Approach to Coma

Presenter: Dr. Anteneh A.( R3)

Moderator: Dr. Birre Direse (Consultant Neurologist, Associate

professor of Neurology)

June 24, 2022

Outlines
Introduction
Definition of terms
Anatomy and physiology of coma
Approach to coma
Causes of coma
Mimickers of coma
Treatment of coma
Brain death

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 Case scenario No: 1
1. A police man bring a gentleman(around 50 years of age) to emergency OPD
after he got him fallen in a street. No one knows him and difficult to dig history.
Upon P/E: V/S: BP=160/100, PR=60 (R), RR=16 T=36.9 c o. There is no visible
sign of trauma externally. On neurology exam GCS of 7/15 with FOUR score of
8/16. Pupils are small and reactive upon arrival and become fixed & mid
position after 2 hrs. Upon head flexion and extension there is no eye movement.
His upper extremities are pronated, extended and hypotonic extremities with no
preference of extremities with positive Babinski sign.

A. How do you approach this patient?

B. What pertinent Ix do you want to do?
C. What do you think is the cause?

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 Case scenario No: 2
A 20 years old university student came to EOPD with failure to communicate
of 2 hours duration by her friends. They don’t know what happen to her. An
intern assess her told you that her GCS of 3/15. Upon evaluation her V/s are
stable, didn’t respond to pin prick and pinching. She resist passive eye opening,
roll over when tickled to avoid the stimulus and turn the eyes towards the floor
always. When cold water was instilled in her rt ear her eye was moving from
right to left fast and repeatedly.

What do you think is the cause?

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Introduction
Consciousness: defined as a state of awareness of self & surroundings.
Consciousness has two major dimensions:
Arousal
Content: cognitive and affective

Delirium: a disturbance in attention and awareness (DSM-V).

Hyperactive delirium: cognition problem
Hypoactive delirium: arousal problem

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Definition
Alterations in arousal: made up of continuum of subtly dynamic
changing behavioral states that range from alert to comatose.
Four points on the continuum of arousal:

Alert refers to a perfectly normal state of arousal.

Lethargy mildly depressed level of consciousness or alertness & aroused with
moderate stimuli. Lies between alertness and stupor.

Stupor is a state of baseline unresponsiveness that requires repeated application

of vigorous stimuli to achieve arousal.
Coma is a state of complete unresponsiveness to arousal.

Alert confusion lethargy obtundation stupor coma.

Coma
Coma, from the Greek “deep sleep or “trance”.
Coma is defined as "unarousable unresponsiveness“.
It is an acute, life-threatening emergency, requiring prompt
intervention.
There are different etiologies of coma.

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 Anatomy and Physiology Of Coma
Almost all instances of coma can be traced to either:
1. Widespread abnormalities of the cerebral hemispheres.
2. Reduced activity of the thalamocortical alerting system, the reticular
activating system (RAS).

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 ARAS
A system of fibers that arises from the reticular formation of brainstem,
primarily the paramedian tegmentum of the upper pons and midbrain.
It projects to the paramedian, parafascicular, centro-median, & intralaminar
nuclei of the thalamus.
Receive collaterals from the ascending spinothalamic pathways and send
projections diffusely to the entire cerebral cortex.
The fibers in RAS are cholinergic, adrenergic, dopaminergic, serotonergic,
and histaminergic.
Stimulation of the RAS produces arousal, & destruction produces coma.

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Arousal can be produced by
stimulation of the posterior
hypothalamic region.
The RAS runs through the core of the
brainstem.
The nuclei & pathways controlling eye
movements occupy the same regions.
It controls arousal and consciousness.

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Mechanisms of coma

Focal lesions within upper brainstem directly damaging the ARAS.

Damage to the cerebral hemispheres.
Impair oxygen or substrate delivery, alters cerebral metabolism or
interferes with neuronal excitability and/or synaptic function.

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Approach To Comatose Patient
Urgent steps may be necessary to avoid or minimize permanent brain
damage.
Acute respiratory & cardiovascular problems should be attended prior
to neurologic assessment.
A complete medical evaluation, may be deferred until severity & nature
of coma is known.
After stabilization:
History
General physical examination
Neurologic examination

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 History
The cause of coma may be immediately evident as in cases of trauma, cardiac
arrest, or observed drug ingestion.
In the remainder, certain points are useful:
Circumstances & rapidity
Antecedent symptoms
The use of medications, drugs, or alcohol
Chronic liver, kidney, lung, heart, or other medical disease.
Direct interrogation of relatives, friends, bystanders in person or by telephone.
Patient’s wallet or purse should be examined
An old hospital chart
Social background and prior medical history
Psychiatric history
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Common presentations
Coma usually manifests in one of three ways.

A. As an expected or predictable progression of an underlying illness

(e.g. Brainstem lesion).

B. As an unpredictable event in a patient whose prior medical conditions

are known to the physician (e.g. Arrhythmia).

C. Coma can occur in a patient whose medical history is totally unknown

to the physician (e.g. trauma).

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General Physical Examination
GA: Signs of head trauma, posturing, cachexic, odor
V/S:
Fever or Hypothermia
Tachypnea/Bradypnea
Tachycardia/bradycardia
Marked hypertension or hypotension
Eye & funduscopic examination
Papilledema
Subhyaloid hemorrhages
Exudates, hemorrhages
CVS: arrhythmia
Abdomen: ascites
IS: petechiae, abrasions, cold/hot, rash/irruptions
Check cervical trauma
Meningeal signs 15
Neurologic Examination
NE of a comatose patient serves three purposes:
1. To aid in determining the cause of coma:
2. To provide a baseline
3. To help to determine the prognosis
Includes:
Level of consciousness
Motor responses
Brainstem reflexes:
 Pupillary size & response, corneal reflexes
 Respiratory pattern
 Spontaneous and reflex eye movements
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Level of Arousal
A sequence of increasingly intense stimuli is first used.
Serial examinations are useful.
Assessed by noise and somatosensory stimulation:
Tickling the nostrils with a cotton wisp
Pressure on bony prominences
Nail bed pressure or pinching the sternum
Pinprick stimulation
Try to avoid pinching the skin as far as possible.
GCS is useful as an index of the depth of impaired consciousness.

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Glasgow Coma Scale
GCS is used widely to assess the initial severity of TBI.
It’s failure to assess other essential neurological parameters limits its utility.
Impractical in intubated or who have suffered facial trauma.

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Full Outline of UnResponsiveness
score

Components of FOUR score:

Eye response
Motor response
Brainstem reflexes (pupillary
reaction, corneal reflex, and
cough reflex)
Respirations

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Cranial nerves
The fundi should be carefully inspected.
The most important cranial nerve reflexes with respect to coma are:
 Pupillary reflex
 Corneal reflex
 Vestibuloocular reflex (VOR)

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Brainstem Reflexes
Brainstem function is essential for localization of the lesion in coma.
Includes:
Pupillary size and reaction to light
Spontaneous and elicited eye movements
Corneal responses
Respiratory pattern
Preserved brainstem reflexes typically have a bihemispheric localization
to coma, including toxic or drug intoxication.
Abnormal brainstem reflexes either have a lesion in the brainstem or a
herniation syndrome from a cerebral mass lesion.

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Pupillary size & reaction
Pupillary reactions are examined with a bright, diffuse light.
Depends on the level of illumination & state of autonomic innervation.
Efferent vs afferent innervation

Abnormalities in pupil size and reactivity help:

To delineate structural damage between the thalamus and pons.
Act as a warning sign heralding brainstem herniation.
To differentiate structural causes from metabolic causes.

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Sympathetic Vs parasympathetic pathways

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 Reactive & round pupils of midsize (2.5–5 mm) essentially exclude upper
midbrain damage.

 One enlarged (>6 mm) & poorly reactive pupil signifies compression of
the third nerve from the effects of a cerebral mass above.

 The most extreme pupillary sign, bilaterally dilated and unreactive

pupils, indicates severe midbrain damage.

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Midbrain lesions produce three types of pupillary abnormality:

1. Dorsal tectal lesions interrupt the pupillary light reflex, resulting in

midposition, fixed pupils to light.

2. Nuclear midbrain lesions affect both sympathetic & parasympathetic

pathways, resulting in fixed, irregular midposition pupils, which may
be unequal.

3. Third nerve fascicle in the brainstem lesions, or after the nerve has
exited the brainstem, cause non-responsive, wide pupillary dilation.

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Thalamic lesions:
Cause small, reactive pupils, which often are referred to as
diencephalic pupils.
Similar pupillary findings are noted in many toxic-metabolic
conditions resulting in coma.
Hypothalamic lesions or lesions elsewhere along the sympathetic
pathway result in Horner syndrome.

Lesions above the thalamus and below the pons should leave pupillary
function intact.

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Con…
Reactive & bilaterally small (1–2.5 mm) but not pinpoint pupils are seen in:
Metabolic encephalopathies
Deep bilateral hemispheral lesions such as hydrocephalus
Thalamic hemorrhage

Pin pointed pupils (pontine pupil):

Lesions in the pontine tegmentum selectively disrupt sympathetic outflow.
Pontine hemorrhage is the most common cause.
Opiate overdose can also produce this sign.

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Eye movements
Voluntary ocular motility cannot be judged in the comatose patient.
Rely on reflex eye movements to assess the ocular motor system.
Examine resting, spontaneous & reflex eye movement.
The eyes look toward a hemispheral lesion & away from a brainstem
lesion.
Roving eye movements are slow, conjugate, lateral to and fro movements.
In comatose patient, bilateral conjugate roving eye movements that
appear full indicate an intact brainstem.
“Ocular bobbing”: bilateral pontine damage.
“Ocular dipping”: diffuse cortical anoxic damage.

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 Reflex ocular movements
Oculocephalic reflex (doll’s eye
maneuver)
Oculovestibular response (caloric
testing)

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Corneal reflex
Integrated by pontine pathways between the 5th (afferent) & both 7th
(efferent) cranial nerves.
Elicited by touching the cornea with a wisp of cotton and observing
bilateral lid closure.
The eyeballs move upward in concert with lid closure.
It is a useful test of pontine function.
Loss of the corneal reflex is also an index of the depth of metabolic or
toxic coma.

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 Respiratory Patterns
Have less localizing value in comparison to other brainstem signs.
Shallow, slow, but regular breathing suggests metabolic or drug-induced
depression of the medullary respiratory centers.
Cheyne-Stokes respiration signifies bihemispheral damage or diencephalic
insults and commonly accompanies light coma.

Kussmaul (Rapid, deep) breathing usually implies metabolic acidosis but

may also occur with pontomesencephalic lesions.
Agonal gasps are the result of lower brainstem (medullary) damage.

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Respiratory patterns
Cheyne-Stokes respiration (A)
Central neurogenic hyperventilation (B)
Apneustic breathing (C)
Cluster breathing (D)
Ataxic respiration (E)

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Motor examination
Assess muscle tone, spontaneous & elicited movements and reflexes.
Head & eye deviation to one side, with contralateral hemiparesis, suggests
a supratentorial lesion.
Whereas ipsilateral paralysis indicates a probable brainstem lesion.
Reflex posturing can occur in deep metabolic coma.
Muscle tone is generally not affected by most metabolic conditions.

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Posturing
Decorticate posturing
Upper-extremity adduction & flexion at elbows, wrists, and fingers, with
lower-extremity extension & adduction at hip, knee & plantar flexion with
ankle inversion.
It is a much poorer localizing posture, though usually above brainstem.
It is not as ominous sign as decerebrate posture.
It has a better prognosis than those with decerebrate posturing.
Decerebrate posturing
Upper-extremity extension, adduction & pronation with lower-extremity
extension.
Traditionally implies dysfunction below the red nucleus.
Bilateral midbrain or pontine lesions usually are responsible.
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Adventitious movements
Tonic- clonic: seizure
Myoclonic jerking: anoxic encephalopathy or other metabolic comas.
Rhythmic myoclonus: sign of brainstem injury.
Tetany: hypocalcemia
Cerebellar fits: tonsillar herniation
Tremor and asterixis: metabolic coma

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 Coma Syndromes
There are numerous etiologies of coma.
Diseases that cause coma are categorized into three groups:
1. Structural lesions
2. Metabolic and toxic causes
3. Psychiatric causes

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Plum and Posner’s landmark study (1980, see 2007 revision):
500 comatose patients:
 326 patients had diffuse and metabolic brain dysfunction
Half were drug poisonings
 101 had supratentorial mass lesions
77 hemorrhagic lesions and 9 infarctions
 65 had subtentorial lesions, mainly brainstem infarctions
 8 had psychiatric coma

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DDx of coma

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Structural causes

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 Herniation syndromes
Herniation: displacement of brain tissue by an intracerebral or overlying mass
into a contiguous compartment that it normally does not occupy.
There are different types of cerebral herniation:
A. Uncal
B. Central
C. Transfalcial
D. Foraminal

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Transtentorial herniation

The most common form of herniation.

Brain tissue is displaced from the supratentorial to the infratentorial
compartment through the tentorial opening.
The cause is often a mass hemispheral lesion.
It can be either uncal or central.

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Uncal transtentorial herniation

Impaction of the anterior medial temporal gyrus (the uncus) into the
tentorial opening just anterior to and adjacent to the midbrain.
The uncus can compress the third nerve as it traverses the
subarachnoid space.
Results in early signs of third nerve (ipsilateral dilated pupil) and
midbrain compression (mid position pupil).

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Central transtentorial herniation

Symmetric downward movement of the thalamic structures through the

tentorial opening with compression of the upper midbrain.
Miotic pupils & drowsiness are the heralding signs.

Cause progressive compression of the brainstem & RAS, with initial damage
to the midbrain, then pons, and finally medulla (rostrocaudal manner).
Result an approximate sequence of neurologic signs that corresponds to
each affected level.
Respiratory centers in the brainstem often spared until late in the herniation
syndrome.
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Transfalcial herniation
Displacement of the cingulate gyrus under the falx and across the
midline.

Foraminal herniation
Downward forcing of the cerebellar tonsils into the foramen magnum.
It causes early compression of the medulla, respiratory arrest, and
death.

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Primary Brainstem lesions
Coma from a primary brainstem process usually occurs in the setting of
infarction or hemorrhage of the upper pons and/or midbrain.
ODS and brainstem encephalitis are other causes.

Bilateral long tract involvement is usual and may manifest with flaccid
quadriparesis or decerebrate posturing.
Brainstem reflexes are affected.
Eye movements may be notably asymmetric or absent and pupils are
classically fixed.

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Bilateral Hemispheric Dysfunction
Coma results from extensive bilateral structural cerebral damage.

Unilateral hemispheric mass lesions compress or displace the diencephalon

and brainstem.
Intact brainstem reflexes (particularly in less severe forms), and variable
motor responses.

Generalized myoclonus may be seen as a result of severe cortical necrosis.

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 Metabolic coma
Metabolic causes of coma are far more common than structural injuries.
Cause coma by:
Interrupting the delivery of energy substrates (oxygen, glucose).
Altering neuronal excitability (drugs, alcohol, anesthesia, epilepsy).
Most metabolic disorders cause no or only minor neuropathologic
changes in the brain.
Typically produce no focal or lateralizing signs.

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Con…
A cardinal feature of metabolic coma is the symmetrical neurologic
deficits.
 Except hypo & hyperglycemia are frequently associated with lateralized motor
findings.
Fluctuations in the examination are common.
Tremor, asterixis, and multifocal myoclonus strongly suggest metabolic
coma.
Muscle tone is usually decreased.
Decerebrate posturing is less common in metabolic coma, but may occur.
Pupils appear abnormal but almost always are symmetric & constricts to
light.
Suppression of VORs and corneal reflex occur with very deep metabolic
coma.
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Comas due to drugs and toxins

Typically reversible and leave no residual damage.

Produce coma by affecting both the RAS & cerebral cortex.
The combination of cortical and brainstem signs, occurs occasionally in
certain drug overdoses.
Atropinic actions produces signs: dilated pupils, tachycardia, and dry
skin.
Opiate overdose produces pinpoint pupils <1 mm.
Barbiturates, can mimic all of the signs of brain death.
Thus, toxic etiologies should be excluded prior to making a diagnosis of
brain death.

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Epileptic Coma

Generalized electrical seizures are associated with coma, even NCSE.

EEG monitoring is often used in unexplained coma.
The self-limited coma that follows a seizure is postictal confusion.
Postictal coma is due to exhaustion of energy reserves or effects of
locally toxic molecules that are the by-product of seizures.
It typically lasts for a few minutes but can be prolonged.

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 Metabolic-Toxic Coma Vs Structural Coma
Parameters Metabolic/Toxic coma Structural coma
Onset Slowly progressive Abrupt
Response to emergency treatment Rapid response No or slow response
Neurologic exam Symmetric/multilevel Asymmetry or focal features
State of consciousness Milder/fluctuating/wax & waning Same or progressively deteriorate
Fundoscopy exam Papilledema very rare (hypoparathyroidism & Papilledema, SHH
lead intoxication
Pupil size Small with preserved reactivity Asymmetric, dilated or miosis
Ocular motility Symmetric Asymmetric
Reflex eye movements Intact No
Spontaneous eye movements Roving eye mov’t NO
Muscle tone Symmetrical (normal or decreased) Asymmetric (N, de/increased)
Respiration Deep, frequent Shallow

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 Psychiatric & pseudocoma Vs metabolic or structural coma
True coma Pseudocoma
 Passive eyelid opening is easily performed. Active resistance to passive eye opening.
 Followed by slow, gradual eyelid closure. May even hold the eyes tightly closed.
 Blinking decreases or absent. Blinking also increases.
 Pupillary reaction with different response. The pupils dilate with the eyes closed in
 Roving eye movements cannot be the awake state.
mimicked. Opening the eyes of an awake person
 Cold caloric testing: eyes tonically deviate produces pupillary constriction.
to the side of the caloric instillation. Cold caloric testing with the resultant
nystagmus & usually “awakens” him

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 Mimickers of Coma
Locked-in syndrome (de-efferented state)
Patients are alert and aware of their environment but are quadriplegic.
Lower CN palsies resulting from bilateral ventral pontine lesions that
involve the corticospinal, corticopontine, and corticobulbar tracts.
Move their eyes vertically or blink voluntarily.
Causes can be:
 Pontine infarction due to basilar artery thrombosis
 Central pontine myelinolysis
 Brainstem mass lesions
 Severe polyneuropathy

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Persistent vegetative state
Do not engage in any of the following behaviors:
 Awareness of self and environment, interaction with others.
 Sustained, reproducible, or purposeful voluntary behavioral response.
Retain vegetative functions such as cardiac action, respiration, maintenance
of BP, and a sleep/wake cycle.
Spontaneous movements may occur.
The eyes may open in response to external stimuli.
But the patient does not speak or obey commands.
Diagnosis needs extended periods of observation.

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Minimally conscious state

Severe disability accompanies minimal awareness.

10 times more common than PVS.
The patient displays rudimentary vocal or motor behaviors, often spontaneous,
but sometimes in response to touch, visual stimuli, or command.
Respond some yes/no questions or use two familiar objects correctly.
Cardiac arrest with cerebral hypoperfusion and head trauma are the most
common causes.

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Akinetic mutism
Partially or fully awake state in which the patient remains virtually immobile and
mute but can form impressions and think.
Results from damage in the regions of the medial thalamic nuclei or the frontal
lobes or from extreme hydrocephalus.

Abulia
A milder form of akinetic mutism characterized by mental and physical slowness
and diminished ability to initiate activity.
Severe apathy in which patients have blunting of feeling, drive, mentation, and
behavior such that they neither speak nor move spontaneously.
It is due to damage to the medial frontal lobes and their connections.

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Catatonia
It is hypermobile state of muteness, with dramatically decreased motor
activity.
Occurs usually as part of a major psychosis, typically schizophrenia or
major depression.
The maintenance of body posture, with preserved ability to sit or stand,
distinguishes it from organic pathological stupor.

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Pseudocoma
A condition in which the patient appears comatose (i.e., unresponsive,
unarousable, or both) but has no structural, metabolic, or toxic disorder.

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Psychogenic unresponsiveness

 Prolonged, motionless, dissociative attack in which the patient has absent or

reduced response to external stimuli.
 The lack of responsiveness can vary from functional coma to a condition
resembling stupor or catatonia.
 Such patients often:
Resist passive eye opening.
Roll over when tickled to avoid the stimulus.
Turn the eyes towards the floor regardless of which side they are lying on.
Presence of nystagmus with caloric stimulation strongly suggests it.

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 Laboratory Studies
Blood sugar ECG
CBC Neuroradiological Imaging
Serum electrolyte  CT
 MRI
Arterial blood gas
Lumbar puncture
LFT, serum ammonia level
EEG
RFT
Evoked Potentials
TFT, serum cortisol level
Intracranial Pressure measurement
Coagulation profile
Blood alcohol level
Drug and toxin screening
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Treatment of coma
The immediate goal is prevention of further brain damage.
Emergency treatment
ABC of life
Administration of IV glucose & thiamine
 50 cc of 50% glucose (25 gm)
 Followed quickly by 100 mg IV thiamine.
Treat definite seizures
Naloxone & flumazenil: Opate & BDZ overdose
Physostigmine: anticholinergic-type drug overdose
Treat ICP
Consider empiric antibiotic treatments
Gastric lavage and activated charcoal 67
Rx:…..
Hypotension, hypoglycemia, hypercalcemia, hypoxia, hypercapnia, and
hyperthermia should be corrected rapidly.
Hyponatremia should be corrected slowly to avoid injury from ODS.

Tracheal intubation is indicated if there is apnea, upper airway

obstruction, hypoventilation, or emesis at risk for aspiration.
MV is required if there is hypoventilation or need to induce hypocapnia in
order to lower ICP.

Definitive therapy depends on establishing the precise diagnosis.

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Coma cocktail
A combination of substances administered in an emergency to comatose
individuals when the cause has not yet been determined.

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 Prognosis
The outcome cannot be predicted with 100% certainty.
Early prognostication outside of brain death therefore is unwise.
The natural history of coma can be considered in terms of 3 subcategories:
1. Drug-induced coma
 Usually is reversible.
2. Nontraumatic coma
 Only 15% make a satisfactory recovery.
 Structural causes carry the worst prognosis.
 Hypoxia-ischemia causes intermediate prognosis.
 Metabolic causes have best ultimate outcome.
3. Traumatic coma
 May recover up to several months.
 Most left with profound disabilities. 71
Prognosis….
Metabolic comas have a far better prognosis than traumatic ones.

Address metabolic causes as fast as possible.

The fate of comatose patients will be either:

Recover
Evolve into persistent vegetative state
Evolve into minimally conscious state
Evolve into brain death

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Brain death
Brain death is irreversible, permanent absence of cerebral & brainstem
functions.
Irreversibility is determined by absent motor responses, loss of all
brainstem reflexes, and the apnea test.
The most common causes are:
 Severe TBI
 Aneurysmal SAH
 Massive intraparenchymal hemorrhage
 Anoxic-ischemic brain injury

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Con…
Prerequisites be met prior to the clinical examination.
The main confounding factors that need to be excluded:
 Hypothermia (core body temperature should be ≥36°C)
 Drug intoxication or poisoning
 Lingering effects of sedatives, analgesics & neuromuscular blockers
 Severe electrolyte or acid-base disturbances

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Con…
Brainstem reflexes is the crux of the clinical assessment.
In brain death:
 Most pupils are 4 to 6-mm diameter.
 Absent pupillary response in both eyes.
 Constricted pupils should not be seen.
 Corneal reflexes should be absent bilaterally.
 Absent oculocephalic & oculovestibular reflex.
 Absent gag reflex & cough response.
 No grimacing and motor response.
 Lack of respiratory drive by an apnea test.

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Con…
Preserved spinal cord reflex activity may lead to dramatic movements,
such as the “Lazarus reflex”.
Deep tendon reflexes, superficial reflexes, and the Babinski sign may be
present.
There may even be respiratory-like movements.

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Con…
Brain death is a clinical determination.
Clinical Findings Not Compatible with Brain Death
 Nystagmus or other spontaneous eye movements
 Conjugate eye deviation
 Pinpoint pupils
 Grimacing to noxious stimulation
 Decerebrate or decorticate motor posturing

The family should be told that the patient has died but remains supported
by artificial means.

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Management of the Brain Dead Patient
Aggressive critical care measures for potential organ donors.
Supplementation of pituitary axes hormones.
Adequate end organ perfusion: fluid & vasopressors
Additional medications such as antibiotics.
Off the ventilation????

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Reference
Joseph R. Berger, Raymond Price: Bradley and Daroff’s neurology in
clinical practice, 8th ed. 2021: P34-51
S. Andrew Josephson, Allan H. Ropper, Stephen L. Hauser: Harrison’s
principles of internal medicine, 21st ed. 2022: P183-189

Jerome B. Posner, Clifford B. Saper, Nicholas D. Schiff, Jan Claassen:

Plum And Posner’s Diagnosis And Treatment Of Stupor And Coma, 5th
Edition, 2018
G. Bryan Young: Stupor and coma in adults: UpToDate online, 2022

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Thank you!!!

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