are unresponsive) to external stimulation and are either difficult to arouse or are unarousable. Coma is defined
as "unarousable unresponsiveness" [
]. An alert patient has a normal state of arousal. The terms stupor,
generally not be used in clinical situations without further qualification.
An alteration in arousal represents an acute, life threatening emergency, requiring prompt intervention for
preservation of life and brain function [
]. Although discussed separately here, the assessment and
neurons originating in the tegmentum of the upper pons and midbrain, believed to be integral to inducing and
maintaining alertness. These neurons project to structures in the diencephalon, including the thalamus and
hypothalamus, and from there to the cerebral cortex. Alterations in alertness can be produced by focal lesions
within the upper brainstem by directly damaging the ARAS.
Injury to the cerebral hemispheres can also produce coma, but in this case, the involvement is necessarily
bilateral and diffuse, or if unilateral, large enough to exert remote effects on the contralateral hemisphere or
brainstem. Magnetic resonance imaging (MRI) studies have indicated that coma in supratentorial mass lesions
occurs both with lateral forces on the contralateral hemisphere and with downward, brainstem compression
The mechanism of coma in toxic, metabolic, and infectious etiologies and hypothermia is less well understood
and to some extent is cause specific. A simplified explanation is that these conditions produce impaired oxygen
or substrate delivery which alter cerebral metabolism or interfere with neuronal excitability at some level.
Conditions causing stupor and coma cross a broad spectrum of medical and neurologic disease; the list of
potential differential diagnoses is long (
). Most cases of stupor and coma presenting to an emergency
precise case mix varies according to the setting and referral base [
]. Also, case series often do not include
a witnessed epileptic seizure, but these are common causes of coma as well.
can provide valuable information:
It is often useful to obtain a history from witnesses, friends or family members, and emergency medical
technicians who might provide information that suggests the likely etiology.
The patient's personal effects: a Medical Alert bracelet or necklace and/or a card in the wallet may
contain a list of illnesses and medications
An old hospital chart may also contain information not otherwise available
Potentially helpful questions for relatives, friends, and witnesses include:
Official reprint from UpToDate
G Bryan Young, MD, FRCPC
Michael J Aminoff, MD, DSc
Robert S Hockberger, MD, FACEP
Janet L Wilterdink, MD
What was the time course of the loss of consciousness? Was it abrupt (eg, subarachnoid hemorrhage,
seizure), gradual (eg, brain tumor), or fluctuating (eg, recurring seizures, subdural hematoma, metabolic
Did focal signs or symptoms precede the loss of consciousness? As an example, an initial hemiparesis
suggests a structural lesion, likely with mass effect. Transient visual symptoms, eg, diplopia or vertigo,
suggest ischemia in the posterior circulation.
Did the patient have previous neurologic episodes that suggest transient ischemic attacks or seizures?
What recent illness has the patient had? Has there been altered behavior or function recently? A fever
suggests infection; an increasing headache suggests an expanding intracranial lesion or infection; recent
falls raise the possibility of a subdural hematoma; recent confusion or delirium might indicate a
metabolic or toxic cause.
What prescription or nonprescription drugs are used? Are there medical or psychiatric conditions? Is
there history of alcohol or drug abuse?
GENERAL EXAMINATION — A general physical examination should not be neglected in the patient with
coma, as valuable clues to the underlying etiology are often found (
Vital signs — Extreme hypertension may suggest reversible posterior leukoencephalopathy syndrome,
circulatory failure from sepsis, hypovolemia, or cardiac failure, as well as certain drugs or Addison's
Hyperthermia usually signifies an infection; heat stroke, or anticholinergic intoxication are other
possibilities. Hypothermia could be accidental (cold exposure), primary (due to hypothalamic dysfunction
as in Wernicke's encephalopathy or tumor), or secondary (eg, adrenal failure, hypothyroidism, sepsis,
drug or alcohol intoxication).
Ventilatory pattern — An observation of hypo or hyperventilation can be helpful in the diagnosis of a
patient with coma, especially when combined with blood gas results (
Specific breathing patterns, while classically associated with regions of brainstem injury during
transtentorial herniation (
periodic waxing then waning hyperpnea, followed by brief apnea) may occur with either impaired cardiac
output or bicerebral dysfunction, and also in elderly patients during sleep. The shorter-cycle Cheyne-
Stokes respiration linked to brainstem tegmental dysfunction may evolve into irregular respirations with
progression of downward herniation (see
below). Apneustic breathing (in which there
is a prolonged inspiratory phase or end-inspiratory pause) is rare and usually attributed to pontine
Cutaneous and mucosal abnormalities — A rapid survey of the skin can have a high yield in the
evaluation of a patient with coma (
Bruises can indicate head trauma, especially "raccoon eye" (periorbital ecchymosis). Battle's sign
(bruising over the mastoid) and hemotympanum (blood behind the tympanic membrane) are signs of
basal skull fracture. Petechiae and ecchymoses can be seen in bleeding diatheses (eg, thrombocytopenia,
disseminated intravascular coagulation), some infections (eg, meningococcal septicemia, Rocky Mountain
spotted fever), and certain vasculitides. Subungual (splinter) and conjunctival hemorrhages are
sometimes seen in endocarditis. Petechiae confined to the head and neck may be found after convulsive
seizures due to acutely raised venous pressure.
Perspiration is common in fevers, hypoglycemia, and pheochromocytoma. Bullous lesions are
characteristic of barbiturate intoxication (coma blisters).
Jaundice could indicate liver disease. A cherry red color, especially of the lips and mucous membranes,
suggests carbon monoxide intoxication. Pallor, especially with a sallow appearance, may suggest uremia,
myxedema, or severe anemia as in profound pernicious anemia.
Needle tracks suggest intravenous drug abuse. A tongue bitten on the lateral aspect suggests a recent
Other — Most orthopedic injuries indicate trauma. Some, in particular posterior fracture dislocation at the
shoulder, manubriosternal dislocation, and vertebral compression fractures (less commonly fractures of
the femoral neck or acetabulum), also occur with convulsive seizures.
Cerebrospinal fluid rhinorrhea can occur with skull fracture, and is important to recognize, as recurrent
pyogenic meningitis can occur as a later complication.
Resistance to passive neck flexion suggests meningismus, a sign of meningeal irritation occurs in
meningitis and subarachnoid hemorrhage.
Examination of the lungs, heart, and abdomen may also provide clues to other organ system disease.
directed at determining whether the pathology is structural or due to metabolic dysfunction (including drug
effects and infection). The examiner assesses:
Level of consciousness
Brainstem reflexes: pupillary light, extraocular, and corneal reflexes
Important findings are abnormal reflexes that indicate dysfunction in specific regions of the brainstem, or a
consistent asymmetry between right- and left-sided responses.
stimuli than to use terms such as stupor or obtunded. Even coma has a spectrum of possible responses.
Arousability is assessed by noise (eg, shouting in the ear) and somatosensory stimulation. Pressing on the
supraorbital nerve (medial aspect of the supraorbital ridge) or the angle of the jaw, or squeezing the
trapezius, may have a higher yield than the more commonly used sternal rub and nailbed pressure. Important
responses include vocalization, eye opening, and limb movement.
The Glasgow coma scale (GCS) demonstrates a hierarchy of responses in each of these areas which reflect the
severity of the coma (
). The GCS is useful as an index of the depth of impaired consciousness and for
'Glasgow coma scale'
Motor examination — It is important to assess muscle tone, as well as spontaneous and elicited movements
and reflexes. Asymmetries of these often indicate a hemiplegia of the non-moving side, implying a lesion
affecting the opposite cerebral hemisphere or upper brainstem.
Purposeful movements include crossing the midline, approaching the stimulus, pushing the examiner's hand
away or actively withdrawing from the stimulus. In addition to decreased spontaneous or purposeful
movement, acute structural disease usually produces decreased muscle tone or flaccidity. Flexion and
extension movements usually represent reflex responses arising from subcortical structures:
Decorticate posturing consists of upper-extremity adduction and flexion at the elbows, wrists, and
fingers, together with lower-extremity extension, which includes extension and adduction at the hip,
extension at the knee, and plantar flexion and inversion at the ankle (
). This occurs with
dysfunction at the cerebral cortical level or below and may reflect a "release" of other spinal pathways.
Decerebrate posturing consists of upper-extremity extension, adduction, and pronation together with
lower-extremity extension (
) and traditionally implies dysfunction below the red nucleus, allowing
the vestibulospinal tract to predominate.
The traditional neuroanatomic correlates of decorticate and decerebrate postures do not hold as true for
humans as for animals. As an example, often, decerebrate posturing is assumed in patients with bilateral
cerebral lesions well above the red nucleus. In general, patients with decorticate posturing in response to pain
have a better prognosis than those with decerebrate posturing.
Reflex posturing can occur in deep metabolic coma as well. Muscle tone is generally not affected by most
metabolic conditions. Bilateral rigidity occurs in neuroleptic malignant syndrome and malignant hyperthermia,
and has also been described in hepatic coma [
Multifocal myoclonus, which involves brief, random, asynchronous muscle jerks in limbs, trunk, or face,
These occur with the limbs held in a posture against gravity. The tremor is usually fairly rapid and is often
present when the limb is actively moved (postural-action tremor). Asterixis is a transient loss of postural tone,
causing the upper limbs, head and neck, or entire body to suddenly and briefly fall forward. More subtle
myoclonic twitches of the facial muscles or fingers, more synchronous or rhythmic movements, or spontaneous
nystagmus raise the possibility of nonconvulsive status epilepticus.
subhyaloid hemorrhage is virtually pathognomonic for aneurysmal subarachnoid hemorrhage in a comatose
patient. Papilledema suggests raised intracranial pressure or malignant hypertension. Roth spots (white-
centered hemorrhages) are most commonly associated with bacterial endocarditis, but they are also seen in
leukemia, vasculitides, and diabetic retinopathy.
The most important cranial nerve reflexes with respect to coma are: pupillary, corneal, and the vestibuloocular
Pupils — The pupillary light reflex is tested in each eye individually to evaluate direct and consensual
"The detailed neurologic examination in adults", section on 'Pupillary light reflex (CN II and
Downward herniation of mesial temporal structures from an expanding supratentorial mass or
Primary brainstem lesions
In either of these, the third cranial nerves or their nuclei in the midbrain are injured, producing a unilateral or
bilateral oculomotor palsy. When unilateral, the ipsilateral pupil is dilated and unreactive directly and
consensually, but the contralateral pupil reacts to light shone in either eye. When bilateral, there is neither a
direct nor consensual response, the pupils are symmetrically enlarged, and the eyes are deviated outward.
In transtentorial herniation, after initial dilation and loss of light reactivity, pupils become somewhat reduced in
size (4 to 5 mm) and remain unreactive; they are called midposition and fixed (see
Pupil size and symmetry should be noted as well. Pupils are normally between 3 to 7 mm in diameter and
equal, although about 20 percent of normal individuals have up to 1 mm difference in pupillary size. Typically,
the pupils are spared in metabolic and toxic conditions, except in certain toxic syndromes, which are
associated with either miosis or mydriasis (
pupils are midposition and fixed; this syndrome can mimic brain death.
Lesions in the pontine tegmentum, which selectively disrupt sympathetic outflow, can produce very small (<1
to 2 mm) pupils in which a light response is barely perceptible, so-called pontine pupils. Opiate overdose can
also produce this sign.
Eye movements — Central structures involved in extraocular movements (oculomotor, trochlear, and
abducens nuclei and the medial longitudinal fasciculus) lie in the brainstem tegmentum; these are controlled
by the frontal eye fields.
Eye position should be noted. Large cerebral lesions produce a persistent conjugate deviation of the eyes
toward the side of the lesion (contralateral to limb paralysis if present). Persistent eye deviation, especially if
accompanied by nystagmus, may also suggest seizures; in this case, the eye deviation is away from the side
of the lesion. Lateral and downward eye deviation (usually with pupillary involvement) suggests oculomotor
involvement of the nerve or midbrain nuclei, while medial deviation suggests sixth nerve palsy.
In the comatose patient, bilateral conjugate roving eye movements which appear full indicate an intact
brainstem and further reflex testing is not required. This is also a good prognostic sign when seen early after
hypoxic ischemic insult. In the absence of this finding, horizontal eye movements can be tested with two
vestibuloocular reflexes (VORs):
In the oculocephalic maneuver (or doll's eyes), the head is abruptly rotated from one side to the other in
the horizontal plane (
do not turn with the head, but in the opposite direction, as if the patient is maintaining visual fixation on
a single point in space. The cervical spine must be cleared of fracture in any patient with suspected head
trauma before this is performed. This reflex is usually suppressed (and therefore not tested) in conscious
Caloric testing of the oculovestibular reflex provides a stronger stimulus for reflex eye movements. In
this test, the head or upper torso is inclined 30 degrees up from the horizontal. After inspecting the ears
for obstruction from wax or a perforated drum, at least 50 mL of ice water is injected into the ear canal
using a syringe with a small catheter attached. This stimulus has the same effect on the horizontal
semicircular canal as sustained turning of the head in the opposite direction, and results in sustained
deviation of both eyes toward the ear being stimulated (
testing the other side.
A cold caloric response is also present in conscious people, producing not only deviation of the eyes toward the
stimulated ear, but also nystagmus, severe vertigo, nausea, and vomiting. If nystagmus occurs, the patient is
awake and not truly in coma; this can be a useful confirmatory test for psychogenic unresponsiveness.
Vertical eye movements can be tested either by moving the head and neck in the vertical plane or injecting ice
water (causes the eyes to deviate downward in the unconscious patient) or warm water (seven degrees above
body temperature - causes the eyes to deviate upwards) into both ear canals simultaneously.
With brainstem lesions, both VORs are absent or abnormal. If one eye abducts and the other fails to adduct,
this indicates disruption of the medial longitudinal fasciculus in the pons. Upper midbrain lesions, affecting the
third cranial nerve nuclei, may lead to abduction without adduction (usually with pupillary involvement).
Pontine involvement of the sixth nerve nuclei may selectively affect abduction.
Profound toxic or metabolic pathology can also disrupt the VORs, usually the oculocephalic reflex primarily.
Abnormalities are generally symmetric and equally affect abduction and adduction. Absent caloric responses
with normal pupillary reflexes raises the possibility of Wernicke's encephalopathy, which selectively involves
the VOR, sparing other brainstem reflexes. (See
"Wernicke's encephalopathy", section on 'Classic signs'
However, we have also seen this in some cases of drug intoxication, especially with benzodiazepines.
cornea, the fifth or trigeminal nerve and nucleus, and activates the dorsal parts of both facial nuclei in the
pons. Hence, both orbicularis oculi muscles contract when either cornea is touched. There are also connections
with the oculomotor nucleus, so that the eyeballs move upward in concert with lid closure.
The corneal reflex is tested by gently touching the edge of the cornea with a rolled tissue or cotton swab and
observing the responsive blink. (See
"The detailed neurologic examination in adults", section on 'Facial
sensation (CN V)'
The reflex can be suppressed acutely contralateral to a large, acute cerebral lesion, and also with intrinsic
bilaterally brisk corneal reflexes suggest the patient is only mildly narcotized. Absent corneal reflexes 24 hours
after cardiac arrest is usually, but not invariably, an indication of poor prognosis (assuming the patient has not
been sedated). Corneal reflexes may also be reduced or absent at baseline in elderly or diabetic patients [
Coma syndromes — While there are numerous etiologies of coma with diverse presentations as discussed
intracerebral, subdural, or epidural hemorrhage, large ischemic stroke, abscess, tumor, obstructive
hydrocephalus). The initial impairment of consciousness with supratentorial mass lesions usually relates to
lateral rather than downward displacement. Horizontal shifts of midline structures, (eg, the septum pellucidum
or pineal body) of greater than 8 mm are associated with some impairment of consciousness; patients with
shifts of >11 mm are usually comatose [
]. Other signs of increased intracranial pressure (ICP), papilledema,
Further shifts in brain structures can lead to downward, transtentorial herniation (
). It is important to
recognize the clinical signs of this process, as this can be rapidly fatal. While the sequence is relatively
predictable, the timing is not; deterioration can be precipitous.
Two variants are recognized: a central herniation and an uncal herniation syndrome. In the latter, more
laterally directed compressive forces lead to asymmetric herniation of the temporal uncus. An ipsilateral third
cranial nerve palsy (pupillary dilation, downward and outward eye deviation) can occur prior to diencephalic
signs as the nerve is displaced and stretched over the clivus [
]. Loss of reactivity of the contralateral pupil
]. Hemiplegia due to compression of the cortical spinal tract in the
the Figure (