone.308 reflex may be anticipated. After 2 weeks or so, an elec-
tromyographic study can identify involvement of more
Axillary nerve than just the radial nerve.313 Proof of limb sensory loss
Atrophy of the deltoideus and cleidobrachialis mus- is usually equivocal. Some of these cases improve dra-
cles along with very mild gait defect accompanies matically in 2–4 weeks indicating that there has been
axillary nerve damage.291 This occurs with or without neurapraxia without permanent morphologic changes,
other signs of suprascapular nerve and/or brachial otherwise the outlook is guarded. Nevertheless, a few
plexus involvement, although the principal traumatic have progressively improved over 6–18 months with
event is likely to the latter site. physiotherapy such as swimming exercise along with
careful nursing care and cautious use of splinting of
Radial nerve the limb.313 Even with degrees of residual triceps
This nerve is rarely if ever damaged alone by external atrophy, some horses and others have returned to
trauma without there being an open wound or a frac- full performance and a few horses have even galloped
tured humerus.291,311 Most often, functional radial defi- and raced successfully.291
cits are a prominent part of brachial plexus injury. The
animal is unable to bear weight on the affected limb Musculocutaneous nerve
because of a lack of elbow extension.294 The shoulder is Paralysis of the isolated musculocutaneous nerve is
rested in an extended position, and the limb rests with rare. Injury to this nerve probably would not alter
the dorsum of the pastern on the ground. The limb may the gait, although the elbow may be overextended.
be thrust forward by the action of the proximal pectoral Ultimately, the biceps and brachial muscles would atro-
girdle and neck m ­ uscles while the animal walks and phy, with hypalgesia on the medial forearm. Injury to
rests with the foot on the ground after such proximal the musculocutaneous outflow within the brachial
movement. Sensory deficits are irregular and usually plexus occurs, but such insult does not add much to the
not detectable. Although many pathophysiologic mech- clinical syndrome of triceps outflow involvement.313
anisms for radial paralysis have been discussed,311 most
cases are probably like that described below for brachial Median and ulnar nerves
plexus damage. Post-­recumbency radial nerve func- Paralysis of these nerves in the calf and pony results
tional deficits can be the most prominent component of in a stiff, goose-­stepping gait, with hyperextension of
postanesthetic myoneuropathy (Chapter 38). the carpal, fetlock, and pastern joints. In the calf,
 Physical, chemical, and thermal causes 395

there may be cutaneous analgesia of the palmar and paralysis is more probably the result of ventral L3–5
lateral surfaces of the limb from the elbow to the cor- gray matter lesions caused by Sarcocystis neurona.
onet. Three months following sectioning the ulnar
nerve in the pony only an occasional toe drag may be Obturator nerve
evident; no gait abnormality can be detected without The L6 ventral nerve roots that supply this nerve com-
additional median nerve damage. Again, the involve- monly are injured during parturition in cows285 (see
ment of these nerves can add to the clinical deficits Postcalving Paralysis below) and rarely in mares.318
seen with brachial plexus injury.313 Paralysis results in a lack of adductor function because
the obturator nerve supplies the adductor muscles of
Femoral nerve the pelvic limb. In the calf, some abduction of the pel-
This nerve is rarely affected by an external blow to the vic limbs is evident with bilateral obturator neurec-
limb. Paralysis is seen as an inability to support weight tomy. This abduction is unnoticeable at rest and
on the limb as a result of a lack of stifle extension.315 At slightly evident at a walk but is obvious when the calf is
a walk, the limb is advanced with difficulty and the running as it flails the limbs wide during protraction.
length of stride is considerably reduced. The limb In the adult cow, signs of unilateral obturator
buckles when the animal attempts to bear weight on paralysis are more evident, with abduction and cir-
the limb. In the horse, the stifle flexes and the limb cumduction of the limb while walking and difficulty
collapses, and the hock and fetlock flex reciprocally. in rising from recumbency because of lateral slipping
Thus, the patient rests with all the joints flexed in an of the affected limb. Bilateral obturator sectioning in
affected limb (Figure 25.3). Bilateral partial femoral the cow results in collapse of the pelvic limbs because
paresis cases adopt a characteristic crouched posture of total abduction. The syndrome of paraparesis and
with the stifle, hock and fetlock joints flexed, the toe paraplegia in post parturient cattle occurs from dam-
still extended and contacting the ground, unless there age to ventral lumbar spinal nerve roots traversing
is prominent spinal cord disease adding further motor the roof of the pelvic canal as they form the lumbosa-
pathway paraparesis.305,316 Atrophy of the quadriceps cral plexus and divide into the peripheral nerves sup-
muscle is evident within 1–2 weeks, and the patellar plying the pelvic limbs.285 Such post calving paralyses
reflex is depressed or absent (Figures 25.3 and 25.6). are the result of damage to more than just the obtura-
The sensory branch of the femoral nerve is the saphe- tor nerves, although pelvic limb abduction can be the
nous nerve that separates from the femoral nerve at most striking sign.319 We have seen two does suffer
the level of the iliopsoas muscle and supplies sensory from prominent pelvic limb abduction with preser-
innervation to the medial leg from the mid-­thigh to vation of patellar and withdrawal reflexes following
above the hock. Bilateral femoral paralysis has also udder removal under general anesthesia in dorsal
been seen in calves305 and rarely alone in postparturi- recumbency with limbs forcibly abducted and some-
ent downer cows.285 In calves, this usually follows what extended. Unable to rise initially, the does dog-­
assisted dystocia in a hip or stifle-­lock position, which sat but could remain standing and walk reasonably
results in stretching and compression of the femoral well once put in a standing position and both recov-
nerves and a compressive myopathy of the proximal ered over a few days to 2 weeks.
limbs (see Postpartum Paralysis below). This syndrome
has also been reported in horses following general Sciatic nerve
anesthesia, in one case associated with hemorrhage More frequently than other peripheral pelvic limb
along the femoral nerves causing prominent neu- nerves the, sciatic nerve and its branches are affected
rapraxia.316 Following forced limb extension under by various injuries. Paralysis results in poor limb
general anesthesia in lateral recumbency for tarsal/ flexion, with the stifle and hock extended and the fet-
metatarsal MR imaging, 6 of 181 (3.3%) horses sus- lock flexed when the animal is not bearing weight on
tained transient nondependent limb femoral neurop- the limb. Weight can be supported on the limb if the
athy with recovery of pelvic limb function occurring digits are extended, otherwise weight is supported on
within 3 days.317 Bilateral femoral paralysis, with peri- the dorsal surface of the foot and the hock is over-
neural hemorrhage resulting from sacroiliac luxation, flexed (Figure 25.2). Heavy patients with bilateral
has been seen in mares after dystocia. In nonparturi- involvement of the sciatic nerve usually cannot rise
ent horses from the Americas and not associated with unassisted. Limb hypalgesia may occur from the sti-
recumbency or general anesthesia, bilateral femoral fle distally, except for the medial surface between the
396 Large animal neurology

stifle and hock. Sciatic paralysis undoubtedly adds to hock to the fetlock area. Experimental peroneal sec-
the deficit seen with coxofemoral luxations and prox- tioning in the pony results in these signs, but within
imal femoral fractures in cattle and to post calving 3 months postoperatively, minimal, if any, gait abnor-
obturator paralysis as described in the previous sec- mality is evident.279 The peroneal nerve is subject to
tion. Sciatic paralysis, sometimes bilateral, has been injury as it passes across the lateral surface of the
observed with intramuscular injections into the tibia. Thus, peroneal paralysis is seen in adult cattle
caudal thigh in calves, kids and foals, and may be that are recumbent in the postpartum period,285,319
expected in all species under these circumstances. and in horses recumbent because of anesthesia.317
Particularly in animals with minimal muscle bulk,
dorsally placed intramuscular injections risk damage Cranial gluteal nerve
to the sciatic nerve.320 Depending on the site of depo- Most often signs of cranial gluteal nerve dysfunction
sition of the drug, the resulting syndrome may result from central spinal cord lesions with the involve-
resemble tibial or peroneal nerve involvement. ment of L5–6 ventral gray matter neurons. Paralysis
Acquired equine polyneuropathy mostly seen in results in little gait alteration. When turning away
Scandinavia and Finland results in gait and posture from the affected side, there may be a slight abduction
disturbances often characterized as sciatic paresis to or outward rotation of the stifle at the end of the pro-
paralysis,321–323 and an enigmatic syndrome of pulsive phase of stride. Ultimately, atrophy of the glu-
unknown cause in cattle in New Zealand and SE Asia teal region will occur, predominantly involving the
has been referred to as dropped hock syndrome, may middle gluteal muscle, most prominent when the
be a form of sciatic/tibial palsy.324 patient is viewed from the rear (Figure 25.6). The cra-
nial gluteal nerve can be damaged as it traverses the
Tibial nerve shaft of the ilium when the pelvis is fractured, although
This nerve is probably affected less often than the this is rarely seen. Cranial gluteal nerve involvement
peroneal branch of the sciatic nerve. Paralysis in the and middle gluteal muscle atrophy have been observed
horse is reported to result in a hypermetric or most frequently in horses that have spent time in the
stringhalt-­like gait, with flexion of the hock and fet- Americas and have contracted protozoal myeloen-
lock, and an extended stifle at rest. In the calf, the cephalitis due to Sarcocystis neurona when the lesion is
hock is flexed at rest, and the fetlock is knuckled for- confined to the ventral gray columns at L6.
ward (i.e., flexed) while the hooves remain flat on the
ground. There is excessive, jerky, hock flexion when Facial nerve
walking, and there is no dragging of the toes. A considerable length of the facial nerve is subcuta-
Sensation is lost from the caudal aspect of the meta- neous on the side of the face making it quite liable to
tarsus in the calf and probably from areas of the cau- injury (see Chapter 14). Trauma to the facial nerve
dal limb distal to the hock, including most of the can occur in any animal but does so particularly in
caudal and medial coronet, in the horse. heavy animals that become recumbent for any reason
and bang their heads on the ground. It also occurs in
Peroneal nerve horses that have excessively tight halters and that pull
Frequently, injury to this nerve is a component of sci- back on an attached lead rope.325
atic injury. It is also damaged by a kick or by applying As with any peripheral nerve, the facial nerve can
pressure to the lateral stifle. Paralysis results in an be injured to various degrees of severity: neurapraxia
inability to flex the hock and extend the digits. In the being loss of function only; axonotmesis, loss of
acute phase in the horse and calf hyperextension of axons; and neurotmesis, severance of axons, and
the hock and hyperflexion of the fetlock and inter- their nerve sheaths. Closed trauma to the side of the
phalangeal joints cause the animal to drag the fetlock face usually results in degrees of neurapraxia and
along the ground. The animal’s stride has a shorter axonotmesis. With the former, function normally
protraction phase, and weight is taken when the dor- returns within 14 days, and often does so abruptly.
sal surface of the foot is on the ground. If the foot is Axonotmesis requires that the damaged axons regrow
placed in a normal position, weight can be taken down the Schwann cell sheaths, a process occurring
until the animal attempts to walk, at which time the at about 20–30 mm per month. Thus, it can take
fetlock again will knuckle. There is hypalgesia to the 6 months for recovery from facial nerve injury along
craniolateral portion of the limb from the level of the the side of the face in an adult horse; the final quality
 Physical, chemical, and thermal causes 397

of recovery never being 100%. Fortunately, when worse when lunging, moving with twisting of head
no skin is lacerated, some functional recovery is usu- and neck, and worsening of lameness during routine
ally obtained. Degrees of neurotmesis occur with orthopedic diagnostic analgesic procedures.333
open wounds to the side of the face and with
fractured temporal bones (see Traumatic Brain
­ Postanesthetic myoneuropathy—­see
Injury above). Depending on the alignment of the Chapter 38
damaged nerve fibers and the degree of local tissue
Postpartum paralysis; ‘Downer cow
reaction, a proportion of the damaged fibers may
syndrome’
regrow to their respective muscles of facial expres-
sion in 6–12 months; however, this does not result in Most often this syndrome is seen when a small cow
full return of function. delivers a large calf. Also, femoral paralysis in calves
Principles of care for facial nerve trauma are as and various pelvic limb muscle ruptures in foals occur
above, but three additional points are important.326 under similar circumstances with dystocia, and these
Damage to the palpebral branch results in a lack of are likely to occur in other species. Often it is an
blinking and the risk of exposure keratitis. Some assisted delivery when it is termed calving paralysis.
patients are able to intermittently retract the eyeball The syndrome also occurs in high-­producing dairy
allowing the lids to pass over the cornea keeping it cows postpartum as a consequent to recumbency due
moistened while other patients do not appear to to metabolic disorders such as hypocalcemia or milk
manage to do this. Especially, if the lesion is at or fever. Both syndromes are part of the downer cow syn-
proximal to the genu of the facial nerve in the middle drome. Various muscle ruptures occur during attempts
ear cavity where the major petrosal branch leaves, to rise, which complicate the clinical picture.334–336
then keratitis sicca adds to the chance that the eye Muscle ruptures are rare in postfoaling mares.
ultimately must be removed due to severe keratitis There is an onset of stiffness to paraplegia after par-
and ultimately panophthalmitis. Additionally, in ath- turition, sometimes with signs progressing over hours
letic horses with prominent facial paralysis, the flac- to days. Metabolic disorders such as milk fever and
cid alar folds can obstruct airflow during inspiration, evidence of trauma are sometimes also reported.
limiting performance. Removal or augmentation of Sometimes soft tissue, intrapelvic, and even bony pel-
the fold is then an option.327 Finally, unilateral facial vic damage are evident on examination when other
paralysis does not usually have an impact on eating diseases contributing to the downer cow syndrome,
in spite of food often remaining impacted in the flac- such as exhaustion, persistent milk fever, displaced
cid cheek pouch. However, bilateral lesions, espe- abomasum, and pyometra, can be detected.334 With
cially in horses, do interfere with prehension and classic calving paralysis, mild cases may show unilat-
manipulating food within the mouth so that the diet eral abduction paresis of one limb upon rising with a
may need attention to accommodate this disability. normal gait when walking on a firm surface. Typically,
a more severely affected cow can sit with the thoracic
limbs supporting weight but with paresis in the pelvic
Cervicothoracic and thoracolumbar
limbs, and, early on in the syndrome, flexor hypore-
compressive radiculopathy
flexia and mild degrees of limb hypalgesia with intact
The enigmatic clinical syndrome of sore neck and tail and anal function can be detected before decubital
stiff back is well known in human as well as in problems obviate a reasonable neurologic examina-
­veterinary especially equine patients as discussed in tion.285 Patellar hyporeflexia suggests quadriceps
Chapter 30. Arriving at a specific singular causative recumbency myopathy or femoral nerve involvement.
diagnosis is however uncommon, and there does Recumbency following calving thus can be associ-
appear to be a poor direct relationship between vari- ated with many metabolic, infectious, traumatic, toxic
ous ageing and traumatic degenerative vertebral and nutritional disorders.337 The specific neuromuscu-
changes and specific clinical findings in most of such lar syndromes discussed here can be divided into two
cases although compression of intervertebral neuro- forms. The first is primary calving paralysis, which is
vascular bundles is likely operative in some seen in cows that are bright, alert, and appetent but that
cases.264,328–332 Some unusual gaits recorded that may cannot rise on their pelvic limbs, having degrees of
relate to C–T spinal radicular involvement include paraparesis or monoparesis. This is most often associ-
skipping-­like gait only when ridden, hopping gait ated with compression of the ventral branch of L6, less
398 Large animal neurology

often L5 and S1, against the ventral ridge of the wing of weakness that may progress to paralysis (Figure 25.3).
the sacrum during the delivery of a large calf.319,337 Usually, there is a history of dystocia and an assisted
Degrees of neurapraxia, axonotmesis, and even neurot- delivery. Luxated and fractured limb bones may be
mesis occur. Additional ischemic and hemorrhagic evident. Signs of femoral344 or sciatic-­type paralyses
myopathy and neuropathy due to recumbency results are evident in one or both limbs. Swollen and torn
in more profound paraplegia and even tetraplegia. The muscles may be clearly evident345,346 but not necessar-
second form is seen as degrees of recumbency-­induced ily so.347 In addition to just musculotendinous dam-
myoneuropathy subsequent to recumbency induced by age, degrees of femoral nerve compression and
other perinatal factors, which may be no more than stretching, probably in addition to quadriceps mus-
prolonged labor.337–339 The pathophysiologic mecha- cle compression, can occur resulting in inability to
nism for this second form of post calving neuromuscu- support weight. Hip-­lock or stifle-­lock dystocia most
lar paralysis is similar to postanesthetic often will have occurred.305
myoneuropathy.339 Degrees of pressure-­induced neu- Combinations of ruptured extensor and flexor mus-
rapraxia340 and ruptured muscles336 complicate the pic- cles of the hip, stifle and hock, and occasionally elbow,
ture. Some cases of post foaling paralysis in mares may result in obvious defects in limb function following
be the result of ventral branch L5, L6 and/or S1 nerve dystocia with or without assistance. Ultrasonographic
root compression as in the cow, but this has not been imaging studies are ideal to define the sites and extent
proven. Occasionally, in mares there has been hemor- of musculotendinous compromise.347 Interpretation of
rhage in and around the femoral nerves, resulting in the neurologic examination in these patients is some-
extensor weakness, patellar hyporeflexia, and medial what problematic insofar as in normal neonates there
thigh (saphenous nerve) analgesia. This is very similar are hyperactive reflexes present and such patients that
to some cases of postanesthetic femoral neuropathy.316 are physically compromised for any other reason can
The ventral lumbosacral nerve roots are usually not respond poorly to noxious sensory testing. Ruptured
severed, but contused, thus flunixin, phenylbutazone gastrocnemius muscle with or without damage to
(horse only), or aspirin probably are beneficial, at least other pelvic limb muscles occurs in neonatal foals
initially. Appropriate surgical and gynecologic care is resulting in degrees of disability to stand and to
essential. Glucocorticoids may promote complications walk.346,348,349 This is believed to occur during assisted
in post parturient animals. Intravenous 10% DMSO, or spontaneous delivery when the tarsus is maintained
as for spinal cord trauma, has been used in mares but in flexion, and the stifle is extended. Occasionally, the
with equivocal benefit. Nursing care of a recumbent monoparesis or paraparesis may only become evident
dam and support of newborn are major undertakings, when the newborn begins to stand and move at several
but are vital to successful therapy.211,285,337,341 The use of hours or days of age, and other comorbidities such as
water flotation tanks may seem rather extraordinary tibial nerve damage, arthrogryposis, and skeletal inju-
but can be extremely effective in the treatment of post ries can complicate the picture.
parturient alert downer cows.210,342,343 Uncommonly, dystocia with assisted delivery will
The prognosis for survival probably is about 50% cause damage to thoracolumbar nerve roots that
with neuromuscular syndromes of postpartum have been assumed to be from distraction avulsion
­paralysis. Recumbency for up to 2 weeks has occurred injury.350
with cows and with lightweight horses that have Neonatal acquired paraplegia with any of these
­survived, and flotation devices certainly shorten this syndromes warrants a bad prognosis. With time and
period.210,343 The degree of rise in serum creatine nursing care, foals and calves with degrees of femoral
kinase activity and the elevation of serum urea nitro- or quadriceps paresis can recover.305,315,344 Muscle
gen and creatinine concentrations can indicate the ruptures require specific surgical splinting and con-
degree of myonecrosis and renal and prerenal siderable extended nursing care.
azotemia, respectively. Such indicators may help
determine a more accurate prognosis.334,341 Fibrotic myopathy
An abnormal slapping-­type gait developing in one
Neonatal acquired paralysis syndromes
pelvic limb of a, usually athletic, light-­breed horse is
In addition to the paralytic syndromes seen in post regarded as typical for the syndrome referred to as
parturient cows and mares, the newborn calf or foal fibrotic myopathy. The foot is rapidly moved caudally
can suffer from unilateral or bilateral pelvic limb at the end of protraction to strike the ground 5–20 cm
 Physical, chemical, and thermal causes 399

less than a normal stride length.351 It occurs most Chemical causes

often in adult Quarter Horse patients and other
breeds used for fast moving sports, but has been Intracarotid injection
observed as a congenital condition probably result- Most often this occurs in horses but can occur in any
ing from acquired perinatal muscle damage.352–354 A species.364,365 Inadvertent intracarotid injection in
few cases follow single or repeated intramuscular horses may have little effect, but it usually results in
injections in the caudal thigh musculature or exter- an acute seizure, often followed by recumbency and
nal injury to the limb.354,355 paddling with degrees of semicoma or stupor follow-
Upon examination, a firmness or scar, with or ing.366 Initially, there is usually a period of excitement
without mineralization, may be palpable in the semi- and turning or spinning toward the affected side,
membranosus, biceps femoris, gracilis or, most often, with combinations of contralateral facial twitching
in or around the semitendinosus muscle353,356,357—­thus along with apprehension expressed as a startled
akin to the common hamstring injuries in human appearance that may precede the seizure. The onset
athletes. The gait is characterized by sudden cau- of signs is rapid, occurring within a few seconds with
doventral movement of the foot near the end of the ataractic and viscous or irritant drugs. However, a
protraction phase with the hoof striking the ground slight delay in the onset of signs may occur from
with a variably increased force. Although extremely many seconds to a few minutes, and possibly a few
distinctive, there is some likeness to the postural and hours.367 With α-­2 agonist sedatives, acetylproma-
movement changes seen with several other disorders zine, and other water-­soluble drugs, recovery usually
including upward fixation of the patella, stringhalt, occurs with the horse standing in 5–60 min and
and shivering in horses.358,359 Radiographic and, par- totally normal within 1–7 days. Combinations of
ticularly, ultrasonographic imaging studies detect the signs of contralateral blindness with intact pupillary
site and extent of musculotendinous damage.352,356,360 responses, contralateral facial hypalgesia detected
The semitendinosus muscle is most frequently best at the nasal septum, tendency to turn toward the
affected but other muscles affected include the semi- side of the injection, and slow thoracic hopping on
membranosus, gracilis, and biceps femoris.360 the opposite side all tend to abate during this time.
Typically, no weakness or ataxia is present. At the With procaine penicillin, phenylbutazone, chloram-
time of initial injury there can be tenderness in the phenicol, and other insoluble and oil-­based drugs,
caudal thigh, but by the time of the unusual gait recovery usually is unsatisfactory; epilepsy, semi-
being present it is assumed that a mechanical inter- coma and stupor often necessitate euthanasia.365
ruption of normal muscle contraction by the scar tis- With the latter drugs, if the patient survives longer
sue results in the gait abnormality. However, a than a few hours, varying combinations of ipsilateral
sensory neurologic defect disrupting gamma efferent brain neuronal necrosis, vascular engorgement and
function involving the myotatic reflex, like that proliferation, vascular hyaline necrosis, hemorrhage,
occurring in stringhalt, may be operative. Evidence status spongiosis, and astrogliosis occur depending
for a peripheral neuropathy being an unusual cause on the volume and properties of the drug.364,365
of this syndrome in three horses has also been pub- Injected compounds may reach the ipsilateral oph-
lished.352 On occasion, horses with confirmed thora- thalmic circulation to cause a unilateral retinopathy
columbar spinal cord disease, most often caused by and blindness.107
Sarcocystis neurona, have demonstrated a prominent Treatment is usually not required with the tran-
fibrotic myopathy-­like gait, along with other signs of quilizers and water-­soluble agents being injected.
mild paraparesis and ataxia. With other drugs and with prominent encephalo-
Traditionally, surgical removal of the variously pathic signs, immediate hyperosmolar therapy and
affected musculotendinous insertions and associ- NSAIDs should be instituted, and probably gluco-
ated scar tissue usually has resulted in alleviation of corticosteroids and anticonvulsant therapy may
signs in many affected patients,353,355–357,361 although well be necessary. If to be administered immedi-
complications do occur.356 A standing simplified ately and before reperfusion injury sets in, there
semitendinosus tenotomy procedure has been may be an indication for the reactive oxygen spe-
described;353,354,362 however, standing myotomy of cies (ROS)–scavenging benefits of IV DMSO. Once
affected caudal leg muscles probably results in return a prominent chemical encephalitis ensues, the
to athletic abilities in ~75% of patients.360,363 prognosis is grim.
400 Large animal neurology

Paravertebral injection reactions Thermal causes

An unfortunate result of cervical and thoracolumbar Dehorning brain injury
paravertebral injections can be lameness368 and pro-
gressive ataxia and weakness369,370 resulting from Young ruminants undergoing various forms of hot-
localized traumatic and chemical granulomatous iron disbudding can suffer from degrees of enceph-
reactions extending via intervertebral foramina to alopathy due to extension of tissue damage through
involve local nerve roots and the spinal cord the ­ cranium to the cerebral hemispheres
(Figure 33.9). A cluster of cases of paraparesis to para- (Figure 33.10). Usually within a few hours to several
plegia occurred in 25 of 3000 cattle within 2–5 months weeks following thermal disbudding, young rumi-
following paralumbar vaccination using an oily foot nants, especially kids, may circle, become stuporous
and mouth vaccine.371 In at least some cattle, an epi- and blind, and have seizures or be found dead.374–377
dural, granulomatous reactive infiltrate was the cause Pyrexia may be present, and the animal is usually
of the compressive lumbar myelopathy. Another anorectic. Diffuse or asymmetric cerebral signs
graphic example was where ~10% of a large herd of occur, although sudden death is most often
cattle showed signs varying from ipsilateral toe drag- reported. Signs include acute or progressive obtun-
ging to paraparesis to paraplegia beginning 6 days to dation, blindness, circling, opisthotonus, seizures,
4 weeks following paralumbar injection of an adju- and recumbency followed by death. Resulting ster-
vant bacterin.369,372 Of 56 affected out of the herd of ile or septic abscess formation and brain swelling
610 cattle, 19 (3% of total) died or were destroyed, the with herniations occurring can be identified with
remainder recovering to varying degrees to rejoin the advanced imaging studies.378
herd. Young and less well muscled animals are more This condition occurs particularly in young kids
likely to suffer from such mishaps.373 that have a much thinner bony cranium than calves,
and unfortunately up to 20% of kids undergoing dis-
budding have shown evidence of cerebral disease374
Caudal epidural ethanol injections
and up to 8% have died379 following overzealous dis-
Degrees of caudal myopathy and cauda equina budding with hot iron. Such overzealous use of a hot
­neuropathy result from iatrogenic epidural alcohol iron caused coagulative necrosis and infarction of the
injections performed to relax tail extensor function fronto-­parietal and occipital lobes, with or without
in show horses, especially Quarter horses (see secondary infection with various organisms includ-
Chapter 27). ing Clostridium spp. and Trueperella pyogenes.376–379

(A)

(C) (B)

Figure 33.9 One of ten dairy calves (A) affected with degrees of ataxia and tetraparesis after paravertebral injection of adjuvant vaccine into the neck
that were suffering from cervical granulomatous cellulitis and vertebral osteomyelitis (B) with secondary cervical spinal cord compression (C). There is a
radio dense soft tissue mass dorsal to the vertebrae (B, arrow heads) with bone modeling of dorsal C4 and C5 with a destructive osteomyelitis. Blanched
narrowing of the C4–5 spinal cord is evident (C).
 Physical, chemical, and thermal causes 401

the primary process, must be undertaken. Texts on

general medicine should be consulted.

Lightning strike and electrocution

Lightning strike involving humans and animals is a
relatively common phenomenon in some areas of the
world, the frequent result being lethal electrocution.
But, perhaps surprisingly, in humans, only one third
of the cases of lightning strike are fatal. Due to poten-
tial differences and conductivity, large (long) quadri-
peds with metal shoes are most likely to conduct stray
Figure 33.10 Thermal dehorning of small ruminants, especially goat voltage from a field current and suffer electrocution,
kids, can result in catastrophic encephalomalacia consisting of coagula- either as stray voltage or from lightning strike.380,381
tive necrosis and infarction with contribution from secondary sepsis par-
The severity of injury from passage of an electrical
ticularly from anaerobic bacteria. One case is demonstrated here with the
extent of necrosis (black circle) and the extent of midline shift (red) current is directly proportional to the tissue resistivity
evident. (Ohm·meter, Ω·m).382 Thus, tissues tend to be more
affected by electricity in the order bone > fat > tendon
> skin > muscle > blood vessels > nerves (myelin)383,384
Disbudding by physical gouging375 can also cause
that can account for some of the clinical effects of
necrotic encephalitis and allow secondary sepsis and
electrocution and lightning strike. Neurologic signs
acute toxemia.
reported in people and horses surviving lightning
Nonsteroidal anti-­inflammatory agents and anti-
strike include hemiplegia, paraplegia, hypermetria,
biotics along with careful debridement and topical
vestibular syndrome, facial palsy, and sensorineural
therapy are indicated therapy; however, with promi-
and conductive hearing loss.383,385–389
nent signs the outlook is bad. Tetanus prophylaxis
Sometimes large animal patients have been found
should be undertaken. Appropriate, judicious use of
to show only neurologic signs with circumstantial evi-
the hot iron is paramount to preventing this dastard
dence of electrocution. Such evidence may be after a
disease although the use of prophylactic antibiotics
thunderstorm has passed and other livestock have
has been suggested to suppress growth of microbes in
perhaps been killed by lightning, or direct and indi-
any damaged bone and brain tissue.379
rect exposure to high voltage electric fields occurs
with evidence of thermal damage to trees, buildings,
Heat stress and shock
and animals. Three out of eight penned pigs in a
Cardiocirculatory collapse and diffuse organ group exposed to high voltage current390 and three in
­dysfunction is frequently associated with degrees of a group of eight outdoor pigs following a direct local
somnolence and finally coma. Such complications may strike by lightning391 all suffered acute paraplegia due
accompany the systemic component of neurologic to lumbosacral vertebral fractures that were probably
disorders, such as many encephalitides, neurotoxici- due to violent spasms of the longissimus lumborum
ties, and metabolic disturbances with neurologic muscles. Also, a foal exposed to a live electrical cable
signs. Also, profound comatose states may occur in the became paraplegic as a result of fracture of T11.392
terminal stages of shock associated with systemic Such fractures mimic what has been observed when
inflammatory response syndrome, disseminated intra- livestock are humanely destroyed using a high-­voltage
vascular coagulation, sepsis, blood loss, gastrointesti- electrical current. One pony with strong evidence of
nal crises, fulminant liver, and renal disease and heat being struck by lightning suffered an unusual syn-
stress. In some of these cases, frighteningly unexpected drome of tetanic muscle spasms that was relieved by
and erratic behavior can suddenly occur with danger lying down. Laminitis complicated the neurologic
to handlers. Such turns for the worse likely represent syndrome that persisted for many months and
failing forebrain function and are terminal. In all cases, involved a hypometric or goose-­stepping gait and
cardiovascular support, including the maintenance of elevated tail posture.381 It is tempting to speculate that
an adequate circulating blood volume and a physio- this could have been due to caudal thigh, and sacro-
logic body temperature, as well as therapy aimed at caudal myofibrosis, respectively, somewhat akin to
402 Large animal neurology

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of Thoroughbred fatalities in Victoria, Australia between 2001
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324 Topham IA, Dittmer KE, Buckle KN and Gates MC. An over- 347 Jesty SA, Palmer JE, Parente EJ, Schaer TP and Wilkins PA.
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325 Carslake H. Facial Nerve Paralysis – Part 1: Clinical 348 Sato F, Shibata R, Shikichi M, et al. Rupture of the gastrocne-
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326 Carslake H. Facial Nerve Paralysis – Part 2: Differential three cases. J Equine Sci Jpn Soc Equine Sci 2014; 25: 61–64.
Diagnosis. Equ Vet Pract 2018; 43(2): 22–25. 349 Tull TM, Woodie JB, Ruggles AJ, et al. Management and
327 Torre F. Use of autogenous cartilage graft from auricular assessment of prognosis after gastrocnemius disruption in
cartilage in treatment of unilateral paralysis of nostril in Thoroughbred foals: 28 cases (1993–2007). Equine Vet J
racing standardbred horse. Equine Vet Educ 2003; 15(1): 2009; 41(6): 541–546.
10–14. 350 Nishiura H, Jou S, Ogata T, et al. Calving-­related intradural
328 Dyson SJ. Lesions of the equine neck resulting in lameness or avulsion injuries of the thoracolumbar spinal nerve roots in a
poor performance. Vet Clin North Am Equine Pract 2011; calf. J Vet Diagn Invest 2020; 32(6): 968–971.
27(3): 417–437. 351 Janicek J, Lopes MA, Wilson DA, Reed S and Keegan KG.
329 Garcia-­Lopez JM. Neck, back, and pelvic pain in sport horses. Hindlimb kinematics before and after laser fibrotomy in
Vet Clin North Am Equine Pract 2018; 34(2): 235–251. horses with fibrotic myopathy. Equine Vet J Suppl 2012; (43):
330 Espinosa-­Mur P, Phillips KL, Galuppo L D, et al. Prevalence 126–131.
of radiographic osteoarthritis of the caudal cervical region in 352 Valentine BA, Rousselle SD, Sams AE and Edwards RB 3d.
105 asymptomatic warmblood jumpers [ABSTRACT]. Vet Denervation atrophy in three horses with fibrotic myopathy.
Radiol Ultrasound 2019; 61(2): 227–246. J Am Vet Med Assoc 1994; 205(2): 332–336.
331 Cousty M, Retureau C, Tricaud C, Geffroy O and Caure S. 353 Gomez-­ Villamandos R, Santisteban J, Ruiz I and Avila I.
Location of radiological lesions of the thoracolumbar column Tenotomy of the tibial insertion of the semitendinosus muscle of
in French trotters with and without signs of back pain. Vet two horses with fibrotic myopathy. Vet Rec 1995; 136(3): 67–68.
Rec 2010; 166(2): 41–45. 354 Bramlage LR, Reed SM and Embertson RM. Semitendinosus
332 Girodroux M, Dyson S and Murray R. Osteoarthritis of the tenotomy for treatment of fibrotic myopathy in the horse.
thoracolumbar synovial intervertebral articulations: clinical J Am Vet Med Assoc 1985; 186(6): 565–567.
and radiographic features in 77 horses with poor perfor- 355 Turner AS. Large animal orthopedics. In The Practice of
mance and back pain. Equine Vet J 2009; 41(2): 130–138. Large Animal Surgery, Jennings PB, Editor. 2nd ed. WB
333 Dyson SJ. Unexplained forelimb lameness possibly associated Saunders, Philadelphia, PA. 1984; 937–949.
with radiculopathy. Equine Vet Educ 2018; 32(S10): 92–103. 356 Pickersgill CH, Kriz N and Malikides N. Surgical treatment of
334 Poulton PJ. Musculo-­skeletal examination and diagnosis of semitendinosus fibrotic myopathy in an endurance horse –
the downer cow. Cattle Pract 2013; 21: 174–180. management, complications and outcome. Eq Vet Edu 2000;
335 Poulton PJ and Pyman MF. Musculo-­skeletal examination 12(5): 242–247.
and diagnosis for recumbent cattle. Cattle Pract 2017; 25: 357 Dabareiner RM, Schmitz DG, Honnas CM and Carter GK.
153–157. Gracilis muscle injury as a cause of lameness in two
336 Roussel Jr AJ. Downer cow syndrome. Agri Pract 1986; 7: horses. J Am Vet Med Assoc 2004; 224(10): 1605–1606,
31–35. 1630–1633.
 Physical, chemical, and thermal causes 411

358 Valentine BA, Lahunta Ad, Divers TJ, Ducharme NG and attempted intramuscular injection. J Vet Intern Med 2012;
Orcutt RS. Clinical and pathologic findings in two draft 26(6): 1481–1484.
horses with progressive muscle atrophy, neuromuscular 374 Sanford SE. Meningoencephalitis caused by thermal disbud-
weakness, and abnormal gait characteristic of shivers syn- ding in goat kids. Can Vet J 1989; 30(10): 832.
drome. J Am Vet Med Assoc 1999; 215(11): 1661–1665. 375 Nation PN and Calder WA. Necrosis of the brain in calves
359 Valentine BA. Equine polysaccharide storage myopathy. following dehorning. Can Vet J 1985; 26: 378–380.
Equine Vet Educ 2003; 15(5): 254–262. 376 Dickson J. Brain damage in dehorned goat kids. Vet Rec 1984;
360 Noll CV, Kilcoyne I, Vaughan B and Galuppo LD. Standing 114(15): 387.
myotomy to treat fibrotic myopathy: 22 cases (2004–2016). 377 Wright HJ, Adams DS and Trigo FJ. Meningoencephalitis
Vet Surg 2019; 48(6): 997–1004. after hot-­iron disbudding of goat kids. Vet Med Sm Anim
361 Turner AS and Trotter GW. Fibrotic myopathy in the horse. Clin 1983; 78: 599–601.
J Am Vet Med Assoc 1984; 184(3): 335–338. 378 Dennler M, Carrera I, Beckmann K, et al. Imaging diagno-
362 Suarez-­ Fuentes DG, Tatarniuk DM, Caston SS, et al. sis – conventional and functional magnetic resonance imag-
Tenotomy of the semitendinosus muscle under standing ing of a brain abscess in a goat. Vet Radiol Ultrasound 2014;
sedation versus general anesthesia: outcomes in 20 horses 55(1): 68–73.
with fibrotic myopathy. Vet Surg 2018; 47(3): 350–356. 379 Thompson KG, Bateman RS and Morris PJ. Cerebral infarc-
363 Noll CV, Kilcoyne I, Vaughan B and Galuppo LD. Standing tion and meningoencephalitis following hot-­iron disbudding
myotomy to treat fibrotic myopathy: 22 cases (2004 –2016). of goat kids. N Z Vet J 2005; 53(5): 368–370.
Vet Surg 2019; 48(6): 997–1004. 380 Novales M, Hernandez E and Lucena R. Electrocution in the
364 Christian RG, Mills JH and Kramer LL. Accidental intraca- horse. Vet Rec 1998; 142(3): 68.
rotid artery injection of promazine in the horse. Can Vet J 381 Williams JB. Survival of lightning strike and its sequelae in a
1974; 15(2): 29–33. native pony. Equine Vet Educ 2001; 13(1): 25–28.
365 Rousseaux CG and Wenkoff M. Fatal intracarotid artery 382 Kroll MW and Panescu D. Physics of electrical injury. In
injection of chloramphenicol in a cow. J Am Vet Med Assoc Atlas of Conducted Electrical Weapon Wounds and Forensic
1984; 184(10): 1287–1288. Analysis, Ho JD, Dawes DM and Kroll MW, Eds. Springer,
366 Gabel AA and Koestner A. The effects of intracarotid artery NY. 2012; 25–46.
injection of drugs in domestic animals. J Am Vet Med Assoc 383 Ogren FP and Edmunds AL. Neuro-­otologic findings in the
1963; 142: 1397–1403. lightning-­injured patient. Semin Neurol 1995; 15(3): 256–262.
367 Straub A. Temporary unilateral blindness in a horse following 384 Kleinschmidt-­DeMasters BK. Neuropathology of lightning-­
inadvertent intracarotid injection – A case report. strike injuries. Semin Neurol 1995; 15(4): 323–328.
Pferdeheilkunde 2000; 16(1): 68–70. 385 Lalor AG and Sparling PS. Lightning Stroke. J Roy Army Vet
368 O’Toole D, Steadman L, Raisbeck M and Torpy R. Myositis, Corps 1935; 6: 200–204.
lameness, and recumbency after use of water-­in-­oil adju- 386 Holgado Rivas DE. Harmful effect of lightning on horses.
vanted vaccines in near-­term beef cattle. J Vet Diagn Invest Gaceta Vet 1970; 32: 124–126.
2005; 17(1): 23–31. 387 Williams MA. Lightning strike in horses. Compend Contin
369 O’Toole D, McAllister MM and Griggs K. Iatrogenic com- Educ Pract Vet 2000; 22(9): 860–867.
pressive lumbar myelopathy and radiculopathy in adult cattle 388 Evans PM, Armour MD and Dubielzig RR. Ocular lesions
following injection of an adjuvanted bacterin into loin mus- following suspected lightning injury in a horse. Vet
cle: histopathology and ultrastructure. J Vet Diagn Invest Ophthalmol 2012; 15(4): 276–279.
1995; 7(2): 237–244. 389 Bedenice D, Hoffman AM, Parrott B and McDonnel J.
370 Andrew-­Jones L, Siger L and Janovitz E. Tetraparesis follow- Vestibular signs associated with suspected lightning strike in
ing paravertebral vaccination in calves (Abstract). J Comp two horses. Vet Rec 2001; 149(17): 519–522.ww
Pathol 1996; 33(5): 593. 390 Steffen DJ, Schoneweis DA and Nelssen JL. Hind limb paraly-
371 Ubiali DG, da Cruz RAS, Lana MVD, et al. Spinal cord com- sis from electrical shock in three gilts. J Am Vet Med Assoc
pression in cattle after the use of an oily vaccine. Pesquisa Vet 1992; 200(6): 812–813.
Brasil 2011; 31(11): 997–999. 391 Van Alstine WG and Widmer WR. Lightning injury in an out-
372 McAllister MM, O’Toole D and Griggs KJ. Myositis, lameness, door swine herd. J Vet Diagn Invest 2003; 15(3): 289–291.
and paraparesis associated with use of an oil-­adjuvant bacterin 392 DeBowes RM, Wagner PC, Gavin PR and Roden PH.
in beef cows. J Am Vet Med Assoc 1995; 207(7): 936–938. Vertebral compression fracture in a foal following electric
373 Johnson AL, Alenghat T and Engiles JB. Cervical myelomala- shock. J Vet Orthop 1981; 2: 14–19.
cia in a lamb (Ovis aries) and an alpaca (Vicugna pacos) after
 34
Toxic diseases

Disease  Page Metallic myelopathy—direct heavy

metal toxicity 416
Chemical and organic toxins 413
Sodium salt poisoning and water
Lead poisoning  413
intoxication416
Selenium toxicity 415
Ammonated forage toxicity 417

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Toxic diseases 413

Disease  Page Eggplant429

Bracken fern and horsetail-induced
Urea (non-protein nitrogen) intoxication 418
thiamine deficiency 429
Cyanide poisoning 418
Pasture-associated stringhalt 429
Organochlorine compounds 418
Toxic plants and mycotoxins producing
Organophosphate and carbamate
ataxia, weakness, and tremors 430
compounds418
Weakness and ataxia syndromes  430
Strychnine420
Tremor syndromes 431
Metaldehyde420
Cerebellar disorders 436
Fluoroacetate (compound 1080) 420
Tutu: Coriaria spp. poisoning 437
Arsanilic acid and 3-nitro-4-
Plant-induced arthrogryposis 437
hydroxyphenylarsonic acid (3-nitro):
Atypical myopathy (seasonal pasture
Arsenic toxicoses 421
myopathy) in horses 437
Aminoglycoside toxicity 421
Ataxia associated with stinging nettle 438
Chronic toxicity by organomercury
Miscellaneous toxic plants 438
compounds421
Bacterial toxins  439
Ionophore toxicity—monensin, salinomycin
Botulism and the shaker foal syndrome 439
and lasolocid 422
Tetanus due to Clostridium tetani
Ivermectin and moxidectin 422
neurotoxin443
Methyl bromide 422
Enterotoxemic encephalopathy: Focal
Procaine penicillin reaction 423
symmetrical encephalomalacia in
Miscellaneous known and suspected drugs
ruminants and edema disease of pigs 445
and toxins 423
Equine mycotoxic encephalomalacia
Plant and plant-related toxins 425
associated with moldy corn 446
Locoweed and Darling pea—swainsonine
Miscellaneous biotoxicities 448
intoxication425
Tick paralysis 448
Ataxia associated with sorghum spp. grasses 426
Seizures and muscle spasms associated
Nigropallidal encephalomalacia 427
with ticks and mites 449
Kochia scoparia (Mexican fireweed) 428
Snake bite paralysis 449
Stypandra and Helichrysum spp. poisoning 428
References450
Coffee senna (Cassia spp.) plant
neuromuscular toxicoses 428

Chemical and organic toxins Animals of any age can be affected, although
calves and adult cattle are most involved because of
Lead poisoning their tendency to lick and chew on objects. Horses
In spite of a large reduction in the use of lead in rarely if ever show any cerebral signs other than
­products such as paint, petrol, and batteries, from a somnolence associated with weight loss, although
worldwide and economic perspective, lead poison- ataxia and mania followed by recumbency may occur
ing is probably still the most significant chemical at high levels of intoxication.15,16 This species also
intoxication in large animals especially in cattle, shows selective signs of cranial neuropathy, par-
and large outbreaks continue to be reported.1–8 ticularly involving laryngeal, pharyngeal, and tongue
Widespread and devastating consequences have paralysis.12,17–19 Although these descriptions are
resulted from contamination of animal feed with strongly suggestive of cranial nerve final motor neu-
about 15,000 animals exposed in one outbreak, ronopathy or neuropathy,20 the evidence for such is
consuming an estimated 1000 kg of lead!9–11 As well, not strong. Superficial evidence for motor neuropa-
this reflects environmental contamination for thies may actually represent the apparent central
human exposure to lead, milk, and meat products motor (forebrain) syndromes of dysphagia, dyspho-
from clinically and subclinically affected nia, and even laryngeal paralysis as seen in prosen-
livestock.1,3,6,8,11–14 cephalic syndromes such as polioencephalomalacia,
414 Large animal neurology

hepatoencephalopathy, and cerebral abscessation. in horses is reported to result in diffuse signs of motor
Indeed, the nature of any motor and sensory neurop- weakness as in equine motor neuron disease,36
athy present in pure lead poisoning is rather enig- although the clinicopathologic evidence that such
matic without strong electrophysiologic, histologic, cases were indeed due to lead poisoning alone is
and ultrastructural evidence available;21,22 this debate lacking.
having been elegantly reviewed by Beritić and No consistent gross neuropathologic findings are
Feldman in 1984.23 present in affected horses. The presence of acid-­fast
Historically, cases occur adjacent to refineries intranuclear inclusions in tissues such as renal tubu-
and smelters,6,24–26 and there may have been contact lar epithelium is strong evidence for lead poisoning
with lead-­ based paint, linoleum, caulking com- but not always present.4,30 The primary effect is on
pound, and old machinery oil.1,2,21 Discarded lead– neurons, but vascular endothelium and peripheral
acid accumulator batteries remain an important and nerves are also affected. Histologically, in ruminants
preventable source of lead to poison livestock.1,27 In there is modest cerebral laminar necrosis with vacu-
ruminants, seizures, hysteria, hyperactivity, and olation of parenchyma, gliosis, ischemic neuronal
tremor occur with acute lead poisoning.28–33 necrosis, and neovascularization particularly involv-
Diarrhea or constipation may be evident in chronic ing the tips of gyri.3,4,30 The extent and severity of
lead poisoning. Blindness, aimless and compulsive these lesions is not as profound as can be seen with
walking, head pressing, and bellowing are common polioencephalomalacia in ruminants, although the
complaints in cattle. Pigs appear to be quite resist- primary neuronal lesion may also be due to inhibition
ant to poisoning.34 Exposure of goats to cement kiln of energy metabolism as opposed to defective ion
dust pollution has resulted in raised blood lead lev- transport or to collagen synthesis in capillaries.29
els with resulting clinical signs of toxicosis ranging This proposal may have implications for therapy dis-
from locomotor disturbances to complete hindlimb cussed below. A breakdown in astrocyte function at
paralysis.35 the blood–brain barrier may account for the capillary
Clinical examination often reveals nothing and astrocyte proliferation, perivascular and peri-
remarkable, but sometimes lead-­based paint is on the neuronal edema, and neuronal necrosis seen
hair coat and ill-­thrift or weight loss may be evident. histologically.37
Bloat and tenesmus with diarrhea or constipation Lead interferes with normal heme synthesis,
frequently are present in ruminants, and rectal pro- resulting in erythrocytes with decreased oxygen-­
lapse associated with straining has been seen in carrying capacity so that it has been proposed that
affected calves. Roaring to advanced inspiratory clinical signs are caused by a hypoxic effect on cere-
dyspnea and degrees of dysphagia are the most con- bral cells; cerebral edema may develop. However, in
sistent signs in horses.12,17–19 large animals the hemogram usually reveals no ane-
Affected animals may be ataxic and generally weak, mia, but nucleated erythrocytes are occasionally
and may be irritable and convulse during examina- present. Elevated delta-­aminolevulinic acid concen-
tion. Amaurosis, wandering, head pressing, opistho- trations to >200 μmol/L can be detected in urine in
tonus, odontoprisis, and bellowing often are seen in lead-­intoxicated cattle but this can be an inconsist-
cattle.11,28–33 Commonly, inspiratory stridor or roaring ent finding.38 Estimation of blood Zn-­protoporphyrin
caused by bilateral laryngeal dysfunction is seen in may be a sensitive and specific marker for lead toxic-
horses, possibly the result of a vagal neuropathy, and ity in cattle.11 Blood lead concentrations may or may
other motor nerves may also be involved, resulting not be elevated. Greater than 0.6 ppm (0.6 mg/L) is
in pharyngeal, esophageal, facial, and anal paralysis, probably diagnostic of lead poisoning but finding of
but see comments above. Weakness and ataxia are a >4-­fold increase in urinary lead excretion follow-
reported, but most severely affected horses become ing disodium Ca-­ethylenediamine tetra acetic acid
somnolent, lose weight, and develop inhalation pneu- (EDTA) chelation therapy is more sensitive. A dis-
monia making interpretation of these signs diffi- tinction must be made between exposure to lead
cult.18,19 As with other causes of bilateral laryngeal with resulting elevated blood lead concentrations
paralysis such as hepatoencephalopathy, affected and lead poisoning.31 Free erythrocyte protoporphy-
horses can become frantic in attempts to breathe and rin estimations appear to be closely correlated with
become uncontrollable—­usually as a terminal event blood lead concentrations and inversely correlated
unless a tracheotomy is performed.17 Lead poisoning with time since last lead exposure.31 Estimation of
 Toxic diseases 415

very high total and relative lead intake from analysis accompanied by weight loss, hair loss, and coroni-
of forage and feedstuff is very strong evidence for tis.47–49 Some recumbent pigs can rise on to the tho-
toxicity.5,6,9,10,12 Measurements of lead concentrations racic or the pelvic limbs. Flaccid areflexia, reflecting
of up to 3% in grass on an old military shooting loss of final motor neuronal function, occurs in the
range where an outbreak of poisoning occurred have thoracic and/or the pelvic limbs. Pigs still standing
been documented!7 may show lameness with the separation of the hoof
Removal from access to lead may be all that is at the coronary band.48–50 Results of cerebrospinal
required to halt an outbreak, and a slow reversal of fluid analysis have revealed a mildly elevated pro-
mild signs can occur.31 Therapeutically, chelation tein content of 40–130 mg/dL.51 Dramatic increases
regimens of 50–110 mg/kg CaNa2-­EDTA, IV, once or in cell counts would not be predicted. Needle elec-
twice daily for 3–4 days and repeated once or twice tromyographic studies should document final
over a week or two are recommended.32,36,39 Successful motor neuron lesions. Some mildly affected pigs
lead chelation may also be achieved with meso-­2,3-­ can be salvaged and marketed once the toxic feed is
dimercapto succinic acid at 25 mg/kg, IV, daily for removed.52
4 days and may be more effective.39 The prognosis for An acute poliomyelomalacia, particularly in the
even moderately affected cattle cases is fair provided ventral gray horns at the brachial and the lumbosa-
aggressive chelation treatment is initiated early in the cral intumescence, occurs to account for the flaccid
course of the syndrome, otherwise it is bad. The paralysis.48,51–53 Histologically, lesions can occur in
laryngeal paralysis seen in horses carries a bad several brainstem nuclei, including nucleus cuneatus,
prognosis. nucleus gracilis, facial nucleus, trigeminal motor
As alluded to above, because lead may interfere nucleus, and reticular nuclei.43,50,51,54 Clinical defi-
with neuronal cellular energy metabolism, empirical ciencies of brainstem nuclear function including
treatment with vitamin B1 often has been included in tongue and lip twitching, hypersalivation, mydriasis,
treatment protocols.1,36 Experimental evidence for diminished or absent palpebral reflexes, and nystag-
including vitamin B1 in treating lead poisoning in mus are also reported54. Acutely, there are fibrinoid,
ruminants is somewhat conflicting,28,32,40,41 though on degenerative vascular changes, neuronal degenera-
balance it probably should be recommended and as tion, and some eosinophil infiltration. In chronic
with polioencephalomalacia should be in gram doses cases, significant necrosis of neurons and glia with
repeated frequently. microglial infiltration occurs, often resulting in
Residual signs of poor body condition and reduced microcavitation, neuronal loss, chromatolysis, neu-
fertility can remain in affected and exposed animals ronophagia, microgliosis, Alzheimer’s type II astro-
for several months following an outbreak.5,42 cytes, and proliferation of endothelial cells.43,48–50,53 It
may be that the disruption of the blood–brain barrier
due to astrocyte edema is the most likely mechanism
Selenium toxicity
of CNS lesions.54
Neurologic signs due to selenium toxicity are usually Whole blood selenium concentrations in clinically
seen in feeder pigs.43 Historically, blind staggers with (0.57 ± 0.06 μg/mL or 0.57 ± 0.06 ppm) and experi-
widespread losses of cattle, sheep, and horses in the mentally (3.7 ± 0.2 μg/mL) affected pigs have higher
Southern Plains states in the USA was ascribed to sele- values than control (0.13 ± 0.01 μg/mL) values. Also,
nium toxicity associated with selenium-­accumulating fresh liver selenium concentrations in clinically (3.8 ±
(seleniferous) plants such as locoweed and other 0.4 μg/g of liver) and experimentally (17.8 ± 2.3 μg/g
Astragalus spp. Signs of weight loss, mania, and ataxia of liver) affected pigs have ben far above control val-
predominated. Following an insightful analysis of the ues (0.45 ± 0.01 μg/g of liver) and are the best diag-
evidence and publication of a rigorous and scathing nostic test available.43 Blood selenium concentrations
report,44 it transpires that this syndrome known as in a separate outbreak of acute toxicity have been
locoism is an induced mannosidosis due to swainso- recorded as 3.2 ± 2.6 μg/mL reducing to 0.4 ± 0.1 μg/
nine toxicity.45 Rare cases of selenosis do occur in mL after 46 days on a standard commercial ration
horses, but result in weight loss and epithelial damage containing approximately 0.5 ppm (dry weight) sele-
with hoof lesions and loss of mane and tail hairs.46 nium.55 Dietary selenium from added selenite or
There is a sudden onset of ataxia and recumbency selenate in excess of 20 μg/g of dry matter is sufficient
in several feeder pigs in a group that may be to produce the syndrome.49,51,52 Oral dosing of pigs
416 Large animal neurology

with 1.4–4.2 mg/kg sodium selenite daily50 and occasionally been seen in young piglets, cattle, and
3.54 mg/kg in feed54 resulted in the syndrome Zebra foals.69–71 Widespread neurofibrillary accumu-
between days 3 and 20. Recommended, safe dietary lations within neurons and degrees of spinal neu-
selenium for growing swine is 0.24 ppm.43 Of 44 pigs ronal fiber degeneration have been present, and such
surviving in an outbreak of selenium toxicity, 33 neurofilament accumulations have been shown to be
(75%) exhibited signs of selenosis including anorexia, a characteristic of aluminum intoxication in other
alopecia, and hoof lesions.55 species.72–75
A similar clinicopathologic syndrome with perhaps
sparing of neurons and more white matter damage
Sodium salt poisoning and water
has been produced experimentally with induced nic-
intoxication
otinic acid deficiency in pigs.56,57 This mechanism
should be given consideration if selenium deficiency Feeder pigs, range cattle, feeder calves, and lambs
can be ruled out in an outbreak. That nicotinamide have been documented to suffer neurologic signs
supplementation could protect pigs from the toxic associated with various combinations of access to
effect of selenium toxicity has been investigated, and excess dietary salt, or to water loss or deprivation,
although not definitive, some retardation of the onset and to subsequent free access to water.76–84 Pigs are
of signs, but not mortality of selenium toxicity, was most susceptible, and morbidity and mortality are
recorded.58 much higher in young, small animals. Acute water
Finally, partly due to the nature of the lesions par- overload per se in relatively normal animals usually
ticularly involving ventral gray matter, some interest results in colic, diarrhea, and hemoglobinemia that
has been garnered for the hypothesis that low-­level only sometimes progresses to develop neurologic
selenium toxicity is implicated in the etiology of signs.85
amyotrophic lateral sclerosis.59 Often access to water is restricted because of mis-
management, drought or frozen water supply, and
this is usually followed by free water access.76,77 High
Metallic myelopathy—­direct heavy metal
Na+ salt in the diet and high ambient temperatures
toxicity
can be very important contributing factors77. In one
If paravertebral, usually cervical, injected compounds report,81 pigs were fed salinated whey containing
contain copper salts and are given into musculature >400 mmol/L sodium, yet signs did not occur until
quite close to the spinal cord, these salts can be the piglets were deprived of water for 48 h. Colic, a
imbibed by neural tissues and result in marginal fluid-­filled rumen, diarrhea, cardiac arrhythmia, and
myelopathy causing ataxia and tetraparesis and hemoglobinuria may be seen in calves.85,86 Hyper-
recumbency in sheep.60 The subpial rim of white thermia has also been reported and may be contrib-
matter necrosis can be spread through the whole spi- uted to by hemoglobinemia, high ambient
nal cord and medulla oblongata indicating that cop- temperatures, and seizure activity.79,81,82 Hyperexcita-
per salts are injected into or diffuse into CSF. This bility in several animals or a herd may be a premoni-
process is the same as marginal cuprosis and mar- tory sign of salt poisoning.87
ginal siderosis causing diffuse subpial leukomyelopa- The neurologic syndrome reflects diffuse brain
thy occurring when copper or iron salts or disease with abnormal behavior predominating.
hemoglobin are released into the subarachnoid space Lethargy, aimless wandering, bumping into and
in natural and experimental situations.61–66 Heavy pressing against objects, and ataxia occur, then a tor-
metals and blood products appear to be directly toxic pid state, muscle twitching, and seizures eventu-
to CNS white matter when present in CSF. Whether ate.76,77,79–82,84,88 Loss of squeal is characteristic in pigs.
heavy metal chelating therapy is useful or not has yet Focal seizure activity involving facial and jaw mus-
to be determined.67 cles may precede generalized seizures, and in pigs,
Paravertebral injection reactions to adjuvant-­ the latter can initiate as the animal shuffling back-
containing vaccine can result in local compressive ward rapidly to sit on the haunches. Generalized sei-
myelopathy in cattle68 and are discussed in Chapter 33 zures are followed by recumbency, coma, and death.
(see Figure 33.9). Not well documented are the clinical and pathologic
Syndromes of tetraparesis progressing to tetraple- syndromes of hypernatremia in horses. An unusually
gia, sometimes with evidence of a weak neck, have hyper-­ responsive state, flinching excessively when
 Toxic diseases 417

touched, partial prolapse of the third eyelid, general- Mannitol, 0.25 g/kg IV, may be worth trying in
ized muscle hypertonia, sham drinking, and shuf- water intoxication, but it should not be used in the
fling backward have been seen in documented89 and hypernatremic state of salt poisoning. A general
suspected cases with serum Na values of 167 and rule of thumb is that therapeutic alterations in
174 mmol/L, respectively. serum osmolality can be made quite quickly during
Neurologic signs in neonatal foals treated for neo- acute (<24–48 h duration) hyponatremia or hyper-
natal encephalopathy and for sepsis are not likely to natremia, but for longer (or unknown) durations,
be due to any accompanying moderate hyperna- serum Na+ concentration should be corrected at a
tremia (serum Na > 145 mmol/L).90 On the other rate not to exceed 0.5 mmol/L/h. Individual mortal-
hand, severe hyponatremia (serum Na <122 mmol/L) ity is approximately 50%. Spontaneous recoveries
that can be present with other diseases, especially do occur with adequate water available; therefore, if
renal disease, enterocolitis, and uroperitoneum, the serum osmolar status is not known, then con-
likely accounts for accompanying neurologic signs servative therapy is indicated.79,82,86 There is a well-­
that have included obtundation, ataxia, apparent established link between osmotic demyelination
blindness, and seizures.91,92 Similarly, although hyper- syndromes (previously known as central-­and extra-­
natremia and abnormal neurologic signs were both pontine myelinolysis) and rapid osmolar shifts,
common and significantly associated with mortality particularly precipitous correction of sodium in
in 1,440 critically ill diarrheic calves, it was not pos- chronically hyponatremic patients.97–100 Indeed,
sible to determine whether hypernatremia was an rapid correction of especially hypernatremia
independent cause of neurologic signs in this cohort (hyperosmolality) may allow serum osmolality to
of calves.93 fall, but because of failure of brain amino acids and
Brain edema and a laminar cerebrocortical necro- idiogenic osmoles to dissipate as plasma [Na+] is
sis are the basis of the CNS lesions,76,81,83,84,86,94,95 and decreased to normal, brain cells may swell fur-
Alzheimer type II astrocytes are reported.96 ther.101–103 It needs to be iterated that aggressive cor-
Eosinophils are characteristically seen in the menin- rection of osmolar deviations in acute cases <48 h
ges and Virchow–Robin spaces in affected pigs, pre- duration, begun before full intra/extra-­ cellular
sumably attracted by the cellular necrosis.94 The equilibration occurs, can be lifesaving; however,
pathophysiology probably involves hyposmolality corrections must be cautiously monitored in chronic
and hyponatremia in water intoxication, and hyper- situations to be successful. Glucocorticosteroid
osmolality and hypernatremia in salt poisoning.79,83,95 therapy may assist in some recovery from osmotic
It is sudden shifts in osmolality that produces rapid demyelination disorders.104 One prevents recur-
alterations in intracellular water and electrolyte con- rences by correcting not ignoring management
centrations and a subsequent metabolic blockade to errors.81
neuronal substrate utilization.
In conjunction with corroborating historical and
Ammonated forage toxicity
clinical evidence, serum osmolality >320 mOsm/L or
<210 mOsm/L, or serum sodium concentration Cattle of all ages and occasionally horses are affected
>160 mmol/L or <105 mmol/L, with concomitant by a syndrome of hyperexcitability associated with
changes in CSF osmolality and CSF sodium concen- the consumption of excessive nitrogen-­containing
tration, as well as the presence of hemoglobinuria compounds in the diet. A new batch of ammoniated
and hemoglobinemia, all are helpful diagnostic find- cattle feed may have been fed to the animals, or
ings, although not always present at the time of ammonated molasses or molasses/urea/protein
presentation.76,77 blocks are available.105,106
Low doses of furosemide (0.5 mg/kg), along with Dead animals or some showing terminal seizures
IV normal saline, are indicated if hyponatremic may be found, or one or several in a group can dem-
water intoxication has occurred. A regimen of small onstrate a wide range of strange behaviors. Bloat,
but frequent amounts of water PO and IV 5% dex- dyspnea, muscle tremor, ear twitching, jaw champ-
trose is indicated for correction of acute (<24 h ing, salivation, frequent urination and defecation,
duration) hypernatremia, while half-­ strength bellowing, stampeding, and galloping in circles can
Ringer solution with 2.5 % dextrose is reasonable be seen.105–108 Signs often subside after affected ani-
treatment for chronic hypernatremic salt poisoning. mals are left to remain quiet. The disease associated
418 Large animal neurology

with ammoniated forage feeding in cattle is referred hydrocyanic acid (HCN) in the digestive tract.
to using the descriptive terms bovine hysteria and Examples include bird cherry tree Prunus padus,
bovine bonkers.105,107–111 Toyon shrub Heteromeles arbutifolia, Sorghum spp.
The syndrome of abnormal behavior associated with grasses, Brassica spp. crops, poison hemlock Conium
feeding ammoniated feedstuffs to cattle appears to maculatum, laurel hedge plants Prunus laurocerasus,
result from the production of (nitrogenous) intoxicants Pteridium spp. ferns, and many other weeds.115–118
other than ammonia. Ammoniated carbohydrates such Dyspnea, excitement or lethargy, and tremor can be
as pyrazoles and substituted imidazoles are suspected seen with convulsions and sudden death ensuing in
to play a role in the ensuing encephalopathy.107,110 One fulminant cases. Because of histotoxic anoxia that
such compound that has been suspected to be respon- occurs, bright red blood and mucous membranes
sible for the syndrome in calves is 4-­methylimidazole,110 can be readily seen. This is due to the CN− ion bind-
but this substance appears to lack toxicity at appropri- ing with Fe in cytochrome oxidase to interfere with
ate dosages in goats and heifers.111 cellular respiration. A picric acid paper test is avail-
Symptomatic therapy and removal of any incrimi- able for detecting HCN, and many laboratories can
nated feed are the only real options of treatment. perform semiquantitative assays on blood, ingesta,
and feed samples for cyanide content.116,119 Outbreaks
Urea (non-­protein nitrogen) intoxication do occur with known and suspected environmental
contamination.120,121
Ruminants can tolerate diets containing up to ~1% of
Systemic sodium nitrite and sodium thiosulfate
the total diet as urea and as other non-­protein nitro-
(aka photographic fixer) therapy can be rewarding
gen (NPN) containing soluble compounds. Incorrect
when instituted early in the course of the disease. This
amounts and failure to slowly build up the amount of
mixture first produces methemoglobin from hemo-
urea fed result in intoxication. Access to or spoilage
globin that combines with HCN to produce nontoxic
of feed or water with a nitrogen-­containing fertilizer
cyanmethemoglobin. Initially, low doses for small to
may occur.112,113
large ruminants of 6 mg/kg sodium nitrite slowly IV
The urea and other nitrogen sources are converted
and 66 mg/kg sodium thiosulfate orally have been
to ammonia in the rumen and the liver, and alkalosis
recommended.116 However, sodium thiosulfate given
and ammonia encephalopathy can result.106,114
at the high dose of 660 mg/kg appears to be the
Although not consistently present, elevated blood
antidote of choice, in conjunction with sodium nitrite
and CSF ammonia concentrations, in the absence of
or not.122
evidence of liver disease, will assist with the diagnosis
of urea/NPN intoxication.106
Organochlorine compounds
Animals may simply be found dead. Early signs
may be restlessness that may progress into muscle Organochlorine insecticides were used extensively in
tremors, excitation, belligerence, and bellowing, fol- pest control and agriculture from the 1950s until the
lowed by terminal convulsions. 1970s and toxic concentrations persist in contami-
In suspected clinical cases of urea toxicity, the nated soils and dump sites. Hyperexcitability, jaw
stomach or rumen should be lavaged and evacuated. chomping, nystagmus, opisthotonus, tremor, ataxia,
Acidifying solutions, such as 5% acetic acid or vine- and seizures described as running fits are character-
gar, can be given orally at doses between 0.5 L for istic of chlorinated hydrocarbon poisoning in sheep
sheep and 5 L for cattle along with additional water. and cattle.123,124 Death occurs due to respiratory fail-
Sedation may be necessary. The disease is most often ure and cardiac arrest. A more chronic condition of
fatal. Preventive measures to manage and prevent the anorexia and somnolence leading to recumbency
syndrome are usually obvious. and death after 2–3 weeks may also occur in flock
outbreaks.

Cyanide poisoning Organophosphate and carbamate

compounds
Goats and other ungulates can develop cyanide poi-
soning when eating plants containing high concen- Both organophosphates and carbamates act as
trations of cyanogenic glycosides that release anticholinesterase toxins. Toxicity usually results
 Toxic diseases 419

from exposure to animal and plant parasiticides and acute anti-­ acetylcholinesterase organophosphate
to industrial lubricants.125–130 Acute toxicity from toxicity with others showing little or no ill effect.
exposure to organophosphates may produce saliva- Then, a few weeks pass before some animals have
tion, miotic pupils, diarrhea, and bradyarrhythmia. rapidly progressive, symmetric paraparesis, and
Muscle tremors, seizures, and weakness dominate ataxia of the pelvic limbs with signs suggestive of
the neurologic signs with coma and death ensuing. final motor neuron sciatic paralysis such as knuck-
Body tremor and apprehension are usually ling over at the fetlocks sometimes being present.
present.37,125,131,132 The animal then becomes paraplegic, sitting on its
An intermediate form of organophosphate toxic- haunches, occasionally becoming tetraple-
ity is recognized in humans and small animals with gic.129,134,141,144,145 Pigs may initially have hypermetria
syndromes consisting of acute paralysis and weak- and even a stringhalt-­like gait in the pelvic limbs.142
ness of several cranial and cervical and brachial The effects of delayed organophosphate polyneu-
motor nerves a few days following exposure.37,133 ropathy probably are more likely to resolve when
Generalized weakness and localizing signs may last a young animals are involved.146
few days to several weeks.37,130 An intermediate tox- The classical central and peripheral dying back
icity may be represented by selective cranial and axonopathy accounting for the delayed
other nerve syndromes in large animals. Evidence of organophosphate-­ induced neurotoxicity is more
laryngeal paralysis and straining to urinate have thought to represent a distal, preterminal, central
occurred in cattle suspected of suffering organo- and peripheral axonopathy.138,144–148 However, dis-
phosphate toxicity,130,134 presumably due to laryngeal ruption to many neural pathways may well occur.144
and urinary bladder paralysis. Affected cattle and Organophosphorus compounds covalently phos-
horses have also demonstrated dyspnea presumably phorylate and inhibit many serine hydrolases. When
the result of such laryngeal paralysis. In the horse, inhibition of neuropathy target esterase (NTE)
repeated doses of certain organophosphates such as occurs, followed by an aging process, distal degen-
haloxon have been associated with bilateral laryn- erative axonopathy ensues, known as organophos-
geal paralysis.135,136 Signs partly improved with sup- phorus compound-­ induced delayed neurotoxicity
portive care that included tracheostomy in some (OPIDN). Chemicals producing this are termed
affected horses. Also, a form of widespread myopa- neuropathic organophosphorus compounds.149
thy may well occur in horses exposed to these com- An acute onset of paresis or paralysis, several
pounds.137 This may occur in certain genetically hours to a few days after systemic organophos-
predisposed lines of horses, and subclinical selenium phate antiparasitic therapy in cattle, is likely to be
deficiency may be a cofactor to the myopathy. Signs the result of death of epidural Hypoderma bovis
may be expected to be generalized with malaise, larvae and subsequent necrotic myelitis rather
weakness, muscle tremors, and dysphagia being than the direct effects of the organophosphate
likely.137 compound.150,151
Pandemics of so-­called Ginger paralysis, a form Finally, more selective neurologic syndromes
of delayed organophosphate-­induced neurotoxicity, occur as an in utero neurotoxicity with certain organ-
caused illness and death in thousands of people ophosphates. Newborn piglets and calves, exposed in
worldwide in the early half of last century. Any age utero to organophosphate compounds, have been
and all species of animals and birds are susceptible found to have forms of cerebellar hypoplasia and
to delayed neurotoxic organophosphate poisoning, degrees of ataxia. Congenital tremor is usually prom-
although younger animals and particular family inent (see Chapter 31). The syndrome of acquired,
lines may be more resistant than others.138,139 It is postnatal tremor associated with the use of organo-
mostly reported in young and adult sheep, cattle, phosphate compounds probably results from a
and pigs. Most often an outbreak of acutely progres- peripheral neuromuscular blockade or a nicotinic
sive ataxia and paraplegia occurs one week to sev- effect.152
eral months after the use of organophosphate spray The potent neurotoxins triorthocresyl phosphate
or drench or after accidental or suspected access and triaryl phosphate can be found in industrial
to certain industrial organophosphates.129,139–143 lubricants and wastes.130 Haloxon and possibly other
Some may die at the time of contact with signs of organophosphate anthelmintics, and isofenphos and
420 Large animal neurology

other insecticides, have been involved in large animal contortions of facial muscles referred to as risus sar­
neurotoxicity. The disease is not primarily related to donicus can be expected. This compound is a direct
suppression of blood cholinesterase activity, but as convulsant drug by acting as a selective competitive
indicated above, results from inhibition of neuropa- antagonist of the inhibitory effects of glycine at the
thy target esterase resulting in distal axonopathy153 glycine receptors of motor neurons and interneurons
and subsequent symmetric fiber degeneration in the in the brainstem and spinal cord.
CNS and PNS.138,144,145,148 Initially, the signs of strychnine poisoning mimic
Certain breeds of animals such as Suffolk sheep those of early tetanus caused by C. tetani. Five of six
have a familial predisposition to the delayed horses that had accidental access to barley contami-
organophosphorus compound-­ induced delayed nated with “Gopher Bait” showed clinical signs and
neurotoxicity.139,149 Therefore, great care must be two died. Initial clinical signs consisted of stiffness of
taken if exposing them to organophosphate gait, muscle fasciculations, and stumbling progress-
compounds. ing rapidly to seizures.158 Two horses were treated
Diagnostically, attempts should be made to iden- with a combination of pentobarbital, diazepam, and
tify the contaminant organophosphate and remove xylazine to maintain a light plane of anesthesia for up
it from the environment using appropriate person- to 12 h after which these horses stopped convulsing
nel barrier protection. Blood and tissue cholinester- and slowly recovered in a further day. Activated char-
ase activity may be circumstantial evidence of coal and mineral oil was given by stomach tube. The
intoxication.154,155 Erythrocyte and serum cholinest- measured strychnine content of the contaminated
erase concentrations are reduced acutely but not barley was >100 mg/kg. Other horses have been suc-
necessarily in delayed toxicity, and this test may not cessfully treated with sedation and anesthesia with
be valid in cattle because values can be low in nor- acetylpromazine and pentobarbital159 plus gastric lav-
mal animals. A toxicology laboratory should be age and catharsis.
consulted.130,156
Therapeutically, the seizures should be controlled
with either diazepam or pentobarbital to effect, but Metaldehyde
this may be very difficult to achieve. With organo- Tremor and tetany, usually leading to severe status
phosphates, treatment should include atropine and epilepticus and death, caused by slug/snail bait
possibly pralidoxime chloride (2-­PAM) if acute sys- ingestion has been seen in cattle,160–163 sheep,164 and
temic signs of organophosphate toxicity coexist. horses.131,165–168 Anticonvulsant therapy, which may
Diphenhydramine hydrochloride may be used to entail general anesthesia with sodium pentobarbi-
decrease the amount of atropine required to achieve tal, as well as attempted gastric lavage and intestinal
a central anticholinergic (nicotinic) effect and to catharsis are indicated. The complete mechanism
control the neuromuscular blockade effect;157 how- of action of metaldehyde is unclear, but in mice at
ever, the dose for large animals is not known. least, metaldehyde led to an increase in monoam-
Intravenous crystalloid fluids should aid in diuresis ine oxidase activity and to a decrease in GABA,
and elimination of toxins. Bathing the animal to norepinephrine, and 5-­ hydroxytryptamine levels
remove residual toxins in the hair and gastric rumen that lead to neuronal excitation and decreased sei-
lavage is sensible to undertake for oral intoxication. zure threshold.169
Saline, nonoily cathartics should be used. Prognosis
for survival may be fair if treatment begins early, but Fluoroacetate (compound 1080)
often the syndrome is too profound for survival by
the time seizures and recumbency occur. Mildly The principal toxic effect of monofluoroacetate
affected sheep have been salvaged but considerable (sodium fluoroacetate; ten-­eighty, 1080) is well rec-
weight loss occurred.141 ognized. After absorption, it is converted to fluoroci-
trate that is a potent inhibitor of the enzyme aconitase
in the tricarboxylic acid (Kreb) cycle. It has been
Strychnine
extensively employed as a pesticide in several coun-
Strychnine toxicity is rarely seen in large animals, tries, including Australia, Israel, Japan, Mexico, New
although generalized tonic/clonic convulsions with Zealand, and the United States, 170–172 not without
 Toxic diseases 421

some controversy and welfare concerns.173 At least 40 Aminoglycoside toxicity

toxic plants of many families, mainly found in the
These antibiotics are commonly used in large ani-
southern hemisphere in Africa, Australia, and South
mals but may cause sensorineural clinical deafness
America, contain monofluoroacetate and cause sud-
due to damage to inner ear hair cells.188 Neomycin
den death in livestock.37 In most mammals and birds,
given to calves at 2.25 and 4.5 mg/kg, BID, IM, for 12
1080 produces convulsions, urination, vomition, and
or 13 days resulted in clinical deafness, which was
ventricular fibrillation within minutes to a few hours
confirmed by recording brainstem auditory evoked
following exposure.37,170,174 The poisoning is highly
potentials.189 Reported auditory effects of gentamicin
fatal, and there is no antidote.
in horses have varied. Dosage of 5 mg/kg TID, IM, to
ponies for 7–14 days reportedly did not affect BAEP
Arsanilic acid and 3-­nitro-­4-­ hearing test recordings.190 By contrast, and worry-
hydroxyphenylarsonic acid (3-­nitro): ingly, 7/10 horses given typical IV therapeutic doses
Arsenic toxicoses of 6.6 mg/kg SID for 7 days had degrees of auditory
dysfunction as determined by BAEP recordings.
These relatively safe compounds are used less and Signs persisted for >20 days in 3 of these horses.191
less nowadays as growth promoters and for the con- Rarely, these antibiotics might be expected to cause
trol of enteric infections. Overdose has resulted in a vestibular signs.192,193
wide spectrum of syndromes, including seizures,
peripheral blindness, tremor, and ataxia.175–177 The
precise clinical syndrome and specific neuropatho- Chronic toxicity by organomercury
logic lesions associated with each compound is not compounds
clear, and it is thought that there may be other dietary
and infectious factors interacting.178 However, it has Chronic organomercury intoxication in pigs and
been shown that pentavalent organic arsenicals such sheep may induce neurologic syndromes related to
as 3-­nitro causes selective, central, and peripheral cerebral and cerebellar pericapillary and pericellu-
axonal degeneration.179,180 Most likely, both com- lar edema and neuronal necrosis.194–197 In pigs, alky-
pounds can result in a subacute ataxia and tetrapare- lmercurial poisoning produces weakness and ataxia.
sis from which mildly affected animals can recover Usually, the syndrome progresses to include head
following withdrawal of the intoxicating feed.175–179 signs, including blindness, wandering, and recum-
Relapses may still occur.178 bency. Cerebral neuronal necrosis, endothelial pro-
Organic arsenic salts cause acute gastrointestinal liferation, and peripheral axonal degeneration
upsets, cardiovascular shock, and death.181 account for the clinical signs.198,199 The ataxia, rest-
Ingestion of ash from burnt treated or painted lessness, and hypersensitivity described likely is cer-
wood is the most common source.182 Suspiciously ebellar in origin.196 In cattle and horses, a
malicious or accidental exposure of livestock to predominantly cerebellar syndrome results from
these compounds can result in neurologic signs of chronic organomercury toxicity. Early signs of
staggering, ataxia, and muscle tremors.182–186 The intoxication in calves include ataxia and swinging
outcome is generally regarded as consistently fatal, head movements and probably relate to degenera-
although two of four cattle with acute arsenic toxic- tion of cerebellar granular cells.200 Prominent hyper-
ity survived with intensive IV fluids and sodium metric ataxia and head nodding were seen in a horse
thiosulfate resulted in decreased blood arsenic con- with chronic methylmercurialism. Focal atrophy of
centrations in all four cases. Balances of other granular cells in the cerebellum as well as more
nutrient minerals such as Zn and Se may be of widespread neuronal and axonal necrosis was
some significance in arsenic metabolism.187 Finally, present.201
lead arsenate was used as a pesticide, and heavy Mercury, like other heavy metals, accumulates at
metals frequently occur together as by-­products in the end of the food chain and in a water environment
smelter works. Thus, combinations of arsenic, lead, thus ends up in fish that have been the source of epi-
and other elemental toxicoses can occur concur- demic mercury poisoning in several human popula-
rently, complicating the diagnostic and therapeutic tions expressed as somatosensory and cerebellar
approach taken.181,184 syndromes.202
422 Large animal neurology

Ionophore toxicity—­monensin, salinomycin, received 10 times the normally recommended dose

and lasolocid of ivermectin217,225 or moxidectin.224 There is some
evidence that there is a peripheral component to the
Monensin and lasolocid are two of the more com-
blindness that has resolved with time.226 In addition
monly used polyether antimicrobial agents that
to ataxia and blindness, calves and foals have shown
have been used in feedstuffs for cattle, pigs, and
final motor neuron signs including profound weak-
chickens as growth promotants and coccidiostats.
ness, knuckling over on the fetlocks, drooping facial
All large animals, particularly horses, are suscepti-
muscles, absent or poor palpebral reflexes, and pro-
ble to poisoning with these carboxylic ionophores,
truding tongue.222,223,227
which interfere with metal ion transfer across
Calves, kids, and foals are several fold more sensitive
biomembranes.203–205 The myoneurotoxic potential
to signs of toxicity than adults.218,220–224,228–230 Also,
of these compounds likely is in the increasing order
there is evidence that animals with low body condi-
of salinomycin < lasalocid < narasin < monensin <
tion scores are also more susceptible to toxic effects
maduramicin.206
of these drugs.231 Thus, all 330, 2 to 4-­week-­old calves
Acute intoxication can result in hypovolemic
showed signs and 14% died after receiving eight
shock and rapid death.207 Less severe intoxication
times (1.75 mg/kg) the therapeutic dose of ivermec-
causes degrees of ataxia, weakness with muscle
tin PO.218
tremors, and recumbency with hyporeflexia.204,208–210
There likely is a breed susceptibility with Murray
Evidence of myonecrosis, heart failure, and renal
Gray cattle being more susceptible with evidence of
failure are variably present to account for acute
greater penetration of the avermectin into the brain
deaths.203,205,207,211 In horses, ataxia and paraparesis
tissue of affected versus unaffected cattle.227 Such a
may persist for several weeks, and signs of chronic
breed predilection is present in dogs where an
heart failure may become apparent.203–205,212–214
ABCB1-­1Δ polymorphism in the MDR1 gene is
Experimental intoxication in horses and swine has
associated with increased susceptibility to many
caused early signs of hypermetric ataxia, which may
adverse drug reactions. Dogs with the ABCB1-­1Δ
result from an ionophore interfering with central or
mutation lack functional P-­glycoprotein, a substrate
peripheral neurotransmitter activity.203,205,209 How­
transporter that normally prevents the entry of many
ever, central and peripheral neuronal fiber degen-
drugs across the blood–brain barrier, thus allowing
eration and striking vacuolation of dorsal root
compounds such as macrocyclic lactones to be con-
ganglia neurons likely account for the persistent
centrated in the CNS.232–234 A SNP in the
syndrome of ataxia in horses surviving acute salino-
3’-­untranslated region of the MDR1 gene was sus-
mycin toxicity.215 Vitamin E and selenium may ame-
pected to be the cause of doramectin sensitivity in a
liorate some of the toxic effects of these compounds,
Thuringian goat.235
whereas other antibiotics such as tiamulin and fura-
Supportive nursing care, seizure control, and
zolidone may exacerbate the toxicity, at least in
fluid therapy can assist survival and no permanent
pigs.205,206
side effects are to be expected.218,219,224,227,228 Whether
or not antagonists of gamma-­aminobutyric acid
function or analeptic drugs are necessarily indi-
Ivermectin and moxidectin
cated treatments is not clear.228,230 The use of IV lipid
Ivermectin, an avermectin, and moxidectin, a milbe- emulsion to form a new intravenous lipid compart-
mycin, are both macrocyclic lactones and are widely ment as a “sink” for lipophilic compounds such as
used as antiparasitic agents in all large animals.216,217 macrocyclic lactones is quite effective in treating
Their effectiveness results because of potentiation of such poisonings.226,236,237
gamma-­aminobutyric acid (inhibitory) neurotrans-
mission in parasitic arthropods and nematodes. The
Methyl bromide
avermectins are safe drugs, but temporary ataxia and
blindness have been reported in equids, cattle, sheep, Methyl bromide is used as a plant and soil fumi-
goats, and pigs with overdosing, which can progress gant, particularly prior to planting grapes. Hay har-
to coma and death.218–224 Adult horses have shown vested from ground treated with it has resulted in
temporary central blindness and ataxia when they ataxia, weakness, and lethargy in horses, goats, and
 Toxic diseases 423

cattle.238,239 Signs are seen when serum bromide In a study of 59 generalized reactions to IM
concentrations reach about 30 mmol/L (c. ­ enicillin, the following signs were recorded most
p
2400 mg/L). Spuriously high laboratory chloride frequently: galloping off, crashing into stable walls,
estimations might be expected in patients with expo- sudden backing, rearing and kicking, ataxia, recum-
sure to (methyl) bromide. KBr is being used more as bency, gasping, groaning, snorting, tachypnoea, sei-
an anticonvulsant in animals,240–243 and toxicity is as zures, and acting blind—­with one death reported.246
for methyl bromide.243 The ataxia and soporific A typical acute procaine reaction is heralded by the
effects can be expected to wane in about 14 days horse acting startled and snorting, then compulsively
from discontinuing the source of bromide.239 moving forward or backward, staggering, and then
either moving in a crazed manner or falling with
muscle rigidity and spasms. It appears that the
Procaine penicillin reaction quicker the initial abnormal behavior and locomo-
Procaine penicillin G is an extremely safe and widely tion begin, the worse the prognosis is although many
used antibiotic in large animals, and although thank- horses survive with or without (pre-­) treatment with
fully uncommon, all clinicians must be aware of the diazepam.244
sometimes-­violent acute reaction that can occur dur-
ing or immediately following an IM injection of pro- Miscellaneous known and suspected drugs
caine containing drugs—­ usually benzyl penicillin and toxins
(penicillin G).
There are a very large number of reports of suspected
untoward neurologic syndromes that may well fit a
It is indeed a frightening experience to witness a known toxicity to a specific chemical agent. Below
patient react uncontrollably and violently several sec- are a few of those that are reasonably well docu-
onds to minutes following initiation of IM procaine mented and demonstrate a wide variety of syndromes
penicillin administration, but it happens to the most that can occur with toxic and probably idiosyncratic
experienced of us. adverse reactions.
Postanesthetic myasthenic syndrome is a rare clini-
Rarely, such an injection has caused thrombosis cal phenomenon that mimics acute, temporary botu-
of a coronary artery, presumably via pulmonary lism and tick paralysis and is seen in horses that
A-­V shunting, and immediate cardiac standstill, remain in a state of flaccid paralysis following anes-
and yet full doses of procaine penicillin G have thesia. Usually, combinations of aminoglycoside or
been seen to be given via indwelling IV catheters tetracycline antibiotics and halothane and succinyl-
sometimes—­not always—­with no adverse effects. choline were used. Hypocalcemia, complicated sur-
If there is inadvertent intracarotid injection of the gery such as ovarian tumor removal, and drug
drug, a response occurs while the injection is being combinations may play a role in the diffuse neuro-
given or immediately after a small volume is muscular blockade that is evident. Facial, tongue,
injected rapidly (see Chapter 33). Most anaphylac- pharyngeal, body, and limb musculature are affected.
tic or anaphylactoid responses would be expected Calcium salts and neostigmine are worth trying, but,
to take minutes to hours to become fulminant with as for treating botulism, nursing care is most impor-
pulmonary and cardiac failure occurring. Many of tant. Three affected horses recovered with nursing
the responses occurring within a few to 60 s of care were able to walk in 5–7 days and were totally
injection mimic the effects of procaine administra- normal within 4 weeks.
tion, and such responses following intramuscular Closantel and the related compound rafoxanide
injection can be made more possible if the pro- are halogenated salicylanilides with wide anthel-
caine penicillin formulation becomes heated and if mintic activities which are used to treat ruminants
it is deposited in a very vascular site such as exists for liver fluke and Haemonchus sp. infections.
immediately following exercise, or into a previous Sheep and goats have become peripherally blind
injection site reaction.244,245 Procaine is metabo- with moderate overdosing,247–249 even at 1.5 times
lized by esterases quite quickly into nontoxic the dose rate recommended for sheep, given to
metabolites. kids. There is neuronal degeneration in the
424 Large animal neurology

photoreceptor cells of the retina and the fibers of The long acting phenothiazine drugs perphena­
the optic nerves, optic tracts and some white matter zine, fluphenazine, and trazodone are phenothiazine
fascicles of the cerebrum, brainstem, and cerebellar derivatives with anti-­ dopamine activity that are
peduncles.250 Even inadvertent access of ewes to a used as long acting anxiolytics.262,263 As in humans
cattle pour-­on containing closantel and ivermectin treated for psychiatric disorders, a few treated
has been associated with typical clinical and patho- horses have shown toxic effects of movement disor-
logic findings.251 The optic nerve lesions can be ders perhaps representing extra-­ pyramidal dys-
spectacular with focal cavitations likely contributed function akin to a Parkinson-­like syndrome. What
to by the optic nerve swelling within the optic canal is seen is fluctuant somnolence and abnormal,
and subsequent compressive pressure necrosis. repetitive activity that can consist of adopting
Because of this, the early use of mannitol possibly abnormal postures and displaying incredibly fran-
would be indicated in any therapy. This toxicity is tic, repetitive movements.262–266 Thus, an affected
very similar to that caused by stypandrol-­containing horse may stand fixated by an object and appear to
plants (see below). watch unapparent images move, stand with the
Furazolidone and nitrofurantoin are infrequently forelimbs placed well forward and the head flexed
used orally-­administered nitrofuran antimicrobial between the knees, and perform tonic repetitive
compounds that, with overdosing, can cause acute movements such as incessant pawing with one limb,
neurologic signs and also subacute hemorrhagic head swinging, and pseudo-­ rubbing on objects.
diathesis associated with pancytopenia in calves Recumbency without somnolence and seizure-­like
and pigs.252–254 The neurologic syndrome is quite activity also occurs. Repeated doses of the anticho-
like that with lead poisoning with bellowing, linergic drugs benztropine mesylate and diphenhy-
hyperexcitability, frenzied charging, ataxia, muscle dramine hydrochloride given cautiously to effect
tremors, and convulsions reflecting cerebral dys- can contain the clinical signs,263,265,266 although anti-
function. Histologically, there is focal vacuolation convulsants, narcotic, and sedative drugs may also
and small hemorrhages within cerebral and cere- help control some of the severe signs.266
bellar white matter. Whether any anti-­ thiamin Metoclopramide, a serotonin agonist and dopa-
activity of these compounds plays a role in toxicity mine receptor antagonist, is used for gastric outflow
is unclear.255 disorders and can result in similar, fluctuant, so-­
Doxycycline overdosing of cattle results in myo- called extra-­pyramidal, movement disorders as do
cardial and skeletal muscle necrosis,256 but in calves the phenothiazine-­derivative drugs.267
the tongue, myocardium, diaphragm, and pharyn- Sulpiride is another selective dopamine antagonist
geal muscles may be targeted to produce syndromes used in equine reproductive disorders that can also
of inappetence, respiratory difficulties, lingual and produce compulsive and repetitive syndromes as can
pharyngeal dysphagia, sialorrhea, and tachyarrhyth- the phenothiazine drugs above.268,269
mias.257,258 Many of the oral and pharyngeal signs in Commercial acrylamide mostly comes as polymers
several species may well be due to the erosive nature that are nontoxic. When broken down in the envi-
of the acidic (pH ~ 1) doxycycline hyclate salt in ronment to monomeric acrylamide, it is quite toxic
preference to the more neutral, but more expensive, to man and other animals resulting in central and
monohydrate salt. peripheral distal axonopathy270 although the clinical
Lithium salts, drugs used for human psychomotor descriptions of known poisonings are not well docu-
and depressant conditions, appear to be relatively mented for large animals. However, there is one well-­
safe in horses when used in doses useful to determine documented report of exposure of a herd of beef
cardiac output.259 Although the Fédération Equestre cattle to acrylamide that leached from a grouting
Internationale (FEI) classifies lithium as a banned agent into the drinking water and caused clinical syn-
substance,260 it has been used in horses illicitly as a dromes of central and peripheral neuronal involve-
purported mood stabilizer. Unwanted exposure to ment.271 Central signs consisted of fasciculations,
medicinal lithium chloride, or possibly access to tremor, convulsions, ataxia and weakness, and
industrial compounds such as grease, may result in peripheral axonal lesions probably accounted for the
neurologic signs probably characterized by ataxia, dragging of the toes and knuckling over of the
lethargy, and seizures.261 fetlocks.
 Toxic diseases 425

A vast array of plants are toxic to large animals and very many result terminally in general and neurologic signs includ-
ing somnolence, weakness, ataxia, muscle tremor, diarrhea, involuntary urination, blindness, compulsive movements,
recumbency, and seizures in various combinations. Many plants are endemic to specific countries and climatic and
geologic regions. Others have been distributed worldwide. Full coverage of all such plants is not possible here. Many
of the plant-­associated neurotoxicities of large animals of more than local interest and those with interesting and
distinctive clinicopathologic expression are discussed below, and a selection of extensive sources of further information
can be found in Veterinary Toxicology resources including:
Beasley V. Veterinary Toxicology. International Veterinary Information Service. 2004. Retrieved from https://www.ivis.
org/library/veterinary-toxicology
Dalefield R. Veterinary toxicology for Australia and New Zealand. Elsevier. 2017. https://www.elsevier.com/books/
veterinary-­toxicology-­for-­australia-­and-­new-­zealand/dalefield/978-­0-­12-­420227-­6
Gupta PK. Poisonous plants. In Illustrated Toxicology, Gupta PK. Editor. Ch 11. Academic Press. 2018; 309-­329.
https://www.elsevier.com/books/illustrated-toxicology/gupta/978-0-12-813213-5
Gupta RC. Veterinary toxicology: basic and clinical principles, 3rd ed. Academic Press, an imprint of Elsevier. 2018.
https://www.google.co.nz/books/edition/Veterinary_Toxicology/OG_Oz58xq6kC?hl=en&gbpv=1&dq=veterinary+Tox
icology+gupta&pg=PP1&printsec=frontcover
Kellerman T S, Coetzer JAW and Naude TW. Plant Poisonings and Mycotoxicoses of Livestock in Southern Africa.
Oxford University Press, Oxford, UK. 1988. https://biblio.co.uk/9780195704884
Knight AP and Walter RG. A guide to plant poisoning of animals in North America. Jackson WY, Editor. USA. 2004.
Teton NewMedia. https://www.ivis.org/library/guide-­to-­plant-­poisoning-­of-­animals-­north-­america
McKenzie R. Australia’s poisonous plants, fungi and cyanobacteria: a guide to species of medical and veterinary
importance. Collingwood, CSIRO. 2012. https://catalogue.nla.gov.au/Record/5758191
Osweiler GD, Carson TL, Buck WB and Van Gelder GA. Clinical and Diagnostic Veterinary Toxicology. 3rd ed. Kendall-­
Hunt Publishing Co, Dubuque, Iowa. 1985. https://pdfmedia.net/book/CYs2vwEACAAJ/clinical-and-diagnostic-
veterinary-toxicology/william-b-buck-gary-d-osweiler-gary-arthur-van-gelder/unknown/380/1976/0987650XXX/
uncategoriezed
Parton KH, Bruere AN and Chambers JP. Veterinary Clinical Toxicology. 3rd ed. Publication No. 249. Palmerston
North, NZ: Massey University Press. 2018. https://www.masseypress.ac.nz/
Penrith ML, Botha CJ and Tustin RC. Plant poisonings in livestock in Brazil and South Africa. J S Afr Vet Assoc 2015;
86(1): 1200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138183/
Riet-­Correa F, Medeiros RMT, Pfister JA and Mendonça FS. Toxic plants affecting the nervous system of rumi-
nants and horses in Brazil. Pesquisa Veterinaria Brasileira 2017; 37: 1357-­1368. https://www.scielo.br/j/pvb/a/
4mzZTPkDhYcsB3MRypTZ58z/?lang=en
Riet-­Correa F, Medeiros RMT, Pfister JA, Schild AL and Dantas AFM. Toxic plants and mycotoxins affecting the nerv-
ous system. In Poisonings by Plants, Mycotoxins and Related Substances in Brazilian Livestock, Patos PB, Editor. 1st ed.
Sociedade Vicente Pallotti – editor, Brasil. 2009; 99-­147. https://www.cabi.org/bookshop/book/9781845938338/
Tokarnia CH, Döbereiner J, Peixoto PV, Brito MDF and Barbosa JD. Plantas tóxicas do Brasil para animais de produção.
Editora Helianthus. Rio de Janeiro 2012. https://www.worldcat.org/title/plantas-toxicas-do-brasil-para-animais-de-
producao/oclc/820422983

Plant and plant-related toxins with periods of aggression and hyperesthesia when
handled, along with cerebellar ataxia, which in
Locoweed and Darling pea—­swainsonine North America and elsewhere is referred to as
intoxication locoism.272–275 The alkaloid toxin swainsonine is
Poisoning by locoweeds (Astragalus and Oxytropis produced in these plants by endophytic fungi
spp.) in North America and China, and by Darling (Alternaria spp. sect. Undifilum)276,277 and induces
pea (Swainsona spp.) in Australia can produce a a lysosomal storage disease, α-­mannosidosis, in
syndrome of progressive weight loss and dementia affected animals.272–274,278,279
426 Large animal neurology

Accompanying poor reproductive performance in Ataxia associated with sorghum spp. grasses
livestock exposed to swainsonine-­containing plants is A syndrome of progressive ataxia and bladder paraly-
a huge economic factor to the importance of this dis- sis occurs in cattle and horses in southwestern and
ease.45 Mimicking lesions present in inherited man- western USA, Argentina, Australia, and India where
nosidosis, there is widespread cellular and particularly Sorghum spp. grasses are used as forage. The syn-
neuronal vacuolation, being quite prominent in cere- drome is more frequently reported in horses of all
bellar Purkinje cells, with loss of neurons and axonal ages, less often in cattle and sheep.296–302 However, a
dystrophy occurring.45,281 Hypomyelination of brain large outbreak of ataxia without urinary bladder
axons was demonstrated in fetuses and newborn incontinence is described in lambs and ewes grazing
calves of cattle that consumed the swainsonine-­ Sorghum bicolor stubble and lush Sudax (sorghum-­
containing plant Sida carpinofolia.282 Sudan) grass pasture in Australia.296,303
There should be a history of access to Sorghum spp.,
such as Sudan, Sorghum, and Johnson grass, with signs
This syndrome of blind staggers or locoism was thought beginning 2–8 weeks from initial exposure.296,303,304
to be the result of chronic selenium intoxication Fresh Sudan grass hay and grain sorghum stubble are
­(selenosis) of horses that ingest selenium-­accumulating also toxic when fed, but well-­cured Sorghum spp.
locoweeds, whereas it is in fact the result of a plant/ hay is not toxic.
endophyte symbiosis-­ induced mannosidosis rather In affected horses, symmetric ataxia and weakness
than simple selenium toxicity.44,46,277,280 of the pelvic limbs occurs with dribbling of urine in
about half the cases when a distended urinary bladder
with a thickened wall is usually palpable through the
Progressive cerebellar ataxia in browsing animals rectum. Paraparesis can ultimately progress to para-
is the hallmark of the syndrome that occurs in live- plegia. Hypalgesia but not analgesia of the perineum
stock and wild ungulates.273,279,283 Removing the ani- and hind quarters is reported. The bladder paraly-
mal from the plants can result in alleviation of some sis and description of sinking on the pelvic limbs
of the prominent ataxia, but behavioral changes may suggests final motor neuron involvement.301,302,304,305
be permanent.280 Affected lambs do not show urinary incontinence and
Reversal of signs with an apparent permanent cure can have evidence of vestibulocerebellar involvement
has been achieved using combinations of the mood with loss of balance, with falling and head and body
elevators tranylcypromine and protriptyline along tremors all becoming worse with forced exercise.303
with reserpine.284 In early cases, this can be achieved The primary lesion in affected cattle and horses is
by simply withdrawing the patient from the toxic neuronal fiber degeneration and possibly demyelina-
plants. A withdrawal period of 28 days should be tion throughout the spinal cord white matter, par-
allowed for the clearance of swainsonine from ticularly in the thoracolumbar segments. Also, a
affected livestock.273 A temporary syndrome of inter- degenerative neuropathy of spinal nerves probably
mittent excitement and variable hypermetric ataxia, occurs. Urinary bladder paralysis results in second-
accompanied by oliguria, has been associated with ary cystitis and ulceration. Interestingly, in affected
the ingestion of swainsonine in a horse in Europe.285 sheep this Wallerian-­like degeneration is minimal
The horse totally recovered over several months fol- and there is neuroaxonal dystrophy with focal proxi-
lowing immediate therapy with IV fluid and electro- mal axonal swellings in brainstem and cerebellar
lyte therapy with supplementation of potassium, a nuclei and in ventral horn spinal gray matter.303
dopamine drip, and administration of diazepam. One suggested mechanism for this neurotoxicity is
However, no therapy has been shown to be beneficial that it is related to high hydrocyanide content of
in preventing the disease.45 Sorghum spp. grasses and there are elevated thiocy-
Many other species of related plants such as anate blood levels in poisoned horses. A lathyrogenic
Sida carpinifolia (syn. Sida acuta), Sida rodrigoi principle, β-­cyanoalanine, is another possible cause
Monteiro, Turbina cordata, Ipomoea verbascoidea, of the lesions; however, neither of these proposed
Ipomoea carnea, and Oxytropis glabra cause the neurotoxic mechanisms is proven.296,297,300,303,304,306
same clinicopathologic syndrome in horses, sheep, Mares, cows, and ewes may deliver or abort off-
and goats, most probably due to the action of spring with arthrogryposis, and lambs may be born
swainsonine.282,286–295 with limb paresis. Signs stop progressing and may
 Toxic diseases 427

partially regress if animals are removed from Nigropallidal encephalomalacia occurs when
Sorghum spp. pastures.296,303 A similar syndrome of horses have access to hay or pasture containing yel-
progressive tetraparesis and ataxia—­without urinary low star thistle or Russian knapweed for at least a
bladder paresis—­has occurred in dairy cows fed sor- month and a history of an acute onset of rigidity of
ghum beer residues that was rather thought to be the muscles of prehension and mastication and facial
associated with the fungus Aspergillus clavatus.307 expression (Figure 34.1). These plants grow in west-
Primary cystitis should be ruled out if possible. ern USA, and Rhaponticum repens also grows in
Complete analgesia of the perineum and tail and a Australia where it is known as yellow burr and in
totally flaccid tail are rare in this disease compared with South America where it is known as abrepuño or
signs seen most often with fractured sacrum and with open fist.308,309
polyneuritis equi, both of which cause a more profound Yellow star thistle poisoning, also called chewing
cauda equina syndrome. No ancillary aids have been disease, results in excessive and inappropriate muscle
reported to be useful in confirming the diagnosis. tone or dystonia present in the jaws, resulting in a
There is no specific treatment. Removal from the horizontal movement without the ability to close or
offending pasture and treatment of cystitis are neces- open the mouth completely or to chew.310–313 The
sary if the animal is to survive. Signs will improve with tongue may be drawn into a longitudinal trough, and
removal from pastures, although residual ataxia will facial muscles can be taut giving a wooden or fixed
remain in severe cases. For prevention, avoid pastures expression. Affected muscles show prominent fascic-
and fresh hay containing Sorghum spp. grasses. ulations. Unable to prehend food and water normally,
but usually being able to swallow, affected horses may
Nigropallidal encephalomalacia bury their heads in water to attempt to drink, although
Horses of any age, gender, or breed can become they ultimately will die of dehydration and starvation.
affected with this devastating condition and demon- This syndrome is archetypical for central motor
strate profound difficulty eating and chewing with lesions controlling the final motor neuronal pathways
subsequent weight loss, but no loss of appetite. This for the muscles of the head wherein there is no loss of
rather unique disease is caused by plants of the daisy motor or sensory or reflex function but a change in
and thistle family (Asteraceae) including Centaurea muscular tonicity and control. Early signs may
solstitialis (yellow star thistle, yellow burr, and St include hyperexcitability and even aggression that
Barnaby thistle) and Rhaponticum repens (syn. could possibly represent hunger. The horses may cir-
Centaurea repens and Acroptilum repens) (Russian cle, wander aimlessly, press their forehead on objects,
knapweed, creeping knapweed, hardheads, hardhead chew on objects, adopt a low head carriage, or occa-
thistle, and blueweed). sionally appear ataxic.308–311,313,314 Experimentally

Figure 34.1 Horses that graze paddocks for

a long time that contain Centaurea solstitialis
(A; yellow star thistle, abrepuño, open fist)
and other plants of the knapweed family can
become affected with nigropallidal encepha-
lomalacia (B). The bilateral, usually symmetric,
necrotic lesions selectively involve the sub-
stantia nigra in the thalamus (top) and mid-
brain and the globus pallidus in the
telencephalon (bottom). Although relatively
small as far as lesions in this part of the brain
go, this disease is clinically lethal because it
causes irreversible dystonic dysphagia and
starvation. Source: Photo of yellow star thistle
courtesy of USDA-­Image K9658-­ 1: http://
www.ars.usda.gov/is/graphics/photos/nov01/
(A) (B)
k9658-­1.htm
428 Large animal neurology

feeding Russian knapweed results in these signs, and America,322 and there is some evidence of neuro-
periodic somnolence, confusion and weakness are intoxication occurring in cattle, along with photo-
also recorded.312 sensitivity. Inactivity, anorexia, nystagmus, head
This is a toxicity produced when horses eat pressing, recumbency, and opisthotonus associated
50–200% of their body weight of the unpalatable-­ with laminar cerebrocortical necrosis were reported
looking thistles that results in necrosis of the sub- to occur. However, the likelihood is that sulfate-­
stantia nigra and globus pallidus, viz. nigropallidal associated polioencephalomalacia complicated the
encephalomalacia (Figure 34.1). With experimen- signs of multiple organ involvement caused by the
tal Russian knapweed intoxication, there are addi- plant.323,324
tional focal necrotic lesions in the caudal colliculi,
mesencephalic motor nucleus of the trigeminal Stypandra and Helichrysum spp. poisoning
(CN V) nerve, and the lateral (dentate) cerebellar Sheep, goats, and possibly horses eating Stypandra
nucleus.312 Horses have to eat the plants for several imbricata (Blindgrass) growing in Australia and
weeks, and it is believed that they may become South Africa can develop blindness, ataxia and
addicted to them. Sheep thrive on a diet of only weakness, and may die. If they survive, permanent
these plants.310 blindness may result because of optic nerve degen-
Some effort has been made to identify lathyro- eration.296,325–328 The compound responsible for
genic and aminoacid neurotoxic principles.315–317 One this toxicosis has been identified as the binaph-
ingredient of the plant, the sesquiterpene metabolite thalenetetrol, stypandrol.329 The toxicity parallels
repin, has induced a clinicopathologic syndrome in that produced by rafoxanide and closantel
rats involving defective dopamine metabolism,318 and anthelmintics.248,249
repin has been put forward as a prime suspect as the Helichrysum blandowskianum (Woolly Everlasting
toxic principle.309,319 Daisy) causes a similar clinicopathologic syndrome
Thus, the toxin responsible for the disease remains in cattle and sheep with hepatic necrosis and status
unknown. However, because of a likeness to the spongiosus and focal areas of hemorrhage, particu-
lesions in human Parkinson disease, interest has been larly in the cerebellum and pons.330
focused on biologic amines in C. solstitialis possibly
being the toxic principles with aspartic and glutamic Coffee senna (Cassia spp.) plant neuromuscular
acids being discussed.317 Further work indicated that toxicoses
there was not a particularly high level of free aspartic Coffee senna plants are widespread in tropical and
and glutamic acids in polar extracts of the plant, subtropical regions, and are used as human bever-
although tyramine appeared as the most important ages, medicine and food. The most studied toxicities
biologically active amine present.315 Also, yellow star caused by these plants are due to Senna obtusifolia
thistle poisoning has been referred to as equine (Sicklepod and Coffeeweed) and Senna occidentalis
environmentally acquired toxic parkinsonism, but (Septicweed, Coffee Senna, and Coffeeweed).
although the lesions have been clearly defined as Worldwide, Coffee senna plants are probably the
necrosis of the globus pallidus and substantia nigra commonest cause of a toxic myopathy in large ani-
pars reticulata, there appears to be sparing the cell mals; however, the causative toxins have not yet been
bodies of the dopaminergic neurons in the substantia clearly identified. When ingested by all livestock spe-
nigra pars compacta and in the rostral portion of the cies, the plants, especially the seeds, cause weakness,
globus pallidus. ataxia, stumbling, reluctance to move, recumbency,
The diagnosis is based on signalment, history and and rapid death. Ruminants and pigs will eat the
physical and neurologic findings, and can be con- plants in pastures, and incorporation of the plants
firmed by MR imaging.320 Horses can be maintained in prepared forage such as alfalfa hay has caused
with feeding through a nasogastric tube, but no spe- outbreaks of poisoning, especially in horses.331
cific treatment exists.314 The outlook is grave and Extensive myodegeneration occurs, particularly
affected horses starve to death. involving the limbs and heart, with elevated serum
CK activity and myoglobinemia detectable.332–339
Kochia scoparia (Mexican fireweed) The syndrome resembles nutritional myodegenera-
This plant is a saline-­tolerant forage used for rumi- tion. In some species such as horses, and at least
nants in the Mediterranean region321 and in North experimentally in pigs, hepatic necrosis also rapidly
 Toxic diseases 429

occurs with hepatoencephalopathic signs overshad- condition, but in addition they probably have sup-
owing those of myonecrosis.331,340 Neural lesions are pressed mentation, being described as having an
also reported.341 “unmistakably dejected look” and adopting a
“morose appearance.”347 Death can occur suddenly,
Eggplant probably resulting from the induced cardiomyopa-
Feeding eggplant (Syn. aubergine, brinjal; Solanum thy. Neurologic lesions are not well defined. One
melongena) plants to cattle after the fruit had been worker has suggested that a polyneuropathy is
harvested has rarely been associated with multiple associated with a B1-­avitaminosis referred to as
cases of continual tremor and cerebellar signs in Koshifura disease,350 although the clinical syndrome
pregnant cows and their newborn calves. However, indicates a widespread central lesion is likely.345
deaths can also occur following recumbency and Treatment of affected horses includes removing them
seizures. Histologically, evidence of disruption of from abnormal diets and systemic administration of
myelin with diffuse status spongiosis in cerebral and grams of thiamine. Recoveries are possible when the
cerebellar white matter was present in some cases. patients are ataxic with no major weight loss or
Of course, it cannot be ruled out that the syndrome bradyarrhythmia.347,348,351
was due to residual agricultural chemicals. Dairy Amprolium-­induced thiamine deficiency in horses
heifers have been reported to suffer incoordination has resulted in bradycardia, arrhythmia, ataxia, mus-
and walking blindly, along with gastrointestinal cle fasciculations, and hypothermia, with blindness
signs, after eating berries from a wild variety of the and weight loss seen in some of the experimental
edible African eggplant Solanum macrocarpon.342 cases.352 Amprolium-­induced thiamine deficiency in
Both plants belong to Solanaceae, a family with sev- calves and sheep resulted in classical
eral species that contain glycoalkaloids which are polioencephalomalacia.353,354
quite toxic for mammals. However, it is unknown
whether eggplant glycoalkaloids (α-­solamargine and Pasture-­associated stringhalt
α-­solasonine) have any role in the tremor syndrome Stringhalt, also known as springhalt and Hahnentritt
described above.343 (“rooster kick”), is an anciently recorded disease that
is characterized by a sudden, apparently involuntary,
Bracken fern and horsetail-­induced thiamine exaggerated flexion of one or both hindlimbs during
deficiency attempted movement.355 In a more general sense, the
This is a rare syndrome of horses that may have been unusual pelvic limb movement can be referred to as
recorded in the nineteenth century344 that follows hyperflexion of the hock.356 The hindlimb motion
prolonged ingestion of bracken fern, Pteridium may be as mild as a slightly excessive flexion to vio-
aquilinum,345–347 horsetail Equisetum arvense348 and lent movements during which the fetlock or toe will
probably rock fern, Cheilanthes sieberi, and other contact the abdomen, thorax, and occasionally the
related species.344,349 The disease is caused by the thia- elbow with attempted strides leading to a peculiar
minase activity in these ferns, and bracken fern does bunny hopping and plunging gait.357
contain the highest thiaminase activity and lowest The form that usually occurs as outbreaks has
thiamine content of several related ferns studied.349 been referred to as Australian stringhalt, but is also
A very similar if not identical syndrome has been seen in many other countries such as New Zealand,358
seen associated with unusually restricted, poor diets United States,359,360 Chile,361 Brazil,362,363 Colombia,364
such as turnips and sugar beet pulp. Horses are reluc- France,365 Netherlands,366 Germany,367 Italy368 and
tant to consume these ferns unless other forages are Japan,369 and thus should be referred to as bilateral,
not available, or the plants are incorporated into for- plant-­or pasture-­ associated stringhalt.355 Usually,
age. Signs include ataxia, muscle tremors, inactivity, there is symmetrical or slightly asymmetrical involve-
weight loss, and bradyarrhythmia.344,347,348 The horses ment of the pelvic limbs, with prominent distal mus-
being “afraid rather than unable to move,” being cle atrophy in severe cases. The thoracic limbs are
“unable to coordinate movements” when forced to also affected in severe cases with knuckling of the
move, and “when moved, would stagger in a drunken forelimb fetlocks, prominent extension of more prox-
fashion”348 indicated likely signs of vestibulocerebel- imal joints and atrophy of the distal musculature, in
lar ataxia rather than general proprioceptive ataxia. association with prominent stringhalt in both
Descriptions are that affected horses are in poor body hindlimbs. Bilateral stringhalt has been associated
430 Large animal neurology

with exposure to several plants notably Hypochaeris Trauma to the tarsometatarsal region, spinal cord
radicata (false dandelion), Taraxacum officinale and disease, hock osteoarthritis, and likely other condi-
Malva parviflora (mallow weed).358,360,363,367,370,371 tions can result in a syndrome of hock hyperflexion
These are related species of flat weeds, Taraxacum during movement that can be difficult to differentiate
officinale being the common dandelion. Experimental from pasture-­associated stringhalt.356,383
sweet-­pea poisoning suspected to be due to neuro- A stringhalt-­like gait has been reported in a ewe384
lathyrism causes a similar syndrome, but is likely and calf,385 and upward fixation of the patellar in
accompanied by signs of brain and spinal cord dis- bovids causes an abrupt hock hyperflexion during
ease.372–375 It is interesting that size and age are predis- protraction that is called stringhalt.386,387
posing factors in bilateral pasture-­ associated
stringhalt, in so far as older and taller horses tend to Toxic plants and mycotoxins producing ataxia,
become affected376 in preference to smaller horses weakness, and tremors
such as ponies and native Chilean breeds.361 There is a plethora of clinicopathologic neurologic
Huntington et al.371 determined nerve conduction syndromes resulting from known and suspected
velocities (NCVs) in the peroneal nerve of four toxic plants affecting livestock.170,171,351,388,389 Some of
horses affected with plant-­associated stringhalt. The the mycotoxicoses that relate to specific plant species
mean NCV was 19.5 ± 4.3 m/s compared with an and that mimic pure plant toxicoses are included
NCV of 61 m/s in one control horse. In one of the here.37,170,171,351,390,391 For some such as Locoism caused
affected horses, the NCV was repeated after it had by swainsonine as outlined above, the pathologic
clinically recovered, and it was then determined to be lesions, toxic principle, and clinical spectrum of signs
48.6 m/s. These findings are consistent with a loss of are well studied. Other plants appear to result in a
large diameter fibers and possibly a degree of demy- great variety of signs perhaps varying greatly by dose
elination. Ultrasonographic evaluation of the digital of toxic principle, target species, environmental fac-
extensor myotendinous region can reveal changes in tors, and even by individual animal (genetic) suscep-
cases of hyperflexion of the hock that likely includes tibility. Perhaps reflecting the verdant environment
some cases of pasture-­associated stringhalt.356 of soil types, climate, and agricultural practices, a
The pathological lesions present in bilateral, large proportion of the toxic plants producing neuro-
plant-­associated stringhalt have been well studied logic gait abnormalities are described from tropical
and undoubtedly represent a distal axonopathy and subtropical regions. Clinical neurologic syn-
preferentially affecting large diameter axons in long dromes vary considerably, but many plant toxins
nerves.376,377 This explains the muscle atrophy, but result in degrees of paresis to paralysis and tremor to
there must also be selective involvement of γ-­ convulsions—­several described above. For concise-
efferent fibers to account for the movement disor- ness, examples of plant toxicities that occur over wide
der with abnormal input via the 1a-­afferent fibers to geographic regions and those representing the spec-
the α-­efferent final motor neurons resulting in inap- trum of signs and lesions are noted here as those pre-
propriate firing of lateral digital extensor and other dominantly resulting in (1) proprioceptive ataxia and
muscles. weakness (Table 34.1); (2) acquired tremor syn-
Removal of affected horses from suspicious dromes (Table 34.2); and (3) cerebellar and cerebell-
pastures often results in improvement in the gait ovestibular signs, although there is certainly quite an
and in some there is full recovery after several overlap among these syndromes.
months.362,363,365,367 Mephenesin,378 baclofen,379 and
particularly phenytoin365,367,369,370,380 appear to be Weakness and ataxia syndromes
somewhat useful in the symptomatic treatment of The differential diagnosis of the various locomotor
bilateral stringhalt cases. Many clinicians will empir- disorders affecting sheep in Australia is well catego-
ically treat neuropathy cases such as pasture-­ rized.296 Two other disorders with very different sus-
associated stringhalt with thiamin without any pected pathogenesis are exemplars of the spectrum of
evidence for efficacy.381 these disorders, the first being Indigofera linnaei tox-
Although simply palliative, removing a long sec- icity, seen in horses in Australia as Birdsville dis-
tion of the myotendinous region of the lateral digital ease.392 Signs include weight loss, progressive ataxia,
extensor muscle does relieve the syndrome quite and weakness, usually with some oral signs and
spectacularly in many, but not all cases.355,362,364,368,382 sometimes corneal opacity. Affected animals may
 Toxic diseases 431

collapse and show convulsive episodes. Complete Sheep, cattle, goats, New World camelids, and less
recovery can occur but toe dragging may persist. The often, horses, are affected by these plant toxicities,
arginine antagonist indospicine has been detected in usually when they are out at pasture. Multiple
the plant, and the toxicity appears to be at least par- animals can be affected, with ataxia, tremor, recum-
tially prevented and treated by feeding arginine-­rich bency, and sometimes death being the early evidence
sources such as gelatin and possibly alfalfa.393–396 This of toxicity. The number affected may fluctuate day
disease closely resembles a syndrome seen for dec- to day. Outbreaks are seasonal and often occur later
ades in Florida referred to as grove poisoning that is in the period of plant growth. A spectrum of the
caused by creeping indigo, Indigofera spicata,392,397,398 major types of these plant-­associated toxicities is
and to a similar disease in Brazil caused by Indigofera given in Table 34.2. The congenital and genetic
lespedezioides.399 l-­Indospicine and 3-­nitropropionic causes of tremor syndromes are covered in
acid, a nitric oxide synthase inhibitor and potent Chapter 31.
neurotoxin, respectively, are thought to be responsible Generally, signs include a stiff, ataxic, sometimes
for the syndromes,392 and an assay for plasma hypermetric gait, with a prominent, although often
l-­indospicine and 3-­nitropropionic acid to aid diag- fine, muscle tremor that worsens when animals are
nosis is available.400 disturbed and focus on the disturbance. Usually, the
The second model disorder of note involves adult tremor is seen best in the head, neck, and trunk.
horses, indigenous to, or brought in to one part of When forced to move, animals may fall to the ground
New Caledonia in the South Pacific, that show pro- with tetanic movements, jerky eye movements, and
gressive incoordination, debility, and death through paddling of the limbs in a convulsive-­like episode
misadventure.401 There is widespread loss of Purkinje without losing consciousness, so can suffer from
cells in the cerebellum, with pigment accumulation misadventure.296,440 They may die, especially with
in neurons throughout the central nervous system.402 phalaris toxicity for example, although with peren-
The disease is thought to be an environmentally nial ryegrass staggers, most recover if left undis-
induced lipofuscinosis and is likely to be caused by a turbed. The diagnosis is made clinically, ruling out
toxic plant or by a plant/endophyte mycotoxicosis. other possibilities, and observing the affected ani-
Table 34.1 outlines many of the remaining syn- mals’ responses to moving from the suspected pas-
dromes of weakness and ataxia caused by plant tox- ture. Identification of some tremorgenic toxins is
icities as examples of the wide diversity of such possible.300,441–444
diseases occurring worldwide.171,351,390,403 As indicated, the pathogenesis of these diseases
mostly involves plant and symbiotic and pathogenic
Tremor syndromes fungal and bacterial toxins. Thus, phalaris grasses
In many of these syndromes, the neurologic signs produce numerous alkaloid toxins some of which
are due to indole-­diterpenoids that are a large class result in neurologic signs. As examples, paspalum
of secondary metabolites found associated with fila- and Bermuda staggers result from infestation of grass
mentous fungi of the genera Aspergillus, Claviceps, with the ergots of Claviceps spp. which produce pas-
Neotyphodium and Penicillium, and these toxins palitrem neurotoxins. In contrast, the toxic bacte-
include penitrems, janthitrems, lolitrems, aflatrems, rium Rathayibacter toxicus (ex. Corynebacterium
terpendoles, shearinines, sulpinines, paxilline, and rathayl) colonizes seedhead galls of annual ryegrass
paspaline/paspalinine/paspalitrems.433 Biological (Lolium rigidum) plants invaded by a parasitic nema-
effects of such indole-­ diterpene and other co-­ tode (Anguina funesta), producing corynetoxins, one
secreted fungal alkaloids include insect-­ feeding of which appears to be the major cause of annual
deterrence, modulation of insect and mammalian ryegrass toxicosis. In this respect, plants are associ-
ion channels, modulation of GABAA-­receptor func- ated with the production of a tremendous array of
tion, and inhibition of specific enzymes. However, intrinsic and extrinsic defensive substances that are
the most dramatic clinical effect is the tremorgenic poisonous to grazing and other animals and insects.
activity produced in large animals associated with When there is a mutualistic symbiosis between plant
lolitrem B, paxilline, terpendole C, and paspalitrems and microbe that is associated with toxicity to herbi-
A and B, among others.433,434 vores, the control of the microbial disease is prob-
The large animal tremorgenic plant and fungal toxi­ lematic as grasses free of their microbial partners are
coses occur worldwide.37,170,171,300,306,351,388–390,403,429–432,435–439 generally ecological failures.37,170,445
Table 34.1 Examples of several poisonous plants that cause degrees of paraparesis, tetraparesis, recumbency, and proprioceptive ataxia in domestic herbivores

Plant (Ref) Species affected Neurologic signs Suspected pathophysiology Neural lesions Treatment* Prognosis

Birdsville indigo, Indogofera Horses (Birdsville Weight loss, ataxia, weakness ataxia, Arginine antagonist None Arginine-­rich Good
linnaei300,392,393,395 disease) paresis, depression, muscle fasciculations, alkaloids: indospicine, feeds (gelatin,
dysphagia, ptyalism corneal opacity canavanine lucerne)
Creeping indigo, Indigofera sp.397 Horses (Grove Ataxia, wide based stance, cerebellar Arginine antagonist None Gelatin, alfalfa Good if early signs
Indigofera lespedezioides399 poisoning) convulsions, mucosal erosions alkaloid indospicine
Cycad plants404–408 Cattle, sheep, Ataxia, recumbency Possibly toxic glycosides, Spinal cord fiber – Bad
goats, horses cycasin, and macrozamin degeneration
(Zamia
Staggers)
Solanum esuriale409,410 Sheep (humpyback) Exercise intolerance, weakness, Suspected toxin in Spinal cord fiber – Bad
arched back S. esuriale degeneration, myopathy
Sudan Grasses, Sorghum Horses, cattle, Ataxia, bladder paralysis Possibly HCN or Neuronal fiber – Poor to fair
spp.302,303,411 sheep lathyrogenic toxins degeneration, spinal cord
Coyotillo, Karwinskia Goats, sheep, cattle Hypersensitivity, tremor, marked Unknown Peripheral neuropathy, – Bad
humboldtiana412–414 hypermetria, weakness central neuroaxonal
dystrophy, myopathy
Melochia pyramidata415,416 Cattle (Derrengue) Ataxia, recumbency Unknown Spinal and nerve fiber – Bad
degeneration
Carpet weed, Kallstroemia Cattle, sheep, goats Knuckling, weakness, recumbency Unknown Unknown – Good
hirsutissima296,417
Peganum spp.419 Cattle, sheep None Bad
Yellow vine, Tribulus Sheep Ataxia, weakness, head swaying, Beta-carboline alkaloids Unknown – Very good
micrococcus418 convulsions
Cathead, Tribulus terrestris419–422 Sheep Paraparesis becoming asymmetric, Harmane alkaloid None – Bad
(Coonabarabran tremor in some accumulation in neurons
disease)
Stagger weed, Stachys Sheep Paraparesis, fine tremor, hunched posture, Unknown Spinal fiber degeneration; – Poor
arvensis423,424 collapse myopathy
Branched onion weed, Trachyandra Sheep, horses, Weakness, paralysis Possibly an induced Neuronal lipofuscin-­like Very poor
divaricata296,425,426 goats, pigs ceroid-­lipofuscinosis pigment accumulation;
Trachyandra laxa427 axonal degeneration
Trachyandra divaricata426
Gomen disease401,402
Bamboo, Bambusa vulgaris f. Horses Ataxia, somnolence, tongue paralysis Unknown Axonal degeneration None Probably bad
vulgaris428

* This also must include removal of toxic plant and catharsis as appropriate.
Sources: Based on Gupta37; Dalefield170; Parton et al.171; Jolly272; Bourke296,419; Cheeke306; Beasley351; Penrith et al.388; Gupta389; Kellerman et al.390; Riet-­Correa et al.391,429; Osweiler et al.403; Barbosa et al.428; Riet-­Correa et al.429; Tokarnia
et al.430; McKenzie431; Riet-­Correa et al.432
Table 34.2 Several acquired tremor syndromes affecting domestic herbivores associated with ingestion of plant biotoxins

Disease Associated plants Clinical signs Toxin source Suggested Neural lesions Prognosis*
pathogenesis

Ryegrass staggers Perennial ryegrass (Lolium Ataxia, tremor, tetany Neotyphodium lolii fungal Lolitrem B, A, C Secondary Purkinje axon Excellent
perenne) endophytes alkaloids degeneration?
Phalaris staggers Canary grasses (Phalaris spp.) Tremor, tetany, seizures; Phalaris grasses Tryptophan-­related Neuronal pigmentation Poor
cardiac arrhythmia and alkaloids with indole melanins,
sudden death axon degeneration,
astrogliosis
Nervous form of Paspalum, Dallis, Tobosa, Bahia, Ataxia, tremor, rarely Claviceps paspali and other Ergot indole-­ None Good
ergotism Knot, Galleta grasses convulsions ergot sclerotia diterpenes, the
(Paspalum spp.) and Bermuda paspalitrems
grass (Cynodon dactylon)
Annual ryegrass Annual or Wimmera ryegrass Tremor, tetany, Bacterial galls Rathayibacter Tunicamycin-­like Edema in cerebellar Bad
toxicity (Lolium rigidum) opisthotonus, toxicus (Corynebacterium corynetoxins meninges
convulsions rathayi) introduced by
nematode Anguina funesta
(A. agrostis)
Aspergillus tremor Sorghum beer residue (+others) Tremor, ataxia, paralysis, Aspergillus clavatus Aspergillus Degeneration of motor Bad
syndrome death tremorgens neurons
Miscellaneous Rayless goldenrod (Iscoma Trembling, ataxia, Plant or associated mycotoxin Mostly unknown; Variable: none to Poor to bad
plants wrightii), paralysis, death (others) Tremetol for white axonopathy to
Coyotillo (Karwinskia snakeroot myopathy
humboldtiana),
Mountain laurel
Mescalbeen (Sophora spp.),
Coconut meal (Cocos nucifera),
White Snakeroot (Ageratina
altissima)

* Treatment includes removing animal from access to known or suspected toxin and catharsis. Diazepam and chlordiazepoxide for control of tremor and phenobarbital as an anticonvulsant may be tried when indicated.
Sources: Based on Gupta37; Dalefield170; Parton et al.171; Bourke296; Seawright300; Cheeke306; Beasley351; Penrith et al.388; Kellerman et al.390; Riet-­Correa et al.391; Osweiler et al.403; Smith and Towers435; Bailey436; di Menna et al.446;
Morris et al.447; Johnstone et al.449; Garthwaite452; Gallagher et al.457; Bourke478; Finnie487; Chang and Korolev492; Botha et al.498; Plumlee and Galey500; El-­Hage and Lancaster506; Hartley and Clarkson507; Olson et al.508
434 Large animal neurology

Perennial ryegrass staggers is one of the best when movements are initiated with subsequent
s­tudied mycotoxicoses affecting herbivory.446–451 immobility or recumbency. Use of an ophthalmo-
Nomenclature here is important. Perennial ryegrass scope allows any eyeball trembling to be magnified
staggers associated with the endophyte Neotyphodium when this may not be externally visible. Currently,
lolii (ex. Acremonium lolaei) is to be distinguished confirming the presence of an obvious clinical syn-
from annual ryegrass toxicity also producing a trem- drome of paroxysmal spinovestibulocerebellar dis-
orgenic ataxia, and from grass staggers due to ease in a group of herbivores is the best means of
hypomagnesemia. Lolitrem B, an indole-­diterpene, is diagnosing the disease. However, the confirmation
the most important of the tremorgens produced by of the diagnosis in an individual patient, especially
N. lolii when the endophyte infests perennial ryegrass with very subtle clinical signs present, is problematic,
(Lolium perenne) plants.452 Ryegrass plants have been although lolitrem assays of feed and blood can be
shown to be able to take up tremorgenic mycotoxins helpful.449,468,469
through intact roots and concentrate it in the grow- The biochemical and electrophysiological effects
ing shoots.453 All parts of the plant contain toxin, but of the various tremorgenic mycotoxins have been
greatest amounts are in the leaf sheath and oldest well studied, and as with other penitrem and paxil-
leaves. Thus, toxicity occurs more in heavily grazed line toxins, lolitrem B acts on mammalian BK,
pastures. Particular cultivars of ryegrass that are calcium-­activated potassium channels to inhibit out-
insect resistant allow the production of highest con- ward potassium currents and produce its clinical
centrations of lolitrem B.446,448 Forage contents of loli- effects.456,470 Consistent histopathological lesions
trem B of 2–5 mg/kg (2000–5000 ppb) are tremorgenic have not been well documented but consist of
to herbivores.437,442,443,454 Other lolitrem and paxilline Purkinje cell vacuolation, pyknosis of granular neu-
alkaloids, among many toxins produced by such rons, and proximal axonal spheroids forming on
ryegrass and symbiont fungi, result in even more Purkinje cells most apparent within the vestibulocer-
economically important syndromes of ill thrift ebellum in sheep.171,468,471
and poor reproductive performance in grazing her- If affected animals are removed from toxic pastures
bivores.443 Also, other stagger toxins, such as janthi- or forage and are not disturbed, the majority will
trem A or penitrem A produced by Penicillium sp. recover completely. Whether the use of magnesium
growing on ryegrass litter, can produce ataxia and and potassium salts is of any use is questionable,472,473
tremors.171,300,390,403,431,437,450,452,455–458 However, although although a single oral dose of 300 mg/Kg KBr miti-
ergot alkaloids may be present in pasture swards con- gated the ataxia and tremor of experimental lolitrem-
current with tremor syndromes, ergovaline at least ­B induced perennial ryegrass staggers in young sheep
probably does not contribute to the severity of the and is worth considering where some control—­or
syndrome produced by lolitrem B.459 even prevention—­of the syndrome is attempted.471
This disease is widespread where livestock are There are reports of some lessening of signs of
intensively grazed and has occurred in captive and ryegrass toxicity using commercial products, but the
wild animals. It has been imported from one coun- validation of any benefit awaits further investiga-
try to another and has been associated with N. tions.474 Current preventive strategies should be con-
lolii—­ infected native grasses. The production sulted, which in future will continue to include genetic
losses sustained from occult and mild disease, and selection of animals as well as plants.171,447,450,475
the deaths from hyperthermic syndrome ascribed Phalaris staggers is caused by several genera of
to ergovaline in particular, are economically very phalaris or canary grasses, notably Phalaris aquatica
substantial. Finally, it appears that lolitrem B is pre- (syn. P. tuberosa = Harding grass), P. arundinacea
sent in adipose tissue of clinically affected cattle, (=reed canary grass), P. coerulescens, P. paradoxa,
though meat is regarded as safe for human P. angusta, and P. caroliiana. Phalaris grasses contain
consumption.306,435–437,442,444,448,450,454,458,460–467 at least eight indole alkaloids producing two syn-
Clinical signs vary from ataxia only when exer- dromes, sudden death476,477 and tremorgenic ataxia. It
cised forcibly, to muscle tremors over the neck, is the substituted tryptophan alkaloids that likely are
trunk, and limbs at rest that worsens with exercise the cause of the latter by interfering with serotonergic
along with cautious gait at walk and dysmetria with neurotransmitter release in particular brainstem
complex maneuvers, to marked disorientation nuclear neurons.296,306,351,390,403,450,476,478–480 Delayed
 Toxic diseases 435

onset times of up to 4–5 months have been reported Annual ryegrass toxicity is a fascinating tale of sym-
in sheep after removal from Phalaris spp. pastures. biotic neurotoxicity in herbivory,487 and although
Accumulation of pigment that is distinct from lipo- truly is a bacterial toxicosis, it is covered here as the
fuscin, in serotonergic tracts of the brainstem and disease is most akin to the plant-­associated mycotoxi-
spinal cord, is typical for Phalaris spp. toxicoses.479,480 coses than to those caused by other bacterial toxins.
The syndrome in sheep typically includes muscle The disease occurs particularly in sheep and cattle,
fasciculations about the head, muscle tremors of the less often in horses, in Australia but also in other
head, neck and body, and a dysmetric ataxia and southern hemisphere countries and probably North
weak gait that becomes much worse with excitement America.171,296,300,306,351,488 It is different to most other
and exercise to become a bounding, jumping move- tremor syndromes herein described in that the signs
ment with the animal often falling down on the tho- are even more profound with cerebellar fits being very
racic and pelvic limbs.481 In cattle, the ataxia and like true cerebral convulsions. Occasionally, cattle and
weakness are often accompanied by excitement that horses can be affected, and the prognosis is bad
results in inappropriate accidents with fences and although some sheep survive.
objects. Brainstem signs including difficulty pre- It takes many years for an annual ryegrass (Lolium
hending and chewing food, protruding of the tongue, rigidum, stiff darnel, and Wimerra ryegrass) pasture
and drooling saliva are quite distinctive when present to become toxic to herbivores after the plants become
and are reminiscent of nigropallidal encephalomala- infected with the bacterium Rathayibacter toxicus
cia in horses.171,478,479,482,483 (syn. Clavibacter toxicus; Corynebacterium rathayi).
The staggers syndrome is more common in live- Toxicity is said to take 10–15 years after the bacte-
stock in areas with limestone soils, which contain less rium is newly introduced into an area.487 This bacte-
cobalt than basalt soils. Phalaris neurotoxicity to rium infects the flowers and seed heads of the plant
ruminants may be controlled by cobalt administra- by accompanying the nematode Anguina funesta
tion <28 mg/sheep/week PO, by intraruminal “bul- (syn. Anguina agrostis) where it can produce highly
let” and by topdressing of pastures, although this has toxic glycolipids almost identical to the tunicamycin
not been always substantiated.482,484 antibiotics, possibly only when infected with a bac-
Accumulation of pigment in neurons, axonal teriophage. Other grasses including poison darnel
degeneration, and fibrillary astrogliosis all have been (Lolium temulentum), annual beard grass (Polypogon
found in sheep with canary grass staggers.479,483,485 monspeliensis), blow away grass (Agrostis avenacea),
Penicillium sp. molds that can produce tremorgenic and red fescue (Festuca rubra commutate) can har-
indoles such as penitrems may account for some bor the toxin-­producing bacteria. Streptomyces spp.
outbreaks of these syndromes. Cattle, sheep, pigs, growing on damaged wheat (Triticum aestivum) can
and horses can be affected by a tremor syndrome also produce the toxins from ingesting which, pigs
similar to ryegrass staggers, which results from pre- likely have developed the syndrome. This biotoxico-
sumed ingestion of mycotoxins in stored feeds or logic saga is made more florid by some of the apt
while grazing. One of these disorders is caused by colloquial terms used for the disease—­flood plain
Penitrem A, a neurotoxin produced by Penicillium staggers, Stewart Range syndrome, Wimerra grass
cyclopium.300 toxicity, and water-­damaged wheat poisoning. An
In one outbreak of canary grass staggers, CSF from enzyme-­linked immunosorbent assay (ELISA) for
affected sheep had slightly increased protein content the presence of the offending bacterium
and a mild mononuclear pleocytosis, with pigment Rathayibacter toxicus has been described.489
granules present in some of the macrophages.485 Tunicamycin-­like corynetoxins interfere with glyco-
Faced with an outbreak, the clinician should sylation of a wide range of proteins and brain edema
ensure that the animals are quickly and quietly and cell necrosis occurs, particularly in the cerebel-
removed from the pasture or suspect contaminated lar meninges.487,489–492
feed taken away. Some sedation, possibly with benzo- Again, affected sheep may appear relatively nor-
diazepine drugs,486 and nursing care may be required. mal while resting and grazing but exercise precipi-
Cautious administration of cathartics seems appro- tates episodes of a high-­ stepping ataxia, muscle
priate, but procedures that excite the patients to exac- fasciculations and head and body tremor, and even
erbate signs must be avoided. degrees of opisthotonus. This usually suddenly
436 Large animal neurology

progresses to hypertonic paddling with recumbency. example outbreaks with residual minimal gait abnor-
Whether these episodes are true cerebral seizures malities seen in long-­term survivors.501,502
with synchronous electrical activity in the forebrain Most frequently, affected herbivores have had
is not known. Signs continue after removal from an access to fermenting or spoiled fodder such as silage,
infected pasture that likely remains potentially toxic corn, brewers grains, hydroponic grass, barley
until replaced.171,296,300,306,351,493 byproducts, sprouted grains, and beetroot screen-
Attempts have been made to develop toxin binding ings.307,455,503–506 Putalin is one neurotoxin associated
compounds to assist in treatment,494 and ­benzodiazepines with Aspergillus clavatus and other fungi and may
have been shown to be at least palliative.486,493,495 Cobalt cause the syndrome.455
does not appear to play a role in this disease. Chromatolysis of brainstem nuclei and ventral spi-
Cases of the nervous form of ergotism are less com- nal gray matter and fiber degeneration in spinal cord
mon than the above causes of tremors and ataxia in white matter are the substrate for the clinical
livestock.171,306,390,403,496–498 Intoxication by toxins pro- ­syndrome.307,501–505
duced by the Claviceps spp. ergots is the oldest known Several plant-­ associated tremor syndromes are
mycotoxicosis. Major clinical syndromes related to outlined in Table 34.2.
ergotism in large animals relate to the vasoconstric-
tive and other cardiovascular effects of the major Cerebellar disorders
ergot alkaloids ergometrine, ergotamine, and ergot- Coyotillo (Karwinskia humboldtiana) produces cere-
oxine, produced particularly by the Claviceps purpu­ bellar ataxia and progressive weakness in livestock,
rea ergots on cereal crops. Claviceps paspali ergots particularly goats, in southwestern USA.413
infect the heads of Paspalum dilatatum (paspalum, Intoxication of cattle with Solanum fastigiatum in
dallis grass), P. notatum (bahia grass), and P. disti­ Brazil,509 Solanum bonariensis in Uruguay,509,510
chum (knotgrass) producing the honeydew-­ like, Solanum kwebense in South Africa,511 Torry’s night-
toxin-­containing, sclerotia. When cattle, sheep, and shade (Solanum dimidiatum) in the USA,512 and many
sometimes horses consume Claviceps paspali-­ more poisonous plants513–515 result in cerebellar
infected seed heads, they can show a syndrome of degeneration. Goats poisoned with tropical soda
ataxia and tremors akin to perennial ryegrass stag- apple (Solanim viarum) in USA516 and Narrawa burr
gers, referred to as paspalum staggers.171,306,496–499 (Solanum cinerium) in Australia440 also demonstrate a
The tremorgenic toxins in Claviceps paspali ergot-­ prominent cerebellar syndrome that includes nystag-
infested paspalum is predominantly the indole-­ mus and periods of disorientation. There are wide-
diterpene paspalitrems with similar effects to spread lesions with prominent Purkinje cell
lolitrems and penitrems produced by Lolium perrene vacuolation and degeneration in each of these neuro-
and Penicillium sp., respectively.171,496,500 Cattle have toxic diseases, and some appear to be induced lysoso-
been affected with staggers while grazing Bermuda mal storage diseases, possibly gangliosidoses.272,517–520
grass (Cynodon dactylon) infected by the ergot Mannosidosis is induced in animals by Darling Pea
Claviceps cynodontis with several indole-­diterpenes plants in Australia, by locoweeds in the USA, and by
including paspalitrem B being identified in the grass other swainsonine-­containing plant/endophyte sym-
seedheads.433 As with perennial ryegrass staggers, bionts (see above) in which cerebellar signs and
affected animals usually recover if removed from the lesions are prominent, along with aggression, sei-
source of toxin and are left relatively undisturbed. zures, and weight loss.273,274,278,283,285–288,291,293,519
Aspergillus tremor syndrome is associated with Seeds from the flowering legume Aeschynomene
tremorgenic mycotoxins produced by fungi including indica have contaminated cereal rice crops that, when
Aspergillus clavatus. The syndrome includes spinoves- fed to pigs, produces a wide base stance, ataxia, fall-
tibulocerebellar dysfunction and final motor neuron ing episodes, and finally recumbency with signs
deficits.307,455,501–505 Thus, affected sheep and cattle show beginning within hours of ingestion.521,522 There is
exercise-­exacerbated ataxia, falling, muscle tremors, focal symmetrical degeneration of cerebellar and ves-
head nodding as well as sinking and knuckling over on tibular nuclei with neuronal sparing. Some moder-
the fetlocks, and progressive paraparesis leading to ately affected piglets have survived.
recumbency. Some affected cattle show hyperesthesia Diplodiosis is a neuromycotoxicosis occurring fre-
and drooling. The prognosis is worse than with peren- quently in Southern Africa and mainly affecting cat-
nial ryegrass staggers, and 30–50 % have died in tle but also sheep and goats eating corn spoiled by
 Toxic diseases 437

Stenocarpella maydis (Diplodia maydis) resulting in arthrogryposis in up to 40% of beef calves in some
cerebellar ataxia, weakness, and recumbency.390 herds in the Western United States.
There are no consistent morbid neural lesions in The identified principal toxins in all these plants
early cases, and animals recover in days to weeks with that cause arthrogryposis—­and a few other congeni-
nursing attention, but die from bloat and neglect if tal malformations—­ are several potent piperidine
left prostrate. Diffuse status spongiosus is reported in alkaloids acting as nAChR agonists or antagonists
chronic cases.391 There are other quite rare neuromy- and hence subsequent congenital musculoskeletal
cotoxicoses resulting in cerebellar and spinal syn- contractures due to fetal immobilization.527,528
dromes in grazing animals in Southern Africa.390
Atypical myopathy (seasonal pasture myopathy)
Tutu: Coriaria spp. poisoning in horses
There are about 30 species of Coriariaceae worldwide These worldwide clinicopathologic syndromes com-
and, known as tutu, the plant has garnered a notori- prising acute metabolic necrotic myopathy are
ous reputation in New Zealand because of its devas- caused by ingestion of hypoglycin A (HGA) and
tating effect on livestock, but particularly because it methylene cyclpropylglycine (MCPrG) in vegetation
has a remarkable history having killed the first two of certain Acer spp. trees including A. pseudopla­
sheep brought to New Zealand by Captain James tanus (maple sycamore) and A. negundo (box
Cook in 1773 soon after their release in Queen elder).538–547 Affected, often young, pastured horses
Charlotte Sound. A number of early settlers, includ- have consumed particularly the winged seeds
ing children who partook of the somewhat palatable (samaras) of Acer spp. trees such as Acer pseudopla­
berries, also died of tutu poisoning.523–525 There have tanus and Acer negundo that belong to the
been many cases of illness and four deaths in humans Sapindaceae family of plants.544,548 Domestic rumi-
in New Zealand from ingesting honey containing nants are less susceptible to HGA than are horses
toxic honeydew from tutu. A further 30 cases of chil- although this relative resistance is not due to intraru-
dren becoming ill occurred in an English school when minal degradation of the pretoxin.549 Other species
tutin-­containing honey was exported to England.523 of herbivores may be susceptible.549,550
Grazing and browsing animals, particularly sheep Environmental risk factors include full-­time pas-
and cattle, are affected170 but fatal poisoning has also ture access in autumn or spring season, the presence
been reported in elephants.526 of trees, steeply sloping pasture, and access to piled-
Tutin is the picrotoxin-­like sesquiterpene com- ­up dead leaves.551 Affected horses tend to be young,
pound present in all varieties of tutu that acts as a sedentary, with thin or average body condition and
GABAA receptor antagonist resulting clinically in sei- fed hay in the autumn as the only supplement to
zures and usually death. Benzodiazepines are recom- pasture grass.551 Typically, several animals in a group
mended as therapy.523,524 are found dead or, more often, showing various
signs of reluctance to move, stiff and short strides,
Plant-­induced arthrogryposis apparent sedation, and fine muscle tremors. They
Several known and suspected toxic plants probably quickly become laterally recumbent, and urine
account for a majority of cases of congenital arthro- becomes dark with myoglobin staining although
gryposis in ruminants in North America.527–529 more subacute cases do occur.546,547,552 Tachypnea
Certainly in other countries outbreaks of viral-­ and even difficult respiration can mimic primary
induced arthrogryposis, usually associated with pulmonary disease with an accompanying tachycar-
degrees of hydranencephaly and other CNS malfor- dia. Outbreaks do occur, usually in the colder
mations, are very important causes. A minority of months, more frequently with young adult horses
cases are shown to be inherited in large animals. and can occur repeatedly on a property. Substantial
Lupine, locoweed, sweet pea, tobacco, poison hem- cytosolic muscle enzyme release into the circulation
lock, and jimsonweed ingestion have been shown to occurs with CK ranging from >10,000 to >100,000
produce the syndrome in pigs and cattle.530–535 Also, U/L and this, along with confirmation of myoglobi-
ingestion of Sorghum spp. grasses by pregnant cows nuria, forms the basis of the initial clinical diagno-
and mares has been associated with the disease in sis.553 Hyperglycemia, hyperlactatemia, and
offspring.536,537 Ingestion of lupines by pregnant beef hyperlipidemia are indicators of disrupted energy
cows on days 40–70 of gestation is associated with metabolism in affected horses.553
438 Large animal neurology

The myopathy-­ associated, predominant toxin, recovery occurs with or without sedation, topical
hypoglycin-­A, remains in sycamore seedlings despite vinegar, and systemic antihistamine or glucocorti-
mowing, and herbicidal spraying, and survives in costeroid treatment.
stored contaminated forage.554 It is likely that about
20 g of samaras, 50 seedlings, 150 g of inflorescences, Miscellaneous toxic plants
or2 L of water that has been in contact with seedlings Sweet pea and Caley pea (Lathyrus spp.), Buckeye
all could contain the maximal tolerated daily dose of (Aesculus sp.) and yakka (Xanthorrhoea sp.), and a
toxin for a horse.555 It is possible that the toxin(s) can cocoa-­like plant in El Salvador, Melochia pyramidata,
cross the placenta and/or accumulate in mare milk to have been associated with syndromes of ataxia and
cause myopathy in neonatal foals.556 paraparesis, especially in cattle, sometimes sheep and
The chemicals HGA and MCPrG are not inher- horses. In most cases, other signs of cerebral or cere-
ently toxic but are converted to active metabolites bellar involvement are also seen.375,415,444,564,565 Many
that act in mitochondria to potently inhibit acyl other plants cause signs of diffuse encephalopathy,
dehydrogenases and shut down beta oxidation of with various combinations of signs, including blind-
fatty acids. Energy-­depleted myocytes undergo lysis, ness, somnolence, seizures, and behavioral changes.
and unreacted acyl CoA is scavenged into acylcarni- Some reported examples are Jamaican nettletree or
tines that produce a characteristic blood acylcarni- guacimilla (Trema micrantha) in horses in the
tine profile in horses with atypical myopathy that is Americas,566 yesterday, today and tomorrow plant
consistent with a multiple acyl-­CoA dehydrogenase (Brunfelsia sp.) in cattle and donkeys in Brazil567 and
deficiency phenotype.557 Each of these elements, in horses in North America (RJM, pers. obs.),
namely, the pretoxins, the toxic metabolites, and the Helichrysum sp. in South African cattle,327,568
acylcarnitine profiles, is measured in horse blood Halogeton glomeratus poisoning in range cattle in
and urine for the purposes of diagnosis and, to a lim- western USA,569 and Nardoo ferns (Marsilea spp.) in
ited extent, prognosis.557,558 Australian sheep,570 the later plant probably contain-
Symptomatic fluid and analgesic therapy with ing thiaminase. Sleepygrass, Stipa robusta, appears to
attentive nursing care for severely ill and often result in a stuporous state in affected cattle and horses
recumbent patients are called for. Recommendations that may be associated with ergot alkaloids or with an
for empirical therapy include restricted movement, alcoholic compound present in the grass.306 Quite
keeping warm, rehydration, glucose and insulin sup- devastating outbreaks of black soil blindness in
plementation, and administration of carnitine, vita- Australian cattle have occurred with blindness
min E, selenium and riboflavin. Acepromazine can accompanied by somnolence, weakness, and inani-
be used as a muscle relaxant when indicated, and tion followed by death.571 This is associated with a
nonsteroidal anti-­inflammatory drugs may be used Corallocytostroma sp. fungus growing on Mitchell
for pain relief.538 Activated charcoal can bind hypo- grass (Astrebla spp.) pastures and is assumed to be a
glycin-­A at a pH equivalent to the pH in the equine mycotoxicosis. Whether this is central or peripheral
small intestine, possibly reducing its uptake by jeju- blindness is unclear, but no lesions have been detected
nal epithelium. Thus, the administration of activated on routine sections of the eye, optic nerve, optic
charcoal to horses cograzing with affected horses tracts and lateral geniculate nuclei, and other brain
might prevent further clinical cases in the early stages sections.
of an outbreak of the syndrome.559,560 However, lethal- If feasible, any therapeutic regimen should
ity of overt clinical disease is about 75–90%, with the include removal of the offending plant from the
average survival time of 2 days.543,553 environment, gastric lavage, catharsis, diuresis,
sedation as necessary, large doses of thiamine, and
Ataxia associated with stinging nettle nursing care.
Although not often reported, a syndrome of ataxia Being an amateur aficionado of edible and toxic
or recumbency associated with agitation and fungi, one author (JM) was quite interested to see
degrees of distress that may follow contact with that there was once a horse with a similar though
stinging nettle Urtica dioica in thin-­coated horses apparently morbid interest that consumed a fatal
and in a foal is clearly recognized to occur.561–563 dose of the destroying angel, Amanita verna, perhaps
This may or may not follow a topical urticarial due to its deranged behavior associated with diffuse
response to contact with the plants. Spontaneous meningioangiomatosis;572 suicide?
 Toxic diseases 439

Bacterial toxins in pigs,602 goats, and sheep603,604 than in cattle.

However, 329 out of 900 sheep in a feedlot died within
Botulism and the shaker foal syndrome 9 days of each other and 100 sheep and goats out of
Botulism is seen in adult horses, mules, cattle, deer, 330 succumbed over 3 weeks due to botulism.587
sheep, and goats worldwide.573–591 The shaker foal syn- Dead livestock can herald an outbreak of botulism.
drome is frequently seen in 1–3-­month-­old foals592–597 Onset of the disease in individual animals usually
Outbreaks of botulism can be absolutely devastat- consists of flaccid tetraparesis leading to tetraplegia,
ing.573,574,582,593,598 For example, 20% (ca. 5500) of 30,000 dysphagia, and muscle tremor, usually with an
head of feedlot cattle599 and at least 31 of 42 abrupt onset, with no associated illness or trauma
Thoroughbred sale yearlings600 died in outbreaks in (Figure 34.2).579,581–585,587–589,591,593,596,605–608 Sometimes
Australia, representing dramatic veterinary problems slow eating habits, dysphagia, lying down to rest
and economic impact.601 The disease is less common excessively, and inappetence and inactivity are

(A) (B)

50 µV

(C) 100 ms

Figure 34.2 A tentative diagnosis of botulism is arrived at quickly when there are multiple cases of recumbency (A) and tetraparesis with evidence of
appetence but oral and pharyngeal dysphagia present (B). These cases of suspected bovine botulism were nursed using fresh soft bedding, supply of fluids
and nutrients via ororumenal intubation (A), and frequent removal of excreta. More consistent with a diagnosis of presynaptic neuromuscular blockade
is finding brief, small amplitude, and abundant action potentials on needle electromyography in the face of complete flaccidity of the tested muscles (C).
A diagnosis of botulism in cattle can be confirmed by enzyme-­linked immunosorbent assay (ELISA) for C and D toxin in serum, liver, and gut contents. The
use of bivalent vaccine in cattle and other large animals is recommended where the disease is commonly diagnosed.
440 Large animal neurology

evident in the prodromal phase. Suckling foals typi- as in people but should be interpreted cautiously
cally show repeated episodes of trembling just before especially when performed on a dehydrated, very
becoming recumbent, hence the term shaker foal dis- weak and recumbent adult cow.588 Pupillary dilation,
ease. Multiple cases of type B botulism in cattle have urine retention, and ileus and constipation may be
been characterized by salivation and regurgitation.588 evident. Intercostal, phrenic, and cranial nerve
A change in feedstuffs may have occurred. New involvement may result in dyspnea and pharyngeal
batches of oat, rye and corn silage, big bale grass paralysis. Affected foals and calves will spend far
silage, and even grass clippings and commercial more time recumbent than normal, and liquids often
feeds and grain have been associated with outbre appear at the nares after sucking or drinking. Soft
aks.37,573,584,585,589,607–610 When processed and preserved feces and even diarrhea are reported in adult cattle
forages remain anaerobic and the pH remains above and occasionally seen in adult horses, probably
4.5, then Clostridium botulinum continues to grow reflecting degrees of ileus and subsequent maldiges-
and produce toxins.608 The presence of animal and tion37,581,588 or perhaps indicate concurrent
bird carcasses in processed food materials is incrimi- Clostridium difficile enterotoxaemia.612 Further very
nating evidence for a diagnosis of botulism,582,604 and important signs to be cognizant of in evaluating a
access to or feeding poultry litter, with or without possible early case of botulism reflect mild diffuse
bird carcasses, has been responsible for many out- cranial nerve paresis and include a silent chewing
breaks in ruminants.578,586,603,604,606,611 Finally, some action, increased number of chewing motions per
large clusters and outbreaks of bovine botulism have swallow, lack of click sound when palpebral reflexes
occurred when there is a phosphate deficiency with are tested vigorously, mydriasis, and a very wet
resultant ill thrift and subsequent deaths from many tongue that is easily caught and pulled from the
causes, and then phosphate deficiency carcass oste- mouth and feels like a slippery eel. The “time to eat
opica promoting further toxin ingestion.37,578 250 g of sweet feed” and a “time to withdraw the
tongue” tests in horses are worth considering to assist
It is important to remember that with suspected botu- in the diagnosis of a diffuse myasthenic syndrome,
lism cases (and probably with any marked diffuse likely to be botulism.613
weakness syndrome) any motor activity will promote In a suitable anaerobic environment, different
further weakness due to the poor supply of acetylcho- strains of Clostridium botulinum organisms can pro-
line at neuromuscular junctions; therefore, repeat duce one of at least eight serotypes (A, B, C, D, E, F, G
examinations must be kept to a minimum. and AH) that include many distinct metalloprotease
neurotoxins (types A, B, Cα, Cβ, D, E, F, G, and AH)
with many sub-­types. Botulinum neuroparalytic tox-
On physical examination, there may be dyspnea and ins are metalloproteases that after absorption and
cyanosis evident in severe cases. Initially, muscle circulation are internalized in presynaptic terminals
atrophy is not present but muscle trembling reflect- to act inside nerve terminals. They cleave various
ing the postural, extensor weakness may be promi- protein components of the neuroexocytosis appara-
nent. Ileus and pupillary dilation may be present tus in neurons to block neurotransmitter release,
indicating more widespread anticholinergic action. importantly blocking exocytosis of acetylcholine at
Tachycardia and urinary incontinence have been the presynaptic membrane of the neuromuscular
reported in cattle. Apparent sialosis and drooling junction (Figure 34.3).37,614–617
reflects poor swallowing ability and decreased jaw The toxin is usually preformed and ingested by the
movement. animal in carrion or in feedstuffs.573,589,610,613 Forage
Closer neurologic examination reveals character- poisoning is the term used for the syndrome having
istic degrees of tetraparesis with poor muscle tone identical signs but no isolated toxin; therefore, it is
and reflexes. Reduced tone and hyporeflexia is often only a presumptive diagnosis of botulism. There can
most evident in the eyelids, lips, and tongue reflect- be wound contamination with C. botulinum as a
ing the cranial nerve involvement. Horses tremble, source of botulinum neurotoxins, and the organism
sometimes violently from weakness before becoming can grow in anaerobic areas such as abscesses.618,619
recumbent. There is normal sensation with depressed This generation of the disease can be considered a
reflexes, although some reports of reduced sensitivity toxicoinfectious cause.37,592,594,612,620 The shaker foal
to needle pricking may reflect degrees of hypalgesia syndrome in suckling foals is also a toxicoinfectious
 Toxic diseases 441

Motor neuron

Nucleus
Inhibitory interneuron

ER
Tet-NT
Golgi

Retrograde
Tet-NT
Inhibition
carriers
of
exocytosis

Synaptic
vesicles

Bot-NT
Tet-NT
Neuromuscular junction

Figure 34.3 Schematic view of a motor neuron and an interacting spinal inhibitory interneuron. The sites of action of tetanus (Tet-­NT; yellow star) and
botulinum neurotoxins (Bot-­NT; red star) are shown, together with their specific intracellular trafficking routes. At the neuromuscular junction, Bot-­NTs
are internalized in synaptic endosomal compartments, one of which might coincide with synaptic vesicles. By contrast, Tet-­NT is sorted to the retrograde
transport pathway involving microtubules and actin microfilaments (shown as green tracts) required for fast retrograde transport of Tet-­NT in motor
neurons. The final common pathway of both NTs is to inhibit exocytosis of appropriate synaptic vesicles, at inhibitory neuronal endings (Tet-­NT) and
neuromuscular junctions (Bot-­NT), respectively. Source: Modified with permission from Lalli et al.614

form of botulism associated with C. botulinum type B botulinum toxin was detected compared with control
growing in inflammatory lesions such as wounds, farms. Human cases of chronic “visceral botulism”
gastrointestinal ulcers, liver abscesses, and probably have also been proposed in people associated with the
in the intestinal ingesta.595 The latter is referred to as dairy farms.624,625 This visceral botulism has also been
enteric or infantile botulism in humans. The bacterial likened to equine grass sickness (see Chapter 38) in
and toxin types involved vary in different areas and in which the unusual role of botulinum toxins killing
different countries, but individual cases and outbreaks autonomic neurons is still being studied.626
of botulism in large animals in general involve sero- The needle EMG may be characterized by short-­
types A, B, Cα, D, and mosaic–type DC.37,575,621,622 A duration, low-­ amplitude, abundant motor action
chronic form of the disease has been proposed as “vis- potentials (Figure 34.2). These have the appearance
ceral botulism”623 where decreased production, stiff and sound of high amplitude end plate noise in the
stilted gait, recumbency, intestinal upsets, inappe- face of complete muscle flaccidity; there is far more
tence, peripheral edema, and unexpected deaths have activity than expected for the amount of muscle con-
been experienced in some dairy herds in Germany traction occurring.627,628 On nerve stimulation, small
from which higher identification of C. botulinum and action potentials occur, which usually do not
442 Large animal neurology

decrement with repeated (5–10 Hz) stimulation but such bactericidal drugs may well release further toxin
may be augmented by tetanic (50 Hz) stimulation, a from killed organisms, and this is cited as a reason to
phenomenon characteristic of presynaptic as opposed not use antibiotics in both wound, toxicoinfectious
to postsynaptic neuromuscular blockade.627,629,630 and enteric botulism.612 Procaine penicillin, tetracy-
Such EMG characteristics of infantile botulism627,628,631 clines, and aminoglycosides should be avoided due
have been detected in the shaker foal syndrome and to their potential to exacerbate a neuromuscular
in affected recumbent adult cattle. This can be useful blockade.612 In one rather poorly substantiated
in supporting a clinical diagnosis and in monitoring ­documentation of 74 hospitalized cattle with botu-
improvement, or not, in the disease process. lism, no animal that received antibiotics recov-
Detection of circulating toxin by mouse inocula- ered.577 Nursing care is paramount to success, and
tion is possible. Such toxin-­detection has been found body hydration, alimentation, metabolic status,
to have a positive predictive value of 100% for foals body waste elimination and patient comfort all
and 89% for adult horses and a negative predictive require consideration574,588,595,596,613,619,638 Oxygen sup-
value of 51% for foals and 67% for adults,632 although plementation is indicated if PaO2 is low, and assisted
most laboratories now do not undertake this in vivo ventilation then needs to be an option if this does
testing in preference for PCR assays (below). There not relieve the hypoxemia. The latter can be lifesav-
can be no detectable toxin circulating in some affected ing, especially in young foals, but is fraught with
large animals, particularly in horses and cattle that are complications in young animals and especially in
extremely sensitive to botulism toxins.584,589 It has adult patients.595,597,619,639
been determined that cattle are about 13 times more The outlook varies from poor to very good without
sensitive than mice to botulinum toxin Type C.590 the use of specific antitoxin566 due to the amount of
Detection of circulating antibody (antitoxin) in toxin available to each animal and true recovery rates
recovered animals by ELISA techniques is useful in of 1–90% are recorded for affected cattle in individual
monitoring disease outbreaks but again is not com- outbreaks.573,582,587,593,608,611 As a general rule, adult cat-
pletely accurate or timely for the diagnosis in indi- tle and horses that remain recumbent for a day or so
vidual cases.590,633,634 usually do not survive,574,588, although there are excep-
Isolation of C. botulinum organisms from grain, tions, especially if appropriate antiserum has been
silage, carrion-­contaminated feedstuffs, patient feces, administered.581,589,595,597,605,613 The rate of progression
and from lesions or wounds in the patient is strong of signs is directly related to the dose of toxin and to
circumstantial evidence of disease;579,589,592,618,620,635 prognosis with cases in which signs do not rapidly
unaffected horses and foals rarely shed C. botulinum progress to recumbency have a better prognosis than
in feces.632,635 those that show fulminant tetraplegia.584,588,589,613 With
The preferred test for diagnosing botulism is now polyvalent antiserum and intensive support facilities
the detection of C. botulinum type A, B, and C toxin and staffing available, survival rates of 50–90% may
genes by real-­time PCR in vegetative cells after a cul- be achieved for severely affected foals with
ture enrichment step. Finding C. botulinum genes in botulism.587,595,597
feed, fecal, or gut content samples is strong evidence As humans, especially infants, are quite susceptible
of a diagnosis of botulism in animals exhibiting com- to botulism, there is a public health and food safety
patible clinical signs, samples from normal animals risk of disease transfer when botulism is suspected in
rarely being positive.635,636 animals on a premise.583 Thus, infants must not be
Botulism antitoxins are expensive, and the specific taken to the site of an outbreak, and restriction of
serotype is required but they are strongly recom- movement of livestock and sale of milk from affected
mended on suspicion of botulism where availa- farm premises should be restricted for, say, 14 days
ble.596,613,637 There are two commercial botulinum from the onset of the last case and the removal of
antitoxin products currently available in the United incriminated feed640 or for the duration of affected
States, a trivalent product containing type A, B, and C animals on the farm.641 The botulinum toxin is too
antibodies, another which is labeled for type B, but large a molecule to cross the placenta,642 but unborn
also contains type C antibodies.613 If wound botulism fetuses may suffer from the effects of weight loss and
is suspected, some clinicians consider using antibiot- recumbency suffered by their affected dam. Also,
ics such as crystalline penicillin or metronidazole but there seems to be some conflicting evidence for
 Toxic diseases 443

transmission in milk643,644 to either suckling offspring Recumbency with profound opisthotonus and limb
or to humans. Thus, a cautious approach should be extensor rigidity is present in severe cases, with bloat
advised for the use of milk on and from affected in ruminants being life threatening. All signs are exag-
premises. gerated with any stimulation such as in response to a
Vaccinating mares with C. botulinum type B tox- hand clap, and especially to a light tap on the nose.
oid twice in the last trimester of pregnancy is prac- Hypertonia and hyperreflexia are the result of
ticed in some areas where the shaker-­foal syndrome Clostridium tetani neurotoxins interfering with
is common, and it appears to be successful in pre- interneurons in the CNS. As with botulism toxins,
venting the disease.594 The protective value of differ- tetanus toxin is a neurotropic metalloproteinase that,
ent vaccines is noted,645 and local advice needs to be after entering circulation and reaching systemic neu-
obtained as to the best active preventive strategy to romuscular end plates, is internalized in the presyn-
be recommended. aptic terminal. Unlike botulinum toxins, it then joins
the rapid retrograde transport mechanism to reach
the neuronal soma of the motor neuron from which
Tetanus due to Clostridium tetani
it is transferred to the inhibitory internuncial neu-
neurotoxin
rons in the spinal cord and brainstem (Figure 34.3).
Worldwide, young and adult animals, especially Here, it binds with gangliosides to interfere with the
equids, are often affected by tetanus as singular cases release of inhibitory neurotransmitters thereby
as are postpartum and neonatal ruminants. The teta- allowing excessive firing of motor neurons, muscle
nus organism usually grows in anaerobic sites in the hypertonia, and tetany to occur.614–616 Being bound to
body to produce its toxin that is circulated to act gangliosides in the CNS, the effects of tetanus neuro-
systemically. Multiple cases can occur when a predis- toxin wear off as the gangliosides are replaced.
posing anaerobic lesion occurs in multiple animals Clusters of generalized idiopathic tetanus cases,
associated with various management procedures. particularly occurring in ruminants, result in the
Many cases can occur over a short period of time fol- same syndromes but an anaerobic site for C. tetani to
lowing routine management procedures such as tail produce toxin is not evident on clinical or postmor-
docking, castration,646,647 and even ear-­tagging648,649 tem examinations.651,654,655 This can occur after a
and anthelmintic injection.650 Outbreaks of so-­called change of feed such as adding frozen turnips to the
idiopathic tetanus also occur, particularly in cattle, winter feeding of heifers, but also occurs in young
when there is no evidence of such common anaero- housed calves.656 Idiopathic tetanus possibly occurs
bic lesions as contemporaneous sources of toxin.651,652 because there is absorption of toxin formed in the
Local tetanus occurs when one body part, usually a proximal gastrointestinal tract652,657–659 and is akin to
limb, is involved without full somatic spread.653 infantile and intestinal, toxicoinfectious botulism
Often the disease involves neonatal animals with associated with an altered digestive (anaerobic)
omphalitis, postpartum breeding animals, and postsur- milieu or acute mucosal damage from rough feed
gical animals of any age. Owners usually report that occurring in multiple animals simultaneously.656
there is a sudden onset of a stiff gait, bloat, strange Localized tetanus is seen as hypertonia to tetany in
appearing eyes, difficulty in eating, or recumbency. one body part in the region of toxin production. This
Retained placenta, wound, omphalitis, and surgical inci- occurs when more toxin is taken up by neuromuscular
sion in all species, pus in the foot in horses, and bloat in end plates at the site of production than reaches circu-
ruminants can be evident on physical examination. lation without being neutralized by the animal’s defense
Mild cases may only show a stiff gait. The nostrils mechanism—­ including tetanus antitoxin—­ such that
are flared, the animal is hyper-­responsive to auditory generalized tetanus is curtailed or delayed.653,660,661
and tactile stimuli, and the nictitating membrane Colic, pleuritis, laminitis, meningitis, epilepsy,
appears prominent and briefly protrudes further when myopathy such as white muscle disease and fractured
the head or especially the muzzle is tapped or in cervical vertebra can be important diseases to rule
response to a hand clap. Erect and caudally retracted out in individual cases from a clinical point of view.
ears, stiff jaw, opisthotonus, reluctance to move, and In clinical cases, the demonstration of circulating
an awkward, stilted, hypometric gait with the tail– neurotoxin does not appear to have been achieved,
head held elevated are usually present (Figure 21.4). and the isolation of the fastidious organism from
444 Large animal neurology

patients to assist in positively diagnosing the disease although adequate TAT given concurrently should
can be difficult. Animals that have not been vacci- mitigate this.
nated and do not have clinical tetanus can have circu- Intrathecal TAT might be theoretically indicated if
lating tetanus antibodies, and C. tetani is ubiquitous treatment is begun in the early stages; however,
in the environment of animals. the benefits of this over standard systemic administra-
Treatment of tetanus in animals is similar to the tion are not clear for humans and for large animal
treatment of tetanus in humans.37,652,657,662–664 patients.647,662,665,667,668 Such additional intrathecal TAT
Minimizing any human interference and keeping the may give quicker improvement in signs and symp-
animal in a quiet, undisturbed place is paramount toms.662,669 Performing a subarachnoid injection may
from a welfare point of view as this is a very painful however give the clinician the opportunity to rule out
condition in humans, and stimulated spasms are meningitis by analyzing a sample of CSF. The dose of
excruciatingly painful. Placing cotton wool plugs in subarachnoid TAT probably should be 5000 to 10,000
the ears seems a good idea but often causes the units for an adult horse, although up to 50,000 IU have
patient to shake its head and to self-­stimulate muscle been used.647,670 When using the higher volumes, one
spasms; it certainly does not alter the BAEP record- must be concerned about subarachnoid hemorrhage
ings in normal animals to any great extent. Placement due to CSF pressure changes. Using subarachnoid
of a rumen fistula will often be required in ruminants TAT, one group670 reports a survival rate in horses of
for both relief of bloat and as a portal for feed and 77%, up from their expected 50% without using
water. Adequate sedation with phenothiazine (e.g., intrathecal dosing with TAT. In a large survey of
acetylpromazine) and alpha-­2 agonist drugs, some equine tetanus, intrathecal TAT administration was
GABAA inhibitory effect on neurotransmission with performed in 16 adult horses using 8000–58,000 IU
benzodiazepine and barbiturate drugs, and muscle TAT; one horse collapsed during administration and
relaxation with glyceryl guaiacolate, MgSO4, 12 of those 16 did not survive tetanus.647 Another
methocarbamol and alpha-­2 drugs, in various com- study failed to show any benefit if intrathecal TAT664
binations, are the basis of relieving the muscle rigid- and treatment of three cases with intrathecal TAT was
ity and spontaneous and reflex muscle spasms of less positive with only one foal surviving.671
tetanus. A balance between the amount of sedation The actual contribution that any TAT makes to
and the degree of muscle relaxation is important so survival of unvaccinated equids suffering from teta-
that all drugs should be given to effect and preferably nus has been brought into question.663 In that retro-
via an indwelling intravenous catheter. If expense is a spective study, routine treatment consisted of basic
major issue, acetylpromazine and MgSO4 are proba- nursing care, procaine penicillin, and acetylproma-
bly the drugs of choice. Splenomegaly and subsequent zine. Overall survival was 46%, and survival for those
pseudoanemia may occur with chronic usage of phe- receiving no TAT, low dose TAT (1000–20,000units),
nothiazine drugs in adult horses. Assisted hydration and high dose TAT (20,000–70,000 units systemi-
and alimentation can be given via an indwelling cally) was not significantly different (p = 0.8) at 50%,
nasogastric tube or rumen cannula as required. 59% and 52%, respectively.663 Of course, the use of
The optimal dose of homologous tetanus anti- any biologic therapeutic agent such as TAT must be
toxin to treat tetanus is still not clearly defined in accompanied by strict drug handling, especially in
humans665,666 and horses,647 but current trends in hot climates. A study involving 155 adult horses and
human cases are to use modest doses of TAT or 21 foals with tetanus indicated a poor prognosis
human intravenous immunoglobulin.662 A moderate (excluding euthanasia for financial reasons) of ~33%.
dose of 10,000 IU of equine TAT per horse IV and Although higher therapeutic doses of TAT were not
IM, or a high dose of heterologous TAT, should bind related to better survival, a trend was present indicat-
residual circulating neurotoxin. All wounds should ing that this could be looked at in future.672
be debrided. Penicillin or, preferably, metronidazole Recumbency, dysphagia, and dyspnea can be
administration is advisable, although wound cleans- considered as indicating a poor prognosis, but if the
ing should be the earliest priority of reducing further animal can still drink the prognosis is better with
bacterial growth and toxin production. Again, as nursing care.647,648,663,672,673 If the animal is not recum-
with botulism, the caveat of possible release of more bent, the prognosis is better and may be as good as
toxin following bacterial lysis may be considered about 75% where intensive support is given. If the
before using bactericidal antimicrobial agents, animal is recumbent, the prognosis is poor for a
 Toxic diseases 445

small patient and bad for a heavy, adult patient. revaccination is not likely to be necessary,682 booster
Recovery from tetanus does not protect against the vaccination at two or three yearly intervals, or when a
disease; therefore, patients still must be vaccinated. wound occurs, is necessary for guaranteed protection
Vaccination of all other animals at risk is advised. against the disease. Tetanus toxoid and TAT can be
Decubital lesions, fractured bones, and scoliosis can administered at separate sites at one time to give
be lethal complications of the disease. Recovery with- immediate protection and to prime or boost a vaccina-
out adequate muscle relaxant therapy has been seen tion program.683 Should a patient be on glucocorticos-
to cause permanent fibrous fixation and contracture teroid therapy at the time of requirement for additional
of limbs, although this is uncommon in horses.647,663 protection against tetanus, then exogenous TAT
Overall, the recovery rate for horses and foals suffer- should be relied upon for protection. Although active
ing from tetanus with hospital care is likely to be priming can be achieved while on immunosuppressive
30–40%,647,673 and in sheep under field conditions it doses of a glucocorticoid drug, it may be only after the
has been recorded as 50%.648 third dose that an anamnestic response occurs.684
Preventative vaccination programs are as important
in large animals as in humans674 and have substantially
Enterotoxemic encephalopathy: Focal
reduced the incidence of tetanus worldwide.662 Use of
symmetrical encephalomalacia in ruminants
homologous TAT and a booster tetanus toxoid or both
and edema disease of pigs
is recommended at the time of occurrence of surgical
and other wounds, at least in horses. Some guidance Usually, feedlot lambs, adult sheep and goats, and
for protective animal vaccination can be gleaned from growing feeder pigs are affected. Young cattle have
human studies and it is accepted that one dose of teta- been reported to have a similar disease.685–695
nus toxoid confers little long-­ lasting immunity in Outbreaks of overeating disease or enterotoxaemia
humans. A second dose confers protection in approxi- (ruminants) and edema disease (pigs) frequently
mately 90% of individuals within 2–4 weeks, but occur in young production animals usually resulting
immunity is short-­lived in many individuals. A third in diarrhea and sometimes neurologic syndromes
dose ensures almost universal protection for at least relating to forebrain and/or brainstem disease. The
5 years.675 resulting enterotoxemic encephalopathy is caused by
Horses require at least two doses of aluminum-­ the multiplication of some serotypes of Escherichia
precipitated tetanus toxoid for protection,676 although coli in the intestine of pigs producing an angiotoxin
some foals may be poor responders and even called verotoxin 2e or Shiga-­like toxin 2e, and from
8-­month-­old weanlings required a third dose of vac- Clostridium perfringens type D growing in the gut of
cine before a protective immunity was achieved.677 ruminants with production of ε-­toxin.685–687,689,695–698
Also, it was found in another study that maternal anti- Changes in the ration being fed are often part of
body had a significant inhibitory effect on active the history. Thus, weaning of piglets and movement
immunity in foals such that positive primary responses to lush pasture and tapeworm infestations in small
could not be demonstrated consistently until 6 months ruminants can be precipitating factors in these dis-
of age.678 Further doses have been suggested as being eases. If the animals survive the peracute phase of
required annually678 or biannually679 for adult horses, enterotoxemia, then some will show signs due to the
or may be given triannually if the three doses are given neuropathologic effects of the enterotoxins.699 An
after 5 months of age.680 A booster vaccination acute onset of head pressing, aimless wandering,
2–4 weeks prior to parturition protects the dam and opisthotonus, recumbency, and death in several ani-
the offspring assuming that there is passive, colostral mals are usually the primary clinical signs of entero-
transfer of antibodies around this period. Unprotected toxemic encephalopathy although it can occur as an
newborn foals should receive one dose of TAT. isolated event.686,687,689–693,695 Survival showing a
Summarily, the initiation of a two-dose vaccination chronic, somnolent, dummy syndrome is described
program should probably begin around 4 months of in sheep.692 This probably relates to lower doses of
age when both maternal and any neonatally-­ toxins and the classical malacic lesions in the internal
administered exogenous TAT antibody titers are capsule, basal nuclei, cerebellum, and brainstem.690,693,697
reduced to minimal levels in about 75% of foals.681 On examination of affected patients, diarrhea may be
Then, a third dose of toxoid should be given in the first present especially in sheep. The animal may become
year to ensure protection.677 Although yearly recumbent some time prior to presentation. Edema
446 Large animal neurology

common in affected lambs. The so-­called classical

lesions of autolytic renal cortices and some evidence
of tubular necrosis—­colloquially referred to as pulpy
kidney disease—­ is completely nonspecific for this
enterotoxaemia and may partly reflect consequences
of the encephalopathy and/or the hyperglycemia.698
When the disease is suspected, any major change
in diet such as access to excess carbohydrate should
be corrected. Clostridium perfringens type D antise-
rum has been useful in lambs and kids, and the
remainder of the at-­risk flock should receive anti-
(A) toxin or Clostridium perfringens type D vaccine.686,698
Diuretics and antihistamines may be of some use in
treating pigs with acute edema disease, and furosem-
ide and mannitol probably are worth trying.703 Oral
antibiotics such as chlortetracycline or trimethoprim-­
sulfadiazine should be administered early during the
disease. A recombinant verotoxin 2e vaccine for the
prevention of edema disease has recently become
available and appears highly effective at least in both
farm and experimental settings.704,705
Mortality is high with these diseases. The farmer
should be reminded to make slow dietary changes.
(B)
Vaccination with C. perfringens type D toxoid is an
important prophylactic measure in ruminants, and
Figure 34.4 Focal symmetric leukoencephalomalacia in young rumi-
verotoxin vaccination will probably become so for
nants likely results from enterotoxaemia due to Clostridium perfringens
type D ε-­toxin. Lesions can be evident on gross inspection of the fixed pigs in the near future.695,704
brain, especially evident in the internal capsule (blue ellipses) of the cer-
ebrum (A) and thalamus (B) and in basal nuclei, cerebellum, and medulla
oblongata. Equine mycotoxic encephalomalacia
associated with moldy corn
of the forehead in pigs along with acute diarrhea may Equidae of any species, breed, sex, or age that are
be detected. Neurologically, there can be dementia, eating predominantly fodder that usually includes
head pressing, wandering, blindness, bruxism, opis- corn are affected by this disease, and major out-
thotonus, seizures, and coma. breaks do occur. There is one unconfirmed report
The pathogenesis of the encephalopathy relates to of a white-­tailed deer, Odocoileus virginianus, being
the direct effects of the bacterial exotoxins from affected.706 The disease has been reported exten-
C. perfringens type D and E. coli on blood vessels in sively from North America and now appears to be
the brain and spinal cord causing necrosis of smooth worldwide in distribution being documented in
muscle and endothelial cells in brain microvascula- equidae from at least South Africa, Australasia, the
ture, resulting in the leakage of protein-­rich fluid and Pacific Islands, Central and South America, China,
brain edema with brain swelling.685,693,695,697–699 The ini- Japan, Egypt, Hungary, and Germany.390,391,707–719
tial effect of large doses of toxin is widespread within Most probably, it can occur wherever corn or maize,
the CNS, but with lower doses the predilection for Zea mays subsp. Mays, is grown and the environ-
specific brain areas is evident (Figure 34.4).685,700 ment is warm and moist enough for spoiling by
These include the basal nuclei, internal capsule, thala- fungi especially Fusarium moniliforme (Syn. F. verti­
mus, midbrain, vestibular nuclei, and cerebellar white cillioides)720 and occasionally F. proliferatum and F.
matter.697 Spinal cord gray matter may also be affected, subglutinans.391,721 Outbreaks have been devastating,
and all these brain and spinal cord lesions are visible and generally the overall morbidity is low, less than
with advanced imaging techniques.701,702 Glycosuria, 25%, but mortality usually approaches 100% in
caused by hyperglycemia and possibly nephrosis, is affected animals.707
 Toxic diseases 447

Dementia, blindness, convulsions, and sudden death cranial nerve deficits such as facial paralysis being
are likely to be the first signs of an individual case or recorded.390,391,500,710,714,716,718,719,721,723–728
outbreak, although any combination of forebrain, Fumonisin toxins produced by Fusarium spp. in
brainstem, and cerebellar signs occur. A history of moldy corn cause prominent encephalomalacia and
ingestion of (usually moldy) corn over approximately modest hepatopathy in horses, pulmonary edema
one to several weeks with the development of such cer- syndrome in pigs and other organic disease in a variety
ebral signs or sudden death is typical. However, the of species, and are incriminated in being carcinogenic
source of the putative mycotoxin can be elusive, and in humans.707,709,726,729–733 Horses ingesting moldy corn
the disease has occurred when feeding cornstalk hay contaminated with fumonisin B1 toxin develop lique-
(stover), commercial horse rations and hay.391,707,721–723 factive cerebral necrosis, especially in the subcortical
Usually, there are no contributory general physical white matter, hence the common name, equine leu-
findings although occasionally there may be evidence koencephalomalacia (Figure 34.5).390,391,712,715,716,718,719,728,7
of liver disease such as jaundice in affected animals or 34
These lesions are frequently quite ­massive, bilat-
herd mates. Dementia, drowsiness, blindness, circling, eral, but asymmetric and can be hemorrhagic. Less
immobility, excitability, seizures, and ataxia are found often, gray matter can be affected in the forebrain
in various combinations. Signs are frequently slightly and brainstem, and the cerebellum may even be
or markedly asymmetric. There may be brainstem involved. The massive liquefactive necrosis often
involvement with pharyngeal paralysis and other contains ­ characteristic reactive glial cells with

(A) (B)

(C) (D)

Figure 34.5 Equine leukoencephalomalacia is usually associated with horses ingesting moldy corn contaminated with fumonisin B1 toxin for a month
or so. They develop liquefactive cerebral necrosis (A and B), especially in the subcortical white matter but sometimes extending to gray matter (yellow
ovals), that can be massive (C). The subsequent brain swelling is evident on the right side of an affected brain viewed caudally (D), resulting in herniation
of cerebral tissues across the midline (dotted line) and caudally under the tentorium cerebelli (red arrow), compressing the midbrain and subsequently
the medulla oblongata—­a process that is quickly fatal.
448 Large animal neurology

abundant eosinophilic cytoplasm, sometimes called small ruminants but also in cattle, llamas, pigs, foals
clasmatodendritic astroglia along with axonal sphe- and horses,739–751 but smaller individuals are more
roids.391,734 An associated inflammation may include often affected.742 Offending ticks include the soft
macrophages, plasma cells, and eosinophils.711,718 ticks Dermacentor variabilis and Dermacentor ander­
Secondary brain swelling frequently results in lobar soni in North America, and the hard ticks Ixodes
herniations, brainstem compression, and death. holocyclus and to a lesser extent Ixodes cornuatus in
Other fungal species including Fusarium prolifera­ Australia, Ixodes rubicundus in South Africa, and
tum can produce fumonisin B1, and other fumoni- Ornithodros lahorensis in Eurasia. The ixodid, hard
sins such as B2 and B3 may also cause equine ticks generally produce the most rapid and profound
mycotoxic encephalomalacia. paralysis compared to the argasid, soft ticks. Paralysis
A clinical diagnosis is based on the history and the and death due to hard ticks in South Africa is called
neurologic examination findings, the equine viral Karoo and along with the disease occurring on the
encephalitides being primary differential diagnoses eastern seaboard of Australia accounts for the loss of
until there is pathologic confirmation of this disease. thousands of livestock annually.745,747,749,750 Outbreaks
Analysis of CSF taken from affected horses may be may involve importing stock to a high tick area when,
normal or may reveal protein leakage into CSF or later for example, death of 170 of 404 young sheep suffer-
a marked pleocytosis that includes neutrophils as well ing tick paralysis occurred in Victoria, Australia.
as moderately elevated protein content.708,710,735 There is a breed predisposition as to general tick
Identifying Fusarium spp. in feed is not very useful as resistance, and grazing patterns of different breeds
a high proportion of corn samples contain this fungus and ambient humidity do play roles in which animals
and even fumonisin toxins. Concentrations of fumoni- are mostly affected in a tick region.741,745,752
sin toxins in feed being fed to affected horses have var- The tick salivary gland toxins responsible for paral-
ied from <1 ppm (=mg/kg and μg/g) to 126 ppm with ysis act at the presynaptic level of neuromuscular junc-
the majority of samples containing >10 ppm with a tions resulting in reduced amplitude of compound
length of exposure of 1 week to 1 month.736 motor units, but surprisingly, without evidence of a
Horse feeds that have not been associated with fatiguing decremental response,747,750,753 however such
clinical disease usually contain <8 ppm fumonisin findings may vary depending on severity and duration
B1, and a level of administration of the toxin not of paralysis. Holocyclotoxin (HT-­1) is the neurotoxin
associated with clinical signs has been estimated to be from Ixodes holocyclus that inhibits neurotransmitter
0.01 mg/kg IV q24h for 28 days.708,720,722,725–727,731,735–737 release via a calcium-­dependent mechanism resulting
Thus, in general, feed containing concentrations of in reduced quanta of acetylcholine with loss of effec-
fumonisin B1 over 10 ppm is strong evidence of neu- tive neuromuscular synaptic transmission.751,754
rotoxic exposure to horses. Paraparesis progressing to tetraparesis and recum-
Removal of the moldy feed and the use of cathar- bency usually occurs over hours to days, and facial,
tics and analgesic drugs seem appropriate palliative tongue, jaw, pharynx and larynx can become affected
treatment. Glucocorticosteroids and other drugs before the patient succumbs to respiratory paralysis.
such as dimethyl sulfoxide to reduce brain swelling The number of ticks required to paralyze a calf or
may be tried,710,721,724,727 but patients with prominent sheep is interesting but at the time of examination
signs usually die shortly after the onset of the signs in there may be none present.741,742,751 Focal neurologic
a few hours to a few days. If only mildly affected, the signs such as unilateral facial paralysis, anisocoria,
animal may be taken off the diet and live with resid- unilateral loss of the cutaneous trunci reflex, and
ual or no permanent signs.724 Horner syndrome may be expected to occur, at least
with Ixodes spp. With tick removal or application of
topical or systemic acaricides, signs can abate rapidly
Miscellaneous biotoxicities with soft ticks, but may take a few days to resolve
with ixodid hard ticks.739,742,743,747,748,755 Thus, polyva-
Tick paralysis
lent tick antitoxin is used for Ixodes spp. paralysis in
Tick paralysis resulting in rapidly progressive, Australia where finances allow.742,748,756 Complications
ascending, flaccid paralysis that mimics botulism of recumbency in adult patients add to morbidity and
occurs in many animals including humans738 and mortality. Use of treatments other than tick antise-
birds. Among our large animals, it occurs in not only rum has no influence on recovery.742
 Toxic diseases 449

Prior experience of the ticks on sheep and calves completely resolve.762 The mechanism for increased
has given protection from a challenge which would muscle contractility in this myotonic syndrome is not
have paralyzed and killed tick-­naive animals, with known.764 As an aside, is it not interesting that as a
immunity developing to the paralysis toxin rather mating signal female Otobius megnini produce rat-
than to tick feeding.757,758 Some progress has been tling vibrations that can be audible;761 could the sere-
made in developing a vaccine against the neuropara- nade from parasitic foreplay-­induced tinnitus play a
lytic tick toxins.746,759 role in episodic muscle spasms in the host?
Similar seizure-­like episodes that can last 10–20 min
Seizures and muscle spasms associated have been seen in sheep badly infested with sheep
with ticks and mites scab due to Psoroptes ovis, usually following frantic
episodes of scratching at local lesions. These signs can
The spinose ear tick Otobius megnini is a soft tick that
abate with appropriate acaricide treatment, but some
infests a wide range of wild and domesticated ani-
sheep have succumbed during seizures.765
mals including goat, cattle, zebra, deer, pig, pony,
mule, donkey and horse, and occasionally humans. It
is now distributed widely throughout the Americas, Snake bite paralysis
Asia and Southern Africa, and can be very common
Although snake bites are reasonably common in
in horses that are in close contact such as in
domestic animals where venomous snakes occur, it is
Thoroughbred racing facilities.760–762
estimated that only about 5% of cases reported in
Infestation of adult horses with ear ticks has been Australia involve cattle and horses.766 A simplistic
associated with nonspecific signs of colic and muscle division of common venomous snakes into two
spasms but also with severe regional prolonged myo- groups is given in the boxed table.
tonic muscle contractions, intermittent flicking of Local necrosis and generalized illness usually
the nictitating membrane across the eyeball, limb occur with pit vipers,767 but confirmed neuropara-
stamping, and seizure episodes.762,763 There was no lytic envenomation involving large animals seems to
evidence of any metabolic derangement except for be extremely rare. The main nervous signs observed
increased circulating muscle enzyme activities, and with natural and experimental South American rat-
no myotonic discharges were detected when exam- tlesnake (Crotalus durissus terrificus) envenomation
ined for. Episodic hyperesthesia with stomping, of cattle were somnolence, hypotonic reflexes, drag-
tremors, limb muscle hypertonia, and prolapse of the ging of the hooves, difficulties in moving around
third eyelid, all reminiscent of tetanus, occurred in a obstacles, ophthalmoplegia, lateral and sternal
2-­year-­
old Quarter Horse that recovered quickly recumbency, and tongue paralysis.768 Marked sys-
after tick removal and acaricide application to be temic muscle necrosis also occurred. In Australia,
totally normal in 3 days.764 Similarly, 9 out of 10 pre- elapids including tiger and brown snakes are impli-
sumptively affected horses in South Africa recovered cated in envenomation of horses.769 Neuromuscular
1–3 days after tick removal, and only one of these was weakness, altered mentation (somnolence or agita-
given an acaricide. The other case took 10 days to tion), and recumbency were the most common
abnormal neurologic signs among 52 horses with
Simplified categorization of venomous snakes of suspected elapid snakebite. Of the 49 horses, 42
­veterinary importance to large animals. (86%) survived when given at least one round of
combination tiger snake/brown snake antivenin
Family Common name Examples Principal toxicity treatment.769 Coral snake neuroparalytic toxins and
Crotalinae Pit vipers Moccasins Cytotoxic likely those from many other elapids are very heter-
Rattlesnakes ogenous which has traditionally made production of
Vipers
universal antivenins quite problematic and costly.770,771
Elapidae Elapids Cobras Neurotoxic More recently, novel immunization strategies have
Mambas
enabled the production of pan-­specific antisera capa-
Coral snakes
Black snakes ble of neutralizing a wide spectrum of neurotoxic
Brown snakes snake venoms. For example, one such antivenom
Sea snakes neutralizes 36 snake venoms belonging to 10 genera
from four continents.772
450 Large animal neurology

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D epsilon toxin: A review. Aust Vet J 2003; 81(4): 706 Howerth E, Wyatt R and Hayes D.
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 35
Nutritional diseases

Disease Page Disease Page

Vitamin A deficiency 482 Nicotinic acid deficiency 486

Mulberry heart disease of pigs—­vitamin E Equine motor neuron disease 486
deficiency482 Equine degenerative myeloencephalopathy
Polioencephalomalacia and cerebrocotical (equine neuroaxonal dystrophy) 489
necrosis in ruminants 482 Enzootic ataxia—­swayback—­copper deficiency 490
Pantothenic acid deficiency 484 Nutritional myodegeneration—­white muscle
Masseter myopathy in horses (myopathy of disease—­myodegeneration and steatitis 492
muscles of mastication and deglutition) 485 References492

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
482 Large animal neurology

Vitamin A deficiency vitamin A depletion even in mature cattle. Serum

vitamin A concentrations are below 20 μg/dL, and serum
Experimental and naturally occurring vitamin A total carotene below 0.7 μmol/L in affected calves10,11
deficiency in calves and adult cattle can result in neu- and fresh liver vitamin C concentrations below a
rologic syndromes. In calves, signs include domed reference range of 100–175 mg/kg fodder have been
forehead, blindness, weakness, ill thrift, diarrhea, regarded as deficient in cattle grazing arid pasture.20
dermatitis, and pneumonia. In cattle, signs include Of interest is that beef cattle diets that are margin-
blindness, convulsions, cerebellar ataxia, diarrhea, ally deficient in vitamin A result in better marbling of
and generalized edema.1–7 Night blindness, ill thrift, meat without apparently reducing growth productiv-
and seizures have been reported to occur in young ity,18,21 and ocular measurements can be proxy for the
horses fed with a vitamin A-­deficient diet.8,9 induced vitamin A deficiency state for such desired
Blindness in affected calves is peripheral, with beef production.19
absent menace responses, absent pupillary light Affected animals should receive parenteral vita-
reflexes, poorly-responsive dilated pupils, and tapetal min A at 440 IU per kg BW once followed by a bal-
hyper-­reflectivity in severe cases; the terms cécité anced, vitamin-­replete diet. Prominent blindness is
merveilleuse, Schönblindheit, and beautiful blindness probably not reversible, and ocular and cardiac
being quite apt.7 anomalies will remain, although signs of other organ
Visual loss is apparent if the animal becomes con- involvement may regress rapidly with vitamin A
fused when moving, is unable to negotiate its pen, supplementation.3,4,7,13
has a high-­stepping gait, or adopts an extended neck
or star-­gazing attitude, signs being more evident at
night.3 Fundic examination reveals pale tapetum Mulberry heart disease of pigs—­
lucidum, papilledema, indistinct disk margins, and vitamin E deficiency
tortuous retinal vasculature.2,3,10 Cardiac and optic Young swine surviving an episode of vitamin E
globe anomalies have accompanied neurologic signs deficiency-­related mulberry heart disease22 may be
in newborn calves,6,11 and probably in a young drom- obtunded, blind, wander in circles, convulse, and
edary camel.12 show ataxia. Signs result from a microangiopathy
Vitamin A deficiency in calves can result in altered and encephalomalacia, particularly in the pons and
in utero bone growth and a deformed cranium, par- midbrain.23,24
ticularly involving thickening of the sphenoid, occip-
ital, and temporal bones that may deform the Polioencephalomalacia and
cerebellum.6,10,13,14 This is associated with stenosis of
the optic canals and subsequent peripheral blind-
cerebrocotical necrosis in ruminants
ness.3,15 The deficiency also results in dural fibrosis Generically, these synonymous terms refer to necrosis
that interferes with CSF absorption at arachnoid villi and softening of cerebral cortical gray matter and
resulting in CSF hypertension.7,16,17 This interference can result in various forms from a number of toxic,
to CSF outflow results in increased intracranial pres- metabolic, and nutritional deficiency states including
sure and hydrocephalus that can be seen as epilepsy thiamin-­ responsive polioencephalomalacia, sulfur-­
with gait abnormalities, particularly in growing and induced polioencephalomalacia, salt and water intoxi-
adult cattle with diets poor in vitamin A.1–3,7 Ill thrift cation, lead poisoning, and even petroleum toxicity.25–27
and night blindness can be an early manifestation of Polioencephalomalacia was first described in rumi-
vitamin A deficiency in growing cattle and horses.9,13,18 nants in North America over 50 years ago,28 and later
The clinical syndrome in calves is associated with the concept of a possible association with defective
papilledema and retinal and optic nerve degenera- thiamin (vitamin B1) metabolism was introduced
tion,4,6,10,11,19 sometimes associated with epilepsy.7 from the UK.29,30 Subsequently, the possibility that
Reserve hepatic stores of vitamin A are low in fetal there was an association between polioencephaloma-
and young animals making them more susceptible to lacia and high sulfur intake began investigations into
dietary deficiency. Also, access only to poor quality, this form of the disease.31,32 These forms of polioen-
yellow forage such as present in Mitchell grass (Astrebla cephalomalacia that occur worldwide are by far the
spp.) bioregions in Australian droughts,20 and other most common and important and can be clinically
chronic disease states such as diarrhea4 can precipitate and pathologically identical; they are discussed here.
 Nutritional diseases 483

Both thiamin-­responsive and high sulfur-­induced due to inorganic and organic sulfur toxicity, viz.
polioencephalomalacia are common in calves sulfur-­induced polioencephalomalacia. In summary,
6–12 months old,33 lambs and kids 2–6 months high morbidity, lack of response to vitamin B1 ther-
old,34,35 and less commonly in adult ruminants.36 apy, and the presence of subcortical necrotic lesions in
Outbreaks occur in feedlots and under pasture graz- the thalamus and caudate nuclei, with none in cere-
ing management. Drought conditions can precede bellum and hippocampus, distinguish sulfur-­induced
sulfur toxicity by necessitating the use of deep well polioencephalomalacia from thiamin-­ responsive
water and supplemental nitrogen sources of feed, and polioencephalomalacia.
access to lush pastures and high soluble carbohydrate Several mechanisms are accepted as being able to
grain feeds can be associated with disruption of thia- induce a thiamin-­deficient state in ruminants includ-
min activity.25,37–40 The same disease may occur in ing the production of vitamin B1 antimetabolites in
camelids,41 and a variable neurologic syndrome the rumen, abnormal or overpowered vitamin B1
accompanied by pulmonary edema and other organ metabolism, synthesis of thiaminase by rumen
lesions that probably responds to thiamin therapy microbial metabolism, administration of thiamin
has been recorded in pigs.42,43 The neurologic lesions analogs or antagonists, and dietary depletion of thia-
were variable but quite often included laminar corti- min, most of which have been reproduced experi-
cal necrosis with prominent Alzheimer type II astro- mentally.37,44,51–55 Several rumen organisms have been
cytosis. The direct relationship between the latter isolated that produce thiaminase and a high carbohy-
lesions and pure thiamin deficiency in pigs needs drate diet of grains and lush forage promotes prolif-
corroboration.43 eration of these organisms in the animal. Thiaminase
With polioencephalomalacia usually there is an activity has been found in pasture swards. Also, it is
acute onset of disorientation, wandering and central proposed that some thiamin analogs can be pro-
blindness, progressing to ataxia, tremor, hyperesthe- duced in the rumen. Type I thiaminase production
sia, opisthotonus, convulsions, and recumbency. No by Bacillus thiaminolyticus and growth of the organ-
overt systemic signs of illness occur, but decreased ism in rumen liquor are significantly depressed by
performance due to subclinical disease may be pre- the presence of thiamin hydrochloride and thiamin
sent in the flock or herd.44,45 Amaurosis, staggering propyldisulfide,56 and this is the basis for the use of
gait, aimless wandering, profound extension of the oral therapy for thiamin deficiency and associated
head and neck or opisthotonus, and dorsal rotation subclinical polioencephalomalacia. Laminar cere-
of the medial pole of the eyeballs (eye deviation; stra- brocortical necrosis results from lack of glycolysis,
bismus) are very characteristic. Muscle tremor, with resulting brain edema, brain swelling, and ulti-
recumbency with decerebrate posturing, tonic– mately regional brain herniations. The administra-
clonic seizures to status epilepticus, and coma tion of competitive thiamin analogs such as
eventuate.33–35,41,46–50 coccidiostat drugs (e.g., amprolium) may be a factor
Some of the affected patients would respond dra- in the pathogenesis of individual cases and outbreaks,
matically to high and repeated doses of vitamin B1, and anthelmintic use may be a triggering factor that
hence the term thiamin-­responsive polioencephalo- has been associated with the onset of clinical signs.34
malacia. Evidence of a thiamin-­deficient state could Subclinical thiaminase production in the bowel has
also be detected in these cases:25,50 reference range for been related to poor weight gain in sheep. Thus, from
blood thiamin in ruminants being 50–150 nmol/L an economic viewpoint, subclinical thiamin defi-
with <50 nmol/L consistent with thiamin-­responsive ciency may be more significant than the overt clinical
polioencephalomalacia although much lower levels disease.50,57
often are recorded in suspected clinical cases. The With increasing frequency, sulfur-­associated poli-
disease can be reproduced in ruminants by the oencephalomalacia is reported in young and mature
administration of amprolium, a competitive thiamin ruminants, occurring with very high morbidity
analog.51,52 approaching 100% both in cattle and sheep.27,58–61 All
Other clinical cases have had no evidence of altera- forms of sulfur are converted into sulfide by rumen
tion of thiamin status and would respond marginally microflora and recycled as part of sulfur-­containing
or not at all to thiamin treatment. In many of these, amino acid production. Thus, H2S is a normal product
mounting clinical and experimental evidence has in rumen liquor and rumen gas such that periodic
accumulated of high rumen and tissue sulfide levels excess of ruminal sulfide can be regarded as a
484 Large animal neurology

biological hazard of ruminant life.55 Indeed, it is likely Atlantooccipital CSF analysis is usually abnormal
that the inhalation of H2S is an efficient means of get- with a slight mononuclear pleocytosis (5–50 × 106 /L)
ting sulfide into the systemic circulation.62 The associa- and a mild protein elevation (0.5–2.0 g/L) with xan-
tion of elemental, inorganic, and organic dietary sulfur thochromia. A rapid and prominent positive response
in clinical outbreaks of polioencephalomalacia is irref- to large doses of vitamin B1 is an extremely helpful
utable, and experimentally dietary levels of >5000 ppm diagnostic and therapeutic tool when thiamin metab-
(0.5%) of sulfur as sodium sulfate consistently pro- olism is a primary factor in the disease process.
duces the disease.63,64 Exactly how excess sulfide or sul- Assays for sulfide in rumen liquor and gas are pre-
fur metabolites result in polioencephalomalacia in mortem tests that may help in making a diagnosis.
ruminants is not clear,65 but an effect on neuronal mito- High sulfur content in water and feed sources should
chondrial respiratory chain enzymes or a direct neuro- be determined so that an outbreak can be thwarted
cytotoxic effect has been proposed.66 More recently, it and preventive measures put in place.53,54,72 Detailed
does appear that high sulfur/sulfate/sulfide diets result brain imaging studies can reveal the necrotic lesions.73
in reduced activities of brain thiamin pyrophosphate-­ Administering high doses of, say, 10–20 mg/kg
dependent enzymes and cytochrome oxidase, events thiamin IV or IM, BID, for 1–5 days can be remark-
that are associated with the pathogenesis of sulfur-­ ably therapeutic in thiamin-­responsive polioenceph-
induced polioencephalomalacia.67,68 alomalacia and may even halt onset and progression
At postmortem examination, a swollen, slightly of the clinically significant lesions in sulfide toxico-
yellow cerebrum is usually evident, and cerebral and sis.27,51,55,70,74,75 Nursing care is important when the
cerebellar herniations with their associated secondary animal is recumbent and anorectic. Many large ani-
hemorrhagic necrosic regions may occur in the acute mal practitioners will use a single dose of a glucocor-
disease. Autofluorescence of a freshly cut surface of ticosteroid drug such as 1.0 mg/kg dexamethasone
cerebral cortex placed under ultraviolet light is good IM or IV once as part of initial therapy27,70 or spread
presumptive evidence of polioencephalomalacia.62,69 over 2 days46 particularly if polioencephalomalacia
Histologically, there is patchy, sometimes laminar, associated with excess sulfur intake is suspected.
necrosis of cerebral cortex. Local porosity, vascular If the animal is not recumbent, the prognosis is
prominence, ischemic neuronal change, and glial good. Even recumbent animals can survive, but may
activation are present with micro and macro, yellow-­ remain blind and somnolent or develop epilepsy, all
surfaced cavities resulting. Additional findings can associated with the porencephalic healed cerebral
sometimes assist in distinguishing cases of thiamin-­ lesions.49,51,52
responsive polioencephalomalacia from sulfur-­ Reducing grain and increasing roughage in the diet is
induced polioencephalomalacia.62,70,71 In the former, suggested if possible and any excessive sulfate content of
neuronal necrosis can also be detected in cerebellar diet should be reduced.25 Supplementing the diet with
vermis, corpora quadrigemina, medial and lateral thiamin hydrochloride or mononitrate at 10–30 mg/kg
geniculate nuclei, and thalamus and hippocampus in of feed or 300 mg/head daily is useful as a prophylactic
some cases although generally regarded as somewhat measure if the problem persists in a herd. Immediately
inconspicuous.71 Additional subcortical lesions in the increasing the forage allotment and changing the water
sulfide-­related disease can often be apparent as gross source available to feedlot animals often prevents fur-
softening and discoloration or cavitation in the ven- ther cases from developing.27,55 Should ruminal trans-
tromedial thalamus and caudate nucleus, very unu- faunation be available, then this procedure should be
sual sites for the sister form of thiamin-­responsive considered where finances are available.
polioencephalomalacia.
As well as low blood thiamin levels recorded in Pantothenic acid deficiency
cases,25,50 elevated blood pyruvate and lactate concen-
trations, low activity of erythrocyte, thiamin Ataxia and weakness with prominent high stepping
diphosphate-­dependent transketolase, and finding of or goose-­stepping action of the pelvic limbs appear to
thiaminase activity in feces44,50 all can indicate sup- be related to pantothenic acid (vitamin B5) defi-
pression of thiamin activity. These changes are pro- ciency in swine (Figure 35.1). Initial signs described
found with the vitamin B1 deficiency state, whereas are of lumbar lordosis and flexion of pelvic limbs
they are normal or slightly abnormal during sulfide while standing, followed by hyperflexion of the pel-
toxicity.27,44,55 vic limbs during protraction, very much as seen with
 Nutritional diseases 485

Figure 35.1 Montage of images from video showing aspects of the pelvic limb gait abnormalities seen in fattening pigs in a presumptive outbreak of
pantothenic acid deficiency. There are signs of hypermetria (left) and hypometria (right) at different stages of strides in different cases. Two accompanying pen
mates are showing paraplegia (top). Delayed organophosphate toxicity should still be a diagnostic consideration (Chapter 34).

pasture-­associated stringhalt in horses (Figure 21.8).76–78 steatitis may have a swollen, painful tongue in con-
The pigs generally became paraplegic but then still junction with generalized stiffness and reluctance to
demonstrated unusual dysmetric movements of the move as part of the syndrome of myodegeneration
paralyzed pelvic limbs.77 Mildly affected pigs may and steatitis.82–84 This may be part of the more gener-
improve with pantothenic acid supplementation, but alized polymyopathy seen as nutritional myodegen-
prominent signs appear to be permanent. There is a eration with or without steatitis.85 Horses with
degenerative polyneuropathy and possibly a central masseter myopathy usually present with firm, appar-
axonopathy as well.78,79 ently painful muscles of mastication and degluti-
tion.80,86 Associated swelling may induce
Masseter myopathy in horses (myopathy exophthalmos and chemosis, and cardiac involve-
of muscles of mastication ment as evidenced by arrhythmias may result in sud-
den death. Affected horses have difficulty in chewing
and deglutition) and swallowing, and manipulation of the swollen
This is a rare disease affecting adult horses and affected muscles appears to be painful. Histologically,
ponies of all breeds, particularly those stabled and in there is a degenerative myopathy with few inflam-
poor condition. There is usually a sudden onset of matory cells.81,85 The disorder has been related with
complete anorexia or of swollen masseter muscles vitamin E and selenium deficiency and to poor
and difficulty in chewing. Some are presented after nutrition.80,81 Differential diagnoses include tetanus,
much atrophy has occurred, and they may have dif- traumatic and inflammatory masseter scarring, par-
ficulty opening the mouth as well as with chew- asitic myositis, nigropallidal encephalomalacia,
ing.80,81 Foals with diffuse myodegeneration and brainstem diseases including Sarcocystis neurona
486 Large animal neurology

infection in horses, and snake bite.85,87–90 Parasites Initially, the majority of cases were seen and
causing masseter myositis and fibrosis would include reported on from northeastern United States,109,110
Trichinella spiralis, Halicephalobus gingivalis, and although EMND has been reported in many other
possibly Haycocknema perplexum. countries.95–101,107,111–117 Quarter Horse, Thoroughbred,
Alimentation and maintenance of fluid and elec- and related breeds may well be overrepresented with
trolyte requirements are important aspects of ther- the disease, and older horses were at a higher risk than
apy. Vitamin E and selenium certainly are worth young animals, the peak occurring at 16 years of age
administering, and phenylbutazone and aspirin for and then declining. The majority of cases have little or
pain relief are reasonable to include in the therapy. If no access to green forage.92,104,105,110,118,119 A survey of
the condition is associated with marked debility, then European cases indicated that 40% were grazing on
the prognosis is poor. The prognosis is bad if the green grass at the onset of signs, 15% grazing full
heart is involved, and muscle atrophy is likely to per- time, but affected animals also had low circulating
sist if the animal survives. alpha tocopherol levels.93 Some cases have been iden-
tified as having infiltrative bowel disease and chronic
hepatic disease that may well be associated with dis-
Nicotinic acid deficiency rupted absorption, metabolism and storage of anti-
A syndrome like selenium toxicity in pigs with oxidant compounds, including vitamin E.96 Generally,
more white matter damage has been produced experi­ one to a few cases occur on individual properties over
mentally with a nicotinamide analog to induce several years, although at one urban equine establish-
acute nicotinic acid deficiency.91 There is demyeli- ment in a very large city there were 69 new cases
nation in dorsal funiculi and final motor neuron recorded over 8 years before corrective measures were
loss in ventral gray matter of the cervicothoracic instituted.120 This amounted to a true yearly incidence
and lumbosacral enlargements with ultimate of 1–10 new cases of EMND per year over the 8 years.
denervation muscle atrophy in pelvic limbs. Early
signs are probably reversible with withdrawal of A clinical truism for the syndrome of EMND is:
the analog. Affected horses move better than they stand.

The clinical syndrome expressed (Figure 35.2)

Equine motor neuron disease depends on the stage of the disease.92,104,105 Weight
Acquired equine motor neuron disease (EMND) is loss in the face of a good to increased appetite,
a fascinating neuromuscular disorder of horses that increased recumbency, and slight resting muscle
does not appear to have existed prior to 1982 and tremors are consistent findings in early cases. Weight
was first described by the late John Cummings and loss often precedes the onset of trembling by several
co-­workers from Cornell University in New York in weeks. Trembling may be exacerbated by forcing the
1990.94 A very large number of aged horses now horse to stand in one location such as stocks or a
have since been definitively diagnosed with EMND trailer, and they appear to be unable to lock their sti-
elsewhere in North America and from around the fles and constantly shift weight from one hindlimb to
world.95–101 Its striking resemblance to progressive another. Affected horses adopt a characteristic stance
muscular atrophy, one of the forms of human motor with all four limbs close together and frequently have
neuron disease, increases the significance of this an abnormally low head carriage, some animals rest-
disease well beyond its relatively low frequency of ing their heads on the ground while recumbent or
occurrence.102,103 The disease is characterized by the on an object when standing. A short-­strided gait is
death of final motor neurons in the brainstem and commonly seen that can show a rapid placement of
especially in the spinal cord leading to characteris- the foot at the end of the protraction phase akin to
tic clinical signs, underpinned by progressive and that seen with fibrotic myopathy; however, there
fluctuant weakness.92,94,104,105 Acquired equine motor appears to be no loss of proprioception, and affected
neuron disease is an example of the large family of horses are not ataxic. Cases are reported with lesions
devastating neurodegenerative disorders in animals of EMND and equine degenerative myeloencep­
including humans that for the most part are geneti- halopathy with combined syndromes including
cally determined or, as with EMND, are acquired by ataxia.121,122 On the other hand, some cases reported as
probably multifactorial mechanisms.96,99,102,106–108 EMND are likely not simply that disease.100 Indeed,
 Nutritional diseases 487

Figure 35.2 A clinical diagnosis of EMND was substantiated by demonstrating denervation atrophy in a sacrocaudalis dorsalis medialis muscle biopsy
from this paint gelding. Note the good appetite, slight cranial placement of hind feet, and constantly elevated tail head posture. Inset shows latter and
site for muscle biopsy (arrow).

there does appear to be a subset of the classical clinical Table 35.1 Proportion of major clinical signs recorded for 104 cases
syndrome of diffuse weakness and muscle atrophy of EMND.
in adult horses consisting of cases with no angular
myocyte atrophy typical of denervation, but having Clinical sign Occurrence %
myopathic changes characterized by abnormal mito- Muscle loss 100
chondria, and responding relatively rapidly compared Muscle trembling 95
with horses having EMND, over a few months, to Increased lying down 93
Excellent appetite 90
vitamin E supplementation.123 Many animals display
Shifting weight 90
an extended tail head position, and excessive sweating Extended tail head 76
is seen in perhaps half of the cases. Ophthalmic exam- Lowered head posture 62
ination reveals varying degrees of a mosaic pattern Retinal lesions 18
with dark brown to yellow brown pigment (ceroid
Source: Adapted from Divers et al.92 and McGorum et al.93
lipofuscin) deposited in the tapetal zone, coupled
with a horizontal band of pigment at the junction of
the tapetal and nontapetal fundus.121,124,125 Relative signs and nutrient sources have been improved.
occurrence of the more frequently occurring signs of Affected horses may then not tremble or have muscle
EMND is given in Table 35.1. fasciculations or lie down frequently, but marked
Although the clinical syndrome and course in muscle wasting is common and particularly promi-
severe cases is characteristic, important differential nent in the triceps, quadriceps, neck, scapular, and
diagnoses must be considered including laminitis, lumbar musculature. Progression of signs after a
botulism, grass sickness, myopathies, dental prob- period of stabilization however is not uncommon.
lems, malabsorptive disorders, and neglect. Certainly, In a third or so of cases, body weight returns to pre-­
the stance and muscle trembling is very similar to disease levels if antioxidant levels are restored or
that seen in chronic grass sickness and in mild botu- the patient is moved to another environment as the
lism. The clinical syndrome often stabilizes or horse accumulates fat, but the athletic ability of
improves somewhat 1 or 2 months after onset of surviving animals is permanently impaired to varying
488 Large animal neurology

degrees.92,95,97,98,100,120 About half of the cases are eutha-

nized for a lack of response to vitamin E supplemen-
tation or other reasons and others lost to follow up.
Clinical improvement may be associated with a shift
in contractile and metabolic characteristics of muscle
fibers from slow twitch (type I) to fast twitch (type II) (A) (B)
allowing continued function in an antioxidant replete
environment.126
Antemortem diagnosis can be difficult and labora-
tory findings are not specific. Generally, serum CK
and AST activities initially are variable but moder-
ately increased. Plasma vitamin E concentrations for
affected horses are generally lower than those of ref-
erence ranges and on-­farm control horses,95,97,98,127
although there are exceptions128 when the role of
other anti/oxidant compounds such as iron may play
(D) (C)
a role. Needle electromyographic studies have been
consistently abnormal in affected animals with pro-
Figure 35.3 The pathologic substrate of EMND is neuronal degenera-
longed insertional activity, fibrillation potentials, and tion in ventral gray matter (A and B) and brainstem nuclei associated with
positive sharp waves recorded, particularly in the antioxidant (vitamin E) deficiency. Early changes seen (A) are partial
proximal thoracic appendicular muscles and in the (arrowhead) and complete (black arrows) neuronal chromatolysis and
easier to access dorsal tail muscles.128,129 Evaluation of death that in chronic disease (B) is seen as loss of neuronal somata
replaced by glial scars (open arrows). Neuronal fiber degeneration (C)
biopsy samples, particularly of a type-­1 predominant
then follows in affected nerves (e.g., between arrowheads) with resulting
muscle such as sacrocaudalis dorsalis medialis (tail– neurogenic atrophy particularly in type-­1 predominant muscles such as
head), by an experienced histologist can be useful in sacrocaudalis dorsalis medialis (D). This is seen as increased disparity in
confirming the diagnosis with a sensitivity and speci- fiber size and angular atrophy (black and white arrows) with small group
ficity both greater than 90%.101,128,130,131 atrophy (blue dashed ovals).
Definitive diagnosis is dependent on the postmor-
tem demonstration of degeneration and loss of cell subjected to prolonged dietary restriction of vitamin E
bodies in the ventral horn of the spinal cord for up to 4 years, with or without excess copper and
(Figure 35.3) and in motor nuclei in the brainstem iron, showed clinical signs of EMND and/or had his-
except for those supplying cranial nerves III, IV, and tologic lesions consistent with the disease. Affected
VI. Cell bodies swell, lose the Nissl substance, become and unaffected experimental horses all had very low
chromatolytic, and have accumulations of neurofila- serum vitamin E levels, and the supplementation of
ments in perikarya and proximal axons before dying some of those unaffected resulted in the repletion of
and being removed. Concomitantly, there is degenera- serum vitamin E status. Additionally, some unaffected
tion of axons in the ventral roots and peripheral nerves but vitamin E depleted horses had histologic lesions
and neurogenic muscle atrophy that predominantly consistent with some final motor neuron loss.92,127,137
affects type 1 fibers.94,107,122,132,133 Of clinical interest is Thus, in experimental cases and in naturally occur-
that approximately 30% of final motor neurons need to ring cases of EMND in North America and in Europe,
be affected in the spinal cord before there are clinical vitamin E deficiency has been the only consistent
signs evident.134 As with many diseases associated with nutritional or toxic-­related abnormality determined.
antioxidant deficient states, including vitamin E defi- Upon diagnosis of EMND, it is reasonable to supple-
ciency, endothelial lipopigment is prominent in small ment with natural α-­tocopherol vitamin E and added
vessels of the spinal cord99,135 and elsewhere.121,122 intakes of 4000–6000 IU per horse per day have been
Although circulating and tissue depletion of vita- recommended.138 Green forages are by far the major
min E stores occur with EMND and vitamin depletion and best source of vitamin E and at times some grain-­
has been shown to produce the clinical and pathologic based concentrates have less vitamin E than the NRC
disease,120,127 there is some evidence for a role for ele- recommendations for horses of 50 IU/kg dietary dry
vated body stores of copper and iron being invol matter—­possibly related to tocopherols being heat-­
ved.92,99,119,128,136 Experimentally, 10 horses out of 11 labile. Horse feeds with increased amounts of vitamin
 Nutritional diseases 489

E have become available, and increased owner aware- United States and northern Europe in most breeds of
ness of the possibility of vitamin E deficiency and the domestic horse as well as Burchell zebra and
increased use of vitamin E supplements may partially Przewalski horse. The disease has been shown to
explain the rather dramatic apparent decline in the have a familial and likely hereditary basis in the
frequency of reported cases of EMND. Perhaps of Appaloosa, Standardbred and Paso Fino breeds, and
some pertinence here is that despite constant surveil- is suspected to be inherited in Norwegian fjord,
lance over 15 years there has not been a case of EMND Arabian, Quarter Horse, Welsh pony and Haflinger
identified in New Zealand, a country where grass breeds, and in Burchell zebra and Przewalski
feeding of horses is the norm. Notwithstanding, fur- horses.149–154 The neuraxonal dystrophy of Morgan
ther studies are warranted to explain the development horses and Burchell zebra and other breeds of
of hypovitaminosis E and EMND in horses that have equids144,146,147 is likely to be another expression of
adequate access to pasture.93 Genetic factors for alter- EDM155–157 with reviewers indicating that the axonal
ations in amount or activity of the alpha-­tocopherol dystrophy is the early expression of EDM.144,147 The
transfer protein, such as the 744 del A mutation of the assumed genetic predilection to EDM has yet to be
alpha-­TTP gene operative in humans with some confirmed.
forms of hypovitaminosis E,139,140 will need explora- The neurological examination reveals essentially
tion in this situation. Finally, the use of other bio- symmetric ataxia, weakness, and hypometria, usually
markers for motor neuron degeneration that have affecting all four limbs. The relative abnormality of
been studied in humans may be pertinent to the gait in the limbs may not be consistent with a classi-
equine disorder.141 cal focal cervical compressive lesion of short dura-
tion. Thus, the thoracic limbs may be mildly affected
Equine degenerative while the pelvic limbs profoundly affected. In severe
myeloencephalopathy (equine cases, there is prominent hyporeflexia over the neck
and trunk, specifically involving the thoracolaryn-
neuroaxonal dystrophy) geal (slap test), local cervical, cervicofacial, and cuta-
Equine degenerative myeloencephalopathy (EDM) is neous trunci reflexes.154 Other signs including poor
a disease that has been recognized as a clinical and menace responses and degrees of somnolence have
pathological entity in various equidae for nigh on 50 been recorded.144,147 Severely affected foals and zebras
years.142,143 Equine neuroaxonal dystrophy describes a have been known to temporarily adopt a paraplegic
similar if not identical disorder.144–147 Reported most or dog-­sitting posture but only rarely does the dis-
often in North American horses, EDM has occurred ease progress to recumbency.
in Great Britain and Continental Europe, and per- The lesions that account for the clinical syndrome
sonally in Central and South America. Most fre- are a combination of degrees of neuroaxonal dystro-
quently, signs are first seen in suckling and weanling phy affecting spinal cord and brainstem sensory, pro-
foals with evidence of a lack of access to vitamin prioceptive relay nuclei, and neuronal fiber
E-­rich forage. Rarely if ever are signs documented to degeneration within ascending and descending spinal
begin after 2 years of age in comparison to the adult cord pathways, particularly prominent in the thora-
onset of signs in cases with equine motor neuron dis- columbar region.142,154,158 Lesions of sensory general
ease that is also associated with a vitamin-­E deficient proprioceptive pathways may include dorsal root gan-
state. Signs are often insidious in onset and slowly glia soma degeneration.158 As occurs in most vitamin E
progressive; however, a rather dramatic onset of deficiency states in mammals, the accumulation of
severe ataxia and weakness in the pelvic limbs or all free and endothelial-­associated lipopigment in CNS
four limbs may be apparent. At that stage, closer tissue is a prominent histologic feature of EDM,135
inspection of other foals on the farm may reveal fur- and lesions of lipopigment accumulation and retinal
ther cases. Clinical signs occasionally progress to degeneration are also seen in severely affected
recumbency, although most frequently they plateau patients.121 Quite to be expected is documentation that
with maturity. It is most common in the northeast there is severe disruption to axonal transport proteins
United States where the disease has been relatively in affected nuclear regions and ganglia of horses with
under diagnosed,148 and the prevalence has been esti- EDM,158,159 and markers of lipid peroxidation are
mated at between 23 and 45% of horses with spinal altered in affected spinal cords.160,161 Neuroaxonal dys-
cord disease. EDM has been recognized all over the trophy has been regarded as the prominent lesion in
490 Large animal neurology

Morgan horses having a similar, if not identical, dis- alpha-­TTP gene, develop ataxia and hyporeflexia
ease that appears to be familial.144,155,156 when plasma vitamin E levels drop markedly, and
Phosphorylation of axonal proteins is found in this can be at least partly prevented by vitamin E sup-
neurons degenerating from a variety of insults. Thus, plementation.139,140 Alpha-TTPA was excluded as a
one approach to aiding diagnosis of equine degenera- candidate gene for EDM in the Quarter Horse.146 On
tive myeloencephalopathy is confirming a high con- the other hand, because many chronically affected
tent of an equine phosphorylated neurofilament animals have been found to have normal serum vita-
(pNF-­H) protein, a biomarker of axon damage, in min E, and because prior use of insecticides and
CSF and blood by ELISA,162 although clinical utility exposure to wood preservatives have been identified,
of such tests need to be confirmed. along with others, as risk factors in EDM, then the
Routine laboratory blood work, cervical radio- hypothesis that extends the pathophysiology to
graphs, cerebrospinal fluid analyses, and electromyo- include exposure to environmental oxidants and lack
graphy are all noncontributory to a positive diagnosis of antioxidants including vitamin E is tenable.167–169
of EDM. Early during the disease, young affected ani- EDM susceptibility in Quarter Horses was mapped
mals very often have serum vitamin E concentrations by genome-­ wide association studies to a 2.5-­ Mb
way below control values and sometimes it is unde- region on chromosome 7, but efforts to identify a
tectable. Normal serum vitamin E concentrations are causative gene or genes within this region have not so
expected to be greater than 1.5 mg/L. Concentrations far been successful.170
less than 0.5 mg/L and probably less than 1.0 mg/L Notwithstanding this, the evidence strongly indi-
are consistent with a deficient state. Unaffected foals cates that supplementation of groups of horses in
on the same farm as affected foals also may have low which there has been a high prevalence of the disease
serum vitamin E concentrations, but generally not as with adequate vitamin E has been associated with
low as affected animals. Conversely, more mature cessation of new cases.144,150,151,154,171 Whether such
affected animals in the chronic stage of disease often effects have represented replenishment of vitamin E
will have normal serum vitamin E concentrations, deficiency, or simply an antioxidant affect, is still of
particularly if they have access to green forage of any some debate.
description after onset of signs. Heat-­treated pellets Treatment and prevention strategies are based on
made of mixed grains or alfalfa, stored oats, and sun- providing adequate fresh green forage. Where this is
baked coastal Bermuda grass hay, used on farms not providing adequate vitamin E (and possibly other
where EDM has occurred at high frequencies, all antioxidants), water-­ dispersible natural d-­α-­
have had measured vitamin E contents of 0–5 IU/kg tocopherol (RRR-­ α-­
tocopherol) is recommended.
dry weight. This can be compared to NRC recom- This should be provided to mares and foals in fami-
mendations of 50–100 IU vitamin E/kg dietary dry lies in which EDM has occurred at 10 IU/kg/d for
matter.163 extended periods.144,172
Access to dirt lots and use of heated, pelleted feed
and sunbaked forages with very low vitamin E con- Enzootic ataxia—­swayback—­copper
tents are predisposing factors to the disease. Of sig-
nificance is the production of prominent neuroaxonal
deficiency
dystrophy in spinal cord and brainstem nuclei in two Congenital swayback occurs in newborn lambs and
foals that were subjected to vitamin E deprivation, goats173–175 that show stable degrees of weakness,
from the last trimester of pregnancy of their dams recumbency, obtundation, blindness, and head
though until 6 months of age (IGM, unpublished). tremor. Copper deficiency is suspected to cause
Also, many workers have observed a familial ten- hypomyelinogenesis and associated porencephaly
dency, and foals from dams that have previously had and hydrocephalus in utero, probably the result of a
an affected offspring are at a higher risk of develop- primary neuroaxonal defect.
ing the disease than foals from other matings. This In comparison, growing, 3–12-­ week-­ old kids,
evidence strongly supports the hypotheses that EDM lambs, calves, and piglets show enzootic ataxia or
is a vitamin E deficiency that has a familial, predis- delayed swayback consisting of ataxia of the pelvic
posing component.150–152,154,164–166 Indeed, human limbs progressing to tetraplegia.174,176–181 A form of
patients with defects of the alpha-­tocopherol transfer ataxia in adolescent and mature captive deer appears
protein, such as the 744 del A mutation of the to be the same disorder.182–184 This enzootic ataxic
 Nutritional diseases 491

syndrome has been recorded in wild, captive and generally accepted that in enzootic ataxia a defect in
farmed, red, Sika and fallow adult deer world- the neuraxon results in secondary myelin degrada-
wide185–188 and in other wild ungulates.189,190 Both tion and is finally reflected in degenerative changes
congenital and delayed swayback mostly occur in hill in the neuronal cell body.179,197,201 Central axonal and
breeds of sheep lambing at grass and following mild myelin degeneration can occur in the fetus and may
winters with soil mineral profiles likely of etiologic be most florid when maximal axonal growth and
importance.191–193 myelination are occurring.198 The disease affects cen-
Other copper deficiency syndromes, such as loss of tral and peripheral neuronal fibers, thus final motor
wool fiber crimping (steely wool), diarrhea, graying neuron signs with electromyographic and histologic
hair coat, spontaneous long bone fracture, epiphysitis, evidence of neurogenic muscle atrophy are present,
and sudden death may occur on a farm having cases especially in goat kids.179,194 This along with the
of enzootic ataxia. Although enzootic ataxia is not as Wallerian-­ like neuroaxonal degeneration concen-
common in calves as in other growing animals, these trated in dorsolateral and ventromedial spinal cord
other syndromes of copper deficiency/molybdenum tracts strongly suggests that there is a central and a
excess are more frequent in adult cattle. Progressive peripheral distal axonopathy underlying the
paraparesis of young sheep, goats, and deer usually lesions.194 There can also be Purkinje cell degenera-
first becomes evident when animals trail behind the tion.178 Piglets suspected of dying of copper defi-
mob and drag the pelvic limbs while being moved. ciency with fulminant neurologic signs also
Final motor neuron involvement with flaccid paraly- frequently had intimal hemorrhages in the great
sis of the limbs, hypotonia, hyporeflexia, and muscle vessels.196
atrophy is particularly evident in growing kids that That copper deficiency alone is the cause of enzo-
are affected and is of considerable help in arriving at a otic ataxia is not well documented. Interpretation of
clinical diagnosis.179 Occasionally, young goats with blood and liver copper concentrations and their rela-
the disease demonstrate clinical signs of cerebellar tionship to the presence and severity of clinical signs
dysfunction and have underlying cerebellar degenera- is obscure, notably in the syndromes in goats and
tive lesions.177,179,194,195. Degenerative cerebellar disease deer.179,183,195 Blood and tissue copper levels of affected
has been associated with low copper status in a and unaffected herd mates indicate whether or not a
moose.189 Piglets having copper deficiency may have a low copper status exists on a farm.179,183 In using
rapidly progressive syndrome of ataxia, intention blood copper measurements to assist in diagnosing
tremor, weakness, nystagmus, recumbency, and mus- copper deficiency, plasma samples are more consist-
cle atrophy, with death in 3–5 days from onset of ent than serum samples and a range of copper con-
signs,178,196 and affected suckling calves have been centrations of 4.5–9 μmol/L in plasma have been
noted to have urinary incontinence.176 offered as marginal status for sheep. Most likely other
nutritional and possible toxic factors play a role in
In diagnosing this disease in a cluster of cases, it some forms of enzootic ataxia, and excess sulfur,
should be iterated that lambs with no clinical molybdenum, and iron in the feed and soil may well
signs may have forebrain and/or spinal lesions and be important associated factors.191–193 There may be a
lambs with clinical signs may have very minimal familial aspect to the disease, at least in sheep and
lesions. Lambs with clinical congenital copper goats.179,193
deficiency and cavitated lesions in the forebrain Copper supplementation is recommended,
also have ­s pinal neuroaxonal degenerative lesions. although topdressing pastures with copper salts can
be expensive and can cause blood copper concentra-
tions in stock to rise erratically. Thus, copper sulfate
Delayed forms of copper deficiency appear to drenches and injections with copper glycinate (50
result from some defect in maintenance of neuroax- –120 mg SC) have been used successfully in rumi-
onal function, which may begin in utero,197,198 and nants but need to be repeated frequently.183,191,202
one suggested mechanism is that the lesions are asso- Using orally administered oxidized copper wire,202,203
ciated with reduced activity of cytochrome oxidase in cupric oxide particles in gelatin boluses204,205 or
neural tissues.199,200 There is axonal loss with associ- soluble glass copper boluses206 for cattle and sheep
ated myelin depletion and neuronal cell body swell- result in more sustained blood copper status and is
ing caused by filamentous accumulations.179 It is probably the preferred treatment and prophylactic
492 Large animal neurology

regimen. Affected growing lambs and kids can defi- myodegeneration in susceptible patients.218,229,238,239
nitely improve with therapy,193 but residual neuro- Experimentally, elevated muscle enzyme activity in
logic deficits might be expected.173,191 serum and subclinical myopathy can be achieved
with vitamin E and selenium depletion. However,
Nutritional myodegeneration—­white factors including the addition of polyunsaturated
muscle disease—­myodegeneration fatty acids, such as linolenic acid in the form of pro-
tected linseed oil to the diet, appear necessary to
and steatitis trigger the typical clinical syndrome.230
This condition is recorded in domesticated large Elevated serum muscle enzyme activities,
animals of all ages, but most frequently is seen in reduced glutathione peroxidase enzyme activity,
calves and lambs, less frequently in piglets, and and detection of myopathic potentials on needle
infrequently in goat kids and horse and pony EMG examination help to confirm the presence of a
foals.207–220 Yearling and adult cattle sometimes are myopathy.226,231,240 In markedly affected foals, con-
affected in outbreaks,221–224 and the disease can be comitant neonatal encephalopathy and sepsis likely
congenital.220,225–227 Congenital nutritional myode- play a role in precipitating the syndrome. Such foals
generation can occur, usually with a hopeless prog- can have life-­threatening electrolyte abnormalities
nosis, and this seems to be the usual syndrome seen including hyperkalemia, hyponatremia, hypocalce-
in captive wild herbivores.220,226–229 mia, and hyperphosphatemia.241 Low serum vitamin
Frequently, there is peracute to slowly progressive E concentration and, more often, low serum and tis-
weakness and stiffness of the limbs or neck. Some sue selenium concentrations and depressed serum
are presented for treatment because of tachypnea glutathione peroxidase activity help incriminate
and occasionally may be found dead. Unaccustomed low vitamin E and selenium status as factors in the
exercise, inclement weather, or transport may pre- myodegeneration. Rest and nursing care for recum-
cipitate and exacerbate the signs.217–219,230 Palpably bent and dysphagic patients along with analgesic
swollen and painful muscle masses may be found. drugs and vitamin E and selenium are particularly
In foals and ponies, the base of the tail, the neck useful in treatment,81,226,229 and some spectacular
tissues, the tongue, and submandibular area may responses can be seen. The deranged nutritional
appear to be painful on palpation,216,218,219 possibly state of this disorder does appear to be associated
due to accompanying steatitis.83 Reluctance to move with alterations in circulating thyroid hormone
and a stiff, sometimes weak, gait are evident. This levels that are corrected with vitamin and selenium
can mimic diseases such as pleuritis, acute pneumo- therapy.240
nia, laminitis, and polyarthritis. Limb reflexes can be The prognosis is bad if the heart or respiratory
surprisingly normal or slightly hypoactive, and sen- musculature is affected, and permanent muscle atro-
sation remains intact. The syndrome can be difficult phy may occur with recovery. Results of treatment of
to distinguish from spinal cord disease in an indi- equids with steatitis and myodegeneration have been
vidual lamb or calf. Myoglobinuria may be found in variable84,214,232 but with up to 75% surviving, often
the severe syndrome, particularly in adult cattle.222 with prolonged recoveries.83
Involvement of muscles of the head occasionally
occurs in adult, often aged, horses as a masseter
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 36
Metabolic diseases

Disease Page Disease Page

Hepatic encephalopathy 504 Hypoglycemia511

Hyperammonemia507 Hyponatremia512
Uremic encephalopathy 508 Hypernatremia512
Hypocalcemia (milk fever) Hypokalemic syndrome in cattle 512
Hypomagnesemia (grass staggers) 509 Anesthetic-­related hypoxia and anoxia 512
Ketosis (with hypoglycemia) in Cardiocirculatory collapse—­shock 513
ruminants510 References513

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
504 Large animal neurology

Hepatic encephalopathy subclinical.14,15,18–26 Also, hepeviruses similar to hep-

atitis-­E virus of humans have been found in ­cattle
Severe acute and chronic liver disease from many and are excreted into milk. Although pigs,27 poultry,
causes can result in systemic illness and less com- and other animals act as reservoirs for human hepe-
monly in hepatic encephalopathy.1 The complex met- viruses, there is no evidence that bovine hepeviruses
abolic derangements present in liver failure can or, indeed, the equine hepatitis-­associated viruses,
interfere with central and peripheral neuronal func- pose a zoonotic risk.
tion, and in large animals this syndrome of hepatic Hepatotoxicity associated with ingestion of pyr-
encephalopathy is usually observed as waxing and rolizidine alkaloid-­containing plants, notably Senecio
waning, often fulminant, signs of diffuse and some- spp. and Crotalaria spp., occurs in any grazing a­ nimal
times focal brain disease.2–6 Hyperbilirubinemia per and is a major if not the main cause of hepatic failure
se probably does not contribute to the specific syn- and hepatic encephalopathy in domestic large ani-
drome of hepatic encephalopathy apart from gener- mals.28,29 The toxic principles can cross the placenta
alized malaise. However, in neonates, bilirubin to affect unborn offspring resulting in congenital
toxicity to neural parenchyma (kernicterus) may liver failure.30 Herbage from the pantropical coffee-
result from isoerythrolysis, when hypoglycemia is weed (Senna occidentalis), and to a lesser extent sick-
also considered as being contributory to any lepod (Senna obtusifolia), causes myopathy in many
encephalopathy. species, and particularly causes liver failure in pigs,
Acute hepatic necrosis in adult horses, often asso- cattle, and horses.31,32, 33 Several plants such as
ciated with prior administration of equine-­origin Switchgrass (Panicum virgatum), Fall panicum
biologic substances, has been recognized since the (Panicum dichotomiflorum), and kleingrass (Panicum
early twentieth century because of the pioneering coloratum) as well as blue-­green algae related cyano-
work of Sir Arnold Theiler in South Africa. Theiler toxins34,35 are associated with chronic hepatic lesions
described a syndrome of often-­ fatal hepatitis in and liver failure. Aflatoxicosis resulting in mycotoxic
horses that had previously been given equine serum hepatopathy can occur in all large animals including
as part of a vaccination protocol.7–11 Evidence is horses,36 although pigs are more often affected.37
mounting that a recently identified copiparvovirus, Especially in New Zealand ruminants, cirrhosis com-
equine parvovirus-­hepatitis (EqPV-­H), is the princi- monly is associated with the ingestion of sporidesmin
pal cause of Theiler disease worldwide, including produced by the toxigenic pasture fungus Pithomyces
cases not associated with biologics.11–15 The virus chartarum causing hepatic encephalopathy, usually
was found in 27/28 prospectively identified horses referred to as facial eczema.38–42 The hepatotoxicity
with Theiler disease, and experimental infection can be ameliorated by supplemental zinc, and a
has consistently produced subclinical or clinical genetic tolerance is known.43
hepatitis.14,15 Three flavivirus homologs of hepatitis The evidence for alsike clover, Trifolium hybridum,
C virus (HCV) with potential to cause hepatitis producing toxic hepatopathy in horses does appear
infect horses, each with viral prevalence of 1–32% to be lacking.44,45
have been i­ dentified. These are: hepacivirus A (aka As a reflection of the diverse causes of toxic
equine hepacivirus, nonprimate hepacivirus hepatopathy, exposure of horses to high environmen-
(NPHV)), pegivirus E (PgV-­E, aka equine pegivi- tal levels of iron in groundwater has been associated
rus), and pegivirus D (PgV-­D, aka Theiler disease-­ with hepatic failure,46 and ferrous fumarate appears
associated virus). A hepatitis B-­related virus (HBV) to have been the compound present in a now discon-
was recently detected in samples from donkeys and tinued microorganism culture-­ based product that
zebras from Europe and Africa; horse samples were caused the unfortunate death of many foals between
negative and infections were subclinical.16 An 1981 and 1983 in North America.47,48 Fulminant
unclassified agent, Kirkovirus Equ1virus, was iden- hepatic failure followed the administration of one or
tified by deep sequencing the liver of a horse with two doses of this nutrient supplement to foals.47,49
fatal idiopathic hepatopathy.17 NPHV appears able Neonatal foals administered large volumes of blood
to cause mild liver disease in horses, whereas are at risk of liver failure presumptively associated
infection with either pegivirus has invariably been with iron overload.50 The odds of liver failure in foals
 Metabolic diseases 505

given at least 4 L of blood were 19.5 times higher than anatomic diagnosis of spinal cord disease can initially
that of foals given a smaller volume. be confounding to appropriate workup of such cases.79
Tyzzer disease is a form of necrotizing bacterial If one sign was put forward as the most common and
hepatitis caused by Clostridium piliforme (formerly typical early sign of hepatic encephalopathy in adult
Bacillus piliformis) that results in acute somnolence horses, it would be repetitive yawn. Tenesmus with
and death in foals and occasionally in young rumi- urine spillage and, occasionally, rectal prolapse can be
nants.51–57 Also, suppurative cholangiohepatitis, seen in cattle and horses with hepatic encephalopathy.
often accompanied by cholelithiasis, can result in Also, bilateral laryngeal paralysis with pronounced
liver failure to the point of causing encephalopathy,58 inspiratory stridor has been observed in horses with
and other causes of clostridial hepatitis in several liver disease and is essentially pathognomonic in the
species need to be considered.52 Congenital and appropriate setting.6,29,80 The pathogenesis of these
acquired portosystemic shunts are rare in large ani- findings remains obscure, but a functional metabolic
mals, although both intrahepatic and extrahepatic neuropathy or central neuronopathy seems likely.
forms have been documented in piglets, calves, Esophageal choke can result from dysfunctional chew-
goats, lambs, and most often in foals, usually dem- ing and swallowing often occurring due to the
onstrating ill thrift and/or variable encephalopa- encephalopathy.
thy.59–70 Probably, the commonest form of liver
disease in dairy cows in production and in all rumi-
nants on high planes of nutrition, with or without The syndrome of hepatoencephalopathy in horses very
additional nutritional derangements,71 is hepatic often includes repeated yawning, leaving unchewed food
lipidosis, but this does not often progress to fulmi- in the mouth, head pressing, playing with water (sham-­
nant hepatic encephalopathy.72,73 Similarly, fatty liver drinking), and inspiratory stridor due to laryngeal paralysis.
syndrome in obese and pregnant ponies and don-
keys usually results in modest cerebral signs, if any, With liver failure, protein, carbohydrate and fat
and may be associated with hyperlipemia and hyper- metabolism are severely impaired and detoxification,
viscosity and the accompanying ominous outlook if particularly of nitrogenous wastes, is defective.
untreated.74 Other forms of familial diseases associ- Hyperammonemia is regarded as the principal factor
ated with liver failure such as bovine lipodystrophy in the development of clinical encephalopathy in
and urea cycle defects in foals are also associated liver failure with other factors involved including
with neurologic signs in newborn or juvenile build-­up of other circulating nitrogenous waste
patients.75–77 products, hypoglycemia, decreased circulating
A history of weight loss or ill thrift, colic, and pho- branched chain to aromatic amino acid ratio,81 excess
tosensitivity may accompany more recent signs of short-­chain fatty acids, and induction of substances
periods of abnormal behavior, sometimes violent. with neurotransmitter activity in the brain such as
Access to toxic plants may be evident. In horses, teta- endogenous benzodiazepines82,83 and higher levels of
nus antitoxin or other equine-­origin biologics may circulating metal ions such as manganese.84,85
have been administered 1–3 months previously. One good evaluation of liver function in horses is
Clinically, there may be ascites or signs of acute liver the measurement of serum total bile acids concentra-
failure with icterus. Rectal prolapse has been a pre- tion which is usually very elevated. This is a less reli-
senting complaint in calves,78 and tenesmus has been able test in cattle and other ruminants because of the
seen in affected horses. radical variations in and between normal animals and
Periods of yawning, central blindness, aimless wan- over time. The total serum protein concentration may
dering, compulsive activity, aggression toward objects, be low, but both albumin and globulin levels are often
animals and people, ataxia, facial and ear tremors, and normal even in advanced liver disease, especially in
seizures are frequently seen in varying combinations in horses. Blood urea nitrogen concentration is not often
all large animals suffering from hepatic encephalopa- low. Blood ammonia concentration is most frequently
thy (Figure 36.1).2–6,8,70,71 Ataxia and weakness may be elevated. Blood glucose concentration may be low but
prominent, and when signs of obtundation and fore- is usually normal or high in horses. Radiographs and
brain and brainstem disease are not evident the neuro- ultrasound of the abdomen may reveal a small
506 Large animal neurology

(A) (B)

(C) (D)

Figure 36.1 Signs of the encephalopathy accompanying liver failure can vary markedly from somnolence to violent behavior. However, four of the more
common signs frequently expressed are shown in these cases as continual yawning (A), leaving food in the mouth (B), head pressing (C), and sham
drinking (D). Laryngeal paralysis with inspiratory stridor accompanied two of these terminal cases (B and C).

shrunken liver, he­patomegaly with lipidosis, patchy cases.61,63,86 Portal thrombosis can also result in
liver disease, choleliths, and vascular anomalies. Liver hyperammonemia and hepatic encephalopathy and
biopsy is very useful to reveal cholangitis, hepatitis, needs to be differentiated from congenital hepatic
hepatocytomegaly, cirrhosis, reactive biliary prolifer- portal shunting, especially when it occurs in quite
ation, and necrosis. young patients.87
Transabdominal ultrasonography may be used to Measurement of pyrrolic metabolites of pyr-
detect a small liver and even indications of aberrant rolizidine alkaloids in blood and tissues appears to be
hepatoportal vasculature when present. Quantitative a sensitive marker for exposure to a wide range of
nuclear scintigraphy and intraoperative mesenteric pyrrolizidine-­containing plants as a likely cause of
contrast portography have been useful in defining the liver disease in individual patients.28–30,88–90
such vascular anomalies,68–70 and, more recently, The typical histologic change seen with hepatic
computed tomographic contrast angiography has encephalopathy is astrocyte proliferation and hyper-
resulted in even better diagnostic accuracy.59,61,63,86 trophy with swollen, pale nuclei containing dispersed
With clear identification of anomalous portosys- chromatin, and sometimes showing marginal inden-
temic vasculature, surgical vascular banding of the tations, as well as increased pale or slightly eosino-
vessels has been successful in treating such philic indistinct cytoplasm that is, uncharacteristically,
 Metabolic diseases 507

glial fibrillary acidic protein (GFAP) negative. These thus decreasing the absorbable ammonia. Lactulose
occur in small and large groups especially abutting has been useful in improving the clinical syndrome
neurons in the cerebral gray matter, basal nuclei, of hepatic encephalopathy in horses.8,82,83 Oral antibi-
thalamus, pons and cerebellum, and are referred to as otics such as neomycin which kill gut bacteria that
Alzheimer type II astrocytes.91,92 This distinctive aid in splitting protein to ammonia may also be of use
finding may be accompanied by generalized porosity in treating the encephalopathy.8,83
to the neuropil and capillary proliferation. Overt
neuronal degeneration is not a feature, although neu-
In horses at least, enteral lactulose therapy does appear to
ronal dropout appears to occur.60,93,94
lessen the signs seen with hepatoencephalopathy;
The pathophysiology of hepatic encephalopathy
whether enteral antibiotics have any effect is less certain.
and associated Alzheimer type-­II astrocytosis has
long been attributed to hyperammonemia, and the
historical contributions of many brilliant physiolo- Tetracyclines can be tried if Clostridium piliforme
gists, philosophers and clinicians to this understand- (Bacillus piliformis) hepatitis is suspected, and anti-
ing make fascinating reading.95–98 In liver failure, biotic treatment of suppurative cholangiohepatitis
muscle, kidney, and the rumen become important cases for 2–18 weeks has resulted in cures.58 If neuro-
means of detoxifying intestinal ammonia, and astro- logic signs deteriorate rapidly and it is decided to
cytes play a role in uptaking ammonia and forming continue therapy, then oral lactulose and nonab-
glutamine, a strong osmolar molecule, to help pro- sorbable antibiotics to reduce the ammonia load
tect neurons from ammonia toxicity. Astrocytes also from the bowel, and mannitol to attempt to stop pro-
play a role in taking up and metabolizing other gressive cytotoxic cerebral edema, are worth trying
proinflammatory and neuromodulating mole- initially. With intensive support, horses with acute
cules.91,99–100 Indeed, increasing CSF glutamine con- (viral) hepatic necrosis have survived. Some horses
tent may indirectly reflect the severity of neuronal with chronic/active, nonsuppurative hepatitis of
toxicity in liver failure. Ultimately, overpowering unknown origin and mild signs of encephalopathy
astrocytic protection of neurons may well be the have recovered with nursing care. With pyrrolizidine-­
major determinant of neuronal dysfunction in clini- containing plant toxicity, by the time significant
cal hepatic encephalopathy.82,93,94 encephalopathy ensues, the liver lesions are perma-
Treatment of advanced hepatic encephalopathy is nent, and regeneration is essentially impossible.
fraught with difficulties and should target the pre- Persistent hyperammonemia post-­weaning may be
cipitating events.83,96 In most cases of profound liver the hallmark of a genetic defect in nitrogen meta-
function loss in horses, the prognosis is grave. Quite bolic pathways.76
reasonably, the most useful noninvasive assessment
of the prognosis likely is the severity of clinical signs,
Hyperammonemia
and not the results of ancillary aids. Removal of any
hepatotoxins from the environment and protection Inadvertent exposure of livestock to excessive, highly
from direct sunlight are appropriate treatment meas- nitrogenous feedstuffs or fertilizer (see Chapter 34)
ures to take. A high carbohydrate diet (with due rec- can result in acute ammonia toxicosis with very
ognition of predisposition to laminitis) and frantic behavior, seizures, coma, and death “bonk-
crystalloid-­and glucose-­ containing fluids IV are ers.”101–105 Additionally, clinical syndromes indistin-
usually indicated. Marked protein restriction is now guishable from hepatic encephalopathy in horses do
not a regarded priority.82,83,94 Glucocorticosteroid occur in the absence of evidence of liver fail-
drugs are not indicated. ure,102,106,107 usually in conjunction with other gastro-
Lactulose (beta-­galactosidofructose) is a nonab- intestinal disorders often presenting abdominal pain
sorbable disaccharide that is metabolized by gut and soft feces.2,108,109 An elevated blood ammonia
microbiota to yield short chain organic acids. The concentration in the absence of clinicopathologic
resultant lower pH appears to prevent the growth of and histologic evidence of prominent liver disease is
NH3-­producing bacteria and even to promote the the hallmark of this syndrome (Figure 36.2). Likely,
growth of beneficial microorganisms. The acidic various factors contribute to the overproduction of
environment also results in the change of ammonia nitrogenous intermediary compounds, including
(NH3) to ammonium (NH4+), which is not absorbed, ammonia, to overcome the hepatic, muscle, renal,
508 Large animal neurology

(A) (B)

Figure 36.2 Hyperammonemia can accompany other disorders especially colitis in horses. This aged mare (A) had a per-­acute onset of inappetence and
intestinal stasis. Soft feces were passed as the mare was being treated for suspected colitis. Within a few hours of observation and empirical therapy, the
horse began circling and head pressing, became centrally blind, and showed mild generalized seizures. There was only partial response to intragastric
lactulose and systemic anticonvulsant therapy. The blood ammonia content was ~2,000 mmol/L (control sample at same time was ~200 mmol/L). At
postmortem examination, there was per-­acute colitis with no evidence of liver disease. Similarly, the other gelding (B) suffered an unknown acute meta-
bolic derangement that included hyperammonemia without evidence of liver failure and demonstrated bizarre behavior including head pressing and
adopting unusual postures for prolonged periods. With empirical supportive care, the patient survived. Unfortunately equine Coronavirus testing was not
undertaken in either case.

and astrocytic biochemical detoxification processes Uremic encephalopathy

and resulting in a metabolic encephalopathy.1,101,110
Enteropathies of various types have been associated Terminal renal disease often causes signs of confu-
with hyperammonemia in affected horses,101,107,109 sion and seizures,1 and a spongiform encephalopathy
and isolation of a heavy culture of Clostridium sor- may be present.92,115 Evidence of acute and chronic
delli, a strong urease-­ producing organism, from renal failure in most large animal species has been
feces of an affected horse implicates colonic bacterial associated with onset of signs of diffuse CNS involve-
overgrowth as being one likely cause of the disease.108 ment including ataxia and weakness, aggressive,
More recently, equine coronavirus has been associ- compulsive and frantic behavior, central blindness,
ated with the syndrome110–112 wherein viral enteritis and seizure activity attributable to uremic encepha-
may allow increased passage of ammonia into non- lopathy.116–119 The hemolytic–uremic syndrome asso-
portal vessels and produce an accompanying sys- ciated with Gram-­negative sepsis may also result in
temic inflammatory response to the infection. Both encephalopathy.120 In affected horses, proliferation of
these processes may play a role in promoting the Alzheimer type II astrocytes is a prominent fea-
neurologic impact of ammonia, and possibly other ture116,118 affecting gray matter and, less prominently,
gut origin toxins, in producing the clinical white matter in the cerebrocortex and brainstem. In
­syndrome.102,107,110,111 It is prudent to recall that ruminants, astrocytosis is not a feature and no
organisms locating elsewhere such as in the urinary n­eurohistologic lesions may be observed, or diffuse
tract that produce ammonia may well be the source myelin vacuolation in white matter can be promi-
of unexplained (hyperammonemic) encephalopathy nent.117,119 Along with toxic azotemia, increases in
as described in humans and small animals113,114 organic acids, amino acid imbalances, electrolyte
A survival rate of 40% has been reported in this changes, and altered neurotransmitter function all
syndrome with blood ammonia concentrations may play a role in overcoming the detoxifying capa-
on admission negatively associated with survival bilities of muscle, liver, and astrocytes to enable the
(p = 0.021) following empirical therapy, including the toxic encephalopathy to occur.1 Altered calcium and
use of lactulose in a few cases.110 Histologic evidence phosphorus fluxes, likely secondary to renal disease-­
of encephalopathy with Alzheimer type-­II astrocyto- associated parathyroid dysfunction, may contribute
sis results.91,110 to clinical signs of uremic encephalopathy in dog and
 Metabolic diseases 509

human; this is probably not the case in large rapidly to flaccid muscles and recumbency with
­animals.118,119 The prognosis for large animals having hypocalcemia, it procedes to hypertonicity and sei-
prominent neurologic signs accompanying renal fail- zures with hypomagnesemia.
ure must be regarded as grave. Tremor and weakness, ruminal atony, and a weak,
slow, arrhythmic heartbeat are characteristically pre-
Hypocalcemia (milk fever) sent in cows with hypocalcemic milk fever. Affected
animals are generally inactive, have sluggish pupils
and hypomagnesemia (grass staggers) and generalized hyporeflexia, and become severely
These metabolic derangements occur in periparturi- paretic and unable to rise. Frequently, they adopt a
ent cows, ewes, sows, and occasionally in mares, both recumbent posture with head and neck turned toward
singularly and concurrently. Occurring as hypocalce- the flank. In contrast, adult horses and foals, some-
mic milk fever and hypomagnesemic grass staggers, times sheep, and rarely cattle, demonstrate seizures
these disorders are of major concern in the manage- with hypocalcemia.127,128 Often the hypocalcemic ani-
ment of milk and meat production herds and readers mal has recently given birth and is lactating, but
are referred to current texts on production animal hypocalcemia also occurs before parturition, particu-
management and diseases for full coverage of these larly in stressed ewes and mares. Horses with low
diseases.121 Overt neurologic syndromes due to only serum ionized calcium concentration show muscle
hypomagnesemia are rare in animals other than tremor and stiffness, a staggering, high-­stepping gait,
ruminants.122 Thus, general neurologic aspects of trismus, seizures, and synchronous diaphragmatic
these syndromes are covered here with an emphasis flutter (SDF). The latter is referred to as thumps, and
on hypocalcemia. presumably arises from spread of cardiac potentials to
Hypocalcemia and hypomagnesemia occur in preg- the adjacent phrenic nerve(s) resulting in extra dia-
nant or lactating animals when subjected to nutri- phragmatic contractions, which may be unilateral or
tional, management, or weather-­ related stress. bilateral. Synchronous diaphragmatic flutter is associ-
Transportation and starvation play a role in hypocal- ated most often with hypocalcemia and with
cemic transit tetany in feedlot animals123 and pregnant hypochloremic metabolic alkalosis. In the absence of
mares.124–126 Animals with high calcium diets prepar- the almost pathognomonic sign of SDF, signs of
tum are predisposed to hypocalcemia that more often hypocalcemia in horses closely resemble tetanus but
is seen in ewes 6 weeks prepartum until lambing, usu- there is not usually eyeball retraction and spasm with
ally associated with some stress factors. Decreased cal- protrusion of the nictitating membrane in response to
cium ions at the axonal membrane initially allow for tapping the head—­a sign so typical of tetanus due to
unstable axonal firing resulting in tetany, as seen espe- Clostridium tetani intoxication. Interestingly, promi-
cially in horses, but ultimately there are insufficient nent hypocalcemia and hypomagnesemia induced in
calcium ions at neuromuscular synaptic membranes adult horses using the chelator EDTA did not result in
to trigger acetylcholine release, causing degrees of clinical signs but did induce considerable spontane-
paresis. Adult dairy cattle appear to be more suscep- ous electrical activity from myomembranes on elec-
tible to the hypocalcemic neuromuscular blockade tromyographic examination.129,130
with associated hypotonia, and this masks the tetany Total and ionized serum calcium and magnesium
seen only in the early course of disease. Younger cattle, concentrations should be determined and compared
and possibly Piedmontese calves, are unusually prone to standard ranges for the laboratory, although there
to hypocalcemic seizures, with or without concur- is not a very strong (inverse) relationship between
rent hypomagnesemia.127 In conjunction with other serum values and the severity of clinical signs, espe-
(enteric) disorders, suckling hypocalcemic foals also cially for magnesium. Calcium gluconate (or boro-
demonstrate hypertonicity, tetany, and seizures.128 gluconate), with or without Mg+2, PO4-­3 and glucose,
Hypomagnesemic grass tetany usually occurs in is given slowly IV to effect with continual monitoring
postpartum cattle on lush pastures, but also in of cardiac function. Recurrences can be prevented
bucket-­fed calves. With either metabolic perturba- with further cations given subcutaneously and as
tion, there is a sudden onset of tetany or tremor asso- prophylactic oral therapy. There most often is a good
ciated with muscle spasms and elevated heart rate. response to calcium therapy given in the early phase
However, in ruminants, but whereas this proceeds of the disorder in dairy cattle, and indeed the outlook
510 Large animal neurology

for recovery of recumbent cows is better if the reason only few cases arise due to the production-­limiting
for recumbency is hypocalcemia compared to other effect of the conditions.141
causes of recumbency.131 Finally, equine familial isolated hypoparathyroidism
Balancing input of Ca+2 with output should be the resulting from a genetic variant in affected
long-­term goal. However, a diet high in Ca+2 prior to Thoroughbred foals results in persistent, variable
calving predisposes the animal to milk fever because hypocalcemic tetany and seizures and is invariably
of the state of pseudohypoparathyroidism that is fatal after becoming first evident at a few days to a
induced. A relatively low calcium–high magnesium few weeks of age (see Chapter 31).128,142
intake immediately prior to parturition, increasing
calcium and magnesium intake during lactation, and Ketosis (with hypoglycemia) in ruminants
avoidance of stress in pre-­and postparturient cows
are factors that can reduce the incidence of clinical Neurologic signs can accompany the general malaise
and subclinical hypocalcemia.132 Altering the dietary and anorexia associated with hypoglycemia and
cation–anion differences (DCAD: [(Na+ + K+) -­ (Cl-­+ S-­2)] excess circulating ketone bodies that occur in rumi-
mEq/100 g of dry matter) to favor an anionic diet can nants around the time of parturition and during lacta-
reduce the incidence of hypocalcemia in at least mul- tion. This is most common in high-­producing dairy
tiparous dairy cows.133 cows at peak lactation time and does and ewes heavily
Turning attention to hypomagnesemia or grass pregnant with multiple offspring.143–145 The syndrome
staggers, a hyper-­alert attitude, high head carriage, in cows is thus referred to as lactational ketosis, and in
tetanic spasms, a pounding heart, and hyperespon- small ruminants it is referred to as pregnancy ketosis,
siveness can usually be expected in cattle, sheep, and also called pregnancy toxemia, twin lamb disease and
captive ruminants.134–136 Whole body tremor, bellow- kidding or lambing paralysis. Ketosis affects over-
ing, and running aggressively or blindly also do occur weight animals using the energy stores in late preg-
in cattle with grass staggers. Eventually, affected ani- nancy and early lactation, or animals receiving low
mals fall on their sides in convulsions. Hypomagnesemic levels of nutrition whose requirements for pregnancy
grass tetany is seen in grazing cattle on lush pasture at and lactation are increasing. It may occur secondarily
peak lactation somewhere around 1–3 months post- to other disease, such as a displaced abomasum. The
partum and may occur more in the Hereford breed. precise relationship between the various metabolic
Transit tetany in horses and lambs is perhaps mostly derangements occurring with ketosis in ruminants
related to low blood calcium rather than just low mag- and the specific early clinical neurologic signs is
nesium concentrations,137 although pure hypomagne- unclear and probably multifactorial. At least in multi-
semia in foals and calves may be associated with tetany, ple pregnancy ewes suffering from occult or from
seizures, and death.138,139 clinical hypoglycemia and ketosis, there can be
Again, total and ionized serum calcium and mag- degrees of laminar cerebrocortical necrosis and
nesium concentrations should be determined and accompanying poor feed intake, making the clinical
compared to standard ranges for the laboratory. and pathological differentiation of ketosis and
Determination of cerebrospinal fluid and aqueous encephalopathy cloudy to say the least. The unborn
humor magnesium concentration may be useful in and newborn lambs also may bear the brunt of such
the diagnosis of grass tetany in cattle, even up to 12 h metabolic (and neuropathologic) derangements.146,147
postmortem.140 Hypomagnesemic animals can die Other periparturient disorders often accompany
suddenly because of the excitement of therapy. Other the syndrome in cattle and may well contribute to its
cases often respond rapidly. Relapses can be pre- development. Diffuse nervous signs with muscle
vented with appropriate dietary and management weakness, tremor, and head pressing, compulsive
changes and magnesium supplementation such as 50 g licking of self or objects and other signs of dementia,
calcined magnesite per cow daily. Use of intrarumi- is one syndrome seen with lactational ketosis.
nal magnesium alloy bullets appears to be a very Wandering, ataxia, depraved appetite, blindness, and
good means of supplementation of magnesium for hyperesthesia may also be present. More frequent
periods up to 1 month. syndromes include anorexia, a drop in milk produc-
For both these conditions, management practices tion and wasting. Pregnancy ketosis in ewes and does
during the prepartum period that help prevent these causes a state of torpor, but behavioral signs includ-
diseases should be implemented in herds where even ing wandering, lip twitching and opisthotonus or
 Metabolic diseases 511

stargazing, as well as blindness and convulsions with resulting modification of the risk of bloat and
occur. Hypocalcemia can accompany ketosis in lactic acidosis. A meta-­analysis reporting 16 studies
sheep, and the signs tend to be the same for the com- of monensin use in lactating cattle showed an overall
bined disorder.143,148 decrease in the risk of ketosis in treated cattle.153 In an
A functional metabolic encephalopathy with no attempt to circumvent this disease, the use of a gluco-
consistent neuropathologic substrate occurs early in corticosteroid (isofluprednone acetate) in the first
the disease. With a more prolonged course over sev- week of lactation, with or without insulin, resulted in
eral days and with severe neurologic signs, brain a higher frequency of subclinical ketosis.154
lesions consistent with hypoglycemic (or at least neu- Finally, as with probably all the metabolic disor-
roglycopenic) encephalopathy are readily evident.149 ders, there is evidence of genetic variability in sus-
Findings of concomitant low glucose and high beta ceptibility to ketosis in cattle, making genetic
hydroxybutyrate content in CSF and aqueous humor selection a possible means of reducing its preva-
to accompany the hypoglycemia corroborated this lence.155,156, 157
conclusion, at least in sheep.150,151 The lesions consist
of diffuse, sometimes superficial and laminar, cere-
Hypoglycemia
brocortical neuronal necrosis, astrocytosis, and cer-
ebellar Purkinje cell necrosis. Cerebral and cerebellar Hypoglycemia is common in neonatal large animals
white matter vacuolation is less commonly apparent. that are suffering starvation, cold exposure, and
Intriguingly, a very similar laminar cortical necrosis other, often infectious, diseases.158 This does not
has been identified in lambs from ewes carrying mul- always lead to overt neurologic signs such as seizures
tiple fetuses that have been nonviable at birth, shown until the magnitude of hypoglycemia is prominent.
inactivity, tremor and ataxia, or survived with resid- Liver failure due to many causes in neonatal foals will
ual cerebellar signs. There is very good evidence that however result in hypoglycemia as one of the factors
this syndrome is the result of an in utero neuroglyco- that causes seizures in this situation, direct bilirubin
penic encephalopathy associated with pregnancy toxicity (kernicterus) probably being far less com-
ketosis in the dams.146 mon.159 Adult horses at least seem to have a higher
A smell of ketones on the breath and the urine of seizure threshold with respect to hypoglycemia than
affected cattle are likely to be detected. Urine and foals and initially tend to show nonresponsiveness
milk will give a positive test for ketones. Identifying and weakness rather than seizures.
elevated serum beta hydroxybutyrate concentrations Cases of persistent and of intermittent hypoglyce-
is a very good means of confirming the disease. mia resulting in weakness, somnolence, collapse, and
Cattle should receive dextrose IV and oral propyl- seizure activity have been associated with various
ene glycol. Glucocorticosteroids may be effective neoplasms in large animals related to production by
because they reduce milk yield but are generally not the tumors of insulin and insulin-­like factors, and to
recommended, at least in cattle.141 Sheep are best paraneoplastic processes.160–166 Signs most often asso-
treated with dextrose and alkalinizing fluids IV and ciated with hypoglycemia in adult horses are obtun-
by force feeding with grain and propylene glycol. dation (100%), seizures (42%) and disorientation
Insulin has been used where economics allow.152 (22%), and it has been determined that marked sup-
Induced parturition or caesarean section may be a pression of consciousness and seizures are most often
viable option to save both dam and offspring. The seen with blood glucose <2.3 mmol/L (<42 mg/dL)167
presence of obesity and fatty liver almost certainly and usually between 0.66 and 1.12 mmol/L (12–
reduces the possibility of recovery. 20 mg/dL). Other causes of hypoglycemia in adult
Matching nutrient intake with requirements horses associated with neurologic signs i­ncluding
should be aimed for during the periparturient seizures are portal thrombosis and malicious insulin
period.141 Reducing the feeding of silage which is administration.168,169
ketogenic and maintaining an adequate roughage Diagnostic therapy with IV dextrose solution
content to the diet during pregnancy can be helpful results in a rapid cessation of seizure activity and
with cattle. The ionophore monensin results in a shift muscle and nerve hyperexcitability within minutes.
in rumen microflora and has been shown to improve Certainly, unless any associated cause can be removed
the efficiency of energy and nitrogen metabolism the outlook for relapses is high.
512 Large animal neurology

Hyponatremia cases. Serum [K+] values are 1.5–2.5 mmol/L. Some

cattle survive with aggressive electrolyte replacement
Foals and calves with severe renal disease, uroperitoneum, and treatment directed at accompanying diseases.
or iatrogenic water overload rarely can lower serum Extreme caution must therefore be taken in adminis-
sodium content rapidly enough that neurologic signs tering calcium-­ rich fluids without potassium to
occur. Patients, especially young, with fluid and elec- ‘downer cows’ because of the possibility of exacer-
trolyte loss through diarrhea that replenish with plain bating hypokalemia by promotion of urinary loss of
water become hyponatremic (Na+ ~ 90–110 mmol/L) potassium accompanying calcium administration.
quite quickly. Central blindness, tremor, hyperes-
thesia, hypermetria, and seizures may begin abruptly
in a healthy foal, or in one that has evidence of Precise identification of the metabolic derangements
systemic illness.170 Overzealous administration of resulting in profound signs of forebrain disease in a
water enemas has been part of the history in some postparturient, high producing, over conditioned dairy
affected neonatal foals. Hyponatremia in foals is cow, and in a post foaling mare with marked enteric
one pathophysiologic mechanism that mimics disease can be problematic at best, and immediate
benign epilepsy of foals. therapy often needs to be empirical.
Azotemia and particularly hyponatremia
(<110 mmol/L) and hypochloremia (<90 mmol/L)
are present with urinary system disorders, and Anesthetic-­related hypoxia and anoxia
degrees of hyperkalemia (>6 mmol/L) and other If an animal survives an episode of an ‘anesthetic
electrolyte derangements occur. Accurate evaluation accident’ or of cardiac or respiratory failure under
of any renal disease is necessary. Slow correction of anesthesia, there may be residual signs of blindness
the low serum sodium and low serum osmolality is with normally responsive pupils and degrees of som-
advisable with normal saline given IV. Low-­ dose nolence and behavioral changes. Signs result from
furosemide with saline administration may be indi- neuronal necrosis, particularly in the cerebral cortex,
cated in severe cases of renal failure. Anticonvulsant hippocampus, thalamus, caudal colliculi, and cere-
therapy should be instituted if seizures are repeated. bellar Purkinje cells.176,177 A similar pattern of involve-
If iatrogenic or diarrhea-­associated water overload ment occurs in humans dying of hypoxic brain
has occurred the outlook is good, but patients with damage.178 The clinical course and histologic findings
severe renal disease have a guarded prognosis. in several cases of neonatal encephalopathy also
strongly resemble diffuse ischemia–hypoxia.
Hypernatremia In this disease, DMSO therapy is possibly primarily
indicated (1 g/kg, 10% in D5W, slowly IV) as a free
See Sodium salt poisoning and water intoxication radical scavenging compound because there is a global
(Chapter 34). hypoxia with oxygen-­derived free radicals produced
during reperfusion and reoxygenation causing sec-
ondary tissue damage.179 Short-­and long-­term Mg++
Hypokalemic syndrome in cattle
treatment has been purported to reduce post-­hypoxic
Hypokalemia inducing profound skeletal weakness, brain damage.180–183 Ideally, such treatment should be
sometimes associated with hypocalcemia as well as started at the time of reperfusion. Supportive care and
decubital myopathy, is seen in dairy cows with anticonvulsant therapy are indicated as needed.
hypokalemia. It can follow protracted diseases such The initial quality of survival can be assessed on
as ketosis, whether being treated with or without recovery from anesthesia. Even with dense periods of
g­
lucocorticosteroids for associated ketosis.171–175 semicoma, treatment should be continued for several
Repeated administration of isofluprednone acetate, a days, monitoring for any improvement in neural
corticosteroid with mineralocorticoid effects, is a function; visual recovery can occur within several
particular risk factor for hypokalemia and recum- days. Considering remarkable long-­term recoveries
bency.172 A distinctively weak, hypotonic neck seen in a few calves, foals, and adult horses, if an
accompanies the profound systemic weakness or owner can accept such a variably somnolent animal,
recumbency. Atrial fibrillation and hypophos- it might be worth persisting with nursing care for
phatemia may contribute to the weakness in some several weeks to months before euthanasia is selected.
 Metabolic diseases 513

Cardiocirculatory collapse—­shock 9 Aleman M, Nieto JE, Carr EA and Carlson GP.

Serum hepatitis associated with commercial
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14 Tomlinson JE, Van de Walle GR and Divers TJ.
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 37
Neoplasms and other tumors

Disease Site Page Peripheral nerves 526

Diagnostic and therapeutic aspects 526
Brain523
References527
Neurocranium and cranial nerves 524
Spinal cord 526

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
522 Large animal neurology

It behooves clinicians and pathologists alike to refer to tissue in abnormal location) as tumor types affecting
the new WHO Histologic Classification of Tumors of the nervous system1,4–13
the Nervous System1 when defining the exact tumor Systemic neoplasia in large animals is not as common
types being considered and when discussing associ- as in small animals and in humans. Of those tumors
ated biologic behavior of them in order to more accu- that do occur with some frequency, the lymphoid
rately define their general frequency, behavior, and tumors, squamous cell carcinomas, and melanomas are
response to any therapy undertaken.2,3 As there are the more common. In large animals, only rarely do
lymphoid, hematopoietic, and melanin-­ containing aggressive and malignant tumors invade or spread to
tissues associated at least with meningeal tissues, it the CNS, and primary CNS neoplasms are extremely
may well be appropriate to consider tumors of these infrequent.6,14–20 Notwithstanding this, the range of pre-
cell lines as primary tumors affecting the nervous sys- senting clinical syndromes for tumors affecting nerv-
tem. Of note is the inclusion of progressive vascular ous tissues of large animals is, just as in other species,
malformation, neural cyst, hamartoma (abnormal tis- essentially endless, particularly depending on tumor type
sue in a normal location), and choristoma (normal and where the nervous system is affected (Figure 37.1).

(A) (B)

(C) (D)

Figure 37.1 Tumors involving the nervous system are not as common as for small animals and humans. Their biology and clinical expression are how-
ever similar. With slowly growing tumors of the forebrain such as this cholesterinic granuloma in an aged horse (A), signs may be very limited to changes
in alertness and slight gait abnormality and can wax and wane over minutes to weeks. Notwithstanding, epilepsy may be the primary clinical complaint.
Neoplasms of CNS neural tissues (primary CNS neoplasms) are quite rare, though most large animal species do occasionally have a congenital primitive
neoplasm of primordial germinal cellular layers such as this neuroblastoma in a young calf (B). The neoplastic cells have replaced much of the cerebellum
(stars) causing progressive cerebellar signs. Interestingly, the neoplastic tissue has formed a midline cleft (between stars) suggesting it arose bilaterally
from primordial cells. Non-­neural tumors certainly can compress (C) and occasionally invade the CNS in large animals. This lymphoid neoplasm (square)
in the foramen magnum of an adult dairy cow is adjacent to and probably compressing the cerebellum, but no clinical signs were evident suggesting
brainstem, cerebellar, or spinal involvement. Finally, peripheral nerves can be entangled by neoplasms such as aggressive sarcomas, and nerve sheath
tumors do occur with some regularity in cattle as well as occasionally in other large animal species. If sensory nerves are involved, then evidence of pain
may be a major presenting sign. Aggressive nerve sheath tumors (D) may spread to involve the spinal cord such as the tumor of the left T8 nerve root
(circle) that intruded into the subarachnoid space (star) to compress the T8 spinal segment in a bull.
 Neoplasms and other tumors 523

There is extensive literature available, especially Brain

­documenting individual cases.
A few comments regarding this spectrum of Intracranial neoplasms are rare in large animals
signs resulting from CNS and PNS tumors is in (Figure 37.2). The most frequently occurring equine
order. Secondary metabolic effects of systemic neo- brain tumor is pituitary adenoma that usually causes
plasia include hypercalcemia and hypoglycemia pituitary pars intermedia dysfunction and hyper-
and can result in waxing and waning prosence- adrenocorticism without classical neurologic signs
phalic disorders including epilepsy.21–25 Perhaps resulting; relevant other literature should be
surprisingly, space-­occupying tumors in both the consulted.42,57-­60 Secondary myopathy and selective
cranium and vertebral column can result in sudden neuropathy may be expected to occur with long-­
onset of severe signs after a considerable size of standing cases of hyperadrenocorticism in aged
tumor mass has been achieved26–29 and subsequent horses as occurs in dogs.61 Rarely, pituitary neoplasia
signs of forebrain disease may wax and wane dra- and abscessation induces other hypothalamic-­related
matically.21,30–33 These characteristics are likely due syndromes,42,58 blindness and fluctuating somno-
to variable supply and sudden decompensation of lence,27,60,61,62,63,64,65 and occasionally ill-­defined syn-
compromised blood flow to adjacent nervous tissue dromes of paroxysmal motor events and collapse that
parenchyma. Focal tumors involving the CNS can are assumed to be seizures have been seen to occur
result in signs by compression or by invasion, with aged horses having hyperadrenocorticism.
destruction, and replacement of tissue. With excep- Primary neuroepithelial and meningeal neoplasia
tion of neurofibromas and neurofibrosarcomas that does occur,6,14,20,21,38,41,46,58,66–84 but these types of
invade and replace peripheral nerve fibers, other tumors are far less frequent than locally invasive
tumors only affect the PNS by entrapping the neu- extraneural neoplasms.6,15,16,20,41,85–100
ral structure against another, usually firm, struc- Hamartomas and large lateral ventricle choroid
ture such as bone or collagenous band.34 Otherwise, plexus cholesterinic granulomata have been associ-
any neural structure adjacent to a growing tumor ated with epilepsy and with intermittent circling,
simply moves away from the mass until the mass blindness, and inactivity.31–33,101-­105 Xanthochromic CSF
gets extremely large. Thus, cranial and spinal nerve can be expected to occur with cholesterinic granulo-
roots passing through neurocranial and interver- mata, but analysis should reveal the presence of choles-
tebral foramina are more often affected by tumors terol and its esters rather than hemoglobin breakdown
at those sites than at more distal sites.35 Finally, products that are expected with yellow discoloration
although rare, the embryonal tumors, especially of CSF following prominent hemorrhage within the
medulloblastoma, involving the caudal fossa struc- neuraxis. Possibly because of the slow growth of cho-
tures, should be strongly considered in young lesterinic granuloma and the p ­ resence of associated
patients with relentlessly progressive, especially hydrocephalus, there can be quite a positive and
asymmetric, signs of cerebellar and medulla oblon- prolonged response to treating such patients with
gata involvement.36–39 glucocorticosteroid drugs. Under the umbrella of gli-
With a plethora of individual case reports and oneuronal hamartomas, a few cases of interesting
such a large number of tumor types under consid- neuroglial proliferations in young animals have been
eration, it is more pertinent in this context to con- regarded as forms of schwannosis wherein Schwann
sider tumors involving the nervous system of large cell proliferation in the CNS is a predominant and
animals under the general sites more commonly possibly major primary feature.106,107
involved and to relate some of their notable As with vascular accidents, vascular malforma-
features.6,15,17–19,26,38,40–44 tions and traumatic brain injury, some neoplasms
Undoubtedly, the application of newer imaging can result in repetitive bleeding, and the subarach-
techniques such as MR and CT has seen a dramatic noid hemosiderin may result in diffuse subpial, mar-
improvement in the accuracy of spinal and especially ginal siderosis and diffuse neurologic signs.73,108-­111
brain disorders, particularly head tumor diagnoses, Lymphosarcoma and medulloblastoma in cattle
and thus has allowed focused therapy to make for and calves, respectively, are two specific neoplasms
better outcomes in human and small animal neurol- that may result in purely cerebellar syndro
ogy.45 Such progress is now being seen in large animal mes.14,20,36,38,39,72,100 Numerous case reports relate various
neurology and will continue.38,46–56 ­neoplasms with various vestibular syndromes. These
524 Large animal neurology

(B)

Figure 37.2 Although primary brain tumors are

exceedingly rare in large domestic animals, when
presented with an aging patient showing a pro-
gressive syndrome related to one site of the CNS,
such a diagnosis must be considered. This pony
was evaluated by colleagues at Glasgow
University (Mike Hewetson and Sandy Love) to
have variable somnolence and postural limb defi-
cits as shown (A). A CT brain scan (B) confirmed
a solitary mass in the forebrain (blue ovoid) that
was confirmed as a primary frontal lobe glial
tumor (blue ovoid) on postmortem examination
(A) (C) (C).

have included primary neuroectodermal intracranial contagious and destructive neoplasm of sheep and of
tumors,112,113 intracranial peripheral nerve sheath goats, caused by the retroviruses enzootic nasal tumor
tumor,114,115 and primary and secondary intracranial virus 1 and 2, respectively, occasionally invades intrac-
tumors (Figure 37.3) affecting the vestibulocochlear ranially or behind the eye of small ruminants to cause
nerve and pontomedullary region of the brain.86,87 various neurologic syndromes.120,121
In addition to paraneoplastic events such as hyper- Primary acoustic nerve tumors have been reported
calcemia, further clinical signs may be expected with in cattle,122 but no cases of bilateral involvement and
any pathologic processes accompanying tumors subsequent deafness have been reported in large
affecting neural tissues including leptomeningeal animals.
carcinomatosis, subependymal ependymoglial pro- Exophthalmos almost always occurs with retrob-
liferation, invasive/destructive ethmoid hematomas, ulbar neoplasia and can be accompanied by strabis-
and possibly parenchymal malacia.76,116,117 mus, with protrusion of the supraorbital fossa
indicating the presence of extra peribulbar tissue.
Lymphosarcoma is the most frequently occurring
Neurocranium and cranial nerves tumor type at this site in cattle,123,124 but various carci-
Osseous and soft tissue tumors involving the neuro- nomas also have been identified with orbital neopla-
cranium and the face can impinge upon and invade sia in horses and ruminants.125–130 Retrobulbar
the brain and cranial nerves. These include osseous neoplasia may cause a dilated pupil because of the
tumors and melanocytic and lymphoid sarcomas as involvement of the oculomotor nerve or ciliary gan-
well as aggressive paranasal carcinomas that selec- glion. Often, degrees of blindness occur due to optic
tively compress cranial nerves as they travel in their nerve involvement.65,124 In addition, variable involve-
intracranial course adjacent to the bones of the cranium ment of branches of the facial nerve makes for an
and as they exit through their respective foramina.118,119 interesting spectrum of clinical syndromes of visual,
Enzootic nasal adenocarcinoma, a transmissible pupillary, and facial motor changes.
 Neoplasms and other tumors 525

(A) (B)

(C)

(D) (E)

Figure 37.3 Melanoma, as seen in this 21-­year-­old gray Arabian stallion, is an example of a locally invasive, extraneural neoplasm that has impinged
upon the cerebellum, the brainstem and several cranial nerves within the caudal fossa of the neurocranium. The horse was examined because of moderate
weight loss over the previous month and an abnormal gait that developed 2 days previously. There was hypermetria of the left thoracic limb (A), over-
reaching of the left pelvic limb (A), and ataxia (A and B) and weakness in all limbs. When blindfolded (C), the horse rotated its head and turned, leaned
and rolled to the right. By the next morning, the horse was dramatically worse. He was moderately obtunded and had developed right sided facial hyp-
algesia and weakness and fasciculations of the tongue (D). The melanoma (E, arrow) had almost filled the cerebellomedullary cistern encroaching onto
the caudal cerebellum and entrapping adjacent cranial nerves.
526 Large animal neurology

Spinal cord have been seen to encompass and compress periph-

eral nerves in cattle and horses,173 and plasmacyto-
Neoplastic spinal cord disease in large animals is mas can invade peripheral and central nervous
extremely rare except for epidural lymphosarcoma tissue.95
that is infrequent in dairy cattle and rare in horses Benign and malignant peripheral nerve sheath
and goats.28,131–141 With this neoplasm, there is often tumors are well documented in large animals and
an acute onset of paraparesis or recumbency and, in particularly cattle to cause a multitude of syndromes
cattle, usually other evidence of bovine leukosis in dependent on the neural structures involved.174–179
the herd. The meninges and epidural space may be In at least the Danish Holstein breed of cattle, there
regarded as a primary site for the disease43 because may well be a genetic basis to forming peripheral
the former contain histologic aggregates of lymphoid nerve sheath tumors180 and consideration of a viral
nodules. Epidural lymphoblastic calls have been acci- cause was raised in conjunction with a study of
dentally sampled to confirm a diagnosis in a cow, and ­clustering of some cases of malignant schwannoma
the spinal fluid may indicate preneoplastic lymphoid in cattle.181
cells being present.138 Trauma, osteomyelitis, spondy- Of note here is that, in human oncology, benign
losis, and parasite migration are primary differential peripheral nerve sheath tumors (PNSTs) are divided
diagnoses for tumors involving the spinal cord into schwannoma (syn. neurilemmoma), neurofi-
whether the syndrome is fulminant or steadily pro- broma, perineurioma, and ganglioneuroma; how-
gressive. Other paravertebral soft tissue neoplasms, ever, in the veterinary literature, the terms peripheral
especially the sarcomas, also encroach into the verte- nerve sheath tumor, schwannoma, and neurofi-
bral canal29,142–155 and at the sacrocaudal site they can broma are often used interchangeably.182 Thus, many
entrap and compress the cauda equina resulting in a of these peripheral neural tumors including those
cauda equina syndrome along with various degrees recorded as benign and malignant schwanno-
of gait abnormalities.151 Cases of paraparesis, tetrapa- mas175,179,181–186 and even post-­amputational neuro-
resis, and ataxia do also occur because of malignant mas187,188 are probably best viewed as variants of
schwannomas, primitive neurectodermal tumors, peripheral nerve sheath tumors until a precise cate-
neuroblastomas, neurofibromas, undifferentiated gorization is agreed.
sarcomas, vascular hamartomas, and meningeal cysts
in large animals.106,149,153,156–159 Osseous vertebral neo-
plasia is rare.144,160 Peripheral neural tumors in horses must be distin-
guished histologically from equine sarcoids as the lat-
ter have such different biologic character from the
Peripheral nerves neural tumors187
Caudal cervical and cranial intrathoracic neoplasia
including carcinoma,15,18,129,161,162 melanoma,163,164
and lymphosarcoma161,165 have caused Horner syn-
drome in horses because of the involvement of the
Diagnostic and therapeutic aspects
cervicothoracic sympathetic ganglia and cervical As indicated above, appropriate use of targeted
sympathetic trunk. Occasionally, retrobulbar and ­imaging38,42,46–54,67,78,188–194 is the prerequisite for
periorbital neoplasms have been associated with diagnostic biopsy, any planned surgical debulking
Horner syndrome. or removal of tumor masses that allow a histologic
Entrapment of the vagus nerve by neoplastic classification of the tumor to be made,5,6,193 and for
­tissue can induce laryngeal paralysis and megae- any follow-­up appropriate radiation-­and chemo-
sophagus.148,166 Neurofibromas are not common but therapy to be planned.2,45,132,195 Some peripheral
do occur in horses and cattle. Localized pain neoplasms can be accessible to direct intralesional
in association with nerve or nerve root deficits chemotherapy.194
that can be multiple are recognized when sensory Reference to described surgical approaches to
nerves are affected.20,167–171 Bovine neurofibromas mass lesions in the equine brain56 and even use of
involving sympathetic neurons of the prevertebral, realistic surgical training models195,196 can be followed
paravertebral, and celiac ganglia can be a nonclini- where open biopsy and/or debulking is to be
cal postmortem finding.167,168,172 Lymphosarcomas considered.192
 Neoplasms and other tumors 527

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 38
Multifactorial and idiopathic disorders

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Multifactorial and idiopathic disorders 533

DiseasePage Embolic myelopathy 551

Equine neonatal encephalopathy 533 Miscellaneous degenerative myelopathies 552
Nervous form of coccidiosis 534 Equine grass sickness (equine
Brainstem neuronal chromatolysis in cattle dysautonomia) 552
(bovine tauopathy) 535 Recurrent laryngeal neuropathy 555
Postanesthetic cerebral necrosis in horses 535 Aortic–iliac–femoral thrombosis and ischemic
Sleep attacks—­adult 535 neuromyopathy 557
Cervical vertebral malformation– Idiopathic neuropathy with knuckling
malarticulation of horses 536 in horses 558
Cervical compressive myelopathy in young Acquired equine polyneuropathy of
Texel and Beltex sheep 547 Nordic horses 558
Congenital spinal stenosis of thoracolumbar Stiff-­horse syndrome 559
vertebrae in beef calves 548 Kangaroo gait in sheep 560
Selective poliomyelomalacia of sheep, goats, Flying scapulae in ruminants 561
and calves 548 Dropped hock syndrome in cattle 561
Postanesthetic myelopathy 548 Exertional rhabdomyolysis and capture
Vascular malformations 549 myopathy 562
Discospondylosis 549 Postanesthetic limb myoneuropathy 564
Neurofibrillary degeneration 551 References565

Equine neonatal encephalopathy for neonatal hypoxemia and CNS ischemia and hem-
Beginning in the 1960s, Peter Rossdale described a orrhage. Then, CNS hypoxia ensues, perhaps exacer-
syndrome of behavioral and other neurologic abnor- bated by reperfusion injury, triggering neuronal
malities in neonatal foals which was not caused by damage and death via depletion of high-­energy phos-
sepsis and named it neonatal maladjustment syn- phates, excitotoxicity, generation of oxygen and nitro-
drome (NMS).1,2 Because evidence of a unifying gen radicals, and release of proinflammatory cytokines.
pathogenesis or even a common pathology for this Synthesis and metabolism of neurosteroids occurs in
condition is still lacking, the term neonatal encepha- neurons and glial cells. Many are metabolites of pro-
lopathy (NE) is now preferred over older terms such gesterone classified broadly as pregnanes and andros-
as hypoxic–ischemic encephalopathy and perinatal tanes. Neurosteroids modulate neuronal and glial
asphyxia syndrome that implied a specific cause or function via selective actions at membrane ligand-­
pathology.3 Neonatal encephalopathy is a common gated ion channels. Specific metabolites either are
problem in newborn foals up to 1 week of age, par- inhibitory, acting at the GABAA receptor, or excitatory,
ticularly in Thoroughbred breeding regions, occur- via glutamate receptors. Inhibitory neurosteroids sup-
ring in up to 2% of live births.4 The same clinical press fetal activity until the immediate perinatal period
syndrome occurs rarely in calves.5 Two types of NE at which time the foal is prepared for birth by a sudden
are recognized:3 (i) after an uneventful pregnancy but tightly regulated transition to steroids of adrenal
and birth, the foal is initially normal with clinical (glucocorticoid) origin. Some evidence points to aber-
signs developing after the first few minutes to days of rant postnatal persistence of neurosteroid suppression
its life, and (ii) foals are born with, or quickly develop, of CNS function as the cause of the obtundation and
signs of NE after adverse gestational or perinatal hypotonia of NE.6,7 Inflammation and cytotoxicity
events associated with maternal, placental, or fetal associated with actions of excitotoxic neurosteroids
abnormalities. The latter type carries a relatively poor may predispose to seizures and other signs of enceph-
prognosis. alopathy. There is as of yet no unified theory of NE
The pathogenesis of NE likely involves various pathogenesis which accounts for the relative contribu-
combinations of CNS hypoxia and ischemia and disor- tions of CNS hypoxia and ischemia and of neuroster-
dered neurosteroid function.4 Abnormal foaling oid dysregulation in all cases of equine NE, although
events, exemplified by premature placental separation, multiple examples of potential “crosstalk” between the
dystocia, and caesarian section, are clear risk factors two pathways have been identified.3
534 Large animal neurology

There is sudden to insidious development of ­ iazepam in 5–10 mg IV doses or phenobarbital at

d
abnormal behavior including loss of udder-­seeking 5–10 mg/kg over 20 min IV and then 2.5–5.0 mg/kg,
behavior and of affinity for the dam, aimless wander- orally BID to TID (see Chapter 6). Corticosteroids
ing, excessive tongue wringing, compulsive chewing are not indicated because of the concern for sepsis.
and licking movements, and somnolence to hyperex- Antioxidants (DMSO, allopurinol, acetylcysteine,
citability. In addition, there may be ataxia and blind- vitamin E, and vitamin C), glutamate blockers
ness, head tilt, dysphagia, abnormal respiratory (MgSO4 and ketamine), respiratory stimulants
patterns, hyporeflexia, convulsions, and signs of mul- (doxapram and caffeine), antiedema drugs (mannitol
tiple organ dysfunction.3 and furosemide), and hyperbaric oxygen therapy are
Evidence of sepsis with or without meningitis, pri- given to foals with NE, so far without any published
mary respiratory disease, and metabolic derange- evidence for efficacy. It is anticipated that better
ments due to failure of other organs can be major understanding of neurosteroids in perinatal foals will
confounding factors, frequently making the specific prompt development of novel drug therapies to
diagnosis of uncomplicated NE difficult and even counteract their presumed adverse effects in some
incorrect.8,9 Hyperextension of fetlocks, thin supple NE cases. A thoracic squeeze technique has been
skin, and soft ears in some cases of NE indicate a pre- developed to simulate the neural response that awak-
mature or dysmature state that can be associated with ens normal neurologic function during transit of the
fading foal syndrome on days 2–4.10–12 Other than birth canal.29 This simple procedure has been suc-
these signs, physical characteristics of NE do not cessful, occasionally dramatically so, in some foals
exist. Diagnosis is based on history, clinical signs, and calves and is definitely worth trying in cases of
and exclusion of possible infectious and congenital NE in which the principal sign is profound obtunda-
causes.4,13–15 Analysis of CSF sometimes reveals mild tion without obvious other cause.30,31
leakage of blood cells and pigments with xanthochro-
mia. Ultrasonographic assessment of the atlantooc- Nervous form of coccidiosis
cipital space, brain MR, brainstem auditory potential
testing, and electroencephalography may each be Calves and young adult cattle, particularly feedlot
useful in tertiary care settings.16–19 calves, can be affected by neurologic signs because of
Combinations of parenchymal and meningeal serious coccidiosis.32 Similar syndromes have been
hemorrhages and edema, neuronal necrosis, and reported in lambs and kids.33 During an outbreak of
even malacia in the brain and spinal cord are consid- intestinal coccidiosis with severe diarrhea apparent
ered to be supportive of the diagnosis.20–22 However, in many calves, up to 30% of affected calves may
there is frequently poor correlation between the pres- demonstrate neurologic signs. Minimal ataxia and
ence, site and extent of such lesions and the presence tremor may occur, but most have seizures and many
and characteristics of the clinical syndrome.20–23 Foals will die. The disease often occurs in cold climates and
that have had numerous uncontrolled seizures or that during cold seasons. Ataxia, muscle tremor, blind-
survive status epilepticus can have neuronal necrosis ness, and hyperexcitability may accompany intermit-
in various areas of the brain, including the cerebral tent or continuous seizures. Typical generalized
cortex, hippocampus, dorsal thalamus, and basal seizures consist of an affected calf becoming recum-
nuclei,21 likely representing effects of severe seizures bent with opisthotonus, tonic–clonic movement,
and hypoxia.24 medial strabismus, and snapping of the eyelids.34–37
At least 80% of foals with NE will recover com- Seizures may be precipitated by stress and handling.
pletely with excellent nursing care and sepsis preven- Many aspects of the pathophysiology of the nervous
tion.10,12–15,25 Concurrent disease, persistent arterial form of coccidiosis have been studied and dis-
hypotension, high plasma calcium concentration, cussed.35,36 A heat-­labile neurotoxin has been identi-
and low activity of plasma alkaline phosphatase were fied in the serum of affected calves, but not in the
factors associated with nonsurvival in a retrospective serum of calves with only intestinal signs of coccidi-
study of 94 foals with NE.26 Sepsis is common in osis or in the serum of control calves.38 Serum from
NE foals so that broad-­ spectrum antibiotics are affected calves caused seizures in mice. Neurotoxicity
always indicated, and colostrum or IV plasma is was found in fractions corresponding to >300 kDa
given as necessary.8,10,13,14,27,28 Seizures must be con- molecular weight.39 Consistently, hyperglycemia, low
trolled. Commonly used anticonvulsant regimens are liver copper and iron stores, and hypochloremia
 Multifactorial and idiopathic disorders 535

­ uring seizure activity are associated with the syn-

d a rare nonprimate acquired tauopathy caused by the
drome.36 The significance of these findings and their widespread accumulation of hyperphosphorylated
relationship to the putative seizure-­inducing toxin tau protein. This puts the disease in the same classifi-
has not been determined, and hyperammonemia cation as Alzheimer, Pick, and Parkinson diseases,
may still play a role in pathogenesis of the severe clin- among others.45,46 Also, fortuitous upon enactment of
ical signs. the regulatory neuropathological survey for BSE sur-
Microscopic examination of feces will confirm veillance, a few other extremely rare pathologic con-
enteric coccidiosis. Sulfonamides or other anticoccid- ditions of cattle have emerged in the UK including
ial drugs, and fluid and electrolyte therapy for enteritis bilateral vacuolation of the substantia nigra.
are indicated. Probably, excessive amounts of intrave- Reasonable possible metabolic, nutritional, and
nous dextrose should be avoided. Placing affected toxic causes of brainstem neuronal chromatolysis
calves in a warm, dry, dark, quiet environment,34,36 and in cattle have mostly been excluded as singular
administering anticonvulsant drugs as outlined in causes,41,46 but exposure to agrochemicals and genetic
Chapter 6 should assist in controlling convulsions. susceptibility are currently under the spotlight as
Whether or not therapy with copper and iron salts is major etiologic factors for this disease.46
beneficial is not known. The prognosis is poor, with
70–100% mortality expected.34–36 Death usually occurs Postanesthetic cerebral necrosis in horses
within the first 5 days of neurologic signs.
An unexpected complication of apparently routine
general anesthesia in some mature horses is diffuse
Brainstem neuronal chromatolysis and severe cerebral necrosis resulting in signs of dif-
in cattle (bovine tauopathy) fuse encephalopathy immediately or some hours to
An interesting disease that almost certainly escaped days after recovery from anesthesia.47,48 There is cere-
detection until the statutory slaughter regulations bral edema and laminar neuronal cortical necrosis,
were introduced in the UK for bovine spongiform and with time, gliosis and small perivascular mono-
encephalopathy (BSE) is idiopathic brainstem neu- nuclear cuffs, most prominent in the watershed zones
ronal chromatolysis with hippocampal sclerosis in between major vascular supplies in the occipitopari-
cattle. This disease was initially regarded as indistin- etal lobes. These lesions are associated with general-
guishable from BSE.40,41 The disease occurs more ized signs predominantly consisting of somnolence to
often in beef breeds than BSE, generally affects older dementia, central blindness, wandering compulsively,
cows, 7–11 years of age, and has a rapid progression pushing against objects, and ataxia. One patient with
of signs often over 3–10 days compared to the more this tentative diagnosis that recovered showed persis-
insidious progression of BSE over 4–10 weeks. tent prominent muzzle and ear twitching,49 very remi-
Combinations of weight loss, temperament change, niscent of patients suffering from bacterial meningitis
ataxia, tremors, and hypersensitivity make the clini- and from West Nile viral meningoencephalitis.
cal syndrome very like that seen with BSE. If there are There certainly must be a compromise to cerebral
differences, they would be the whole body prominent circulation or metabolism, and circumstantially it is
tremor more like diffuse hypomyelinogenesis rather related to the general anesthetic procedure, but no
than the fine cerebellar-­ like tremor of BSE and consistent perturbations predominate.47,50
signs of apparent distress as opposed to that appre-
hension and hyperesthesia seen with BSE.41–43
Sleep attacks—­adult
Hypomagnesaemia is the other major differential
diagnosis to rule out by administering Mg++ salts. Abnormal sleep patterns resulting in inappropriate
The lesions underlying this disease consist of neu- somnolence are seen most often in adult horses but
ronal chromatolysis in vestibular and red nuclei, par- can occur in other large animals including captive
asympathetic nucleus of the vagus nerve and other wild animals.51–54 It is usually seen during times of rest
brainstem nuclear regions, neuronal necrosis and and while the animal is standing, when episodes of
parenchymal gliosis of the hippocampus, and vacuo- buckling, stumbling, or abrupt falling can awaken the
lation and associated perivascular mononuclear cuff- animal, to be repeated. Idiopathic sleep attacks, hyper-
ing in the forebrain.41,43,44 More recently, this disease somnolence and inappropriate siestas are terms used to
has been designated as a bovine tauopathy making it describe these episodes. This syndrome is introduced
536 Large animal neurology

in Chapter 7 and is included here because of its cur- pain may be due to pressure on caudal cervical nerve
rently accepted multiple causes including aging, roots as they traverse the epidural space but probably
chronic orthopedic conditions, disruption to herd more often directly reflects osteoarthritis of articular
structure, loss of herd sentinel activities, and ennui. process joints, especially in older horses with promi-
nent arthropathy at C6–7 or C7–T1.73–76 In addition
Cervical vertebral malformation– to the signs already mentioned, careful neurologic
examination of a horse with moderate CVM usually
malarticulation of horses discloses some of the following:
Cervical vertebral malformation–malarticulation
(CVM) is a common cause of spinal cord compres- a. Abnormal pelvic movements during walking when
sion resulting in general proprioceptive ataxia and observed from behind, including excessive or asym-
weakness. Affected horses commonly are called metric oscillation around a vertical axis (yaw) of the
“wobblers.” CVM occurs in horses worldwide, affect- median furrow of the rump, excessive or asymmet-
ing any age and breed of horse, but especially ric rotation of the pelvis around its long axis (seen as
Thoroughbreds and warmbloods from a few months exaggerated amplitude of the rise and fall of the
to 4 years of age.55–72 tuber coxae), and side-­to-­side truncal sway.
There is progressive spinal ataxia and weakness of b. Less than normal resistance of the horse to having
the pelvic limbs or all limbs (see Neurologic Evaluation, its tail pulled toward one side while walking.
Chapter 2). Occasionally, there is acute onset of tetra- c. Apparent stiffness (straightness) of the thoracic
plegia, especially if external trauma plays a major role, and/or pelvic limbs. This may be associated with
and particularly in association with flexural angular scuffing of the toes. When the horse’s head is
(kyphotic) malarticulation of C2–3 or C3–4. Usually, raised during walking, especially down a gentle
however, onset and progression of signs are insidious, slope, such a stiff hypometric gait of the thoracic
often recognized as clumsiness or stumbling when the limbs may be exaggerated and sometimes is
horse is led into or out of a stall. During exercise gal- described colloquially as a “marching” or “tin-­
lops, the rider may comment on a feeling of looseness soldier” gait.
or “losing the back end” around turns. Reluctance to d. Circumduction of each outside pelvic limb when
change or maintain leads, cross-­cantering or cross-­ the horse is walked forward in small circles.
galloping, or even falls after stumbling are other early e. Interference between the thoracic limbs and piv-
signs in horses while being ridden. With progression, oting around the pelvic limbs when the horse is
affected horses may have an obviously stiff uncoordi- rotated through tight circles.
nated gait at the walk; the prominent truncal sway or f. Absence of the thoracolaryngeal (“slap”) reflex.
“wobble” explains the common name for horses with g. In horses with markedly asymmetric compression
CVM. After they have been recognized, signs typically of the spinal cord (usually horses with asymmet-
worsen progressively for a period of months and then ric osteoarthritis of the caudal articular pro-
may stabilize or even regress. Spontaneous complete cesses), there may also be marked asymmetry of
recovery is very rare, though waxing and waning signs stride length between the pelvic limbs.
frequently occur.
In general, horses with CVM appear physically More severe lesions can produce marked paresis to
normal; however, occasionally, palpable swellings of paralysis with the same signs as any focal cervical
the cervical vertebrae corresponding to enlarged lesion. Pelvic limbs are almost always more severely
articular process joints are palpable. Severe kyphotic affected and typically are one grade worse than tho-
angles, particularly between C2–3 and C3–4, may be racic limbs. However, in chronic cases with signs pre-
externally visible and be palpable. Affected horses sent for a year or so, there may be obvious signs of
tend to be large for their age and breed, and males ataxia with little demonstrable weakness in the pelvic
appear to be more frequently affected than females. limbs and no detectable signs in the thoracic limbs.
Enlarged long bone physes in the limbs can be a Essentially, neurologic signs result from pro-
­concurrent finding in younger patients. Sensitivity of gressive spinal cord compression associated with
the horse to pressure over the transverse processes of one to all of the following structural changes to
the cervical vertebrae and reluctance of the horse to vertebrae and surrounding tissues (Figures 38.1
­
flex the neck laterally are found infrequently. Neck and 38.2).56,59–61,66–68,71,77–82
 Multifactorial and idiopathic disorders 537

(A) (B)

(C) (D)

Figure 38.1 This figure depicts several of the typical radiographic features of CVM. A diagram of idealized C3 and C4 is shown (A) to be contrasted with
a diagram of the radiographic features that may be defined on true lateral, midcervical radiographs of a standing, sedated, young wobbler horse that is
compressing the cervical spinal cord at C3–4 (C4 spinal segment) (B). Changes evident are angular deformity (kyphosis) of α degrees, stenosis of the intra-
­(open column) and inter-­(filled column) vertebral canal diameters, caudal modeling of the dorsal arch of the vertebral canal (stars), and dorsal enlargement
of the physeal growth region of the vertebral bodies (curved arrows). The dashed red column represents the position for measuring the maximal cranial
height of a cervical vertebral body. Most of these changes can be seen on a radiograph from a young wobbler compressing the spinal cord at C3–4 (C4
segment) (C). Additionally, lucent lines across the C3–4 articular process joints indicate osteochondral maldevelopment, and probably osteochondrosis is
present (C). A myelogram with the neck in a neutral position (D) is shown from another wobbler horse that compressed its spinal cord at C5–6 (C6). At this
site, there is stenosis of the vertebral canal and modest arthropathy present. Such compression may be made more obvious with extension of the neck at
C5–6. Such cases fall between the Type I and Type II classes of CVM, and measurements taken from the plain and contrast studies may well be required to
increase the odds for confirming spinal cord compression in individual cases. Sources: Based on Alitalo and Karkkainen 56; Gerber et al.59; Whitwell and
Dyson60; Yamagiwa et al.61; Mayhew et al. 66; Levine et al. 82

i. Stenosis of the vertebral canal. Stenosis may be iii. Angular deformity. Both static and dynamic
absolute (i.e., static) or only occur during vertebral stenosis may be demonstrated at such sites.
flexion or extension (i.e., dynamic). Stenosis is This usually involves flexion of adjacent
dorsoventrally rather than laterally oriented. pairs of vertebrae from C2 to C5 or exten-
Maximal narrowing is usually at the caudal orifice sion at C5 to T1.
of C2 to C5 vertebrae associated with “flared” cau- iv. Proliferation of articular and periarticular soft
dal physes (see (v)) or at the cranial orifice of C5 to tissues with impingement on the spinal cord.
T1 because of exaggerated tapering of the cranial This can include the formation of epidural and
part of the canal within each vertebra (see (vii)). periarticular synovial and dural cysts that com-
ii. Malformation and deformation of the vertebral press the cord, usually at C6 to T1.
articular processes. Delayed ossification, necro- v. Deformity of vertebral bodies associated with
sis and proliferation of cartilage, bone, syn- physeal enlargements.
ovium, and periarticular tissues are associated vi. Caudal extension of the dorsal lamina of the
with osteochondrosis, bone cysts,83 osteoarthri- vertebral arch. This deformity typically involves
tis, and fractures. Enlarged articular process pairs of adjacent vertebrae from C2 to C5 and
joints may intrude into the vertebral canal. In enables dynamic stenosis during flexion.
contrast to the vertical plane of stenosis vii. Extension of the dorsal lamina of the vertebral
described in (i), arthritic articular processes arch in a cranioventral direction thereby enabling
impinge on nerve roots and spinal cord by dynamic stenosis during extension at C6 to T1.
enlarging in medial or ventromedial directions. viii. Vertebral fractures.
538 Large animal neurology

(A) (B)

(C) (D)

(E)

Figure 38.2 The prominent osteoarthritis present in cases of Type II CVM is clear on the lateral cervical radiograph in this case at C5–6 and particularly
at C6–7 (A). This Thoroughbred filly suffered an acute onset of recumbency progressing to grade-­4 ataxia and tetraparesis. On myelography, compression
of the spinal cord was suspected to be occurring at the level of the C5–6 vertebrae (C6 spinal cord site). However, because the next caudal intervertebral
site was badly affected and possibly unstable, it was elected to fuse both C5–6 and C6–7, which was undertaken. The changes seen on the radiographs
(A) were similar to another case of Type II CVM (B) showing a cranial view of the disarticulated C6 vertebra (Cr C6). About 12 months after the time of
surgery in the case shown in (A), considerable modeling had occurred at the surgical sites with marked reduction of the proliferative arthritic process (C);
fusion of C5 to C6 and C6 to C7 appeared to have been successful. The mechanism whereby greater mechanical stressors are placed on intervertebral
sites adjacent to a fused (natural or surgical) intervertebral site has been referred to as the domino effect. On the cervical vertebral specimen from another
wobbler, cut on the median plane, successful surgical fusion has been performed at C3–4 with a stainless-­steel basket but there is now spinal cord
compression at C4–5 (C5 spinal segment), which was confirmed myelographically and histologically (D). This process has only been observed to occur in
immature vertebral columns when fusion has been present, and continued growth and maturation of the bone was still ongoing allowing such pathologi-
cal modeling to occur. Finally, with Type II CVM there occasionally is a parasynovial, epidural cyst formed by exuberant synovial and periarticular fibrous
tissue. Such is seen here (E) attached to and compressing the dorsal cervical spinal cord at the level of C7–T1 (C8 spinal cord site) in a wobbler.

These structural changes cause chronic bony and neuronal fiber degeneration in central sensory white
soft-­tissue impingement on the spinal cord resulting matter tracts cranial to, and central motor tracts cau-
in degrees of white matter necrosis and some focal dal to, the focal lesion. This pattern of fiber degenera-
loss of neurons. With time, there is Wallerian-­like tion can assist the neuropathologist in ­locating one
 Multifactorial and idiopathic disorders 539

or more focal compressive lesions in a wobbler (see osteochondrosis, and physitis (Figure 38.3). External
Figure 23.4). trauma can also play a role in precipitating and pro-
Although the pathological abnormalities underly- gressing the clinical syndrome.
ing CVM exist as a continuum, it is convenient to Horses with Type-­I CVM have various manifesta-
divide CVM into two pathophysiological types, Type-­I tions of osteochondrosis with rapidly growing and
and Type-­II.64,84,85 Osteoarthritis and trauma are the enlarging physeal growth regions along with distort-
major factors in Type-­II CVM, whereas developmen- ing effects of external forces applied to these sites.
tal orthopedic disease with genetic undertones is the Assessment of a group of horses with CVM in the UK
predominant pathophysiologic process in Type-­I. did not support the theory that the disease has a
Type-­I CVM usually occurs in younger animals, genetic basis.86 However, a breeding trial using horses
typically from suckling foals up to 2 years of age with CVM after corrective surgery resulted in off-
(Figure 38.1). The underlying developmental verte- spring with a higher frequency of developmental
bral changes certainly begin in the first months of life orthopedic diseases than expected, but this did not
and likely can begin in utero. Of the structural include CVM.87 One further study88 determined that
changes mentioned above, those most frequently there was a familial predisposition among certain
identified are stenosis of the vertebral canal, angular mare lines to produce foals that developed Type-­I
deformity, caudal extension of the dorsal lamina, CVM. These mares tended to be among the oldest on

(A) (C)

(B) (D)

Figure 38.3 The osteochondral lesions present in cases of Type I CVM vary considerably but collectively result in stenosis of the vertebral canal as seen
here in caudal views of C3 (A) and C4 (B) from two young wobbler horses with CVM Type I. There can be a ventral development of the articular processes
associated with a sagittal narrowing of the canal as in caudal C3 shown here (A). Or there can be asymmetric development of the processes, caudal
extension of the arch of the vertebral canal, and osteochondral fragment formation on the left process (B). Other osteochondral developmental abnor-
malities found on two further cases of young horses with Type I CVM are also shown (C and D). These are closer views of the left cranial articular surfaces
with a subtle visible linear defect in the subchondral bone (C, dashed ovoid) and a separated piece of bone and cartilage (D). These linear abnormalities
were evident on cervical radiographs as seen above (Figure 38.1). Such lesions are not always present but indicate that osteochondrosis plays some part
in the development of bone and cartilage maldevelopment associated with the narrow canal and spinal cord compression.
540 Large animal neurology

the same properties. Some degree of familial predis- body type, marginally abnormal vertebral anatomy
position almost certainly occurs. A high or even or bone quality, participation in competitive events
excessive intake of protein and energy appears to be involving jumping or tight turns, middle or older age,
necessary for expression of the disease; CVM is not long duration of athletic career, or history of one or
seen in malnourished or wild equidae. Calcium/ more falls, flips or other accidents. Indeed, previous
phosphorus imbalance, low dietary copper, and high external neck trauma may be the most important
dietary zinc all have been associated with develop- cause of delayed Type-­II CVM. Obviously, the dan-
mental orthopedic diseases in young animals of vari- ger to the spinal cord posed by enlarging articular
ous species, but any role as risk factors for CVM is process joints is relatively high in small-­ caliber
not entirely clear.89,90 Finally, although cervical artic- vertebral canals and correspondingly low in
­
ular process osteochondrosis is frequently present in ­large-­diameter canals.
young horses with CVM Type-­I, the occurrence of Needle electromyography sometimes reveals mild
such lesions is neither restricted to affected foals nor focal changes consistent with denervation in cervical
to the sites most affected by CVM Type-­I, viz. C2 to paravertebral muscles67 at the level(s) of spinal cord
C5 vertebrae.91 compression but is usually not very contributory to a
Cases of Type-­II CVM (Figure 38.2) tend to be diagnosis or therapeutic plan. A promising diagnostic
older patients with moderate to marked osteoarthritic modality is transcranial magnetic motor-­ evoked
enlargement of cervical articular process joints and lit- response testing. This is a minimally invasive and
tle overt evidence of developmental orthopedic accurate means of assessing electrical conduction
defects.82 These horses likely have an important com- across a suspected lesion site.93–97 Reference values for
ponent of acquired traumatic cervical vertebral dis- normal horses have been published for response laten-
ease. The only reasonably common nonarticular cies from the site of stimulation over the frontal aspect
vertebral deformity in Type-­II cases is elongation of of the head to the sites of EMG recordings in the para-
the cranial edge of the vertebral dorsal lamina in a way vertebral muscles at the level of each cervical vertebra
that extends the progressive tapering of the cranial and in thoracic and pelvic limb muscles.93,95,96,98 Further
part of the canal of the affected vertebra. As a result, studies on many patients will be required to determine
there is often both static stenosis of the canal and the clinical utility of this technique. CSF is generally
dynamic stenosis during extension, usually involving normal in cases of CVM, with occasional slightly high
C5, C6, or C7. There is usually proliferation of articu- protein content, xanthochromia, and erythrophagocy-
lar and periarticular soft tissues at affected articular tosis. Efforts have been made to internally standardize
process joints with impingement upon and injury of cervical scintigraphic examination so that the tech-
the spinal cord. One outcome can be formation of epi- nique can be used reliably to identify pairs of articular
dural and periarticular synovial cysts.58,59,71,80 These process joints undergoing unusually active modeling,
fluid-­filled sacs may be forced unpredictably against but this diagnostic procedure is seldom contributory
the spinal cord, possibly as a result of abnormal verte- to a diagnosis in horses with suspected CVM.99
bral motion or because of bleeding into a cyst, thereby Thermographic imaging100 has generally been quite
triggering sudden onset of ataxia without a contempo- unhelpful in evaluating suspected cases of CVM or
raneous episode of external trauma (Figure 38.2). any other form of spinal cord disease. Endoscopy of
Signs can be very asymmetric and can fluctuate dra- the cervical vertebral canal of horses has been per-
matically over time.58 formed successfully in an experimental setting.101–103 A
The cause of the severe degenerative joint disease narrow flexible endoscope is introduced via the atlan-
characteristic of Type-­II CVM is not fully under- tooccipital opening into the epidural or subarachnoid
stood but likely stems from the repetitive heavy space and advanced to the cervicothoracic junction.
mechanical loads and stresses to which the articular The contours of the vertebral canal and the spinal cord
process joints of the cervicothoracic vertebral region and nerve roots were readily identified during these
are subjected, especially when large horses exercise procedures; however, obvious narrowing of the canal
vigorously. Additional factors must be responsible in at C5–6, which was confirmed postmortem, could not
some horses for evolving common symmetric be documented by epiduroscopy.101 One instance of
arthritic changes from “wear and tear” level92 to subarachnoid ­ hemorrhage during subarachnoid
severe, often asymmetric, joint enlargements of endoscopy was associated with postoperative ataxia.
­clinical significance. It is reasonable to ascribe par- Although this technique has been shown to be feasible,
ticular risk for lesion p ­ rogression to tall and heavy ongoing concerns regarding its safety and diagnostic
 Multifactorial and idiopathic disorders 541

utility mean that the endoscopy of the vertebral canal 13–33% of more than 1000 horses over several studies
is unlikely to find application in the workup of CVM of partial or complete, bilateral or unilateral, transpo-
cases. sition of the ventral laminae of the transverse pro-
Imaging of the cervical vertebrae is central to the cesses of C6 onto the ventral aspect of C7 (or
antemortem diagnosis and management of CVM. occasionally onto C5 or onto T1) must be considered
Despite recent exciting progress in the application of when vertebrae are being identified on radiographs
advanced volumetric imaging techniques, conven- and at the time of any surgery.60,105,107–110 Although
tional digital radiography remains the most important association between this transposition and CVM has
modality for this purpose.77,104 The traditional one-­or not been found, it is not clear whether or not it is clini-
two-­ step approach to CVM diagnosis still applies. cally innocuous. The C6–7 transposition was not asso-
First, screening for compatible vertebral abnormalities ciated with abnormal clinical signs in one study of
in standard laterolateral with or without oblique views warmblood horses,108 but in other studies of horses
of the C1–T2 vertebrae is reviewed, and second, the of several different breeds, combinations of ataxia,
demonstration of spinal cord compression by myelo- ­cervical pain, and vertebral canal stenosis were more
graphic studies can be undertaken in suspected CVM common in horses with this anatomic variant.109,111
cases. This is not to imply that radiographic diagnosis Furthermore, a separate anomaly commonly found in
of CVM, particularly Type-­II, is unerringly accurate! Thoroughbreds, namely complex congenital malfor-
Many horses that do not have CVM, particularly if mation of the first sternal rib, was only found in horses
they have worked hard or suffered occult neck injury, that also had a C6 to C7 ventral lamina transposi-
have degrees of cervical vertebral osteoarthritis that tion.112 It was speculated that the rib malformation was
may appear impressive in lateral radiographs. Also, likely to have clinical locomotive and postural ramifi-
arthritic articular processes can enlarge considerably, cations. Other notable but clinically insignificant find-
especially in lateral and dorsal directions without ings on equine cervical radiographs are listed below.
causing spinal cord compression. Even among horses
with vertebral canal diameters within published nor- • Occipital condyle defects of maturation in foals
mal ranges, those animals with relatively narrow-­bore <5 months old.113
vertebral canals are in danger of spinal cord injury • Variations, which may be asymmetric, in the shape
from even moderate osteochondral lesions whereas a of the intervertebral notches or orifices at the cra-
horse with a relatively wide canal may suffer neck pain nial border of C2.
because of moderate articular process arthritis but spi- • Irregularities of the dorsal aspects of the caudal phy-
nal cord impingement is unlikely. Finally, in cases of ses of C2–C7 projecting into the intervertebral space.
chronic compression of the spinal cord, myelographic • Separate ossification of the caudal pole of the ven-
columns may have normal diameters because of sec- tral laminae of the transverse processes of C6.
ondary spinal cord atrophy. • Serpentine lucent vascular channels in the dorsal
To obtain true lateral cervical radiographs, the spinous process of C2.
horse should be sedated and in the standing position • Irregular border of the caudal aspect of the dorsal
with a handler positioned out of the radiographic spine of C2.
beam and pulling forward on the halter to put trac- • Irregular size and contour of the dorsal borders of
tion on the neck so as to position the vertebrae along the dorsal spinous processes of C3–6.
the median plane without rotation, thus providing • Circular 3–20 mm, cyst-­like lucencies in the arches
optimal alignment of vertebral bodies. Although the and less often bodies of all cervical vertebrae.
accuracy of evaluation is tolerant to minor variations • Presence of one of three morphologic variants of a
in positioning, it is almost impossible to correct for dorsal spine on C7.110
cervical torticollis in big sedated horses and espe- • Tall and short forms of the dorsal spines of T1.110 Short
cially with patients under general anesthesia. dorsal spines on T1 were associated with the absence
Plain radiographs in CVM cases usually identify at of a dorsal spine on C7 and the presence of C6–7 trans-
least one of the following elements: absolute stenosis, position of the ventral laminae described above.
changes predictive of dynamic stenosis, or osteoar-
throsis of articular process joints (Figures 38.1 Because the orientation of vertebral canal stenosis
and 38.2).60,77,78,83,105 Many normal variations or minor is usually dorsoventral, measurements of minimal
abnormalities must be accounted for when i­ nterpreting sagittal diameter (MSD) are used to compare CVM
cervical radiographs.60,78,105,106 Thus, the finding in suspects to a control population.66 The MSD of a
542 Large animal neurology

v­ ertebra is the smallest diameter (aka height) found in

measurements of the canal within that vertebra made
perpendicular to its floor in laterolateral radiographic
projections. Values less than those found in 95% of
the control population67 support a presumptive diag-
nosis of CVM and are justification for a contrast mye-
lographic study. In some cases where MSD values are
normal, the finding of significant angular deformities,
severe osteoarthrosis, or evidence of trauma may also
be enough grounds for a follow-­up myelogram.
To correct absolute MSD for horse size and radio-
graphic enlargement, the maximal sagittal height,
measured perpendicular to the canal floor, of the cra-
nial half of the vertebral body is measured
(Figure 38.1B). The ratio of MSD to this maximal body (A)
diameter within the same vertebra (C3 in the case of
the axis) is termed the intravertebral sagittal ratio (SR).
As a rule of thumb, horses with SR values below 50%
have a high risk of spinal cord compression. With such
a finding, and if there are other characteristics identi-
fied as in (i) through (viii) above, CVM can be diag-
nosed with degrees of confidence. The following points
should be noted when making SR measurements. First,
the MSD within a vertebra may be anywhere along its
length, not only near the cranial orifice or at the point
of the maximal vertebral body measurement. Second,
with poor-­quality definition or in underexposed radio-
graphs, the MSD measurement is often inaccurately
small. Usually, this is because the ventral margins of the
pedicles of the articular processes are misinterpreted as (B)
the dorsal margin of the vertebral canal. In this situa-
tion, the vertebral dorsal lamina should be projected Figure 38.4 Two images from the same average quality lateral
cranially as an imaginary line to then be used as the ­radiograph of C3–4 from a horse after postprocessing to demonstrate the
upper margin of MSD measurements (Figure 38.4). effect of changes in exposure and radiographic factors. In (A), the sites to
Intervertebral MSDs (Figures 38.1 and 38.4 and used in be defined in order to measure the limits for the minimal sagittal diame-
ters of the vertebral canal are indistinct within the circles. Different radio-
Table 38.1) can also be taken from standing lateral
graphic factoring allows the limits for measuring intervertebral (yellow
views and normalized as described for intravertebral bar) and intravertebral (white bar) minimal sagittal canal diameters to be
SRs. In cases of angular vertebral deformity, these identified in (B).
measurements may identify stenosis even when intra-
vertebral SRs are normal.
Table 38.1 Reference table for acceptable minimal intravertebral and intervertebral SR values in horses (n = 19) without CVM, to assist in assessing
the likely presence of cervical spinal cord compression in ataxic, tetraparetic adult horses. SD = standard deviation.

Statistic Sagittal ratio values (%)114

C2 C2–3 C3 C3–4 C4 C4–5 C5 C5–6 C6 C6–7 C7

Mean 72 91 61 71 59 74 61 80 60 71 62
SD 7.9 11.7 5.6 9.3 5.4 11.1 5.4 9.5 6.2 8.8 5.2
Minimum 55 63 52 60 49 56 52 63 54 58 55
Mean less 2 × SD 56 67 49 52 48 51 50 61 48 54 52

Source: Based on Hahn et al.114

 Multifactorial and idiopathic disorders 543

Figure 38.5 Oblique radiographic views of the caudal cervical vertebrae of a 6-­year-­old warmblood gelding with neck stiffness. The image in the upper panel
was obtained by directing the beam from right ventral to left dorsal as indicated by the orange arrows (bottom left). The right APJs are thus imaged perpen-
dicular to the AP joint surfaces while the left APJs are viewed approximately in the plane of the joint surfaces. Reconstructed transverse CT images of the
caudal cervical intervertebral joints of this horse are shown in the lower panels. In each case, the left side of the horse is to the right of the image. When
properly performed, oblique radiographic projections from both sides can reveal some of the changes that are evident in cross-­sectional CT images but not
usually seen in laterolateral radiographic views. Shown here are periarticular osteophytes (yellow circles), ventrally directed modelling of cranial articular
processes (asterisks) and bone lucencies (blue arrows). Also present is collapse of the caudal joint space in the left C6-­7 APJ. Presence of gas pockets in the
CT images resulted from post-­mortem transection of the thoracic vertebral column prior to imaging.

Standardization of the technique for obtaining ues of sufficient quality for useful comparison with
oblique radiographic projections of the caudal cer- values obtained from horses with caudal cervical
vical and cranial thoracic vertebrae has greatly arthropathies.116,117
improved imaging of the articular process joints.115 Prior to deciding on surgical intervention, myelo-
Radiographs are obtained with the beam directed graphic evidence of spinal cord compression is
ventrally to dorsally across the neck at an angle of accepted as being mandatory. Positive-­ contrast
45°–55° from the horizontal to obtain views wherein myelography under general anesthesia is not an
the paired articular process joints are displayed sep- innocuous procedure in the horse.118,119 Hemorrhagic,
arately (i.e., do not overlap): one viewed with their neutrophilic meningitis occurs 6–48 h following the
joint surfaces parallel to the X-­ray beam (skyline procedure, often with fever.119 Difficult recoveries and
view) and the other pair viewed at right angles to reversible signs of forebrain dysfunction including
the beam. Thus, after oblique radiographs have generalized seizures, blindness, and facial hypalgesia
been taken from both sides, complete contours of are infrequent but well-­recognized complications.
the articular process joints on both orthogonal
planes can be seen, allowing careful subjective eval-
Myelography in the standing conscious horse120 is a
uation of the anatomy of each joint (Figure 38.5).
painful and potentially dangerous process that is difficult
However, efforts so far made to quantify the dimen-
to defend on humane grounds such that myelography
sions of the joint contours in oblique radiographs
should only be performed under general anesthesia.
from normal horses have not yielded reference val-
544 Large animal neurology

The advent of digital radiography and nonirritating diameter has been purported to be a very good diag-
contrast agents such as iopamidol and iohexol has nostic benchmark.68,85,125,129,130 Nevertheless, modern
lessened the resulting meningeal irritation and has analyses have not found this criterion to be accurate,
vastly improved both the safety of this procedure and to the extent that it should not be used alone to diag-
the quality of resulting radiographic images.121–123 nose CVM or to plan surgical treatment at a site of
Myelography is used to document impingement suspected compression.64,84,124,126 By contrast, rela-
on the spinal cord by stenotic vertebral canals, tively good accuracy is ascribed to the finding of at
enlarged articular processes, and exuberant periar- least 20% reduction of the total dural diameter in
ticular soft tissue or epidural cysts. Impingement neutral myelographic views of the mid-­cervical and
may be evident when the cervical vertebrae are radi- caudal cervical vertebrae to C6–7 and in flexed views
ographed in neutral position or may only occur with at the level of C6–7.124 It has recently been suggested
neck flexion or extension. Bending of the neck such that, because there is relative dural expansion in the
that the occipito-­cervical region is flexed but the region of C7, the threshold for reduction in dural
mid-­ cervical region is poorly flexed, or even diameter at C7–T1 should be 30%.131
extended, should be avoided when flexed cervical Some cases of both Type-­I and Type-­II CVM can
vertebral column views are required. Considerable involve transverse rather than dorsoventral compres-
care must be taken to avoid further spinal cord com- sion. In Type-­I cases, transverse compression is usu-
promise by excessive manipulations of the neck. ally due to kyphotic angular deformity involving
With forced manual flexion, the dorsal and ventral C2–3, C3–4 or, occasionally, C4–5.60,64,67 This malfor-
contrast myelographic columns can be totally oblite- mation rotates the pedicles of articular processes
rated in normal foals. Cases of unequivocal focal spi- ventrally to where they may abut on and injure the
nal cord compression are readily recognized in adult lateral aspects of the spinal cord.66,84 In this situation,
horses as complete loss of both contrast columns at the intervertebral SR is often abnormal whereas the
the same level of the spinal cord. However, there are intravertebral SR measurement is not. Although the
many more instances in which there are intermediate orientation of compression in many Type-­II cases
degrees of thinning of contrast columns and some can be predominantly transverse, SRs nevertheless
uncertainty as to the diagnostic significance of this are often abnormal. Enlarged articular processes are
finding because definitive evidence-­based criteria for almost always evident. On lateral myelographic views
myelographic interpretation are lacking.66,78,120,123–126 of these cases, the dorsal and ventral contrast col-
The most objective available guidance for interpre- umns may not appear compressed, and MFDD meas-
tation of these “gray area” myelograms comes urements may be within normal limits. In such cases,
from published reference values for minimal flexed spinal cord compression may be evinced as lightning
and neutral dural sagittal diameters and reduction of the overall contrast column, sagittal widening of
ratios for dorsal column and total dural diame- the silhouette of the spinal cord and, sometimes,
ters.64,66,67,77,124,126–128 In a small study of 19 young double upper borders to the dorsal contrast column
horses with ataxia,69 only 5/13 of those with a histo- reflecting asymmetric intrusion of enlarged articular
logic diagnosis of CVM had minimal flexed dural processes. This occurs most often at C6–7 and C7–
diameter (MFDD) values below the published lower T1.66,84 Not surprisingly, initial reports have indicated
limits of normal (i.e., sensitivity of 38%). It is worth that transversely oriented compression of the thecal
noting, however, that an additional five animals had sac and spinal cord in the caudal neck is more readily
values at the reference limits when rounded up to identified in axial CT views than in conventional
whole numbers for consistency between studies. One myelograms.132,133 It should be noted that tomo-
out of six horses without CVM (i.e., specificity of graphic myelograms are usually complemented with
83%) also had an MFDD value below the threshold flexed and extended radiographic views in order to
level. Notwithstanding these results, the authors’ detect dynamic dorsoventral spinal cord compres-
experience is that the use of absolute minimal neutral sion.132 Because validated guidelines for analysis of
and flexed dural sagittal diameter measurements64,66,84 CT myelograms have yet to be developed, the inter-
quite reliably defines sites of spinal cord compression pretation of CT studies thus far has been based on
in CVM cases, albeit so far without the needed vali- visual scoring of abnormalities. A small study in
dation of a large clinical study. Historically, the find- ataxic Thoroughbred foals used spinal cord:thecal
ing of a 50% reduction of the dorsal contrast column sac area ratios, measured in axial CT views, to
 Multifactorial and idiopathic disorders 545

i­dentify likely sites of spinal cord compressive

injury.134 Development of properly validated criteria
for the use of these and other measurements will
hopefully soon allow more objective assessment of
CT myelographic studies.
In summary, using the various subjective interpre-
tations and semiquantitative measurements and cal-
culations discussed above, the presence or absence of
pathologic narrowing of the vertebral canal and con-
(A)
sequent spinal cord compression then can be stated
with some confidence, backed by sensitivity and spec-
ificity accuracy parameters approaching 90%
(Figure 38.6). In selecting criteria of high positive pre-
dictive value or high negative predictive value, it
behooves the radiologist and surgeon to decide
whether it is more advisable to err on the side of false-­
positive diagnosis and perform an occasional unnec-
essary surgical procedure or on the side of
false-­negative diagnosis and leave a possibly surgi-
cally amenable compressive site unattended. Thus, (B)
measurements taken from high-­quality, true laterolat-
eral, standing radiographs of the neck from the base
of the skull to T1 can be used to predict reasonably
well the presence of—­but not necessarily the sites of—­
spinal cord compression in a wobbler. If surgery is an
option in an individual case, then myelography is to
be recommended to help confirm active compression
of the spinal cord at a particular site or sites. If no
compression is deemed to be present and surgery is
thus not an option, then a decision is required as to (C)
whether to euthanize the patient under anesthesia or
to progress to specific therapy for another disease. Figure 38.6 A yearling Thoroughbred gelding with an onset of moder-
Increased access to advanced volumetric diag- ate ataxia and tetraparesis 1 month previously had evidence from plain
nostic imaging techniques (MR, CT) undoubtedly lateral cervical radiographs (A) and flexed cervical myelographic study (B)
of compression of the cervical spinal cord at C3–4 (C4) only*. Cervical
will improve the accuracy of CVM diagnosis and
intervertebral fusion was undertaken at C3–4, and after ~10 months of
the identification of the exact locations of spinal recovery, evidence of modeling of the articulations and vertebral canal
cord compression(s) prior to surgical interven- was evident on radiographs (C). The horse went on to win many races. If
tion.104,132,133,135–139 Although MR is technically the surgery is to be considered in wobblers with CVM, cases such as this are
modality of choice for imaging the spinal cord in good prospects for several reasons including:
other species, bore size limitations and greater 1. signs were moderate not profound;
2. signs had been present for a relatively short period of time;
expense restrict its use in horses. The continued
3. only one site of compression was detected.
development and deployment of CT units that can be
*Sagittal ratios at C3 and C3–4 were 52% and 51%, respectively. Minimal
used in standing horses, particularly recently intro- sagittal dural diameter at C3–4 and C4–5 were 10 and 12 mm, respectively.
duced, robotic, no-­bore versions that even allow for
patient movement, guarantees enhanced evaluations
of CVM patients, particularly those with a surgical ­ ossibly scintigraphic evidence of active arthritis.
p
option pending. Use of intraarticular corticosteroids and other anti-­
Confirmation that apparent neck stiffness and inflammatory drugs in the caudal cervical articular
pain, or thoracic limb lameness is emanating from process joints is often remarkably effective at reliev-
specific arthritic vertebral articulations63,73–75,140 ing signs of neck pain, obscure thoracic limb lame-
requires radiographic, ultrasonographic, and ness, and even mild ataxia associated with enlarged
546 Large animal neurology

articular process joints, allowing return to normal Medical options for CVM in fully grown horses
function for periods up to several months.141,142 The are limited. Treatments may include corticosteroids
appropriate anatomy and ultrasonographically or NSAIDs that can provide transient neurologic
guided method for achieving this are elegantly relief but do not solve the problem and without
described143 and have become a favored diagnostic restricted exercise can allow rapid progression of an
and therapeutic tool.74,76,144 Notwithstanding the unstable situation. Rest, neck braces and correction
generally positive response to this form of therapy in of faulty nutrition have helped stop the progress of
horses with caudal cervical osteoarthritis, empiric the disease, and radiographic as well as clinical
injection of enlarged articular process joints without improvement has occurred in some cases. One retro-
substantive evidence that they are causing a clinical spective study of Thoroughbred horses showed that
problem of neck pain alone, neck pain with ataxia, conservative management can result in approxi-
and ataxia alone is to be discredited. These authors mately 30% of affected horses returning to racing.148
have seen numerous patients with such syndromes Surgical techniques have been developed for vari-
where trauma to the neck has been suspected or not, ous aspects of the disorder.87,129,149–158 Extrapolating
detailed and repeated cervical radiographs have from human and canine neurosurgery, dorsal subto-
failed to detect a cervical fracture and ultimately tal decompressive laminectomy, especially between
osteochondral fragmentation of an articular process C6 and T1, would seem to be indicated for the treat-
joint or even a serious fracture has been found by ment of Type-­II CVM with absolute stenosis associ-
CT145 or postmortem examination. On occasion, ated with osteoarthrosis and proliferation of soft
such injections as well as aggressive physiotherapy of tissues. Unfortunately, postoperative complications
the neck have been undertaken in such patients and are so frequent with this surgery in horses154–156 that
under these circumstances both these treatment it has gone into disrepute. The most used procedures
modalities must be deprecated. are designed to stabilize adjacent pairs of vertebrae
Measurements made from plain cervical radio- through insertion of an interbody fusion implant via
graphs may also have predictive value. A score a ventral approach. Implants that have been used, in
designed to predict the likelihood of the develop- order of their introduction, are stainless-­steel fenes-
ment of CVM in foals was developed that incorpo- trated (“Bagby”) baskets, threaded kerf-­cut cylinders
rated MSD values corrected for vertebral length with with preserved bony isthmus, or polyaxial pedicle
scores for the common vertebral malformations and screw and rod constructs.158,159 An alternative
deformations found in CVM cases (see (i) through approach is the use of locking compression plates.
(viii), above).114,146,147 This CVM score was used to These have been used in a small number of horses to
predict reasonably accurately the onset of signs of fuse two or three cervical vertebrae.160,161 Results
spinal cord disease in young Thoroughbred foals at a have been encouraging although complication rates
single operation.88,146,147 In young horses less than 1 were high.
year of age shown in this way to be at risk for clinical Successful intervertebral fusion prevents the
CVM and even in young foals with neurologic signs flexion-­induced dynamic spinal cord compressive
of CVM, a controlled growth (aka “paced”) program component characteristic of Type-­ I CVM and,
has been used successfully for the prevention or because it results in atrophy of articular enlarge-
treatment of CVM. Foals were put on a regimen of ments and regression of associated soft tissue swell-
limited exercise and a diet restricted in protein and ing at the sites of fusion, it also decompresses the
carbohydrates—­ usually grass hay and a ration spinal cord of horses with Type-­II CVM concomi-
balancer—­ aiming for minimal though adequate tant with reduction in the compressing arthropathy
growth. This program was very effective in prevent- (Figures 38.2 and 38.6). Additionally, patients suf-
ing clinical CVM in at-­risk foals and, in some cases, fering from chronic, persistent, and unremitting
foals with clinical signs of CVM and with high radio- neck pain associated with severe cervical osteoar-
graphic CVM scores improved to show no clinical thritis without ataxia or pelvic limb weakness and
signs and follow-­up cervical vertebral radiographs to with no evidence of fractures to the bodies of the
be no different from those of unaffected siblings.88 vertebrae should also be good candidates for
Whether such a CVM scoring system would be of intervertebral fusion surgery. Minimally invasive
general predictive value requires further clinical and arthroscopic approaches to articular process joints
pathologic data acquisition and analysis. have been devised162–164 and offer the future prospect
 Multifactorial and idiopathic disorders 547

of removal of osteochondral fragments from articu- here is that these surgical procedures have now been
lar process joints and laser-­facilitated ankylosis of adopted worldwide but are performed at relatively
arthritic joints. Use of the ventral interbody fusion few surgical referral centers.64,67,68,85
procedures described above in horses with CVM
resulted in published rates of improvement of neuro- Cervical compressive myelopathy
logic signs in 43–79% of cases.85,130,153,158,161,165–167
Barring complications (Figure 38.2), return to ath-
in young Texel and Beltex sheep
letic function can be expected in approximately 60% A fascinating clinicopathologic entity is recorded in
of CVM horses undergoing intervertebral fusion young, well-­grown Texel and Beltex sheep in the UK
procedures.85,130,149,153 The outlook for horses with (Figure 38.7).168 At about 1 year of age, these animals,
CVM is good if the appropriate surgical technique is predominantly male, show slowly progressive ataxia
performed on young patients with mild ataxia and and tetraparesis associated with compression of the
weakness, having only one or two sites of cervical spinal cord at the C6–7 site (also at C5–6 in one case)
spinal cord compression and being early in the by nodules isoattenuating to fatty tissue, surrounded
course of the disease. With more than two interver- by a thin fibrous capsule protruding into the dorso-
tebral sites involved and with severe, chronic signs in lateral vertebral canal from the intervertebral space.
older patients the prognosis is poor to grave. Of note The lesion was imaged best using CT myelography,

(A) (B)

(C) (D)

(E)

Figure 38.7 Young Texel (A) and Beltex (B) sheep in the UK have been affected with an unusual form of caudal cervical spinal cord compression associ-
ated with exuberant epidural or parasynovial fatty masses that have been identified on CT myelographic contrast imaging (C and D) and at postmortem
examination (E). In these examples, the fatty mass obliterates the dorsolateral subarachnoid space at C7. The disease seems to be familial, occurring in
fast growing progeny, but the pathogenesis is baffling.168,170 One affected ram shows a degree of extensor weakness in the pelvic limbs and hypometric
movement in the thoracic limb as it moves off from a standing posture (A). The other affected ram shows a base wide stance of the pelvic limbs inter-
preted as a conscious proprioceptive abnormality (B).
548 Large animal neurology

and there was no evidence that it was associated with walk somewhat upright on their pelvic limbs.181 Some
any osteochondral vertebral deformity.169 The novel have flaccid paralysis of pelvic limbs alone, and in
aspect to this disease is that the compressing material others both pelvic and thoracic limbs become involved
is predominantly adipose tissue.170 In all other situa- with rapid muscle atrophy occurring.174,177,178,180,181
tions of extradural spinal cord compression, the first There is necrosis of glial and neuronal compo-
material to dissipate from the site is epidural fat. That nents in selective ventral gray matter regions in the
these compressive fatty nodules are contained within cervicothoracic and in the lumbosacral enlarge-
a fibrous capsule may allow them to act as space-­ ments. This can particularly involve the medial, ven-
occupying, compressive lesions. The genesis of these tral regions that contain the final motor neurons for
nodules is not known. axial muscles,177,178 or include the lateral appendicular
final motor neurons, sometimes extending to include
Congenital spinal stenosis of the intermediate regions.175,176,179 Nuclear regions in
the brainstem and cerebellum can also be
thoracolumbar vertebrae in beef calves affected175,176,181 particularly in goat kids;177 from
A syndrome of dwarf-­like appearance, bow legged- these, vestibular signs may be expected to occur.
ness, and progressive paraparesis occurred in all There is no evidence of myeloencephalitis, vasculitis,
10 newborn Angus calves in a Canadian herd.171 thrombosis or embolism, and white matter is essen-
Cases of a similar or identical syndrome, termed con- tially spared. Relative astrosclerosis ensues if patients
genital spinal stenosis, were found in 7 additional beef survive long enough.
herds in western Canada in subsequent years, with There is no treatment and the cause is unknown.
prevalence of 7–100% in affected groups of calves. Possibly, this clinicopathologic syndrome represents
There was no predilection for a particular breed in more than one etiology. Similarities exist between
these later cases.172,173 The signs were associated with this disease and selenium toxicity and experimental
focal premature bony fusion across thoracolumbar nicotinic acid deficiency in swine, focal symmetric
vertebral epiphyseal growth plates, resulting in verte- leukoencephalomalacia in ruminants and pigs, pos-
bral canal stenosis. Other growth plates, especially of tanesthetic hemorrhagic myelopathy in horses, and
the appendicular skeleton and basicranium, were hereditary polioencephalomyelopathy in dogs.182–186
affected. Etiologic possibilities initially considered Because of similarities to other diseases, it would be
included teratogenic plants, chemical toxins, mineral valuable to scrutinize the diet of affected animals and
deficiencies and, particularly, hypervitaminosis A. determine the copper, selenium, nicotinic acid and
Mycotoxicosis associated with feeding of moldy other nutrient concentrations, and the presence of
cereal straw to pregnant cows was a suspected cause possible toxins, including antimicrobial drugs177 and
in 3 herds in Alberta.173 feed additives. The possibility of clostridial and other
biologic toxins should also be considered when eval-
Selective poliomyelomalacia of sheep, uating cases.187
goats, and calves
Postanesthetic myelopathy
Symmetric poliomyelomalacia occurs in lambs,174,175
adult sheep,176 kid goats,177 and in calves178,179 from At least 30 cases of this rare complication of general
several continents175,177–179 with resulting thoracic anesthesia have been reported. It is seen in young
and/or pelvic limb paresis to paralysis. At times, the horses of both sexes after general anesthesia for rou-
clinicopathologic syndrome has occurred in devas- tine surgery.188–198 Postanesthetic myelopathy and
tating proportions in sheep in several regions of cortical necrosis together accounted for 6% of peri-­
Africa174,176,180,181 affecting up to 72% of adult ewes on operative death in a large prospective multi-­center
one farm.176 study.199 Signs are usually seen as the patient attempts
The disease is quite rapid in progression over a few to recover from anesthesia, but onset can be delayed
days to a week or so, and clinically the animals remain several hours thereafter.188,191,200
bright and appetent. Some show areflexic (flaccid) Most often there is diffuse thoracolumbosacral
paralysis of thoracic limbs with preservation of sensa- softening and sometimes hemorrhage of gray mat-
tion so that they scramble using the pelvic limbs only, ter resulting in degrees of paraplegia, areflexia,
and the lightweight, agile ones quickly learning to hypotonia and analgesia involving the trunk, pelvic
 Multifactorial and idiopathic disorders 549

limbs, perineum, tail and anus. The syndrome has ­ uestioned in light of a report that postanesthetic
q
occurred mostly in horses 1–2 years old of large-­ myelopathy has occurred in at least two horses posi-
frame or heavily muscled breeds undergoing gen- tioned thusly.190,191,193,201
eral anesthesia for an hour or more using inhalation The syndrome has been reported in a week-­old
anesthesia for routine surgical procedures, most calf that suffered asymmetric malacia of the thora-
often for castration or arthroscopy, and with few columbar gray matter after abdominal surgery with
exceptions, in dorsal recumbency.188,201 Asymmetric subsequent scoliosis developing prior to euthanasia
signs can be expected in the very rare event of at about 1 month of age.204
postanesthetic myelopathy occurring in patients
­
undergoing surgery in lateral or oblique dorsal Vascular malformations
recumbency.188
The lesion most often occurs in the thoracolum- Various vascular malformations, such as aneurysms,
bosacral segments extending to cranial thoracic hematomata, arteriovenous malformations, and
region in some184,193 and specifically involving the C6– thromboses, have been recognized as causing ataxia
T8 gray matter rarely.192 Congestion, necrosis, and in horses and cattle.66,205–210 They usually occur in
hemorrhage involve the dorsal and particularly the young adult animals. Several of these were in the cer-
ventral gray matter, suggesting interference with ebellomedullary region of the brainstem and resulted
venous drainage in the dorsal and ventral spinal in a progressive wobbler syndrome in affected horses
veins. There is no evidence of myelitis, vasculitis, or without any detectable cranial nerve deficits,210 and
thrombosis, making the suggestion184 that fibrocarti- the clinical signs were likely as due to marginal
laginous thromboembolism may be involved seem siderosis from red blood cell diapedesis into CSF as
unlikely. Compartmentalization of blood flow and to the focal caudal fossa lesions.66, 210, 211 Some of these
local or systemic blood pressure alterations associ- anomalies are possibly best regarded as congenital
ated with recumbency and anesthesia may play roles or acquired neoplasia and others as embryological
in the genesis of the lesion.184, 188, 191, 193, 197 A tenable dysplasia.209, 212, 213
hypothesis is that drug-­induced failure of regulation
of spinal cord blood flow, degrees of hypotension, Discospondylosis
and vena caval and aortic compression result in con-
gestion, hemorrhage, and subsequent tissue necrosis Discospondylosis is the preferred generic term to
in the thoracolumbar spinal cord.190,191,193 A hypothe- describe bone and cartilage lesions not caused by
sis that vitamin E deficiency may play a role has been infectious agents and occurring in the intervertebral
put forward.202 discs and adjacent vertebral bodies of large animals
A clinically indistinguishable bilateral femoral (Figures 38.8 and 38.9). This umbrella term thus
paralysis and paraplegia, associated with hemorrhage incorporates what has been described as interverte-
along both femoral nerves, has been seen post anes- bral disc disease (IVDD), spondylosis deformans, and
thesia.203 Two of three affected horses have survived, spondyloarthrosis214–223 but does not include bacte-
although the precise lesions were not defined in sur- rial discospondylitis or sterile chronic suppurative
vivors. Such lesions also have been present in cases of discospondylitis.224,225
postfoaling paralysis. The process commonly affects the cervical and
A wide array of anti-­ inflammatory and other thoracolumbar regions of adult cattle, pigs and
medical therapy has been undertaken, but all horses, and the pathogenesis likely involves the aging
reported cases have been euthanized or died within process, external trauma, nutritional factors, and
72 h of onset.200 To prevent the condition, careful genetic predisposition.219, 220, 224, 226–228 It results in clin-
attention to maintenance of normal blood pressure, ical signs associated with mechanical restriction of
blood gases, and lactate during anesthesia is likely vertebral movement, neck and back pain, and in rare
critical. It has been suggested that extended with- cases results in ataxia and weakness.
holding of feed presurgery may lessen risk by The underlying vertebral and disc lesions229 and
­reducing the weight of abdominal viscera. A recom- MR characteristics230 of IVDD in horses recently
mendation that heavy horses that require dorsal have been described and grading systems for mor-
recumbency for surgery should be positioned on phologic changes have been developed. In contrast to
a slight angle off perpendicular should now be older descriptions of disc structure in horses, it is
550 Large animal neurology

now clear from these studies that the equine interver-

tebral disc has a grossly and histologically discernible
proteoglycan-­rich nucleus pulposus and a lamellar
collagenous annular fibrosis, which is similar to the
situation in humans and dogs.229, 231 In horses, IVDD
is most pronounced at caudal cervical sites and the
lumbosacral joint, whereas spondylosis seen as verte-
bral epiphyseal sclerosis and intervertebral ankylosis
(A) was more likely at thoracolumbar sites.229, 231 However,
the clinical syndromes resulting solely in IVDD as
defined in these studies have not been clearly defined.
Degrees of mild to moderate thoracolumbar spon-
dylosis are common, and back pain is quite frequently
ascribed to the presence of this process. Physical
examination is usually unremarkable, although there
may be some disuse atrophy in the hindquarters.
True back pain may be demonstrated along with
hyperresponsiveness to induced back movement and
(B) restricted inducible extension and flexion of the
thoracolumbar vertebral column, often with inter-
Figure 38.8 Lumbar discospondylosis shown here in cranial lumbar ver- mittent flexion while standing in place. In horses, there
tebrae (left is cranial), is likely more common than the cervical equivalent
may be excessive wear of the hooves or shoes. Stiffness
but probably has the same pathogenesis. Active hemorrhage and necrosis
at the interbody articulation (A) often accompany a chronic fibrotic and of gait with variable lameness is a major presenting
sclerosing reaction (A and B) as evident here in a horse with severe back complaint along with interference to mounting
pain associated with multiple sites of discospondylosis in the caudal tho- and breeding activity in bulls, stallions, and boars.
racic and cranial lumbar region.

(B)
(A)

(C) (D) (E)

Figure 38.9 Cervical discospondylosis is likely traumatic in origin. The progress from acute disc and vertebral end plate injury (A and B) to chronic,
progressive granulomatous fusion of vertebrae (C and D) can be followed by the cases presented here. Acutely, there is disc necrosis and damage to
vertebral physes, which is often hemorrhagic (A). The resultant reactive granulomatous reaction of the adjacent bone continues as an unstable articula-
tion until fusion does, though rarely, occur (C and D), or pain and especially spinal cord compression ensue. Histologically (E), with a breach (star) in the
physeal end plate (between arrow heads), a fibro-­granulomatous reaction develops. and with further motion, additional necrosis and hemorrhage (dia-
mond) occur, adding to the tissue reaction.
 Multifactorial and idiopathic disorders 551

Reluctance to jump fences may be reported in horses. therapy.237 Rest is indicated but may be impracticable.
Degrees of ataxia and paraparesis are less commonly The outlook is poor as signs will slowly progress. In
seen and reflect compression of the spinal cord or, bulls, there is some hope for possible stabilization if
rarely, spinal nerve roots. A slowly progressive stiff the diet is at fault and is corrected.234
gait and apparent pelvic limb weakness occur. Signs
can fluctuate markedly with time over weeks to
Neurofibrillary degeneration
months. A sudden onset of paralysis or paraparesis
may be reported to occur, particularly in breeding Syndromes of tetraparesis progressing to tetraplegia,
bulls and adult horses.216 sometimes with evidence of a weak neck, have occa-
It has been suggested that, at least in horses, aging sionally been seen in young piglets, cattle, and zebra
wear and tear and trauma from strenuous exercise foals.238–240 Widespread neurofibrillary accumula-
and from injuries due to falls causes damage to cau- tions within neurons and degrees of spinal neuronal
dal cervical and thoracolumbar intervertebral disks, fiber degeneration have been present. Whether these
associated subchondral bone plates and epiphyseal syndromes are related to copper deficiency, other
cortical bone.232 Resulting microfractures and hem- nutritional or toxic disorders, or are familial, is not
orrhage in the disc and adjacent physeal regions known at present. Neurofilament accumulations
often accompany advanced changes in intervertebral have been shown to be a characteristic of aluminum
discs230 and ultimately result in necrosis and a foreign intoxication in other species241–243 and are present as
body reaction to fibrocartilage in the form of granu- microtubule-­associated protein tau in the form of
lomatous inflammation, with secondary osteoid and neurofibrillary tangles in Alzheimer disease,244,245 and
bony proliferation. This results in degrees of progres- form the neurofibrillary tangles reported in the fore-
sive discospondylosis that is self-­ perpetuating if brains of aged ruminants in the absence of clinical
exercise continues (Figure 38.9). Such a process disease.246,247 Note the clinicopathologic similarities
might well account for some of the subclinical thora- and differences of these syndromes to brainstem
columbar ventral spondylosis that is referred to as neuronal chromatolysis in cattle (bovine tauopathy)
aging change (Figure 38.8).216, 217, 221, 231, 233 discussed above.
Proliferation of bony spurs around the vertebral
bodies and dorsal vertebral arthrosis has been tenta-
Embolic myelopathy
tively linked with hypercalcitoninism induced by a
prolonged high calcium diet, at least in bulls.234 In Although acute, single, spinal cord infarcts have been
individual and clusters of cases, the possibility of suspected clinically and seen histologically, in horses
hypervitaminosis D and some 2,4-­dihydroxycholecal at least, usually no proof of the cause has been evi-
ciferol-­like, toxin-­containing plants should be given dent.248 However, as occurs in dogs, cats, and
consideration. humans,249–253 fibrocartilaginous material has been
High-­quality radiography and computed tomogra- found in blood vessels adjacent to such lesions in
phy can detect a collapsed disk space and spondylosis horses,253–255 pigs,256–258 and ruminants.259,260 Although
depending on location. Scintigraphy is useful, but quite rare,256 multiple cases of this disease have
with both these imaging techniques it is extremely occurred over a short period of time in pigs being
difficult to accurately differentiate this traumatically sorted for transportation.261 There was good evidence
induced degenerative process from bacterial dis- that 25 out of 1800, approximately 120-­kg finishing
cospondylitis without histologic and microbiologic pigs at risk developed acute myelopathy due to fibro-
diagnosis or compelling systemic and therapeutic cartilaginous emboli secondary to occult, chronic,
evidence of infection.219, 220, 224–226, 235, 236 Local anesthe- suppurative discospondylitis and the stress and
sia of affected vertebral bodies for more definite movement of preparation for transportation.262 One
diagnosis would be extremely difficult to achieve pregnant sow sustained fractures of the fifth lumbar
consistently. vertebra and a disrupted disc at L5–L6 and had
The NSAID drugs phenylbutazone, firocoxib, infarction of the lumbar spinal cord associated with
meloxicam and aspirin, and corticosteroids are use- intra-­arteriolar fibrocartilaginous material.258 Most
ful for relief of pain and inflammation, but most reports of fibrocartilaginous emboli in horses have
cases are well advanced or generalized with onset of described asymmetric lesions that were limited to the
definitive clinical signs, and this is only palliative cervical intumescence;263 however, the involvement
552 Large animal neurology

of the thoracolumbar segments has also been cies, inherent degenerative processes, and combi-
described.264 nations of these remain as possible etiologic
Fibrocartilaginous emboli are assumed to arise factors.281,282
from intervertebral disc material and to lodge in spi-
nal cord veins and arteries via retrograde blood flow Equine grass sickness (equine
from vertebral ventral venous sinuses.249, 250, 265 An
investigated procedure for the injection of corticos-
dysautonomia)
teroids into the lumbosacral disk in horses is a likely Grass sickness or equine dysautonomia has been
fibrocartilaginous emboli risk.266 On occasion, fibro- described since the early twentieth century and since
cartilage emboli have made their way to the ­brainstem then has had quite a devastating effect on equine
and cerebellum.260, 267, 268 Such emboli have also been populations in parts of Western Europe.283–288 Horses
detected in pulmonary vasculature such that a sys- of all breeds as well as nondomestic equidae and
temic release may be expected. camelids can be affected, and dogs, cats, rabbits and
Antemortem diagnosis of fibrocartilaginous hares are affected by similar dysautonomias.287,280–295
emboli can be suspected in large animals that have Most often, this disease occurs in 3–8-­year-­old horses
acute onset and rapid progression of unilateral or that are kept outside and on pasture during late
bilateral signs of spinal cord injury. Notably, except spring and summer, although cases occur year-­
for transient signs of pain at the onset of signs, local- round, rarely in stalled animals.283,284,296 The disease
ized signs of vertebral pain are not found. occurs commonly in Northern and western Europe,
Characteristic MR features of fibrocartilaginous particularly in Scotland and England,287,288,291 but is
emboli have been described for humans and dogs, now reported further east in Europe, at least in
and the technique has been used to presumptively Hungary and Czech Republic.296,297 It was recorded as
diagnose the condition in two pot-­bellied pigs.269,270 an epizootic in Hungary where 15 out of 55
Probably because diagnosis cannot be confirmed 1–3-­year-­old horses succumbed to the disease over
antemortem in horses, all confirmed equine cases one summer with only three surviving.298 The disease
have been fatal. In species such as dogs and pigs reappeared on the same property in 2009 and has
where presumptive diagnosis is possible, the progno- recurred annually thereafter.283 An identical equine
sis for survival is fair to good. Treatment is support- dysautonomia occurs in at least Argentina and Chile
ive care with analgesics as needed to alleviate pain in South America where the acute form is known as
associated with recumbency. mal hinchado (swollen sickness) and the chronic
Intravascular helminths such as Strongylus vul- form as mal seco (dry sickness), and EGS also has
garis and Halicephalobus gingivalis, fat emboli mobi- been reported to occur in Australia, Falkland islands,
lized by intraosseous procedures, tumor emboli, and in one horse in North America.283,299–301 A horse
inadvertent intravenous aspiration of air via jugular in the United States developed recurrent large intesti-
catheters, or intraarterial injection of drugs during nal impactions associated with loss of large intestinal
paravertebral procedures such as IM injections in the myenteric neurons without involvement of auto-
neck or diagnostic sacroiliac joint injection all have nomic abdominal ganglia.302 Although this horse had
the potential to reach spinal cord blood vessels and been imported from Europe, the condition was
cause vasculitis and embolic episodes resulting in thought to be a primary lymphocytic myenteric gan-
subclinical to catastrophic ischemic spinal cord glionitis rather than EGS. Of 4319 Normandy horses
injury.265,271–273 examined by necropsy between 1986 and 2006, there
were 543 cases of neuropathologic disorders detected,
Miscellaneous degenerative or a total prevalence of 13%, and grass sickness
accounted for 34 of these cases, or 6% of the neuro-
myelopathies pathologic diseases and ~1% of all necropsy cases.303
A multiplicity of clinicopathologic syndromes The history, presenting complaint, and neurologic
exists in camelid, ruminant, and equid patients for signs vary considerably depending particularly on
which there is no obvious suspect cause.274–278 Most the initial severity of signs involving the enteric and
are isolated cases resulting in progressive, sym- autonomic nervous system in general.283,285,291,297
metric gait abnormalities although epizootics are Peracute colic with gastrointestinal stasis and rup-
documented.278–280 Toxicities, nutritional deficien- ture, anorexia with mild signs of colic and ileus, to
 Multifactorial and idiopathic disorders 553

chronic cachexia covers the general spectrum of syn- for the cause of grass sickness, but the disease has not
dromes seen with this very unusual disease. Moderate been experimentally reproduced. Currently, the
tachycardia, indifference to food, difficulty in swal- favored hypothesis involves biochemical changes pre-
lowing, excessive salivation, depressed gastrointesti- sent in grass sickness-­ prone pastures effecting a
nal sounds, abdominal distension, and usually mild change in the intestinal milieu allowing microbes
colic are very often present to varying degrees. such as Clostridium spp. to produce neurocytotoxic
Muscular tremor and patchy sweating may be pri- products that progressively damage enteric and auto-
mary signs or may reflect the dehydration, electrolyte nomic neurons,283,284,296,315–317 but sparing to some
imbalances, and colic that occur. Posturing with all extent the activity of the pacemaker cells in the
feet close together as a weak patient does, ptosis and bowel—­the electrically active interstitial cells of Cajal
especially rhinitis sicca are very distinctive signs discovered by Santiago Ramón y Cajal.305,310,318 Genetic
when present. profiling of the enteric bacteriome has confirmed
Whether there is final motor neuronal necrosis marked intestinal dysbiosis in horses with EGS char-
and diffuse somatic neurogenic muscle atrophy is of acterized by increase in Bacteroidetes and a decrease
debatable interest as this is primarily an autonomic in Firmicutes bacteria compared with healthy
disorder not a somatic neuronopathy. The dramatic matched controls.319 Relative preservation of pace-
weight loss that accompanies the initial course of dis- maker cells may be key to the survival of some horses
ease, the posturing and muscle trembling, some elec- with chronic EGS.310
tromyographic evidence, and modest histopathologic No definitive clinical diagnostic test exists.283 A
observations would indicate that there is involve- degree of esophageal dilatation is usually signifi-
ment of somatic motor neurons.288,301,304 However, cant, and a contrast-­swallow esophagram demon-
although appearing generally weak due to the weight strating ineffective peristalsis in the absence of
loss, affected patients do not lie down excessively, the obstruction, not performed soon after a nasogastric
muscle trembling does continue when they do lie tube has been passed, can assist in supporting a
down, and definitive evidence for somatic neuronal clinical diagnosis.320 Less invasive, and probably the
cell body loss and neurogenic muscle atrophy is best aid to clinical diagnosis, is the observance of a
lacking.290,305,306 rapid reversal of ptosis in one eye with 0.5 mL of
Degenerative changes found in many autonomic 0.5% phenylephrine eyedrops321 to confirm the
neurons, particularly in the thoracic and abdominal presence of Horner syndrome. Histopathologic
ganglia,202,301,306,307 and loss of enteric neurons espe- interpretation of nasal and rectal biopsies may also
cially in the small intestine are presumed to be the improve the diagnostic accuracy for the disease.322,323
pathologic substrates of this form of dysautonomia.290 Metabolomic profiling of urine shows some early
All peripheral and central components of the auto- promise as an antemortem diagnostic tool.319 If nec-
nomic nervous system can be affected, and somatic essary, an exploratory laparotomy reveals colonic
final motor neurons in the brainstem and spinal cord impaction but, more importantly, allows histo-
are reliably markedly chromatolytic.306–309 The result, pathologic confirmation of the disease from an ileal
as seen in recovered cases, is small intestinal dilation biopsy.309,324 Interestingly, on exposure of intestines
and muscular hypertrophy, and gastric mucosal during laparotomy of EGS cases, the bowel often
hypertrophy and ulceration, with dramatic loss of displays considerable localized contractile move-
enteric neurons and autonomic ganglion ments; however, this activity appears to be poorly
neurons.305,310 propulsive in vivo as decreased propulsion of
The disease does not seem to be contagious, but ingesta is the norm in this disease.
multiple cases do occur in certain districts and even Using appropriate criteria for the selection of can-
on particular farms and paddocks.287,296,298 Some evi- didates warranting treatment and for those that
dence of familial clustering was found by pedigree should be euthanized are important clinical decisions
analysis of 1233 horses including 49 affected animals to be made.283,284,325 There is no treatment except pal-
in Hungary.311 Attempts at transferring the disease liative intensive and prolonged nursing care.326 All
through blood transfusions may have reproduced the severe (acute) and moderate (subacute) cases die or
neuropathologic changes, but not the clinical signs.312,313 must be destroyed. Probably 50% of the remaining
Various biologic and chemical toxic factors in pas- chronic cases showing milder signs with a more pro-
tures grazed by affected horses have been candidates tracted course can be nursed to survive (Figure 38.10)
554 Large animal neurology

(A) (B)

(C)

Figure 38.10 Presenting syndromes due to equine dysautonomia (grass sickness) are mostly those of fulminant to extremely chronic gastrointestinal stasis.
However, specific clinical signs of autonomic dysfunction can lead to quite differing additional signs such as Horner syndrome, fixed heart rate of 50–60 bpm,
and repeatable regions of sweating on the body. One sign regarded as almost pathognomonic in the right setting is bilateral spontaneous rhinitis sicca (A).
This occurs without analgesia of the nasal membranes that distinguishes it from that seen with the dry nasal membranes that can accompany trigeminal
neuritis. Also, degrees of drooling and excessive nasal discharge can occur with grass sickness in various combinations. Although impaction of food in the
oropharynx can also occur, there is not often true pharyngeal dysphagia. This horse with grass sickness (B) would drool saliva that appeared to be excessively
produced, and intermittent floods of clear mucus would appear at the nares as shown. This fluid was different to the saliva appearing from the mouth in color
and transparency and was believed to be excessive nasal mucus production helping to distinguish this syndrome from pharyngeal paresis or paralysis when
saliva and ingesta appear at the external nares. One of the authors would be bragging to say that he was involved in the nursing care of each of this group
of five horses recovering from suspected chronic grass sickness (C), all of which were returned to their owners.

with minimal degrees of ill thrift remaining, remain in doubt but with experience the clinical
­sometimes accompanied by chronic hair coat changes diagnosis can be extremely accurate.283–285, 305, 325, 327
and predisposition to mild colicky episodes. Of Treatment supporting interstitial pacemaker cell sur-
course, in such cases the definitive diagnosis might vival and function warrants investigation.310
 Multifactorial and idiopathic disorders 555

Recurrent laryngeal neuropathy lead poisoning and can also occur with liver disease,
following general anesthesia and with organophos-
Idiopathic equine recurrent laryngeal neuropathy phate345–348 and some plant toxicities. The most com-
(RLN) as a singular problem frequently is recognized mon cause of right side laryngeal dysfunction is
in mature, light breed, long-­necked horses used for cricopharyngeal laryngeal dysplasia described best as
performance.328–334 While exercising, the horse is fourth branchial arch defect (4-­BAD).333,334
noticed to make an excessive respiratory noise during Upper respiratory endoscopic examination
inspiration, referred to as roaring or whistling. The reveals an asymmetric position of the arytenoid car-
horse may fail to perform as expected near the end of tilages and poor or no abduction of the vocal fold on
a race. Ponies rarely if ever are affected by the clinical forced inspiration. Poor adduction of the vocal fold
disease and, unless exercised strenuously, the disease is demonstrated with the laryngeal adductor
must be occult in many horses as quite a proportion of response test (see Neurologic Evaluation, Chapter 2).
adult tall horses have asymmetric muscle bulk on From initial work it was concluded that this test was
their larynges with electrophysiologic and pathologic very unreliable for the diagnosis of RLN.349
evidence for there being a large proportion of tall Subsequent clinical data was interpreted that this
horses having subclinical or preclinical disease.335 was a very poor test for diagnosing particularly cer-
The disease does not appear to occur in zebra nor vical spinal cord disease and was very poor for the
in giraffes.336,337 Indeed, phylogenetically and embry- diagnosis of RLN.350,351 The electrophysiologic equiv-
ologically, the recurrent laryngeal nerve has been alent of the laryngeal adductor response test is the
considered an example of “unintelligent design,” electrolaryngogram from which approximate nerve
especially in long-­necked tetrapods, in all of which, conduction latency measurements of the reflex path-
including equids, it travels a path of many meters way are made and found usually to be slower on the
from brain, around the great vessels to larynx.338 left side in normal horses and ponies, and slower
Therefore, if this nerve had the same developmental in horses affected with RLN.352 There is uncertainty
origin and followed the same course in extinct tetra- as to the reliability and sensitivity of this test,353 but
pods such as sauropod dinosaurs, then the neurons it may well assist with the clinical appraisal of
that comprised the recurrent laryngeal nerve in these Thoroughbred horses with RLN.335,355 It has now
grand animals were at least 28 m long.339 been confirmed experimentally that nerve conduc-
There is often palpable loss of dorsal and lateral tion is slower through the distal compared with
musculature on the left side of the larynx,340 render- proximal segments of both recurrent laryngeal
ing the projection of the muscular process of the nerves and is slowest through the distal left nerve.335
arytenoid cartilage relatively prominent. Neurological Thus, a clinical diagnosis of RLN relies especially
evaluation of a horse suspected of having abnormal on a history of variable upper respiratory obstruc-
laryngeal function should include a complete neuro- tion, static and dynamic laryngeal endoscopy, and
logical examination as degrees of left-­sided or right-­ laryngeal muscle ultrasonography.330,332,340,355–358
sided, or bilateral laryngeal paresis may occur in Multiple respiratory conditions frequently compli-
conjunction with other neurological signs.333, 334, 341–343 cate the clinical picture and diagnosis.330
These additional signs rarely relate to brain or spinal In the idiopathic disease, distal axonal degenera-
cord lesions but more often to peripheral nerve tion occurs in the recurrent laryngeal nerves and is
involvement especially within and around the gut- worse on the left side with nerve fiber atrophy being
tural pouch, neck, and cranial thorax. Other signs of worse close to the larynx (Figure 38.11). Degrees of
vagosympathetic trunk involvement especially in the demyelination and remyelination accompany the
form of swallowing difficulties, Horner syndrome, axonal disease.
and sweating over variable areas of the head and neck Although the syndromes overlap histologically,
can accompany such signs of RLN. Dysfunction of the preponderance of evidence is that RLN is a pri-
the recurrent laryngeal nerve can be caused by mary axonopathy with secondary demyelination
perivascular injections, guttural pouch mycosis, cra- rather than a primary myelinopathy. Evidence of cen-
nial thoracic masses, postanesthesia possibly due to tral changes has been sought, but lesions in the neu-
hyperextension within the head and neck during sur- ron cell bodies of the recurrent laryngeal nerves that
gery, and from iatrogenic causes during neck surgery. reside in the nucleus ambiguus of affected horses
Bilateral laryngeal paresis commonly accompanies have not been confirmed.359–361
556 Large animal neurology

and horses with other recognized neuropathies,

for example stringhalt and equine polyneuropathy
(see below), can undergo complete recovery, and
even though there is histological and histochemi-
cal evidence of regeneration of nerves and reinner-
vation of muscles, clinical and endoscopically
evident spontaneous recovery is very uncommon
in RLN.
(A) Thus, the idiopathic form of RLN is an enigmatic
disease that has some characteristics of a hereditary
disorder, but several fundamental questions remain
unanswered that make this assumption somewhat
presumptuous and searches for genetic markers have
been unrewarding.333,371–373 First, why are tall,
modern-­day horses prone to idiopathic RLN? Where
is the primary insult to the recurrent laryngeal nerve
neurons? Is it truly a mononeuropathy or a reflec-
tion of a polyneuropathy? The neural lesions are lik-
ened to those seen in many cases of stringhalt and
representing a distal polyaxonopathy of long nerve
fibers,365,368,369 but further documentation is
(B) required. 333,334,370 On the other hand, meticulous
examination of nerves and muscles of a small num-
ber of cases suggests that this disease may be a bilat-
eral mononeuropathy, with lesions limited to the left
and right recurrent laryngeal nerves.376 In summing
evidence from most pathologic studies of RLN,
Draper and Piercy338 concluded that RLN is best cur-
(C) rently classified as a distal axonopathy with clear evi-
dence of involvement of both recurrent nerves, but
Figure 38.11 Recurrent laryngeal neuropathy (RLN) is an enigmatic neu- that there is insufficient evidence to classify the dis-
ropathy commonly affecting the left recurrent laryngeal nerve (rln) in tall
ease as either a bilateral mononeuropathy or as a
horses. In some of these, there is impedance of performance due to partial
upper respiratory compromise. Some fiber loss occurs in the rln ( fascicles polyneuropathy. If this is a solely inherited disease
compared with fascicles) in the mid to caudal neck near the nerve’s associated with the structural design of tall equids,
origin from the vagus nerve (A). More distal along the rln in the cranial neck then it really can be thought of as “unintelligent
there can be severe neuronal fiber loss (B and C). Schwann cell proliferation design”. The distal axonopathy that is documented in
(C) and unsuccessful attempts at reinnervation do occur. Pallid endoneural
idiopathic RLN in roarers is like that seen from the
connective tissue is replacing neuronal fibers (B), but is not organized into
structures as are Renaut bodies (Figure 4.6). (Toluidine blue, 1 μm epoxy effects of several selective neurotoxins.375,376 Thus,
embedded sections; (A) and (B) 20×, and (C) 100×). chemicals, drugs, mycotoxins, and biotoxins have
been suggested etiologies.
Laryngeal ventriculectomy and laryngeal muscle
All intrinsic laryngeal muscles except the crico- prosthesis are two of the preferred procedures per-
thyroid muscle, but particularly the dorsal cricoar- formed regularly to salvage affected performance
ytenoid muscle, show denervation atrophy.338,362–369 horses for continued use.333 Probably, 50% of early
Similar but much milder nerve fiber loss may cases respond to ventriculectomy. More compli-
occur in other long peripheral nerves in affected cated surgeries, including nerve/muscle pedicle
horses, suggesting that the syndrome is an expres- transplantation into laryngeal musculature, proba-
sion of a diffuse, peripheral, distal axonopathy,335,370 bly give better, albeit delayed, results.331,356,377,382 On
although not all studies concur with this.338 Horses the horizon are genetic transplantation and aug-
with severe RLN do not usually demonstrate clini- mentation techniques to optimize neuromuscular
cal signs of the involvement of other long nerves, regeneration.382
 Multifactorial and idiopathic disorders 557

Aortic–iliac–femoral thrombosis Doppler flow measurements, of the abdominal403 but

and ischemic neuromyopathy particularly the femoral arterial supply to the pelvic
limb can assist in defining the extent of the throm-
Aseptic aortic, aortic–iliac, and aortic–iliac–femoral bus.384,401,404 Scintigraphy and aortic angiography can
thrombosis is most often seen in adult racing and be additional imaging methods to define the reduced
performance horses383–387 and in younger septic perfusion occurring.388,399,400,405
patients.388–392 The adult disease is overrepresented in In adult patients, associations with equine infec-
males, especially stallions.377,378 tious anemia, Strongylus vulgaris arteritis, throm-
Classically, the disease in adult horses is an inter- botic diseases, sepsis, and cardiomyopathy in various
mittent claudication of the hindquarters with signs of cases have been suggested, none of which are sub-
pelvic limb lameness reproducibly elicited by exer- stantiated.385,393,394,396,398 The cause of nonseptic aor-
cise and completely relieved by rest for 5–60 min. tic–iliac–femoral thrombosis in adult horses is not
Initial signs vary from stiffness in the pelvic limbs clear but does not appear to be related to underlying
and slowing near the end of a race, to lameness and cardiomyopathy as is the case in cats406 and also dif-
knuckling in one or both pelvic limbs, to fulminant fers from canine aortic thrombosis that in many cases
paraplegia.393–395 Selective thrombosis of other major is associated with underlying coagulopathy, and can
vessels occurs rarely.396 be slowly progressive.406 As it does occur most often
In mild cases of aortic–Iliac thrombosis, there is a in horses used for strenuous performance, the physi-
decreased arterial pulse pressure in the pelvic limbs cal effects of pelvic limb and abdominal exertion on
and slow saphenous vein refill following exercise. the movement of and blood flow in these major ves-
Severely affected animals are paraplegic with cold sels likely play a role in its pathogenesis. Interestingly,
pelvic limbs and areflexia and analgesia that can be large artery thrombosis causes more severe nerve and
clearly demarcated along with decreased or no muscle damage than purely mechanical occlusion of
regional peripheral perfusion. Weak aortic and iliac the same artery, so it is likely that factors in addition
pulses or thrombosis, and occlusion of the terminal to the physical arterial occlusion contribute to the
aorta or iliac arteries may be palpated through the ischemic neuromyopathy and clinical signs.400,408,409
rectum.386,387,393–395,397–400 Some unusual clinical signs These factors include inflammatory and other hemo-
that may occur are kicking out with the pelvic limbs static agents released from platelets in the initial
as if in response to prominent paresthesia, repetitive thrombus, such as 5-­hydroxytryptamine, suggesting
and prominent lifting of one or both pelvic limbs that antagonists to such inflammatory mediators
during rest as seen with thoracolumbar spondylosis should be considered in treating early cases.409
and other painful back problems, and decreased Clinicians have tried combinations of heparin,
libido and ejaculatory failure in stallions.387,398 aspirin, coumarin derivatives, anthelmintics, NSAID
Thrombi propagate distally from a point of attach- drugs, calcium gluconate, ivermectin and glucocorti-
ment in the distal aorta to extend into and partially coids with variable and equivocal results,387,390,397–400,410
occlude the external and/or internal iliac arteries on and the disease is usually regarded as progressive and
one or both sides with degrees of hypoxic–ischemic the prognosis as poor. Nevertheless, substantial
neuromyopathy resulting from major vessel occlu- shrinkage in size of an internal iliac thrombus
sion. Lameness is usually caused by external iliac– occurred over several months of monitoring.383
femoral arterial thromboses, but has also been Surgical treatment with vascular thrombectomy
reported in a case involving only the internal iliac equipment is feasible in selected cases where the
artery.383 Interestingly, in well-­ established cases thrombi are accessible via the femoral arteries. Good
involving adult horses, superficial collateral perfu- outcomes have been reported with 11/17 horses with
sion is greatly increased such that cutaneous pulses large arterial thrombi returning to exercise and nine
may be felt over much of the hind quarters. competing again at or above their previous level of
Transrectal ultrasonography is better to clearly performance, but complications and recurrences are
define the thrombosis and is the diagnostic test of a problem.383,384,402
choice,383,384,386,387,395,396,398,401–403 although normal ter- Some horses can be maintained in a satisfactory
minal aortic ultrasonographic turbulence can be stable state by exercising them up to the point where
mistaken for thrombus formation. Transcutaneous slight gait abnormalities are seen, thus promoting
ultrasonographic examination, preferably with and maintaining collateral circulation,399,410 and by
558 Large animal neurology

optimizing blood flow by treatment with the rheo- intermittent flexion of the hind fetlock joints during
logic agent pentoxifylline (10 mg/kg orally BID) and exercise or after sudden stress, to continuous knuck-
minimizing thrombus propagation with low-­ dose ling while standing, to recumbency. Thoracic limb
aspirin (5 mg/kg SID) or clopidogrel (2 mg/kg SID). weakness is rare, and there are no reports of laryngeal
Septic neonatal patients are usually quite ill but can dysfunction being present. Most affected horses
be ambulatory with prominent sensory and motor show minimal or no ataxia and have modest or no
deficits to one or both pelvic limbs due to major vessel muscle atrophy in affected limbs. In Norway and
occlusion as part of the sepsis syndrome and the likely Sweden, adult horses present in winter or spring
consumption coagulopathy occurring.390,391,400,403 whereas the profile of disease onset in Finnish horses
Treatment of critically ill septic calves with E. coli-­ is bimodal, either during the late fall or spring.414,417
associated aortic thrombosis is frequently unsuccess- Epidemiologic analyses of cases in Sweden and
ful, but milder cases of such thromboses can be Norway have revealed spatiotemporal clustering of
successfully treated with anticoagulant, NSAID, and cases and an association with the feeding of plastic-­
antimicrobial therapy along with nursing care.389,400,403 wrapped haylage or silage. The specific cause is not
known but is presumed to be toxic or toxicoinfec-
Idiopathic neuropathy with knuckling tious. Typically, more than one horse, but not all
horses, are affected on a single property. Finnish
in horses cases are in horses fed hay (fall) or silage (spring).
Japanese workers411,412 have studied three cases of a Reported mortality rates for the syndrome are
neuropathy present in a superficially described syn- 29–53%413,416,418,419 with deaths typically resulting
drome of growing horses referred to as knuckling. from euthanasia of recumbent horses. Most surviv-
Clinically, this appears to be the not uncommon syn- ing horses recover completely over weeks to months.
drome of prominent upright posture with tendency The clinical syndrome is one of varying degrees
to flex the carpi and fetlocks which occurs during of bilateral sciatic nerve involvement, some horses
weight support as an acquired syndrome in wean- showing more prominently signs of peroneal neu-
lings and yearlings. These patients sometimes ropathy and others showing more prominently
dragged the toes of their forelimbs. The workers signs of tibial neuropathy.420 Occasional cases have
described widespread peripheral nerve Wallerian-­ extensor weakness, also indicating femoral nerve
­
like degeneration, most prominent distally. The for- involvement, and in some affected horses, general
mation of bands of Büngner and regenerative axonal proprioceptive deficits are seen as ataxia.
sprouts do make this pathological process consistent Several detailed postmortem examinations have
with a diffuse distal axonopathy. Neurogenic muscle been undertaken, and in many there was evidence of
atrophy with some regeneration was seen with fiber-­ mild peripheral Wallerian-­like neuronal fiber degen-
type grouping, particularly in distal muscles. The eration on routine light microscopic sections.416,419
comment was made that “laryngeal paralysis was not Minimal to no histologic evidence of denervation of
observed in the present cases.” Unfortunately, the digital extensor muscles has been found, even in
basis for this statement was not given so that evi- chronic cases.421 There is moderate loss of large mye-
dence for the clinical presence of a polyneuropathy linated nerve fibers that may therefore be 1a and 1b
was lacking. sensory rather than motor fibers. More detailed stud-
ies have revealed conspicuous Schwann cell inclu-
Acquired equine polyneuropathy sions associated with neuronal and myelin lesions in
large diameter fibers, although the prominence of
of Nordic horses these lesions was not necessarily related to clinical
Clusters of an unusual pelvic limb knuckling syn- severity.421 Indeed, the clinical syndrome, recovery of
drome in adult horses were reported first from function, and ultrastructural morphological lesions
Norway in 1995,413 Sweden in 1998,414,415 Finland would be more indicative of a primary demyelinating
from 2005416,417 and most recently from Iceland in lesion being operative with some secondary axono-
2019,418 with many hundred cases now documented. pathic lesions occurring,416 and the lesions have been
The syndrome originally referred to as categorized as a schwannopathy.421 In a few cases, the
Scandinavian knuckling syndrome has been renamed thoracolaryngeal response has been intact, strongly
acquired equine polyneuropathy. Signs range from indicating that a distal polyaxonopathy is less likely.413
 Multifactorial and idiopathic disorders 559

Although neurophysiologic studies including elec- ­ rominent muscle contractions. Generally, there is an
p
tromyography and nerve conduction studies are not insidious onset. Exercise intolerance associated with
easily performed in horses and are not reported for mild to moderate muscle stiffness may be the only ini-
this disease, their use could well assist in defining the tial clinical sign. This may easily be attributed to a pri-
type of neuropathy present.375,422–424 mary myopathy, with pain on muscle palpation,
As yet unknown peripheral neurotoxins do appear although serum muscle enzyme concentrations remain
to be the most likely cause of this crippling acquired in the normal range. If untreated, the degree of stiffness
equine polyneuropathy.375,413 Twin weaned calves had seems to progress, and episodes of muscle spasms may
similar signs with knuckling and ataxia progressing to become apparent. The latter are typically initiated if the
recumbency with good evidence of polyaxonopathy.425 animal is startled, although they may occur spontane-
There are certainly numerous other anecdotal reports ously during voluntary movement. In the horse, the
of similar syndromes occurring in adult horses and lumbar and hindlimb muscles are typically involved
cattle, some with strong evidence, others with specula- which may result in a lordotic or kyphotic type stance
tive evidence, of contact with nonradioactive heavy during the more severe episodes.438,439 The head and
metals such as vanadium and other potential neuro- neck may be elevated as well as the tail head. The dura-
toxins exemplified by acrylamide.426–429 tion of the spasmodic episodes may vary from a few
seconds to many minutes. It is likely that there is a sig-
nificant degree of discomfort and pain associated with
Stiff-­horse syndrome these spasms as affected horses will often have an anx-
A stiff-­ person syndrome has been recognized in ious expression during these events. Between episodes
humans for some time.430–434 It is a progressive auto- the horse may appear normal although, if present, the
immune disorder with core features of truncal and generalized muscle stiffness may persist.
limb rigidity and painful muscle spasms leading to Only a low number of cases have been suspected,
gait difficulties, falls, and a tin-­soldier appearance. hence although the syndromes expressed may be
This rare condition is associated with various typical, they are of course not necessarily complete
antineuronal antibodies, one of which is produced nor are they pathognomonic for this condition.
against the enzyme glutamic acid decarboxylase Clinical examination is generally unremarkable.
(GAD) that is responsible for converting gamma-­ A neurological examination will likely fail to detect
aminobutyric acid (GABA) into its active form. In any abnormalities apart from the intermittent hyper-
some cases, the autoimmune response may be tar- tonia and unusual posturing. Components of the
geted against other neuroactive proteins including syndrome bear resemblance to such disorders as teta-
the GABA-­A receptor and the α-­1-­subunit of the gly- nus, equine motor neuron disease, hyperkalemic
cine receptor (GlyR). In other cases (~30%) there are periodic paralysis, the myotonias, and several myo-
no antineuronal antibodies detected.433,435 As GABA pathies. Routine blood screening should eliminate
is an important inhibitory central neurotransmitter, a rhabdomyolysis, hypocalcemia, and hyperkalemia as
reduction in its activity can lead to continuous con- possible diagnoses. A muscle biopsy of the semi-
traction of both agonist and antagonist muscle membranosus muscle may be performed to exclude
groups. Occasional cases of stiff-­person syndrome other muscle disorders such as exertional rhabdomy-
following other diseases such as West Nile fever pos- olysis and equine polysaccharide storage myopathy.
sibly are due to cross reactivity of antibodies to WNV Electromyographic tests may also be performed on
being also directed to effector targets such as GAD.436 the affected resting muscle groups that will likely
The disease also occurs as a paraneoplastic syn- show continuous motor unit activity without neuro-
drome.431,433 Variants of the human condition such as genic or myopathic discharges.437
stiff leg syndrome, which presents muscle cramping The most useful diagnostic test for stiff-­person
restricted to one limb, do occur, such that the broad syndrome is the detection of antibodies against GAD
term stiff-­person spectrum disorder can be used to in serum and cerebrospinal fluid. Although some
encompass the wider clinical–immunologic condi- equine cases have had high cross-­reactive anti-­GAD
tion.433,435 A similar syndrome has been seen in horses titers, several strongly suspected cases have been neg-
and is termed the stiff-­horse syndrome (SHS).437–439 ative on this test, perhaps suggesting the involvement
Clinical signs appear to wax and wane and range of another part of the GABA pathway or poor sensi-
from mild muscle stiffness to sudden and often tivity of the human test for equine anti-­GAD.
560 Large animal neurology

The two main therapeutic options currently avail-

able431,432,440,441 which are of practical use in horses
are benzodiazepines, used for their GABA agonist
activity, and corticosteroids to suppress autoimmun-
ity. The cornerstone of treatment is the use of corti-
costeroids. A suggested regimen is dexamethasone,
0.1 mg/kg IV or IM daily for a week, then tapered over
a month to 0.01 mg/kg/day, and finally discontinued
or maintained with low-­ dose dexamethasone or
equivalent. This regimen can be repeated as necessary
to treat relapses. Other treatment options used in (A)
humans but not yet tried in equine patients include
intravenous gamma-­ globulin, and baclofen and
vigabatrin, both of which enhance GABA neurotrans-
mission. The anticonvulsant phenobarbital is also a
GABA agonist with potential utility in treatment but
appears not to have been used. The prognosis for
recovery is generally poor; however, good responses
to corticosteroid therapy have been recorded.
In some cases of stiff-­person syndrome, lympho-
cytic infiltrates suggesting immune attack can be
found in several organs such as the thyroid and pan-
(B)
creas, and in a severe form there is progressive and
fatal nonsuppurative encephalitis. One horse with
consistent clinical signs and extremely high serum
and CSF anti-­GAD antibody titers did not have infil-
trates in a wide range of organs examined.
The overall message is really that with the array of
enigmatic movement and postural disorders encoun-
tered in equine neurology that appear to be variations
on the themes of stringhalt, shivering and claudica-
tion,442–444 a broad approach to delving into possible
etiologic mechanisms should be taken that includes the
possibility of immune-­associated neurotransmitter and
neuronal derangements such as stiff-­horse syndrome.

Kangaroo gait in sheep (C)

Bilateral loss of extensor function in thoracic limbs Figure 38.12 This ewe suffered from the syndrome of kangaroo gait, and
in smaller ruminants results in most or all weight although would shuffle along in this posture (A), with coaxing she would
borne on the pelvic limbs, as does a kangaroo. spring forward using the pelvic limbs akin to a hopping kangaroo. Pelvic limb
Although first clearly reported in New Zealand sheep reflexes were very good. Being a bright and alert sheep, the thoracic limb
flexor reflexes were difficult to distinguish from voluntary effort. However,
on pasture,445 the syndrome has mostly been seen in the ewe was only able to support weight on either thoracic limb in turn with
the UK particularly in intensively managed ewes.446–450 support (B), and hopping was not possible. Within a week, and before an
The patient positions the pelvic limbs forward under EMG could be conducted, the ewe regained a normal posture and gait (C).
the abdomen and during motion flings the thoracic Although the exact diagnosis was in doubt, a traumatic brachial compres-
limbs to place them without taking much or any sion had to be suspected in this case of kangaroo gait.
weight on them. With severe loss of extensor func-
tion and with time, they often learn to run on the s­ yndrome occurs as a result of bilateral lesions involv-
pelvic limbs without using the flexed thoracic limbs, ing ventral gray matter at C6–T2, the brachial plexus,
a little like a kangaroo (Figure 38.12).446,451 This or the radial nerves.448
 Multifactorial and idiopathic disorders 561

Of note here is that any process causing severe bilat-

Flying scapulae in ruminants
eral forelimb lameness or disuse—­such as bilateral Sudden onset of loss of the support of the pectoral
long bone fractures—­can result in such a syndrome. In girdle occurs in individuals or groups of young rumi-
addition, in so-­affected heavy patients forward pro- nants usually coincident with additional exercise
gress tends to occur in bursts of motion or lunging that such as occurs at the time of pasture turnout in spring
is very difficult to interpret (see Chapter 26). time.453–458 The scapulae become positioned dorsal on
the thorax and protrude well above the cranial tho-
The syndrome of kangaroo gait in sheep is most racic dorsal spinous processes with associated rela-
commonly seen in pregnant and lactating ewes and tive ventral positioning of the sternum, viz. flying
often resolves within a week or so or more slowly scapulae. Degrees of thoracic limb abduction con-
over months.446,448–452 Extensor tone and reflexes are found the limited postural defect seen and can result
reduced or absent in affected thoracic limbs with in severe disability and recumbency. Evidence of
varying reduction in flexor tone and reflexes but no muscle enzyme release is documented in some early
or poorly defined sensory loss. cases, and evidence for the predisposing operative
Lightweight small ruminants, especially goats and role of vitamin E and selenium deficiency and associ-
pigs, suffering bilateral forelimb painful conditions ated widespread nutritional myodegeneration is
such as polyarthritis and foot rot can be seen to move given for some groups of cases,453–455,457,458 but this is
in the same manner in attempts at not weight-­bearing not consistent.453,456,459 There can be rupture of the
on the thoracic limbs. Young pigs with cervicotho- serratus ventralis muscles, specifically m. serratus
racic poliomalacia associated with selenium toxicity ventralis thoracis, confirmed at postmortem exami-
can also show a remarkably similar porcine version nation. The presence of concurrent ruptured limb
of kangaroo gait. This disorder has been likened to flexor apparatus in patients or herd mates after unac-
fenugreek (Trigonella foenum-­graecum) toxicity in customed exercise is strong evidence for exertional
ruminants that causes a polymyopathy.452 injury as the precipitating factor. There is some simi-
Axonal lesions in peripheral nerves in the thoracic larity to bilateral damage to the lateral thoracic nerves
limbs of affected sheep have been demonstrated that such that this possibility could also be considered.460
are consistent with a peripheral neuropathy,446,450–452 Some adult cows that are long-­term survivors have
but this has not been confirmed in all cases.449 had prominent atrophy of the shoulder muscles indi-
Notwithstanding, by far the most likely and common cating a more diffuse neuromyopathy, possibly
cause of kangaroo gait in sheep is bilateral compres- involving the brachial plexus and pectoral girdle
sion to the brachial plexuses, particularly the seg- musculature. The syndrome is seen in cats with many
mental supply forming the radial nerve outflow, and diffuse neuromuscular disorders including hypoka-
subsequent combinations of neurapraxia and axonot- lemia, hyperthyroidism, and myasthenia gravis, so
mesis. As expected with trauma to the brachial region this might be expected in such rare disorders in large
and neural plexus (see Chapter 32), the vulnerable animals. Needle EMG studies may assist in defining
suprascapular nerve likewise can show evidence of the extent of any myopathy and neuropathy in indi-
injury.446 vidual cases. With only little thoracic limb abduction
Detailed EMG studies performed under general being present, the outlook for sedentary survival and
anesthesia a week or more after the onset of signs slow improvement in the postural defect is good but
need to be undertaken to map the distribution of the recumbency has meant the demise of several cases.
affected motor nerves. This should also be combined
with precise histopathologic study of C6–T2 spinal
Dropped hock syndrome in cattle
cord and nerve roots, all thoracic limb peripheral
nerves, and most particularly the brachial plexuses An interesting syndrome has recently been reported
and frozen sections of all major muscle groups to from New Zealand involving mostly 2–3-­year-­old,
substantiate a traumatic pathogenic process. late pregnant dairy cattle showing progressive hock
Additionally, the blood supply to the brachial plexus hyperflexion, sometimes with fetlock flexion, ending
should be included in evaluation as a vascular com- in Achilles tendon rupture.461 The signs were reported
promise as well as compression of the plexuses could to improve or resolve in a large proportion of cases
be operative. over weeks to months. Cursory, routine light
562 Large animal neurology

­ icroscopic screening of sciatic nerve samples failed

m ­ nderstood. When forced exercise results in exhaus-
u
to reveal any consistent changes, and the authors tion with unwilling recumbency, capture myopathy
concluded that the syndrome was most likely a selec- results.462,485,486
tive connective tissue degeneration, although stating When there is an intrinsic abnormality in muscle
that a neuropathy—­as seen in acquired equine poly- function, episodes of muscle disease are recurrent
neuropathy above—­could not be ruled out; indicat- and chronic exertional rhabdomyolysis is diagnosed.463,490
ing that a primary polyneuropathy may well be This may be associated with accumulation of exces-
operating. sive glycogen and/or complex polysaccharide on his-
topathologic examination of muscle biopsy samples.
Exertional rhabdomyolysis and In draft breeds and Quarter Horses, polysaccharide
storage myopathy (PSSM) is predominantly due to a
capture myopathy single gain-­of-­function mutation in the gene for gly-
Readers are referred to general and specific refer- cogen synthase 1 (GYS1) resulting in increased insu-
ences elsewhere for coverage of exertional rhabdo- lin sensitivity to glucose.494 Historically, what was
myolysis and capture myopathy, as well as other almost certainly this form of PSSM (known as
primary myopathies.462–469 However, these particular PSSM1) was also referred to as azoturia, paralytic
disorders are given coverage here as they very fre- myoglobinuria, tying-­up, set fast and Monday morn-
quently are in a differential diagnosis for clinicians ing disease, each of which emphasized components
evaluating gait and posture abnormalities where neu- of the syndrome. A second form of PSSM (viz.
rologic disorders are strongly suspected. PSSM2) accounts for most cases seen in warmblood
Muscle pain with or without muscle damage asso- and light breed horses. In PSSM2, the genetic basis is
ciated with sporting use is very common in animals unknown, and the examination of muscle biopsies is
including human athletes.470–484 Clinical evidence of required for diagnosis.463,495 The most common form
muscle stiffness and release of cytosolic muscle of chronic exertional rhabdomyolysis that occurs in
enzymes also occurs frequently in exercising animals young Thoroughbreds and other light breeds under-
and in wild animals exercised forcibly during cap- going strenuous exercise is recurrent exertional rhab-
ture.468,476,481,485–491 But it needs to be iterated that domyolysis (RER).468,469,475,476,490,496,497 This occurs in
modest increases in circulating activities of muscle 5–7% of Thoroughbred and Standardbred race-
enzymes occur with most forms of strenuous exer- horses463,490,498–500 and is probably also found in
cise, therefore excessive exercise almost certainly Quarter Horse, Arabian, and warmblood breeds.501–503
results in occult and mild or even prominent clinical RER appears to result from an intrinsic abnormality
myopathic changes.481,487 in regulation of intracellular calcium in myocytes,
Extrinsic factors such as concurrent disease, over- provoked by certain kinds of exercise and by nervous
exertion relative to conditioning, and marginal nutri- excitement.497 A genetic basis for susceptibility to
ent deficiencies may well contribute to such a RER has been suggested but not confirmed in
syndrome and this can be referred to as sporadic exer- Thoroughbred horses. Female gender, young age
tional rhabdomyolysis.463 This can be considered as (2 year old most susceptible), nervous temperament,
analogous to the syndrome of delayed-­onset muscle lameness, and daily intake of >2.5 kg of high-­
soreness in human athletes.480,482 Altered total body carbohydrate grain are risk factors for RER.463 In
electrolyte status, detected in affected horses by Thoroughbred racehorses, steeplechasers, and event-
determining the relative loss of electrolytes in the ers after the steeplechase phase, signs more often
urine (FEx), may be of some significance.478,479 Low occur when or after horses are restrained in a “paced”
intraerythrocytic K+ concentrations have been gallop rather than during a full-­out work, race, or eve
detected in affected horses in training compared with nt.472,473,478,479,487,490,498,504 Standardbred horses are more
unaffected horses in training.492 Also, the role of sex prone to develop RER during a prolonged (>15 min)
hormones and thyroid hormones has been dis- continuous jogging session rather than during
cussed.478,479 Finally, the role of vitamin E status and intense interval training or racing. Additional inborn
glutathione peroxidase activity in sporadic cases disorders of muscle function that have been associ-
has been questioned.493 The individual and com- ated with chronic exertional or nonexertional rhab-
bined roles of all these factors and many others in domyolysis are malignant hyperthermia (autosomal
the pathogenesis of this syndrome are not fully dominant mutation in ryanodine receptor 1 gene,
 Multifactorial and idiopathic disorders 563

RYR1),505 and myofibrillar myopathy (dysfunctional stabilizes intracellular calcium and is used to prevent
desmin protein, unknown genetic basis).506,507 ongoing rhabdomyolysis, and methocarbamol may be
The equine patient with exertional rhabdomyoly- given slowly IV at 20 mg/kg every 6 h for additional
sis may be showing exercise intolerance or not train- relaxation of muscle membranes.463,465,472,473,476,504,508
ing as well as expected, or may fade in races or other Corticosteroids are not indicated. Many clinicians
competitions and become stiff and sore after a work- empirically administer vitamin E and selenium, and
out. Alternatively, the horse may suddenly stop some use multigram doses of thiamine IM. The
after beginning strenuous exercise and refuse to effectiveness of these drugs is unknown. The recov-
move.463,472–474,476,478,479,490,497,508–510 The affected horse ering horse may be turned into a small paddock to
is usually in good physical condition but may be self-­exercise after the initial period of intensive treat-
overweight. Discolored, brown urine is present in ment and restricted movement.
severe cases. The horse may stand with a saw-­horse Prevention of recurrent episodes of rhabdomyoly-
posture, is reluctant to move, and experiences sis requires meticulous management of diet and
degrees of p ­ araparesis and stiff slow-­striding pelvic exercise.463 Evidence-­based protocols for RER and
limbs which in extreme cases progresses to recum- PSSM1 have been published and should be con-
bency. Noninflammatory myonecrosis preferentially sulted for detailed guidance.515,516 In general, pad-
affecting Type-­II muscle fibers occurs.473,474,476,504,511 dock turnout should be maximized, intake of
Muscles used most during exercise and work are nonstructural carbohydrates should be controlled,
more severely affected, and muscle fibers demon- especially in Quarter Horses with PSSM, and thus
strate heightened sensitivity to contraction. Pain grain feeding should be minimized with needed
responses are induced on palpation of muscles, espe- caloric intake provided as additional vegetable oil.
cially ­lumbar and sublumbar muscles, which may be Exercise should be increased incrementally after a
swollen. Myoglobin is released and excreted in the tying-­up episode, slowly in the case of PSSM1 and
urine, and myoglobin nephrosis and azotemia thus more quickly in horses with RER, until there is at
may result. With recovery of horses with PSSM or least 15 min of exercise under saddle or in harness
myofibrillar myopathy, severe muscle atrophy may almost every day. Serum CK and AST is followed to
occur.463,470,472,473,476,477,504,508–510,512 help guide the process. Modes of exercise that pre-
In exotic and wild animals, capture myopathy is dispose to RER should be avoided in horses that are
similar if not identical to exertional rhabdomyolysis exercised strenuously. Feeding, social interactions,
in its pathophysiology463,466,477,485,486,488,489,491,513,514 and is and exercise routines should be crafted to minimize
likened to porcine stress syndrome, featuring severe excitement and stress. If necessary, low-­dose acetyl
hyperthermia and various metabolic disturbances in promazine (5–10 mg IM) can be given before exer-
addition to direct signs of muscle injury. cise to highly strung horses prone to RER.463 Adding
With a clinical diagnosis of exertional rhabdomy- 450 mL of vegetable oil per 450-­kg horse/day to a
olysis being made, exercise should be stopped. low carbohydrate commercial diet has also been rec-
Hyperthermia should be treated with alcohol baths ommended.517 At least it does appear to quieten the
and ice. Water, acid base, and electrolyte imbalances patients and that may have an indirect effect on
require correction, but bicarbonate must not rou- reducing rhabdomyolysis. Dantrolene sodium
tinely be added to fluid replacement solutions as (2–4 mg/kg PO 60 min before exercise) and pheny-
most cases are not acidotic. Urgent attention to seda- toin sodium (2–5 mg/kg PO twice daily) reduce pos-
tion and pain management is essential in distressed, texercise serum CK and can be tried in racehorses
painful, tied-­up horses. Intravenous doses of detomi- with RER.463,465,472,474,504,508,518–522
dine and butorphanol, repeated as needed, should be Detection of abnormal fractional urinary excre-
given for the first 1–2 days, evolving, if necessary, to tion ratios allows rational dietary correction of pos-
continuous-­ rate infusions using combinations of sible electrolyte deficiencies in the diet of affected
detomidine, butorphanol, lidocaine, and ketamine horses,479,523,524 and the cation:anion balance in the
in order to make the patient comfortable.463 diet may be manipulated.524,525 Also, on the assump-
Phenylbutazone and flunixin can be used judiciously tion that poor buffering capacity may be related to
if renal function is adequate. Digital cryotherapy exertional rhabdomyolysis, dietary NaHCO3 at 2% of
should be considered for laminitis prevention. total dietary dry matter has been added, supposedly
Dantrolene sodium (4 mg/kg PO, repeated in 4–6 h) with beneficial effects.526
564 Large animal neurology

In some cases, strenuous exercise must be perma- dorsally recumbent horses under general anesthesia
nently curtailed and, with current knowledge, it is rea- whose limbs are forcibly restrained in abducted,
sonable to recommend that such patients should not extended, and/or endorotated positions to facilitate
be used to breed for offspring intended for such use. placement for procedures. Signs of femoral nerve and
brachial plexus/radial nerve paralysis are associated
Postanesthetic limb myoneuropathy in this way with positioning of pelvic and thoracic
limbs, respectively.538–540 The circumstances of these
Complications associated with general anesthesia cases suggest that neurapraxia associated with
characterized by difficulty rising and lameness were stretching of nerves may be responsible, but this has
recorded at 1.5–6.5% of recoveries from anesthetics not yet been confirmed.
in horses with a 0.24–2% lethality risk, increasing to If recumbent, the animal should be allowed to rest
2–10% in horses undergoing celiotomies,527–529 one-­ in a sternal position or, if amenable, be supported in
third to one-­half of these being due to fractures and a sling if necessary and paretic distal limbs placed in
neuromyopathies.529–534 Often the syndrome occurs splints or support wraps. The systemic associations
in fit performance horses, but it does occur in any of postanesthetic myopathies, shock and dehydra-
heavy, large animal after prolonged anesthesia and tion, pain, distress, and toxic nephropathy should be
after recumbency for other reasons.535–537 Overall, the treated as described above for exertional rhabdomy-
frequency of myoneuropathy following general anes- olysis. In brief, pain and excessive excitement can be
thesia in horses is likely around 2–3% with only a treated with combinations of detomidine and
very few cases necessitating euthanasia.527,529 constant-­rate infusions of one to all of butorphanol,
Following general anesthesia, there are degrees of lidocaine, and ketamine. Phenylbutazone and flunixin
difficulty in rising and in remaining standing usually are administered with caution because of potential
with poor function of one or more limbs or of the renal toxicity. Intravenous and nasogastrically-­
back. Pain and swelling may be evident in groups of administered polyionic fluids are necessary to cor-
muscles, not always on the side that was dependent rect any imbalances and to encourage diuresis if
during recumbency.538–546 Characteristics of neu- myoglobinuria is suspected. Vitamin E and selenium,
rapraxia, especially of the radial and peroneal nerves, methocarbamol (10–20 mg/kg, IV, QID), dimethyl
complicate the syndrome of painful myopathy.538,541 sulfoxide, and dantrolene sodium are given empiri-
Postanesthetic myelopathy and myasthenic syn- cally with unproved benefit.203,534,544,548,550,552–554,556,557
drome initially can look remarkably similar193,204—­ Massage and limb manipulations promote muscle
see above. Serum CK, aldolase, AST, and LDH blood flow and reduce the chance of decubital sores
activities are excessively elevated, and myoglobin is occurring. Good padding, turning the patient regu-
often found in the urine. Areas of hypalgesia to anal- larly, and attending to bowel and bladder evacuations
gesia corresponding to mono-­and polyneuropathies, are part of a sensible nursing care protocol for a
and hyporeflexia in the absence of marked swelling recumbent patient. Glucocorticoids are generally not
in the target muscle indicate that degrees of neu- indicated. If the horse remains standing, the outlook
rapraxia are also present. Ultrasonographic examina- is good to excellent depending on the degree of mus-
tion of affected muscles can define the nature and cle involvement.538,540 Attentive nursing care is vital if
extent of myopathy, and such changes can be fol- the animal is recumbent. Loss of muscle mass can
lowed for many weeks during convalescence.543 occur with recovery.
The pathogenesis is thought to involve compo- Adequate padding of heavy animals under general
nents of compartmental pressure elevation, systemic anesthesia, positioning the dependent thoracic limb
hypotension, anaerobic glycolysis, pressure-­induced forward, and elevating and supporting the upper-
and ischemic myopathy, pressure-­induced and, per- most thoracic and pelvic limbs in natural positions
haps, ischemic neuropathy, reperfusion injury with reduces intracompartmental pressures.540,545,549,550,557
oxidant injury, and other factors.530,541,542,545,547–554 Almost certainly, prolonged, halothane-­ induced
Malignant hyperthermia may be involved in some hypotension with a mean arterial blood pressure of
cases.555 Peripheral neuropathy, typically without 55–65 mmHg is a major factor in severe and general-
muscle involvement, may occur either in a nonde- ized postanesthetic myopathy in the horse.548,556
pendent limb in laterally recumbent or bilaterally in Therefore, minimizing the duration of anesthesia,
 Multifactorial and idiopathic disorders 565

supporting normotension with minimal concentra- 11 Leadon DP, Jeffcott LB and Rossdale PD. Behavior
tions of volatile anesthetic agents, use of intravenous and viability of the premature neonatal foal after
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Index

Page numbers in italics refer to illustrations; those in bold refer to tables

abducens nerve, 28 ammoniated feedstuff toxicity, 418 plant‐induced, 437

abiotrophy, 221 amoebae, 84–85, 337–338 arthropod parasites, 85
cerebellar, 221–222, 222, 239 amoebic encephalomyelitis, 337–338 ascending bacterial empyema, 308
accessory nerve, 31–32 anal reflex, 18 ascending reticular activating system
Acer spp., 437 anencephaly, 230 (ARAS), 20
acetylcholine receptors, 258 Angiostrongylus cantonensis, 338, 340 Aspergillus spp., 84, 302, 305, 337, 431
Acinetobacter spp., 301 Angora goats, progressive paresis, 242 A. clavatus, 427, 436
acoustic nerve tumors, 524 Anguina funesta, 431, 435 A. fumigatus, 302
acquired equine polyneuropathy of Nordic Angus calves Aspergillus tremor syndrome, 436
horses, 558–559 bovine familial convulsions and ataxia, 222 Astragalus spp., 425
acquired myasthenia gravis, 348 congenital spinal stenosis, 548 Astrebla spp., 438
acquired peripheral deafness, 157 encephalomyelopathy, 234 astrocytes, 5
acrylamide toxicity, 424 anhidrosis, 207 histopathologic reactions, 82
Actinobacillus spp., 304 anisocoria, 114, 116 ataxia, 35–38, 171–173, 177
A. equuli, 296, 301, 306 annual ryegrass toxicity, 86, 431, 435 bovine familial convulsions and, 222–223
A. lignieresii, 303, 306 anoxia, anesthetic‐related, 512 cerebellar, 36–37
A. pleuropneumoniae, 304, 306 anticonvulsant therapy, 100–101, 231 Charolais cattle, 226, 238
Actinomyces spp., 301 antioxidant failure, 86 enzootic, 490–492
adenocarcinoma, nasal, 514 anus, 46 familial, Merino sheep, 238, 239
adversive syndrome, 122 anal reflex, 18 plant toxin‐induced, 426–427, 430–431,
Aeschynomene indica, 436 dilated, 194–197 438
Aesculus sp., 438 evaluation, 18, 46 subconscious proprioceptive (spinal), 36
aggressive behavior, 92–93, 93, 201 aortic–iliac–femoral thrombosis, 557–558 vestibular, 37
Agrostis avenacea, 435 Appaloosa horses, congenital stationary atypical myopathy, 437–438
Akabane virus, 321, 322 night blindness, 246 atypical scrapie, 328
allodynia, 132, 132, 200–201, 202 Arabian horses autonomic nervous system, 4
Alphaviruses, 310–312 cerebellar abiotrophy, 221 dysfunction, 206–208
Amanita verna, 438 tetany syndrome in foals, 163, 227 avermectin, 422
amaurosis, 111, 230 arboviruses, equine, 310 axillary nerve damage, 394
American Brown Swiss calves, spinal Arnold‐Chiari malformation, 173, 223 axonopathy, Rouge‐des‐pres calves, 240
dysmyelination, 227 arsanilic acid, 421 axonotmesis, 47, 81, 393
American trypanosomiasis, 336 arsenic toxicoses, 421
aminoaciduria, 219 arthrogryposis, 245, 251–253, 252, Babesia bovis, 337
aminoglycoside toxicity, 421 321–322, 322 Bacillus thiaminolyticus, 483

Large Animal Neurology, Third Edition. I. G. Joe Mayhew and Robert J. MacKay.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/mayhew/neurology
 Index 589

back problems, 168–169, 203, 210–212, evaluation, 18, 46–47 brain–heart syndrome, 377
211, 213 blindgrass poisoning, 428 Brassica spp., 418
bacterial diseases, 84, 294–310 blindness, 111–113, 246, 344 Braunvieh calves, spinal dysmyelination, 227
botulism, 439–443, 439 congenital stationary night blindness, bromide toxicity, 422–423
brain abscess, 84, 297–299, 298, 299 246–247 Brown Swiss calves, progressive degenerative
cellulitis, retrobulbar, 301–302 testing for, 21–23 myeloencephalopathy, 238
empyema traumatic optic neuropathy, 380–381, 381 Brucella spp.
ascending, 308 vestibular disease and, 152, 154 B. abortus, 306
basilar, 300–301, 300 vitamin A deficiency, 482 titer and blood and urine culture, 309
retrobulbar, 301–302 blocking tissues, 78–80 buckeye, 438
guttural pouch infection, 302–303 blow away grass, 435 bunny hopping, 49
listeriosis, 127, 131, 131, 154, 294–295, body examination, 18 Burkholderia pseudomallei, 309
294 Border disease, 229, 323
lower glossitis, 303 Borna disease virus, 316–317 Caley pea, 438
Lyme borreliosis, 309–310 Borrelia burgdorferi, 301, 309 Campus Syndrome, 229
melioidosis, 309 botulinum toxin, 86, 439–443 canary grass staggers, 435
meningitis, 108, 132, 296–297 site of action, 441 cannabinoids, 201
suppurative, 84, 301 botulism, 439–443, 439 caprine‐arthritis‐encephalitis, 314, 315–316
myositis, 308–309 antitoxins, 442 capture myopathy, 562
clostridial, 308–309 diagnosis, 442 carbamate toxicity, 418–420
streptococcal, 309 diffuse weakness, 182 carcinoma, 526
neuropathologic responses, 84 dysphagia in, 139, 139 paranasal, 524
otitis interna, 154, 155, 157, 303–305, 304 tongue paralysis, 148 cardiocirculatory collapse, 513
otitis media, 154, 155, 157, 303–305, 304 treatment, 442 Cardiovirus, 319, 320
septic aortic thrombosis, 308 vaccination, 443 carotid air embolism, 380
tetanus, 161–162, 162, 443–445 see also bacterial toxins Cassia occidentalis, 428
thromboembolic meningoencephalitis, bovine castration, 199
295–296 BoHV‐5, 323 cataplexy, 104, 104, 109–110, 231–232
ventriculitis, 296–297 bonkers, 418 cauda equina avulsion, 392
vertebral suppurative osteomyelitis and complex vertebral malformation, 243 cauda equina syndrome, 194–197, 245
discospondylitis, 84, 305–308, 306–308 congenital muscular dystonia‐1, 255 causes, 196–197
bacterial toxins, 86, 439–448 familial convulsions and ataxia, 222–223 clinical signs, 195
botulinum, 86, 439–443 herpesvirus meningoencephalitis, 323–324 treatment, 197
enterotoxemic encephalopathy, 445–446, hysteria, 418 cellulitis, retrobulbar, 301–302
446 progressive degenerative Centaurea solstitialis, 427–428
equine mycotoxic encephalomalacia, myeloencephalopathy, 226, 238 central motor pathways, 6, 7, 8
446–448, 447 pseudomyotonia, 255 paresis/paralysis, 33–34, 45–46, 46
tetanus, 443–445 spinal muscular atrophy, 240 central nervous system (CNS), 4
Bacteroides spp., 305 spongiform encephalopathy, 327–329 central vestibular disease, 153–154
Balamuthia mandrillaris, 337 tauopathy, 535 cerebellar
bamboo toxicosis, 148 bovine viral diarrhea virus (BVDV), 229, abiotrophy, 173, 221–222, 222, 239
barn cramps, 248 321–323, 323 ataxia, 36–37, 171–173
basilar empyema, 300–301, 300 brachial plexus, injury, 186, 187, 191–193, connections, 8
beard grass, 435 192, 193, 394 degenerative disorders,223–224
behavior, 20 bracken fern toxicity, 429 diseases, 171–174, 172
behavioral disorders, 20, 91–96 brain, 4, 4 plant toxin‐induced, 436
Beltex sheep, cervical compressive abscess, 84, 85, 297–299, 298, 299 hypoplasia, 220–221, 321, 322
myelopathy, 547–548, 547 biopsy, 65 lissencephaly with, 221
benign epilepsy of foals, 230–231 herniation, 84 cerebellum, 4, 8
Bermuda grass, 436 postmortem examination, 76–80, 77 cerebral abscess, 85
beta‐cyanoalanine, 426 sections, 78–80, 79, 80 cerebrocortical necrosis, 482–484
bilateral brachial paresis to paralysis, swelling, 26, 84, 84, 85 cerebrospinal fluid (CSF), 5
191–193, 192, 193 traumatic injuries, 374–380, 380 collection and analysis, 52–58, 53–57,
bilateral convergent strabismus and classification, 375 178, 195, 377
exophthalmos, 247–248 primary injury, 375, 376 cerebrospinal nematodiasis, 340
bilateral vacuolation of the substantia secondary injury, 375–376 cerebrum, 4
nigra, 535 thermal disbudding, 400, 401 ceroid lipofuscinosis, 158, 235, 237
biopsy, brain, 65 tumors, 523–524, 524, 525 cervical
bird cherry tree, 418 brainstem, 4 compressive myelopathy, 547–548, 547
Birdsville disease, 430 brainstem auditory evoked potential discospondylosis, 211
birth asphyxia, 85 (BAEP), 58, 59 torticollis, 211, 213
black soil blindness, 438 deafness, 157–158 vertebral malformation (CVM), 179,
bladder vestibular function, 154–155 179, 536–547
distention, 194–197 brainstem neuronal chromatolysis, 535 clinical signs, 536–539, 537, 538
590 Index

cervical (cont’d) C. chauvoei, 308 accessory, 31–32

diagnostic techniques, 540–545, 542, C. difficile, 440 evaluation, 21–33
543, 545 C. perfringens type D, 86, 445 facial, 29–30
treatment, 545–547 C. piliforme, 505, 507 functional assessment, 15
types, 538, 539–541, 539 C. sordellii, 508 glossopharyngeal, 31–32
cervicothoracic luxation/subluxation, 243, C. tetani, 140, 160, 443–445 hypoglossal, 32–33
384, 386, 387 coat color dilution lethal, 227 oculomotor, 23–28
manipulation, 389 Coccidioides immitis, 337 olfactory, 21
cervicothoracic radiculopathy, 397 coccidiosis, 534–535 optic, 21–23
cestodes, 341–342 Coenurus cerebralis, 154, 341–342, 341 trigeminal, 28–29
Chagas disease, 336 coffee senna toxicity, 428–429, 504 trochlear, 28
Charolais cattle, progressive ataxia, 226, 238 collapse, 103–104, 108–110 tumors, 524
Cheilanthes sieberi, 429 coma, 107–110, 375–377 vagus, 31–32
chemical causes, 399 complex regional pain syndrome, 200–201, vestibulocochlear, 30–31
epidural ethanol injections, 400 202 cranial tibial reflex, 45, 46
intracarotid injection, 399 complex vertebral malformation, 243 craniectomy, 77
paravertebral injection reactions, 400, 400 computed tomography (CT), 61–62 cranioschisis, 246
chemical toxins, 86, 413–424 CT myelography, 62, 63 Creutzfeldt–Jakob disease (CJD), 327
aminoglycoside, 421 concussion, 85, 375 crib‐biting behavior, 200, 382
ammoniated feedstuff, 418 congenital crooked calf syndrome, 251–253, 252
arsanilic acid, 421 adductor weakness, piglets, 241–242 crossed extensor reflex, 19
arsenic compound, 421 articular rigidity, 251 Crotalaria spp., 504
carbamate, 418–420 chondrodystrophy in beef cattle, 244 crushed tail head syndrome, 195, 197
cyanide, 86, 418 deafness, 157, 247 cryptococcal infection, 337
fluoroacetate, 420–421 flaccid mandible, 248 cutaneous trunci reflex, 18, 42
heavy metal, 416 hypomyelination sensory neuropathy, 251 cyanide poisoning, 86, 418
ionophore, 422 malformations Cynodon dactylon, 436
ivermectin, 422 vertebral, 244–246, 244, 245 Cysticercus cellulosae, 342
lead, 413–415 viral‐induced, 321–323, 322
metaldehyde, 420 myasthenia syndromes, 258 daft lamb disease type A (DLD‐A), 223
methyl bromide, 422–423 myoclonia, 224, 225 Dallis grass intoxication, 154
moxidectin, 422 myoclonus, 224–227 Dancing Pig Disease, 227
nitrogen‐containing compounds, 418 myopathy Dandy–Walker syndrome, 173, 223
organochlorine, 418 in Beulah speckle‐face lambs, 256–257 Darling pea toxins, 425–426
organomercury, 421 in Braunvieh x Brown Swiss calves, 257 dazzle response, 17, 25, 112, 114
organophosphate, 418–420 spinal stenosis of thoracolumbar deafness, 156–157
procaine penicillin reaction, 423 vertebrae, 548 congenital, 157, 247
selenium, 415–416 stationary night blindness, 246–247 degenerative axonopathy, 224, 225, 226
sodium salt, 416–417 tetany, 163 Tyrolean gray calves, 238–240
strychnine, 420 tremor syndrome, 173, 225, 227–229, 228 degenerative disc disease, 390
urea intoxication, 418 Conidiobolus coronatus, 337 degenerative myelopathy, 239, 552
water intoxication, 416–417 Conium maculatum, 418 degenerative processes, 86
chewing disease, 427 consciousness, 9, 9, 107–108 degenerative thoracic myelopathy, 239
chick pea, 145 altered states of, 107–110 deglutition, muscles of, 485–486
Chlamydia pecorum, 343 contracted foal syndrome, 245, 251 dehorning brain injury, 400–401, 401
cholesterinic granulomata, 523 contrast radiography, 61 Demetz syndrome, 238–240
chondrodystrophy, congenital, 244 contusion, 85 Dermacentor spp.
choroidal cells, histopathologic reactions, 83 convergent strabismus, 121 D. andersoni, 448
chronic exertional rhabdomyolysis, 562 bilateral, with exophthalmos, 247–248 D. variablis, 448
chronic wasting disease, 329 convulsions see seizures Dermanyssus avium, 304
Chrysomia bezziana, 304 copper deficiency, 490–492 dermatophilosis, 183, 184
Churra sheep, lissencephaly with cerebellar Corallocytostroma sp., 438 diagnostic aids
hypoplasia, 221 Coriaria spp., 437 brain biopsy, 65
Cicer arietinum, 145 corneal reflex, 28 cerebrospinal fluid analysis, 52–58
circling, 150–155 corpus callosum agenesis, 223, 230 electrodiagnostic testing, 58
citrullinemia, 219, 225 corticospinal motor pathways, 6, 7 genetic markers, 51–52
Claviceps spp., 431, 436 Corynebacterium pseudotuberculosis, 298, neuroimaging, 59–65
C. paspali, 436 301, 304, 305 routine clinicopathological tests, 51
C. purpurea, 436 corynetoxins, 86, 431 spinal endoscopy, 65
clinicopathological tests, 51 Coxsackievirus A2, 251 diaphragmatic paralysis, 145
clonic response, 19 coyotillo, 436 Didelphis spp., 330
closantel toxicity, 423–424 cranial gluteal nerve injury, 396 diencephalon, 4
clostridial myositis, 308–309 cranial meningocele, 230 diffuse weakness, 181–184
Clostridium spp., 308, 553 cranial nerves, 8–9, 9 dilated esophagus, 142–143, 143
C. botulinum, 139, 148, 440, 441 abducens, 28 Diplodia maydis, 437
 Index 591

diplodiosis, 436–437 uremic, 508–509 facial

discospondylitis endoscopy, spinal, 65 analgesia, 130–132, 130, 131
cervical, 211 Enterococcus spp., 298 hypalgesia, 29, 129–131, 131
thoracolumbar, 211 enterotoxemic encephalopathy, 445–446, 446 hyporeflexia, 129
see also vertebral suppurative enzootic ataxia, 490–492 nerve, 29–30
osteomyelitis and discospondylitis eosinophilic meningoencephalitis, 347–348 damage, 134, 396–397
discospondylosis, 549–551, 550 ependymal cells, histopathologic reactions, 83 paralysis, 29, 134–136, 134, 135, 344
distressing disorders, 198–203 epidural ethanol injection, 400 reflexes, 30, 129–130
complex regional pain syndrome, epilepsy, 97–101, 99 sensation, 129–132
200–201, 202 benign, of foals, 230–231 spasm, 135
headshaking, 201–203 familial, in cattle, 230 tic, 135
pruritus, 199 equine fainting goats, 254–255
psychologic order, 203 arboviruses, 310 familial
self‐mutilation syndrome, 199–200, 200, degenerative myeloencephalopathy, 179, ataxia, Merino sheep, 238
201 179, 236, 489–490 epilepsy in cattle, 230
divergent strabismus, 121, 248 dysautonomia see grass sickness neuropathy of Gelbvieh cattle, 250–251
Doddler calves, 224, 225 familial isolated hypoparathyroidism, femoral
dorsomedial strabismus, 122, 123 261, 510 nerve damage, 48, 395
dourine, 336 glycogen storage metabolic myopathies, paralysis, 395
doxycycline overdose, 424 259–260 fern toxicity, 429
Draschia megastroma, 154, 341 herpesvirus type 4 (EHV‐4), 324 Festuca rubra commutate, 435
droopy‐eared calf syndrome, 344 myopathies, 259–260 fibrotic myopathy, 49, 168, 398–399
dropped hock syndrome in cattle, 561–562 grass sickness see grass sickness filarial nematodes, 340
dropped mandible, 126, 127 herpesvirus‐1 (EHV‐1) final motor neuron, 5–6, 8–9
dysautonomia, 552–554 myeloencephalopathy, 324–327 paresis/paralysis, 33, 34, 45–46, 46, 184
dyskinesia, 98, 160 infectious anemia virus, 321 flaccid mandible, congenital, 248
dysmetria, 36, 172 laryngeal paralysis, 145 flaccid paralysis, 7–8
dysphagia, 137–140 leukoencephalomalacia, 86 Flavivirus, 312, 314
diseases causing, 32 motor neuron disease (EMND), flexor reflex, 43–45, 44
dystocia, 398 182–183, 182, 486–489, 487, 488 flies, 342
clinical signs, 487 floppy kid syndrome, 182
Eastern equine encephalitis (EEE), diagnosis, 488 fluoroacetate toxicity, 420–421
310–312, 311 vitamin E deficiency and, 488–489 fluphenazine toxicity, 424
Echinococcus granulosus, 342 mycotoxic encephalomalacia, flying scapula in ruminants, 561
edema disease, pigs, 445–446 446–448, 447 focal symmetrical encephalomalacia,
eggplant toxicity, 429 neonatal encephalopathy, 533–534 445–446, 446
Eikenella corrodens, 306 neuroaxonal dystrophy, 236, 489–490 forage poisoning see plant toxins
Elaphostrongylus spp., 339 parvovirus‐hepatitis (EqPV‐H), 504 forebrain, 4
E. alces, 339 polysaccharide storage myopathy, functional areas, 9, 9
E. cervi, 339 259–260 lesions, 19, 19, 78
E. panticola, 339 equine protozoal myeloencephalitis behavioral changes, 91–93, 92
E. rangiferi, 339 (EPM), 64, 131, 148, 154, 177, 178, malformations, 230
electrocution, 401–402 179, 329–336, 332 forelimbs see thoracic limbs
electrodiagnostic testing, 58 diagnosis, 332–334, 334 fracture
electroencephalography (EEG), 58 treatment, 334–336, 334, 335 hyoid bone, 147
electromyography (EMG), 58 Equisetum arvense, 429 sacral, 195, 196, 386, 391–392
Elso Heel, 249 ergotism, 436 skull, 376
embolic myelopathy, 551–552 Erysipelothrix rhusiopathiae, 296, 306 vertebral, 383–392, 385, 387
Emericella nidulans, 302 Escherichia coli, 296, 301, 308, 446 fumonisin toxins, 86, 447
empyema esophagus dilation, 142–143, 143 functional neuroanatomy, 5–10
ascending bacterial, 308 European sporadic bovine fungi, 84, 337
basilar, 300–301, 300 ­encephalomyelitis, 342 mycotoxin‐induced tremor, 431–436
guttural pouch infection, 302–303 evoked potential testing, 58, 59, 60 furazolidone toxicity, 424
retrobulbar, 301–302 deafness, 157–158 Fusarium spp., 447
encephalomyelopathy vestibular function, 154–155 F. moniliforme, 447
Angus calves, 234 exertional rhabdomyolysis, 562–564 F. proliferatum, 448
hypoxic and ischemic, 86 exophthalmos Fusobacterium spp., 298, 305
Simmental cattle, 233–234 with bilateral convergent strabismus,
encephalomyocarditis virus, 319, 320 247–248 gait
encephalopathy with retrobulbar neoplasia, 524 abnormalities, 15, 33–38, 48
bovine spongiform, 327, 328–329 extensor hypertonus, 386 subtle, 168
enterotoxemic, 445–446, 446 spasmodic, 248 evaluation, 18–19
equine neonatal, 533–534 external hydrocephalus, 232 kangaroo gait in sheep, 560–561, 560
hepatic, 86, 504–507, 506 eyes, sympathetic innervation, 26–27 two‐engine gait, 34
neonatal, Swaledale lambs, 229 see also nystagmus; strabismus see also movement disorders
592 Index

galactocerebrosidosis, 236 hemagglutinating encephalomyelitis, 320 H. bovis, 342

gamma motor system, 160–161, 161 hematoma, 85, 376 H. lineatum, 342
ganglia, 5 hemolytic–uremic syndrome, 508 hypoglossal nerve, 32–33
gangliosidosis, 236 Hendra virus, 314 damage, 139
gastrocnemius reflex, 45, 46 Henipavirus, 314 hypoglycemia, 86, 511
Gelbvieh cattle, familial neuropathy, 250–251 hepacivirus A, 504 ketosis with, 510–511
Gelbvieh‐cross calves, status spongiosus of hepatic encephalopathy, 86, 504–507, 506 hypoglycin‐A, 437
white matter, 220, 229 clinical signs, 505 hypokalemic syndrome in cattle, 512
genetic markers, 51–52 evaluation, 505–507 hypomagnesemia, 86, 509–510
German White Fleckvieh syndrome, 247 treatment, 507 hypometria, 36–37, 172
Getah virus, 310 Hereford calves hypomyelination sensory neuropathy, 251
Ginger paralysis, 419 cerebellar hypoplasia, 220–221 hyponatremia, 512
Glasgow Coma Scale, 378 congenital myoclonia, 224 hypoparathyroidism, equine familial
glial cells, 5 tetany, 163 isolated, 261, 510
glossitis, 303 herniation, brain, 84 hypotonia, 7–8
glossopharyngeal nerve, 31–32 herpesvirus hypoxia, 86
glutamic acid decarboxylase (GAD), 559 bovine, 323–324 anesthetic related, 512
glycogen storage diseases, 236–237 equine, 324–327 hypoxic and ischemic
equine metabolic myopathy, 259–260 Heteromeles arbutifolia, 418 encephalomyelopathy (HIE), 86
glycogen‐branching enzyme deficiency, 260 hindbrain, 4
glycosuria, 446 hindlimb spasticity in piglets, 251 idiopathic disorders, 87
Gotland ponies, cerebellar abiotrophy, 221 hindlimbs see pelvic limbs aortic–iliac–femoral thrombosis, 557–558
granuloma, 348 histopathologic reactions, 80–83 cervical compressive myelopathy,
cholesterinic, 523 astrocytes, 82 547–548, 547
granulomatous meningeal, choroidal and ependymal cells, 83 eosinophilic meningoencephalitis, 347–348
facial/vestibulocochlear neuropathy, 344 microglia, 83 hypersomnia, 104, 105, 232
meningoencephalitis, 347 neurons, 81–82 neuropathologic responses, 87
meningoencephalomyelitis, 87, 87 oligodendrocytes, 82–83 neuropathy with knuckling, 558
perineuritis, 348 Schwann cells, 83 recurrent laryngeal neuropathy, 555–556
grass sickness, 119–120, 552–554, 554 Histophilus somni, 295–296 immune mechanisms, 85
autonomic dysfunction, 207, 208 history, 12–13 immune‐mediated myositis, 344–345
clinical signs, 207, 552–553, 554 holocyclotoxin, 448 inclusion body myositis, 345
diagnosis, 553 holoprosencephaly, 230 Indigofera spp., 430–431
dilated esophagus, 143 Holstein calves, cerebellar abiotrophy, 221 infarctive purpura hemorrhagica, 345
dysphagia, 140 Holstein–Friesian calves, aminoaciduria, 219 inflammatory and immune mechanisms,
ptosis and, 119 homocitrullinuria, 220 343–348
grass staggers, 509, 510 hopping, 18, 19, 34 acquired myasthenia gravis, 348
gray matter, 4 Horner syndrome, 26, 64, 116–120, granulomas, 348
gross artefacts, 77–78 117–119, 189, 206, 207, 526 granulomatous facial/vestibulocochlear
gross lesions, 78 horsetail toxicity, 429 neuropathy, 344
guttural pouch infection, 302–303 hydatid cyst, 342 granulomatous meningoencephalitis, 347
guttural pouch mycosis, 118, 139, 147 hydranencephaly, 233, 321–323, 322 idiopathic eosinophilic
hydrocephalus, 232–233 meningoencephalitis, 347–348
Habronematoidea, 341 hydrocyanic acid, 418 infarctive purpura hemorrhagica, 345
Haemophilus spp., 304 hyoid bones, 381 myositis, 344–345
Hahnentritt, 429 fractured, 147 optic neuritis, 343–344
see also stringhalt hyperactive reflex, 18–19 polyneuritis equi, 345–347, 345
Hairy shaker disease, 227, 229 hyperadrenocorticism, 523 sclerosing panencephalitis, 347
Halicephalobus gingivalis, 340–341, 486, 552 hyperalgesia, 200 insect parasites, 338
Halogeton glomeratus, 438 hyperammonemia, 220, 505, 507–508, 508 intense heat‐reflex pruritus, 199
Haloxon, 419 hyperesthesia, 132 intervertebral disc disease, 390–391, 549
hamartoma, 523 hyperkalemic periodic paralysis in horses, intervertebral disc trauma, 390–391
Haycocknema perplexum, 486 257–258 intracarotid injection, 399
head hypermetria, 36, 167, 172 intracranial hemorrhage, 377
examination, 14–17 hypernatremia, 416–417 ionophore toxicity, 422
posture and movement, 20–21 hyperornithinemia, 220 ischemic neuromyopathy, 557–558
sympathetic innervation, 26–27, 27 hyperreflexia, 163 ivermectin toxicity, 422
trauma, 110, 154, 374–380 hypersomnia, 104, 105, 232 Ixodes spp., 448
head tilt, 20–21, 93, 150–155, 151–153 hyperthermia, 563 I. cornuatus, 448
headshaking, 95, 201–203 malignant, 258–259, 562–563 I. holocylus, 448
heat stress, 401 hypertonia, 8 I. ricinus, 314
heavy metal toxicity, 416 hypocalcemia, 86, 509–510 I. rubicundus, 448
heel fly, 342 Hypochaeris radicata, 167, 430
Helichrysum poisoning, 428 hypocretin neuropeptides, 104–105 janthitrem A, 434
helminth parasites, 85, 177, 338 Hypoderma spp., 154, 342 Japanese encephalitis virus, 314
 Index 593

Jersey calves, kyphosis, 245, 390 local cervical response, 39 granulomatous, 347
Jittery calves, 227 local cervicofacial response, 39 idiopathic eosinophilic, 347–348
juvenile pendular nystagmus, 248 lockjaw, 140 thromboembolic, 295–296
locoweed toxins, 425–426 meningoencephalomyelitis, protozoal,
kangaroo gait in sheep, 560–561, 560 lolitrem‐B, 86, 434 336–337
Karoo, 448 Lolium spp. see also equine protozoal
Karwinskia humboldtiana, 436 L. perenne, 434 myeloencephalitis (EPM)
kernicterus, 504, 511 L. rigidum, 431, 435 mental status, 20
ketoacidosis, 86 L. temulentum, 435 mercury toxicity, 421
ketosis, 510–511 lordosis, 223, 245, 390 Merino sheep
Klebsiella pneumoniae, 296, 301 louping ill, 314 cerebellar abiotrophy, 221
knuckling, 41, 43, 388 lower motor neuron (LMN), 8 cerebellar degeneration, 223
acquired equine polyneuropathy, 558–559 luxation congenital myoclonus, 224–227
with idiopathic neuropathy in horses, 558 caudal vertebral, 391–392 familial ataxia, 238, 239
Kochia scoparia, 428 cervicothoracic, 243, 384, 386, 387 mesencephalon, 4
Kumri, 340 manipulation, 389 metabolic disease, 86
kyphosis, 245, 390 sacral, 391–392 anesthetic‐related hypoxia and anoxia, 512
in Jersey calves, 257 temporomandibular, 381 cardiocirculatory collapse, 513
Lyme borreliosis, 139, 309–310 hepatic encephalopathy, 86, 504–507, 506
laceration, 85 lymphosarcoma, 87, 526 hyperammonemia, 507–508, 508
lactational ketosis, 510 intracranial, 523, 524 hypocalcemia, 509–510
lameness see limbs; movement disorders spinal cord, 526 hypoglycemia, 511
Landrace trembles, 163 lysosomal storage disease, 234–235, hypokalemic syndrome, 512
laryngeal paralysis / paresis, 31, 144–145 236–237, 259 hypomagnesemia, 509–510
lasolocid toxicity, 422 Lyssavirus, 317 hyponatremia, 512
Lathyrus sp., 145, 438 ketosis, 510–511
laurel, 418 Macavirus, 317 uremic encephalopathy, 508–509
Lavender foal syndrome, 227 maedi–visna virus, 84, 314–315 metaldehyde toxicity, 420
lead poisoning, 413–415 magnetic motor evoked potential (mMEP), metallic myelopathy, 416
dysphagia in, 139 58, 60 Metastrongyloid nematodes, 338–340
lentiviruses, 314–316 magnetic resonance imaging (MRI), 62, 64 methyl bromide toxicity, 422–423
lesions Maine Anjou calves, axonopathy, 240 methylene cyclopropylglycine, 437
finding postmortem, 76–78 mal hinchado, 552 metoclopramide toxicity, 424
location of, 49–50, 49 mal seco, 143, 552 Mexican fireweed, 428
self‐inflicted, 93, 199–200, 200 malformations, 83 microglia, histopathologic reactions, 83
vascular, 86 see also congenital malformations microphthalmia, 246
see also specific lesions malignant catarrhal fever, 317 midbrain, 4
leukoencephalomalacia malignant hyperthermia, 258–259, 562–563 milk fever, 509–510
equine, 86 mallow weed, 430 miosis, 114, 116
Romney sheep, 234 Malva parviflora, 430 Mitchell grass, 438
leukoencephalomyelopathy, Romney mandibular muscle atrophy, 127 mites, 449
sheep, 234 Mannheimia spp., 296, 304, 305 mitochondrial myopathy, 260–261
levator anguli oculi medialis muscle mannosidosis, 173, 236 moldy corn poisoning, 86, 446–448
paralysis, 134 maple syrup urine disease, 219–220, 225 monensin toxicity, 422
light pathway, 25 masseter myopathy, 485–486 monoparesis, 185–189
lightning strike, 401–402 masticatory muscles, 28 monoplegia, 185
limbic system, 9 atrophy, 28–29, 125–127, 126, 127, 128 Mortierella wolfii, 337
limbs myopathy, 485–486 motor neuron disease
ataxia, 171–173, 176 medial longitudinal fasciculus (MLF), 152 equine (EMND), 486–489, 487, 488
examination, 18 median nerve injury, 394–395 Romney lambs, 241
monoparesis, 185–189 medulla oblongata, 4 movement disorders, 159–169
reflex testing, 18–19, 19 medulloblastoma, 87, 523 back problems, 168–169
see also pelvic limbs; thoracic limbs megaesophagus, 142, 143 fibrotic myopathy, 168
Limousin cattle encephalopathy, 225 melanoma, 525, 526 opisthotonus, 161–162
lip paralysis, 138 melioidosis, 309 osteochondrosis, 168
lipofuscinosis Melochia pyramidata, 438 peroneus tertius tendon rupture, 168
ceroid, 158, 235, 237 menace response, 15, 17, 21–22 shivering, 49, 165–166, 166
plant toxin‐induced, 431 cerebellar diseases and, 172–173 spasticity, 163
lissencephaly with cerebellar hypoplasia, meningeal cells, histopathologic reactions, stiff horse syndrome, 165, 166
221 83 stringhalt, 48, 167–168, 167
Listeria monocytogenes, 30, 294, 295 meningitis, 108, 132, 296–297 tetanus, 161–162, 162
listeric encephalitis, 294, 295 suppurative, 84, 301 tetany, 162, 163–164
listeriosis, 127, 131, 133, 154, 294–295, 294 meningocele, 246 tremor, 163–164
lithium toxicity, 424 meningoencephalitis upward fixation of patella, 168
liver disease see hepatic encephalopathy bovine herpesvirus, 323–324 see also gait
594 Index

moxidectin toxicity, 422 clostridial, 308–309 signalment, 12

mucopolysaccharidosis, 236 immune‐mediated, 344–345 neuromyotonia, 254
Mucorales, 337 streptococcal, 309 neuronal cell body, 4
Mulberry heart disease, 482 myotonia, 253–254, 253, 254 neuronal ceroid lipofuscinosis, 158, 237
Murrurindi disease, 176 myotonia congenita, 254–255 neuronal chromatolysis, 535
muscle atrophy, 41, 42, 47, 182, 186–189 myotonic dystrophy, 254, 255–256 neuron
masticatory muscles, 28–29, 125–127, myotonic myopathy, 255–256 final motor, 5–6, 8–9
126, 127, 128 histopathologic reactions, 81–82
muscle spasms, 164–165 NADH coenzyme Q reductase, 261 neuropathologic responses, 83–87
facial spasm, 135 Naegleria fowleri, 337–338 amoeba, 84–85
tick‐ and mite‐associated, 449 narcolepsy, 104–105, 109–110 bacteria, 84
muscle tone control, 160–161, 161 with cataplexy, 104, 231–232 degenerative, 86
muscular dystrophy in adult Meuse‐Rhine‐ without cataplexy, 232 fungi, 84
Yssel and Holstein–Friesian cattle, nasal hypalgesia, 29 idiopathic, 87
257 neck immune, 85
musculocutaneous nerve injury, 394 examination, 18 malformations, 83
myasthenia gravis, 183, 258 pain, 21, 203, 210–212, 212 metabolic disease, 86
acquired, 348 spinal cord diseases and, 38–41 neoplasia and tumors, 86–87
Mycobacterium tuberculosis, 306 necroscopy, 76‐80 nutritional disease, 86
Mycoplasma spp., 301, 304, 305 nematodes, 338–341 parasitic, 85
M. bovis, 296, 304 Filaroidea, 340 physical and chemical, 85–86
M. hyopneumoniae, 304 Habronematoidea, 341 prion agents, 85
M. mycoides, 296 Metastrongyloidea, 338–340 protozoa, 84–85
mycotic encephalomyelitis, 337 Panagrolaimoidea, 340–341 toxic, 86
mycotoxin‐induced tremor syndrome, Stongyloidea, 338 vascular, 86
431–436 nematodiasis, 85 viral, 83–84
mydriasis, 28, 112, 114, 116, 116 neonatal acquired paralysis syndromes, neurotmesis, 47, 81, 393
myelencephalon, 4 398 nicotinic acid deficiency, 486
myelin, 4, 5, 81–83, 85, 86, 163, 164, 220, neonatal encephalopathy, equine, 533–534 night blindness, 246–247, 482
229, 233, 234, 238, 241, 251, 345, neoplasms, 58, 86–87 nigropallidal encephalomalacia, 427–428,
346, 393, 401, 491, 508, 558 see also tumors 427
myelitis, 308 Neospora spp., 55, 336–337 Nipah virus, 314
myelodysplasia, 201, 244–245, 245 N. hughesi, 100, 329 3‐nitro‐4‐hydroxyphenylarsonic acid, 421
myeloencephalopathy Neotyphodium spp., 431 nitrofurantoin toxicity, 424
bovine progressive degenerative, 226, N. lolii, 434 nitrogen‐containing compound toxicity, 418
238 nerve sheath tumor, 526 nociception, 6–7
equine degenerative, 179, 179, 236, neural tube defect, 244–246 nutritional disease, 86
489–490 neurapraxia, 47, 81, 393 cerebrocortical necrosis, 482–484
equine herpesvirus‐1, 324–327 neuraxial edema, 224 copper deficiency, 490–492
myelopathy neuroanatomy terminology, 4–5 equine degenerative
cervical compressive, 547–548, 547 neuroaxonal dystrophy, 235–238, 239, myeloencephalopathy, 489–490
degenerative, 239, 552 489–490 equine motor neuron disease (EMND),
embolic, 551–552 neurofibrillary degeneration, 226, 241, 551 486–489, 487, 488
metallic, 416 neurofibromas, 526 hyperammonemia, 507–508, 508
postanesthetic, 548–549 neuroglia, 5 myodegeneration, 492
progressive, 226, 240 neuroimaging, 59–65 nicotinic acid deficiency, 486
myiasis, 85 computed tomography, 61‐63 pantothenic acid deficiency, 484–485,
myoclonus, 135, 163, 163, 165 magnetic resonance imaging, 62, 64 485
congenital, 224–227 Plain and contrast radiography, 59‐61 polioencephalomalacia, 482–484
myodegeneration, 492 scintigraphy, 64 steatitis, 492
myofibrillar hypoplasia in piglets, 241–242 thermography, 62, 64 uremic encephalopathy, 508–509
myofibrillar myopathy, 563 ultrasonography, 64‐65 vitamin A deficiency, 86, 482
myoglobinuria, 51 neurologic examination, 12 vitamin E deficiency, 86, 482, 488–490
myokymia, 254 basic format, 14 see also metabolic disease
myopathy form, 16 nyctalopia, 246
atypical (seasonal pasture), 437–438 history, 12–13 nystagmus, 30–31, 150–155
congenital, 256–257 interpretation of findings, 19–50 juvenile pendular, 248
fibrotic, 49, 168, 398–399 brain and cranial nerve disease, 19–33
metabolic, 259–260 peripheral nerve damage, 47–49 obturator nerve injury, 395
mitochondrial, 260–261 spinal cord disease, 33–47 occipitoatlantoaxial malformation
muscles of mastication, 485–486 procedure, 13–19 (OAAM), 242–243, 242
myosin heavy chain, 344 body, 18 ocular sympathetic pathway, 24
myosin heavy chain myopathy, 344 gait and posture, 18–19 oculomotor nerve, 23–28
myositis, 308–309 head, 14–17 Odocoileus virginianus, 446
 Index 595

oestrid flies, 342 paralytic gastrointestinal syndrome, 143 peroneal nerve injury, 396
olfactory nerve, 21 paraparesis, 176, 178, 181 peroneus tertius tendon rupture, 168
oligodendrocyte, 5 paraplegia, 44 perosomus elumbis, 251
histopathologic reactions, 82–83 neonatal, acquired, 398 perphenazine toxicity, 424
Onchocera spp., 340 parasites, 85, 338–343 Peruvian Paso foals, congenital myoclonus,
opisthotonus, 161–162 cestodes, 341–342 224–227
optic nerve, 21–23 flies, 342 Pestivirus, 227, 229
hypoplasia, 246 nematodes, 338–341 Phalaris spp., 434–435
optic neuritis, 343–344 paravertebral injection reactions, 400, 400 phalaris staggers, 431, 434–435
oral dysphagia, 127 Parelaphostrongylus spp., 339 pharyngeal paralysis, 31, 138
orexins, 231, 232 P. tenuis, 154, 211, 339, 340, 390 phenothiazine toxicity, 424
organochlorine toxicity, 418 paresis, 33–35 phenylephrine eye drop test, 119–120
organomercury compound toxicity, 421 bilateral brachial, 191–193 physical disorders, 85–86
organophosphate toxicity, 418–420 central motor pathway, 33–34, 45–46 carotid air embolism, 380
Ornithodros lahorensis, 448 final motor neuron, 33, 34, 45–46 fibrotic myopathy, 49, 168, 398–399
Orthobornavirus, 316 laryngeal, 144–145 intervertebral disc trauma and prolapse,
oscillatory nystagmus, 248 one limb, 185–189 390–391
osteoarthritis, 211, 538 progressive, 242 kyphosis, 245, 257, 390
osteochondrosis, 168 spastic, 164, 165 lordosis, 223, 245, 390
otitis interna, 154, 155, 157, 303–305, 304 Paspalum spp., 436 neonatal acquired paralysis syndromes,
otitis media, 303–305, 304 paspalum staggers, 431, 436 398
suppurative, 154, 155, 157 Pasteurella spp., 296, 301, 304, 305 postpartum paralysis, 397–398
Otobius megnini, 98, 304, 449 P. multocida, 304 scoliosis, 245, 390
ototoxicity, 157 pasture‐associated stringhalt, 167, 429–430 squeeze‐chute accident, 381
overeating disease, 445 patella, upward fixation of, 168 temporohyoid osteoarthropathy,
ovine patellar reflex, 5–6, 6, 44, 45, 46 381–383
cerebellar cortical degeneration, 223 pegiviruses, 504 temporomandibular luxation, 381
encephlomyelitis virus, 314 pelvic limbs torticollis, 211, 213, 245, 390
muscular dystrophy, 256 autonomous zones, 40 see also fracture; peripheral nerve
progressive pneumonia virus, 315 examination, 18 damage; trauma
oxidative stress, 384 hindlimb spasticity in piglets, 251 picornaviral encephalitis of pigs, 319–320,
Oxytropis spp., 425 monoparesis, 185–189 320
spinal cord diseases and, 41–42 Pietrain creeper syndrome, 257
P2‐myelin protein, 346 see also limbs Pithomyces chartarum, 504
Paint horse, congenital sensorineural pendular nystagmus, 248 pituitary adenoma, 523
deafness, 247 Penicillium spp., 431, 434, 435 pituitary syndrome, 148
palatine muscles, bilateral paralysis, 138 P. cyclopium, 435 plant toxins, 86, 425–438, 432
Panagrolaimoidea, 340–341 penitrem A, 434, 435 arthrogryposis, 437
Panicum spp., 504 perennial ryegrass staggers, 86, 434 ataxia syndromes, 426–427, 430–431,
panophthalmitis, 317, 320 perineal reflex, 46 438
pantothenic acid deficiency, 484–485, 485 perineum, 46, 47 bracken fern, 429
paralysis periorbital cellulitis, 301–302 cerebellar disorders, 436–437
bilateral brachial, 191–193 peripheral nerve damage, 392–397 coffee senna (Cassia), 428–429
central motor pathway, 33–34, 45–46, 46 axillary, 394 eggplant, 429
diaphragmatic, 145 brachial plexus, 186, 187, 191–193, 192, Helichrysum, 428
facial, 29, 133–135, 134, 135 193, 394 Mexican fireweed, 428
femoral, 395 categories, 47 nigropallidal encephalomalacia,
final motor neuron, 33, 34, 45–46, 46, cranial gluteal, 396 427–428, 427
184 facial, 396–397 sorghum spp., 426–427
flaccid, 7–8 femoral, 48, 395 stringhalt, 167, 429–430
hyperkalemic periodic, in horses, interpretation of signs, 47–50 Stypandra, 428
257–258 median, 394–395 swainsonine intoxication, 425–426
laryngeal, 144–145 musculocutaneous, 394 tremor syndromes, 431–436, 433
lip, 138 obturator, 395 tutu, 437
neonatal acquired paralysis syndromes, peroneal, 396 plasmacytomas, 526
398 radial, 48, 394 plexuses, 5
one limb, 185–189 sciatic, 395–396 poison darnel, 435
pharyngeal, 31, 138 suprascapular, 48, 392–394, 393 poison hemlock, 418
postpartum, 397–398 tibial, 396 polioencephalomalacia, 482–484
sciatic, 43, 395–396 ulnar, 394–395 sulfur‐associated, 483–484
snake bite paralysis, 449 peripheral nerve tumors, 526 poliomyelomalacia, 548
spastic, 8 peripheral nervous system (PNS), 5 Polled Hereford calves
tick paralysis, 448–449 peripheral vestibular disease, 31, 151, 153, bovine familial convulsions and ataxia,
tongue, 147–148, 148 303 222
596 Index

Polled Hereford calves (cont’d) Pseudomonas spp., 301 rooster kick see stringhalt
congenital myoclonia, 224 P. aeruginosa, 298 Ross River virus, 310
maple syrup urine disease, 219 pseudomyotonia, 254, 255 Rouge‐des‐pres calves, axonopathy, 240
Polled Shorthorn calves, maple syrup urine pseudorabies, 320–321 routine clinicopathological tests, 51
disease, 219 Psoroptes ovis, 98, 449 rubrospinal motor pathway, 6, 7
polymyositis psychologic disease, 203 ruminant nervous ketosis, 510–511
protozoal, 343 Pteridium spp., 147 Russian knapweed poisoning, 427–428
septic, 308–309 P. aquilinum, 429 rye grass intoxication, 154
polyneuritis equi, 130, 196, 345–347, 345, ptosis, 27, 116, 119, 133
392 pupillary light pathway, 24 sacral fracture, 195, 196, 386, 391–392
Polypogon monspeliensis, 435 pupillary light reflexes, 23–26, 114–115, 115 sacrocaudal fracture, 391–392
polyradiculoneuritis, 184, 346 purpura hemorrhagica, 345 salinomycin toxicity, 422
polysaccharide storage myopathy, 259–260 Pythium insidiosum, 337 Salmonella spp., 296, 305, 306, 309
polysaccharide‐associated myopathy, 259 Sarcocystis spp., 85, 336–337, 343
pons, 4 Quarter horses, 164, 183, 257–258 S. capricanis, 337
porcine rubuluvirus, 320 S. cruzi, 343
porcine stress syndrome, 258–259 rabies, 317–319 S. fayeri, 343
porcine teschovirus, 319 neurological signs, 319 S. neurona, 30, 55, 100, 127, 127, 128,
portosystemic vascular anomalies, 235 rachischisis, 246 148, 186, 329–336
positive contrast myelography, 61 radial nerve damage, 48, 394 gray column lesions, 192, 193
postanesthetic cerebral necrosis, 535 radiculopathy, 397 life cycle, 330
postanesthetic limb myoneuropathy, radiography, 59–61, 60, 63, 62 sarcoma, 524, 526
564–565 rafoxanide toxicity, 423–424 Scandinavian knuckling syndrome, 558
postanesthetic myasthenic syndrome, 423 Raillietia auris, 304 Schiff–Sherrington phenomenon, 386
postanesthetic myelopathy, 548–549 Rathayibacter toxicus, 431, 435 Schwann cells, 5
postmortem examination, 76–80 rectum histopathologic reactions, 83
blocking tissues, 78–80 dilated, 194–197 sciatic nerve injury, 395–396
finding the lesion, 76–77 evaluation, 18, 46 paralysis, 43, 395, 396
gross artifacts, 77–78 recumbent patient, 43–46 scintigraphy, 64
postpartum paralysis, 397–398 recurrent exertional rhabdomyolysis, 259, sclerosing panencephalitis, 347
posture disorders, 159–169 260, 562 scoliosis, 245, 390
gait abnormalities, 15, 33–38, 48 recurrent laryngeal neuropathy (RLN), scrapie, 327–328
opisthotonus, 161–162 144–145, 555–556, 556 scrapie‐associated fibrils (SAF), 327
spasticity, 163 red fescue, 435 seasonal pasture myopathy, 437–438
stiff horse syndrome, 165, 166 reflex Secretes scabiei, 304
stringhalt, 48, 167–168, 167 clonic, 19 segmental axonopathy, 239
tetanus, 161–162, 162 corneal, 28 seizures, 97–101, 99, 109, 163
tetany, 162, 163–164 crossed extensor, 19 benign epilepsy of foals, 230–231
posture hyperactive, 18–19 bovine familial convulsions and ataxia,
abnormalities, 15, 33–38, 37 pathways, 5–6, 6 222–223
evaluation, 18–19 see also specific reflexes cerebellar convulsions, 173
Powassan, 314 regurgitation, 142, 143 familial epilepsy in cattle, 230
praying posture, 192, 193 Renaut bodies, 80, 81 hypoglycemia, 511
pregnancy ketosis, 510–511 reticular activating system (RAS), 9, 9, intracarotid injection reaction, 399
pregnancy toxemia, 510 107–108 tick‐ and mite‐associated, 449
prions, 85, 327–329 reticulopspinal motor pathways, 6, 7 selective poliomyelomalacia, 548
procaine penicillin reaction, 423 retrobulbar cellulitis, 301–302 selenium toxicity, 415–416
progestins, 200 retrobulbar neoplasia, 524 self‐inflicted lesions, 93, 199–200, 200
progressive ataxia, 239 Rhabditis bovis, 304 self‐mutilation syndrome, 93, 199–200,
Charolais cattle, 226, 238 rhabdomyolysis, 344 200, 201
progressive myelopathy exertional, 562–564 semilobar holoprosencephaly, 230
cattle, 240 recurrent, 259, 260, 562 Senecio spp., 504
spinal, 226 Rhaponticum repens, 427 Senna spp.,
progressive paresis, Angora goat, 242 rhinitis sicca, 130, 132 S. obtusifolia, 428, 504
proprioception, 6–7, 7 Rhodococcus equi, 305, 306 S. occidentalis, 428, 504
assessment, 37–38 rhombencephalon, 4 sensory pathways, 7
prosencephalon, 4 Rift Valley fever, 322 sepsis, 294, 296
protozoa, 84–85, 329–337 risus sardonicus, 420 septic aortic thrombosis, 308
protozoal polymyositis, 343 road traffic accidents, 374 septic polymyositis, 308–309
proximal limb muscle atrophy, 41, 42 roaring, 144–145, 555 Setaria spp., 340
Prunus spp. rock fern toxicity, 429 S. digitata, 340
P. laurocerasus, 418 Romney lambs, motor neuron disease, 241 shaker calf syndrome, 226, 241
P. padus, 418 Romney sheep spongiform shaker foal syndrome, 439–440
pruritus, 199 leukoencephalomyelopathy, 234 Shaking Piglets, 227
 Index 597

shivering, 49, 165–166, 166 reflex pathway, 5–6, 6 Swainsona spp., 425
shock, 401, 513 reperfusion injury, 384 swainsonine intoxication, 425–426
spinal, 386 shock, 386 Swaledale lambs, neonatal ­encephalopathy,
Shorthorn calves, cerebellar hypoplasia, stenosis, congenital, 548 229
220 splayleg syndrome, 241 swallowing reflex, 31, 138
shoulder injury, 48, 392, 394 spondyloarthrosis, 549 swayback, 490–492
Sida carpinifolia, 426 spondylosis deformans, 549 sweating, 27, 39, 42, 116–119, 118,
sidewinder syndrome, 189 sporadic bovine encephalomyelitis, 206–207, 208
signalment, 12 342–343 Sweeney, 392
Simmental cattle encephalomyelopathy, Chlamydia pecorum‐related, 343 sweet pea, 438
226, 233–234 sporadic exertional rhabdomyolysis, 562 swelling
simple reflex, 5–6, 6 spreadleg syndrome, 241 brain, 26, 84, 84, 85
sinking with application of dorsal lumbar squeeze‐chute accident, 147, 381 neurons, 81–82
pressure, 166–167 Staphylococcus spp., 296, 298, 304, spinal cord, 61
skull fracture, 376 305–306 swinging light test, 25, 112, 114–115
slap test, 31, 32, 38–39 S. aureus, 301 sympathetic innervation
sleep disorders, 97, 103–105, 535–536 starvation, 86 eyes, 26–27
see also narcolepsy status epilepticus, 98, 109 head, 26–27, 27
sleepygrass, 438 status spongiosus of white matter, 220, trunk, 27, 27
small ruminant lentiviruse, 314–316 225, 229 syncope, 109
snake bite paralysis, 449 steatitis, 492 syringomyelia, 201
sodium salt poisoning, 416–417 Stephanofilaria zahaeeri, 304
sodium thiosulfate, 418 Stephanurus dentatus, 338 Taenia spp., 341–342
Solanum spp. stereotypic behavior, 199–200 T. multiceps, 341, 342
S. bonariensis, 436 Sternocarpella maydis, 437 T. solium, 342
S. cinerium, 436 stiff horse syndrome, 165, 166, 559–560 Taeniidae, 341–342
S. dimidiatum, 436 stiff neck, 210–212 tail, 46, 47
S. fastigiatum, 436 stinging nettle, 438 atonic, 194–197
S. kwebense, 436 Stipa robusta, 438 evaluation, 18, 46
S. macrocarpon, 429 strabismus, 28, 121–123, 122, 123 tail and halter pull test, 34
S. melongena, 429 convergent, 121 tail blocking, 197
S. viarum, 436 bilateral, with exophthalmos, tail pull test, 34
Sorghum spp., 418, 426–427, 437 247–248 Talfan disease, 319
S. bicolour, 426 divergent, 121, 248 Taraxacum officinale, 430
spasmodic syndrome of cattle, 248–249 dorsomedial, 122, 123 telencephalon, 4
spastic paralysis, 8 vestibular, 122, 124, 123 temporohyoid osteoarthropathy, 133,
spastic paresis, 164, 165 Straight hock syndrome, 249 381–383
calves, 249–250 streptococcal myositis, 309 examination, 382–383
spastic syndrome, 164, 165, 166 Streptococcus spp., 296, 301, 304, 306 survival rate, 383
adult cattle, 248–249 S. equi, 298, 301, 302, 309, 344 treatment, 383
spasticity, 163 S. pneumoniae, 297 temporomandibular luxation, 381
hindlimb spasticity in piglets, 251 S. suis, 296, 304 Teschen disease, 319
spina bifida, 245 S. zooepidemicus, 306 Teschovirus, 319
spinal ataxia, 36 Streptomyces spp., 435 tetanus, 161–162, 162, 443–445
spinal cord, 4 stringhalt, 48, 167–168, 167, 429 antitoxin, 444
diseases, 33–47, 175–179 pasture‐associated, 167, 429–430 site of action, 441
gait and postural abnormalities, strongyloid nematodes, 338 treatment, 444
33–38, 48 Strongylus vulgaris, 154, 338, 552 vaccination, 445
neck and forelimb findings, 38–41 strychnine toxicity, 420 tetany, 162, 163–164
recumbent patient, 43–46 Stypandra poisoning, 428 syndrome in Arabian foals, 227
trunk and hindlimbs, 41–42 subarachnoid hemorrhage, 376 tetraparesis, 176, 178, 181, 182
see also ataxia; paraparesis; subconscious proprioceptive (spinal) Texel sheep, cervical compressive
tetraparesis ataxia, 36 myelopathy, 547–548, 547
malformations, 244 subtle gait abnormalities, 168 thalamic–cerebellar degeneration, 239
postmortem examination, 76–80 sulfur‐associated polioencephalomalacia, Theiler’s diseas, 504
swelling, 61 483–484 thermal causes, 400–402
trauma, 383–390, 385 sulpiride toxicity, 424 dehorning brain injury, 400–401, 401
sunburn in pigs, 183–184, 183, 402 electrocution and lightning strike,
evaluation, 389
suppurative meningitis, 84, 301 401–402
treatment, 388
suppurative otitis media/interna, 154, 155, heat stress and shock, 401
tumors, 526
157 sunburn, 183–184, 183, 402
spinal
suprascapular nerve damage, 48, 392–394, thermography, 62–64
dysmyelination, 225, 227
393 thiamine deficiency, 86, 483
endoscopy, 65
Surra, 336 fern‐induced, 429
muscular atrophy, 226, 240–241
598 Index

thoracic limbs sympathetic innervation, 27, 27 viral infections, 83–84, 310–329

autonomous zones, 40 Trypanosoma evansi, 336 Alphaviruses, 310–312
examination, 18 trypanosomiasis, 336 Border disease, 323
monoparesis, 185–189 tumors, 86–87, 522–523, 522 Borna virus, 316–317
spinal cord diseases and, 38–41 brain, 523–524, 524, 525 bovine herpesvirus meningoencephalitis,
see also limbs neurocranium and cranial nerves, 524 323–324
thoracolaryngeal response test, 31, 32, 38–39 peripheral nerves, 526 bovine viral diarrhea virus (BVDV),
thoracolumbar discospondylosis, 211 spinal cord, 526 229, 321–322
thoracolumbar radiculopathy, 397 Turning calf syndrome, 240 congenital malformations, 321–323, 322
thromboembolic meningoencephalitis, tutin, 437 brain, 230, 233
295–296 tutu poisoning, 437 equine arboviruses, 310
tibial nerve injury, 396 twisted calf syndrome, 245 equine herpesvirus‐1
tick paralysis, 448–449 two‐engine gait, 34 myeloencephalopathy 324–327
tick‐borne encephalitis, 314 Tyrolean gray calves, degenerative equine infectious anemia, 321
ticks, 449 axonopathy, 238–240 hemagglutinating encephalomyelitis,
toe dragging, 167 Tyzzer disease, 505 320
togaviruses, 310 malignant catarrhal fever, 317
tongue abnormalities, 32–33 ulnar nerve injury, 394–395 neuropathologic responses, 83–84
paralysis, 147–148, 148 ultrasonography, 64–65 ovine encephalomyelitis virus, 314
tongue‐sucking, 32, 94, 148 upper motor neuron (UMN), 8 picornaviral encephalitis, 319–320
torticollis, 245, 390 upward fixation of patella, 168 porcine rubuluvirus, 320
cervical, 211, 213 urea intoxication, 418 pseudorabies, 320–321
toxic diseases, 86 uremic encephalopathy, 508–509 rabies, 317–319
see also chemical toxins; plant toxins urinalysis, 51, 53 small ruminant lentiviruses, 314–316
Toxoplasma gondii, 336 urinary bladder distention, 194–197 sporadic bovine encephalomyelitis,
Toyon shrub, 418 urinary incontinence, 58, 195 342–343
transmissible spongiform ­encephalopathy, Urtica dioica, 438 togaviruses, 310
85, 327–329 transmissible spongiform
bovine spongiform encephalopathy, 327, vaccination ­encephalopathies, 327–329
328–329 botulism, 443 West Nile virus, 183, 192, 312–314, 313
chronic wasting disease, 329 bovine herpesviruses, 324 visual pathways, 21, 22, 25, 111
scrapie, 327–328 equine alphaviruses, 312 vitamin A deficiency, 86, 482
trauma equine herpesviruses, 325, 326–327 vitamin B5 deficiency, 484–485, 485
head trauma/brain injury, 110, 154, Histophilus somni, 296 vitamin D deficiency, 86
374–380, 380 listeriosis, 295 vitamin E deficiency, 86, 482
classification, 375 pseudorabies, 321 equine degenerative
management, 378–379, 378 rabies, 318, 319 ­myeloencephalopathy, 489–490
primary injury, 375, 376 tetanus, 445 equine motor neuron disease, 488–489
secondary injury, 375–376 verotoxin, 446
severity scale, 378 West Nile virus, 313–314 warble fly, 342
intervertebral discs, 390–391 vagus nerve, 31–32 water intoxication, 416–417
optic neuropathy, 380–381, 381 Varicellovirus, 320, 323 weakness
spinal cord and vertebrae, 383–390, 385 vascular lesions, 86 diffuse, 181–184
see also peripheral nerve damage vascular malformations, 549 plant toxin‐induced, 430–431
trazodone toxicity, 424 Venezuelan equine encephalitis (VEE), Weaver syndrome, 238
tremor, 163–164 310, 312 Wesselbron disease, 322
tremor syndromes, 163–164 ventriculitis, 296–297 West Nile virus, 183, 192, 310, 312–314, 313
congenital, 173, 225, 227–229, 228 verminous encephalitis/myelitis, 338 Western equine encephalitis (WEE),
plant and mycotoxin‐induced, 431–436, verotoxin 2e, 445, 446 310–312
433 vertebral malformations white matter, 4
annual ryegrass toxicity, 86, 431, 435 bovine complex, 243 status spongiosus, 220, 225, 229
Aspergillus, 436 congenital, 244–246, 244, 245 white muscle disease, 492
ergotism, 436 see also cervical vertebral wobblers, 34, 40–41, 171, 176, 179, 179, 536
perennial ryegrass staggers, 86, 434 malformation see also cervical vertebral malformation
phalaris staggers, 431, 434–435 vertebral suppurative osteomyelitis and woody tongue, 303
Trichinella spiralis, 486 discospondylitis, 84, 305–308, 306, woolly everlasting daisy poisoning, 428
trigeminal nerve, 28–29 307, 308
damage, 129–130 vertebral trauma, 383–392, 385, 387 Xanthorrhoea spp., 438
trigeminal neuritis, 130, 132, 201 vestibular ataxia, 37
Triticum aestivum, 435 vestibular dysfunction, 150–155 yakka, 438
trochlear nerve, 28 vestibular strabismus, 122, 124, 123 yawning, 505
Trueperella pyogenes, 296, 298, 299, 301, vestibular system, 30–31, 30, 150–152 yellow star thistle, 86, 427–428
304, 305–306 assessment, 154–155 yohimbine, 105
trunk vestibulocochlear nerve, 30–31 Yorkshire piglets, cerebellar abiotrophy, 221
examination, 18 vestibulospinal motor pathway, 6, 7
spinal cord diseases and, 41–42 Vicia villosa (hairy/fodder vetch), 347 Zea mays, 446