Coma is unresponsiveness from which the patient cannot be aroused. Impaired consciousness refers to similar, less severe disturbances of consciousness; these disturbances are not considered coma. The mechanism for coma or impaired consciousness involves dysfunction of both cerebral hemispheres or of the reticular activating system (also known as the ascending arousal system). Causes may be structural or nonstructural (eg, toxic or metabolic disturbances). Damage may be focal or diffuse. Diagnosis is clinical; identification of cause usually requires laboratory tests and neuroimaging. Treatment is immediate stabilization and specific management of the cause. For long-term coma, adjunctive treatment includes passive range-of-motion exercises, enteral feedings, and measures to prevent pressure ulcers.

Decreased or impaired consciousness or alertness refers to decreased responsiveness to external stimuli. Severe impairment includes

  • Coma: The patient usually cannot be aroused, and the eyes do not open in response to any stimulation.
  • Stupor: The patient can be awakened only by vigorous physical stimulation.

Less severely impaired levels of consciousness are often labeled as lethargy or, if more severe, obtundation. However, differentiation between less severely impaired levels is often imprecise; the label is less important than a precise clinical description (eg, “the best level of response is partial limb withdrawal to nail bed pressure”). Delirium differs because cognitive disturbances (in attention, cognition, and level of consciousness) fluctuate more; also, delirium is usually reversible (see Delirium

Locked-in syndrome is a state of wakefulness and awareness with quadriplegia and paralysis of the lower cranial nerves, resulting in inability to show facial expression, move, speak, or communicate, except by coded eye movements.

Locked-in syndrome typically results from a pontine hemorrhage or infarct that causes quadriplegia and disrupts and damages the lower cranial nerves and the centers that control horizontal gaze. Other disorders that result in severe widespread motor paralysis (eg, Guillain-Barré syndrome) and cancers that involve the posterior fossa and the pons are less common causes.

Patients have intact cognitive function and are awake, with eye opening and normal sleep-wake cycles. They can hear and see. However, they cannot move their lower face, chew, swallow, speak, breathe, move their limbs, or move their eyes laterally. Vertical eye movement is possible; patients can open and close their eyes or blink a specific number of times to answer questions.


  • Clinical evaluation

Diagnosis is primarily clinical. Because patients lack the motor responses (eg, withdrawal from painful stimuli) usually used to measure responsiveness, they may be mistakenly thought to be unconscious. Thus, all patients who cannot move should have their comprehension tested by requesting eye blinking or vertical eye movements.

As in persistent vegetative state, neuroimaging is indicated to rule out treatable disorders (seeComa and Impaired Consciousness: Diagnosis). Brain imaging with CT or MRI is done and helps identify the pontine abnormality. PET or SPECT may be done if the diagnosis is in doubt. In patients with locked-in syndrome, EEG shows normal sleep-wake patterns.


Prognosis depends on the cause and the subsequent level of support provided. For example, locked-in syndrome due to transient ischemia or a small stroke in the vertebrobasilar artery distribution may resolve completely. When the cause (eg, Guillain-Barré syndrome) is partly reversible, recovery can occur over months but is seldom complete. Favorable prognostic features include early recovery of lateral eye movements and of evoked potentials in response to magnetic stimulation of the motor cortex. Irreversible or progressive disorders (eg, cancers that involve the posterior fossa and the pons) are usually fatal.


  • Supportive care

Supportive care is the mainstay of treatment and should include the following:

  • Preventing systemic complications due to immobilization (eg, pneumonia, UTI, thromboembolic disease)
  • Providing good nutrition
  • Preventing pressure ulcers
  • Providing physical therapy to prevent limb contractures

There is no specific treatment.

Speech therapists may help establish a communication code using eye blinks or movements. Because cognitive function is intact and communication is possible, patients should make their own health care decisions. Some patients with locked-in syndrome communicate with each other via the Internet using a computer terminal controlled by eye movements and other means.


and Dementia).

Brain death is loss of function of the entire cerebrum and brain stem, resulting in coma, no spontaneous respiration, and loss of all brain stem reflexes. Spinal reflexes, including deep tendon, plantar flexion, and withdrawal reflexes, may remain. Recovery does not occur.

The concept of brain death developed because ventilators and drugs can perpetuate cardiopulmonary and other body functions despite complete cessation of all cerebral activity. The concept that brain death (ie, total cessation of integrated brain function, especially that of the brain stem) constitutes a person’s death has been accepted legally and culturally in most of the world.


  • Serial determination of clinical criteria
  • Apnea testing
  • Sometimes EEG, brain vascular imaging, or both

For a physician to declare brain death, a known structural or metabolic cause of brain damage must be present, and use of potentially anesthetizing or paralyzing drugs, especially self-administered, must be ruled out. Hypothermia < 32° C must be corrected, and if status epilepticus is suspected, EEG should be done. Sequential testing over 6 to 24 h is necessary (see Table 6: Coma and Impaired Consciousness: Guidelines for Determining Brain Death (in Patients > 1 Yr)Tables). Examination includes assessment of pupil reactivity, oculovestibular and oculocephalic reflexes, corneal reflexes, and apnea testing. Sometimes EEG or tests of brain perfusion are used to confirm absence of brain activity or brain blood flow and thus provide additional evidence to family members, but these tests are not usually required. They are indicated when apnea testing is not hemodynamically tolerated and when only one neurologic examination is desirable (eg, to expedite organ procurement for transplantation).

Table 6
Guidelines for Determining Brain Death (in Patients > 1 Yr)
All 9 items must be confirmed to declare brain death:

1. Reasonable efforts were made to notify the patient’s next of kin or another person close to the patient.

2. Cause of coma is known and sufficient to account for irreversible loss of all brain function.

3. CNS depressant drugs, hypothermia (< 32° C), and hypotension (MAP < 55 mm Hg) have been excluded. No neuromuscular blockers contribute to the neurologic findings.

4. Any observed movements can be attributed entirely to spinal cord function.

5. The cough reflex, pharyngeal reflexes, or both are tested and shown to be absent.

6. Corneal and pupillary light responses are absent.

7. No caloric responses follow ice water siphoned against the tympanic membrane.

8. An apnea test of a minimum of 8 min shows no respiratory movements with a documented increase in Paco2 of > 20 mm Hg from pretest baseline.

PROCEDURE: Apnea testing is done by disconnecting the ventilator from the endotracheal tube. O2 (6 L/min) can be supplied by diffusion from a cannula placed through the endotracheal tube. Despite the ventilatory stimulus of the passively rising Paco2, no spontaneous respirations are seen over an 8- to 12-min period.

Note: The apnea test should be done with extreme caution to minimize risks of hypoxia and hypotension, particularly in potential organ donors. If arterial BP falls significantly during the test, the test should be stopped, and an arterial blood sample drawn to determine whether Paco2 has risen either to > 55 mm Hg or has increased by > 20 mm Hg. This finding validates the clinical diagnosis of brain death.

9. At least one of the following 4 criteria has been established:

a. Items 2–8 have been confirmed by 2 examinations separated by at least 6 h.

b. Items 2–8 have been confirmed AND

  • An EEG shows electrocortical silence.
  • A 2nd examination at least 2 h after the 1st confirms items 2–8.

c. Items 2–8 have been confirmed AND

  • Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow.
  • A 2nd examination at least 2 h after the first confirms items 2–8.

d. If any of items 2–8 cannot be determined because the injury or condition prohibits evaluation (eg, extensive facial injury precludes caloric testing), the following criteria apply:

  • Items that are assessable are confirmed.
  • Conventional angiography, transcranial Doppler ultrasonography, or technetium-99m hexamethylpropyleneamine oxime brain scanning shows no intracranial blood flow.
  • A 2nd examination 6 h after the first confirms all assessable items.
MAP = mean arterial pressure.
Adapted from the American Academy of Neurology Guidelines (1995).
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Mean Arterial Pressure (MAP)


The diagnosis of brain death is equivalent to the person’s death. No one who meets the criteria for brain death recovers. After brain death is confirmed, all supporting cardiac and respiratory treatments are ended. Cessation of ventilatory support results in terminal arrhythmias. Spinal motor reflexes may occur during terminal apnea; they include arching of the back, neck turning, stiffening of the legs, and upper extremity flexion (the so-called Lazarus sign). Family members who wish to be present when the ventilator is shut off need to be warned of such reflex movements.





Maintaining alertness requires intact function of the cerebral hemispheres and preservation of arousal mechanisms in the reticular activating system (RAS—also known as the ascending arousal system)—an extensive network of nuclei and interconnecting fibers in the upper pons, midbrain, and posterior diencephalon. Therefore, the mechanism of impaired consciousness must involve both cerebral hemispheres or dysfunction of the RAS.

To impair consciousness, cerebral dysfunction must be bilateral; unilateral cerebral hemisphere disorders are not sufficient, although they may cause severe neurologic deficits. However, rarely, a unilateral massive hemispheric focal lesion (eg, left middle cerebral artery stroke) impairs consciousness if the contralateral hemisphere is already compromised or if it results in compression of the contralateral hemisphere (eg, by causing edema).

Usually, RAS dysfunction results from a condition that has diffuse effects, such as toxic or metabolic disturbances (eg, hypoglycemia, hypoxia, uremia, drug overdose). RAS dysfunction can also be caused by focal ischemia (eg, certain upper brain stem infarcts), hemorrhage, or direct, mechanical disruption.

Any condition that increases intracranial pressure (ICP) may decrease cerebral perfusion pressure, resulting in secondary brain ischemia. Secondary brain ischemia may affect the RAS or both cerebral hemispheres, impairing consciousness.

When brain damage is extensive, brain herniation (see Fig. 1: Coma and Impaired Consciousness: Brain herniation.Figures and Table 1: Coma and Impaired Consciousness: Effects of Brain HerniationTables) contributes to neurologic deterioration because it directly compresses brain tissue, increases ICP, may lead to hydrocephalus, and results in neuronal and vascular cell dysfunction. In addition to the direct effects of increased ICP on neuronal and vascular cells, cellular pathways of apoptosis and autophagy, also detrimental to these cells, can become activated.

Fig. 1
Brain herniation.
Because the skull is rigid after infancy, intracranial masses or swelling may increase intracranial pressure, sometimes causing protrusion (herniation) of brain tissue through one of the rigid intracranial barriers (tentorial notch, falx cerebri, foramen magnum). When intracranial pressure is increased sufficiently, regardless of the cause, Cushing reflex and other autonomic abnormalities can occur. Cushing reflex includes systolic hypertension with increased pulse pressure, irregular respirations, and bradycardia. Brain herniation is life threatening.

Transtentorial herniation: The medial temporal lobe is squeezed by a unilateral mass under the tentlike tentorium that supports the temporal lobe. The herniating lobe compresses the following structures:

  • Ipsilateral 3rd cranial nerve (often first) and posterior cerebral artery
  • As herniation progresses, the ipsilateral cerebral peduncle
  • In about 5% of patients, the contralateral 3rd cranial nerve and cerebral peduncle
  • Eventually, the upper brain stem and the area in or around the thalamus

Subfalcine herniation: The cingulate gyrus is pushed under the falx cerebri by an expanding mass high in a cerebral hemisphere. In this process, one or both anterior cerebral arteries become trapped, causing infarction of the paramedian cortex. As the infarcted area expands, patients are at risk of transtentorial herniation, central herniation, or both.

Central herniation: Both temporal lobes herniate because of bilateral mass effects or diffuse brain edema. Ultimately, brain death occurs.

Upward transtentorial herniation: This type can occur when an infratentorial mass (eg, tumor, cerebellar hemorrhage) compresses the brain stem, kinking it and causing patchy brain stem ischemia. The posterior 3rd ventricle becomes compressed. Upward herniation also distorts the mesencephalon vasculature, compresses the veins of Galen and Rosenthal, and causes superior cerebellar infarction due to occlusion of the superior cerebellar arteries.

Tonsillar herniation: Usually, the cause is an expanding infratentorial mass (eg, cerebellar hemorrhage). The cerebellar tonsils, forced through the foramen magnum, compress the brain stem and obstruct CSF flow.

Table 1
Effects of Brain Herniation
Type of Herniation Mechanism* Findings






Compression of ipsilateral 3rd cranial nerve Unilateral dilated, fixed pupil

Oculomotor paresis

Compression of the posterior cerebral artery Contralateral homonymous hemianopia

Absence of blinking in response to visual threat in obtunded patients

Compression of the contralateral 3rd cranial nerve and cerebral peduncle Contralateral dilated pupil and oculomotor paresis

Ipsilateral hemiparesis

Compression of the ipsilateral cerebral peduncle Contralateral hemiparesis
Eventually, compression of the upper brain stem and the area in and around the thalamus Impaired consciousness

Abnormal breathing patterns

Fixed, unequal pupils

Further compromise of the brain stem Loss of oculocephalic reflex

Loss of oculovestibular reflex

Loss of corneal reflexes

Decerebrate posturing

Subfalcine (cingulate)


Trapping of one or both anterior cerebral arteries, causing infarction of the paramedian cortex Leg paralysis
Expansion of infarcted area Edema

Increased intracranial pressure

Increased risk of transtentorial herniation, central herniation, or both



Bilateral, more or less symmetric damage to the midbrain Pupils fixed in midposition

Decerebrate posturing

Many of the same symptoms as transtentorial herniation

Further compromise of the brain stem Loss of all brain stem reflexes

Disappearance of decerebrate posturing

Cessation of respirations

Brain death

Upward transtentorial




Compression of the posterior 3rd ventricle Hydrocephalus, which increases intracranial pressure
Distortion of the mesencephalon vasculature

Compression of the veins of Galen and Rosenthal

Superior cerebellar infarction due to occlusion of the superior cerebellar arteries

Early: Nausea, vomiting, occipital headache, ataxia

Later: Somnolence, breathing abnormalities, patchy and progressive loss of brain stem reflexes

Posterior fossa mass (eg, cerebellar hemorrhage) Ataxia
Progression Increasing somnolence

Respiratory irregularities

Patchy but progressive loss of brain stem reflexes

Tonsillar Compression of the brain stem

Obstruction of CSF flow

Acute hydrocephalus (with impaired consciousness, headache, vomiting, and meningismus)

Dysconjugate eye movements

Later, abrupt respiratory and cardiac arrest

*Not all mechanisms occur in every patient.

Impaired consciousness may progress to coma and ultimately to brain death (see Coma and Impaired Consciousness: Brain Death).


Coma or impaired consciousness may result from structural disorders, which typically cause focal damage, or nonstructural disorders, which most often cause diffuse damage (see Table 2: Coma and Impaired Consciousness: Common Causes of Coma or Impaired ConsciousnessTables).

Table 2
Common Causes of Coma or Impaired Consciousness
Cause Examples
Structural disorders Brain abscess

Brain tumor

Head trauma (eg, concussion, cerebral lacerations or contusions, epidural or subdural hematoma)

Hydrocephalus (acute)

Intraparenchymal hemorrhage

Subarachnoid hemorrhage

Upper brain stem infarct or hemorrhage

Nonstructural disorders Seizures (eg, nonconvulsive status epilepticus) or a postictal state caused by an epileptogenic focus
Metabolic disorders Diabetic ketoacidosis

Hepatic encephalopathy










Wernicke encephalopathy

Infections Encephalitis



Other disorders Diffuse axonal injury

Hypertensive encephalopathy

Hyperthermia or hypothermia

Drugs Sedatives

Other CNS depressants

Toxins Carbon monoxide

Psychiatric disorders (eg, psychogenic unresponsiveness) can mimic impaired consciousness but are usually distinguished from true impaired consciousness by neurologic examination.

Symptoms and Signs

Consciousness is decreased to varying degrees. Repeated stimuli arouse patients only briefly or not at all.

Depending on the cause, other symptoms develop (see Table 3: Coma and Impaired Consciousness: Findings by Location*Tables):


  • Eye abnormalities: Pupils may be dilated, pinpoint, or unequal. One or both pupils may be fixed in midposition. Eye movement may be dysconjugate or absent (oculomotor paresis). Homonymous hemianopia may be present. Other abnormalities include absence of blinking in response to visual threat (almost touching the eye), as well as loss of the oculocephalic reflex (the eyes do not move in response to head rotation), the oculovestibular reflex (the eyes do not move in response to caloric stimulation), and corneal reflexes.
  • Autonomic dysfunction: Patients may have abnormal breathing patterns (Cheyne-Stokes or Biot respirations), sometimes with hypertension and bradycardia (Cushing reflex). Abrupt respiratory and cardiac arrest may occur.
  • Motor dysfunction: Abnormalities include flaccidity, hemiparesis, asterixis, multifocal myoclonus, decorticate posturing (elbow flexion and shoulder adduction with leg extension), and decerebrate posturing (limb extension and internal shoulder rotation).
  • Other symptoms: If the brain stem is compromised, nausea, vomiting, meningismus, occipital headache, ataxia, and increasing somnolence can occur.

Table 3
Findings by Location*
Location Abnormal Findings
Bilateral hemispheric damage or dysfunction* Symmetric tone and response (flexor or extensor) to pain

Myoclonus (possible)

Periodic cycling of breathing

Supratentorial mass compressing the brain stem Ipsilateral 3rd cranial nerve palsy with unilateral dilated, fixed pupil and oculomotor paresis

Sometimes contralateral homonymous hemianopia and absent blinking response to visual threat

Contralateral hemiparesis

Brain stem lesion Early abnormal pupillary and oculomotor signs

Abnormal oculocephalic reflex

Abnormal oculovestibular reflex

Asymmetrical motor responses

Decorticate rigidity (usually due to an upper brain stem lesion) or decerebrate rigidity (usually due to a bilateral midbrain or pontine lesion)

Hyperventilation (due to a midbrain or upper pontine lesion)

Toxic-metabolic dysfunction* Spontaneous, conjugate roving eye movements in mild coma

Fixed eye position in deeper coma

Abnormal oculovestibular reflex

Multifocal myoclonus

Asterixis (may be considered a type of negative myoclonus)

Decorticate and decerebrate rigidity or flaccidity

*Not all of the findings occur in all cases. Brain stem reflexes and pupillary light responses may be intact in patients with bilateral hemispheric damage or dysfunction or toxic-metabolic dysfunction; however, hypothermia, sedative overdose, or use of an anesthetic can cause partial loss of brain stem reflexes.


  • History
  • General physical examination
  • Neurologic examination, including eye examination
  • Laboratory tests (eg, pulse oximetry, bedside glucose measurement, blood and urine tests)
  • Immediate neuroimaging
  • Sometimes measurement of ICP
  • If diagnosis is unclear, lumbar puncture or EEG

Impaired consciousness is diagnosed if repeated stimuli arouse patients only briefly or not at all. If stimulation triggers primitive reflex movements (eg, decerebrate or decorticate posturing), impaired consciousness may be deepening into coma.

Diagnosis and initial stabilization (airway, breathing, and circulation) should occur simultaneously. Glucose levels must be measured at bedside to identify low levels, which should be corrected immediately. If trauma is involved, the neck is immobilized until clinical history, physical examination, or imaging tests exclude an unstable injury and damage to the cervical spine.

History: Medical identification bracelets or the contents of a wallet or purse may provide clues (eg, hospital identification card, drugs). Relatives, paramedics, police officers, and any witnesses should be questioned about the circumstances and environment in which the patient was found; containers that may have held food, alcohol, drugs, or poisons should be examined and saved for identification (eg, drug identification aided by a poison center) and possible chemical analysis.

Relatives should be asked about the onset and time course of the problem (eg, whether seizure, headache, vomiting, head trauma, or drug ingestion was observed, how quickly symptoms appeared, whether the course has been progressive or waxing and waning), baseline mental status, recent infections and possible exposure to infections, recent travel, ingestions of unusual meals, psychiatric problems and symptoms, drug history, alcohol and other substance use, previous illnesses, the last time the patient was normal, and any hunches they may have about what might be the cause (eg, possible occult overdose, possible occult head trauma due to recent intoxication).

Medical records should be reviewed if available.

General physical examination: Physical examination should be focused and efficient and should include thorough examination of the head and face, skin, and extremities. Signs of head trauma include periorbital ecchymosis (raccoon eyes), ecchymosis behind the ear (Battle sign), hemotympanum, instability of the maxilla, and CSF rhinorrhea and otorrhea. Scalp contusions and small bullet holes can be missed unless the head is carefully inspected. If unstable injury and cervical spine damage have been excluded, passive neck flexion is done; stiffness suggests subarachnoid hemorrhage or meningitis.

Fever, petechial or purpuric rash, hypotension, or severe extremity infections (eg, gangrene of one or more toes) may suggest sepsis or CNS infection. Needle marks may suggest drug overdose (eg, of opioids or insulin

). A bitten tongue suggests seizure. Breath odor may suggest alcohol, other drug intoxication, or diabetic ketoacidosis.

Neurologic examination: The neurologic examination determines whether the brain stem is intact and where the lesion is located within the CNS (see Approach to the Neurologic Patient: Neurologic Examination). The examination focuses on the following:

  • Level of consciousness
  • Eyes
  • Motor function
  • Deep tendon reflexes

Level of consciousness is evaluated by attempting to wake patients first with verbal commands, then with nonnoxious stimuli, and finally with noxious stimuli (eg, pressure to the supraorbital ridge, nail bed, or sternum). The Glasgow Coma Scale (see Table 4: Coma and Impaired Consciousness: Glasgow Coma Scale*Tables) was developed to assess patients with head trauma. For head trauma, the score assigned by the scale is valuable prognostically. For coma or impaired consciousness of any cause, the scale is used because it is a relatively reliable, objective measure of the severity of unresponsiveness and can be used serially for monitoring. The scale assigns points based on responses to stimuli. Eye opening, facial grimacing, and purposeful withdrawal of limbs from a noxious stimulus indicate that consciousness is not greatly impaired. Asymmetric motor responses to pain or deep tendon reflexes may indicate a focal hemispheric lesion.

Table 4
Glasgow Coma Scale*
Area Assessed Response Points
Eye opening




Open spontaneously; open with blinking at baseline 4
Open to verbal command, speech, or shout 3
Open in response to pain applied to the limbs or sternum 2
None 1





Oriented 5
Confused conversation but able to answer questions 4
Inappropriate responses; words discernible 3
Incomprehensible speech 2
None 1






Obeys commands for movement 6
Responds to pain with purposeful movement 5
Withdraws from pain stimuli 4
Responds to pain with abnormal flexion (decorticate posturing) 3
Responds to pain with abnormal extension (decerebrate posturing) 2
None 1
*Combined scores < 8 are typically regarded as coma.
Adapted from Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84; 1974.
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Glasgow Coma Scale/Score

As impaired consciousness deepens into coma, noxious stimuli may trigger stereotypic reflex posturing. Decorticate posturing indicates hemispheric damage with preservation of motor centers in the upper portion of the brain stem (eg, rubrospinal tract). Decerebrate posturing indicates that the upper brain stem motor centers, which facilitate flexion, have been damaged and that only the lower brain stem centers (eg, vestibulospinal tract, reticulospinal tract), which facilitate extension, are responding to sensory stimuli. Flaccidity without movement indicates that the lower brain stem is not affecting movement, regardless of whether the spinal cord is damaged. It is the worst possible motor response.

Asterixis and multifocal myoclonus suggest metabolic disorders such as uremia, hepatic encephalopathy, hypoxic encephalopathy, and drug toxicity.

Psychogenic unresponsiveness can be differentiated because although voluntary motor response is typically absent, muscle tone and deep tendon reflexes remain normal, and all brain stem reflexes are preserved. Vital signs are usually not affected.

Eye examination: The following are evaluated:

  • Pupillary responses
  • Extraocular movements
  • Fundi
  • Other neuro-ophthalmic reflexes

Pupillary responses and extraocular movements provide information about brain stem function (see Table 5: Coma and Impaired Consciousness: Interpretation of Pupillary Response and Eye MovementsTables). One or both pupils usually become fixed early in coma due to structural lesions, but pupillary responses are often preserved until very late when coma is due to diffuse metabolic disorders (called toxic-metabolic encephalopathy), although responses may be sluggish. If one pupil is dilated, other causes of anisocoria should be considered (see Symptoms of Ophthalmologic Disorders: Etiology).

The fundi should be examined. Papilledema may indicate increased ICP but may take many hours to appear. Increased ICP can cause earlier changes in the fundi, such as disk hypermia, dilated capillaries, blurring of the medial disk margins, and sometimes hemorrhages. Subhyaloid hemorrhage may indicate subarachnoid hemorrhage.

Table 5
Interpretation of Pupillary Response and Eye Movements
Area Assessed Finding Interpretation




Sluggish light reactivity retained until all other brain stem reflexes are lost Diffuse cellular cerebral dysfunction (toxic-metabolic encephalopathy)
Unilateral pupillary dilation, pupil unreactive to light 3rd cranial nerve compression (eg, in transtentorial herniation), usually due to an ipsilateral lesion (see Symptoms of Ophthalmologic Disorders: Anisocoria)
Pupils fixed in midposition Midbrain dysfunction due to structural damage (eg, infarction, hemorrhage)

Central herniation

Prolonged metabolic depression by drugs or toxins

Constricted pupils (1 mm wide) Massive pontine hemorrhage

Toxicity due to opioids or certain insecticides (eg, organophosphates, carbamates)

Eye movements




Early abnormal pupillary and oculomotor signs Primary brain stem lesion
Spontaneous, conjugate roving eye movements but intact brain stem reflexes Early toxic-metabolic encephalopathy
Gaze preference to one side Brain stem lesion on the opposite side

Cerebral hemisphere lesion on the same side

Absent eye movements Further testing required (eg, oculocephalic and oculovestibular reflexes)

Possibly toxicity due tophenobarbital

or phenytoin

, Wernicke encephalopathy, botulism, or brain death

In an unresponsive patient, the oculocephalic reflex is tested by the doll’s-eye maneuver: The eyes are observed while the head is passively rotated from side to side or flexed and extended. This maneuver should not be attempted if cervical spine instability is suspected.

  • If the reflex is present, the maneuver causes the eyes to move in the opposite direction of head rotation, flexion, or extension, indicating that the oculovestibular pathways in the brain stem are intact. Thus, in a supine patient, the eyes continue to look straight up when the head is turned side to side.
  • If the reflex is absent, the eyes do not move and thus point in whatever direction the head is turned, indicating the oculovestibular pathways are disrupted. The reflex is also absent in most patients with psychogenic unresponsiveness because visual fixation is conscious.

If the patient is unconscious and the oculocephalic reflex is absent or the neck is immobilized, oculovestibular (cold caloric) testing is done. After integrity of the tympanic membrane is confirmed, the patient’s head is elevated 30°, and with a syringe connected to a flexible catheter, the examiner irrigates the external auditory canal with 50 mL of ice water over a 30-sec period.

  • If both eyes deviate toward the irrigated ear, the brain stem is functioning normally, suggesting mildly impaired consciousness.
  • If nystagmus away from the irrigated ear also occurs, the patient is conscious and psychogenic unresponsiveness is likely. In conscious patients, 1 mL of ice water is often enough to induce ocular deviation and nystagmus. Thus, if psychogenic unresponsiveness is suspected, a small amount of water should be used because cold caloric testing can induce severe vertigo, nausea, and vomiting in conscious patients.
  • If the eyes do not move or movement is dysconjugate after irrigation, the integrity of the brain stem is uncertain and the coma is deeper. Prognosis may be less favorable.

Sidebar 1
Pearls & Pitfalls
  • If muscle tone and deep tendon reflexes are normal and doll’s-eye reflex is absent, suspect psychogenic unresponsiveness and check the oculovestibular reflex by instilling only 1 mL of ice water in the ear.

Certain patterns of eye abnormalities and other findings may suggest brain herniation (see Fig. 1: Coma and Impaired Consciousness: Brain herniation.Figures and see Table 1: Coma and Impaired Consciousness: Effects of Brain HerniationTables).

Respiratory patterns: The spontaneous respiratory rate and pattern should be documented unless emergency airway intervention is required. It may suggest a cause.

  • Periodic cycling of breathing (Cheyne-Stokes or Biot respiration—see Approach to the Pulmonary Patient: Inspection) may indicate dysfunction of both hemispheres or of the diencephalon.
  • Hyperventilation (central neurogenic hyperventilation) with respiratory rates of > 40 breaths/min may indicate midbrain or upper pontine dysfunction.
  • An inspiratory gasp with respiratory pauses of about 3 sec after full inspiration (apneustic breathing) typically indicates pontine or medullary lesions; this type of breathing often progresses to respiratory arrest.

Testing: Initially, pulse oximetry, fingerstick plasma glucose measurements, and cardiac monitoring are done. Blood tests should include a comprehensive metabolic panel (including at least serum electrolytes, BUN, creatinine, and Ca levels), CBC with differential and platelets, liver function tests, and ammonia level. ABGs are measured, and if carbon monoxide toxicity is suspected, carboxyhemoglobin level is measured. Blood and urine should be obtained for culture and routine toxicology screening; serum ethanol level is also measured. Additional toxicology tests (eg, additional toxicology screening, serum drug levels) are done based on clinical suspicion. ECG (12-lead) should be done.

If the cause is not immediately apparent, noncontrast head CT should be done as soon as possible to check for masses, hemorrhage, edema, and hydrocephalus. Initially, noncontrast CT rather than contrast CT is preferred to rule out brain hemorrhage. MRI can be done instead if immediately available, but it is not as quick as newer-generation CT scanners. Contrast CT can then be done if noncontrast CT is not diagnostic. MRI or contrast CT may detect isodense subdural hematomas, multiple metastases, sagittal sinus thrombosis, herpes encephalitis, or other causes missed by noncontrast CT. A chest x-ray should also be taken.

If coma is unexplained after neuroimaging and other tests and if there is no obstruction in the CSF flow or ventricular system that would significantly increase ICP, lumbar puncture is done to check opening pressure and to exclude infection, subarachnoid hemorrhage, and other abnormalities. Lumbar puncture is not done until after imaging studies are done to exclude an intracranial mass and obstructive hydrocephalus because if either is present, suddenly lowering CSF pressure by lumbar puncture could trigger brain herniation. CSF analysis includes cell and differential counts, protein, glucose, Gram staining, cultures, and sometimes, based on clinical suspicion, specific tests (eg, cryptococcal antigen, Venereal Disease Research Laboratory [VDRL] tests, PCR for herpes simplex, visual or spectrophotometric determination of xanthochromia).

If increased ICP is suspected, pressure is measured. Hyperventilation, managed by an ICU specialist, should be considered. Hyperventilation causes hypocapnia, which in turn decreases cerebral blood flow globally through vasoconstriction. Reduction in Pco2 from 40 mm Hg to 30 mm Hg can reduce ICP by about 30%. Pco2 should be maintained at 25 mm Hg to 30 mm Hg, but aggressive hyperventilation to < 25 mm Hg should be avoided because this approach may reduce cerebral blood flow excessively and result in cerebral ischemia.

If pressure is increased, it is monitored continuously (see Approach to the Critically Ill Patient: Intracranial Pressure Monitoring).

If diagnosis remains uncertain, EEG may be done. In most comatose patients, EEG shows slowing and reductions in wave amplitude that are nonspecific but often occur in toxic-metabolic encephalopathy. However, EEG monitoring (eg, in the ICU) is increasingly identifying nonconvulsive status epilepticus. In such cases, the EEG may show spikes, sharp waves, or spike and slow complexes.


Prognosis depends on the cause, duration, and depth of the impairment of consciousness. For example, absent brain stem reflexes indicates a poor prognosis after cardiac arrest, but not always after a sedative overdose. In general, if unresponsiveness lasts < 6 h, prognosis is more favorable.

After coma, the early return of speech (even if incomprehensible), spontaneous eye movements, or ability to follow commands is a favorable prognostic sign. If the cause is a reversible condition (eg, sedative overdose, some metabolic disorders such as uremia), patients may lose all brain stem reflexes and all motor response and yet recover fully. After trauma, a Glasgow Coma Scale score of 3 to 5 may indicate fatal brain damage, especially if pupils are fixed or oculovestibular reflexes are absent.

After cardiac arrest, clinicians must exclude major confounders of coma, including sedatives, neuromuscular blockade, hypothermia, metabolic derangements, and severe liver or kidney failure. If brain stem reflexes are absent at day 1 or lost later, testing for brain death is indicated. Prognosis is poor if patients have any of the following:

  • Myoclonic status epilepticus (bilaterally synchronous twitching of axial structures, often with eye opening and upward deviation of the eyes) that occurs within 24 to 48 h after cardiac arrest
  • No pupillary light reflexes 24 to 72 h after cardiac arrest
  • No corneal reflexes 72 h after cardiac arrest
  • Extensor posturing or no response elicited by painful stimuli 72 h after cardiac arrest
  • No N20 on somatosensory evoked potentials (SEP) or a serum neuron-specific enolase level of > 33 µg/L

If patients were treated with hypothermia, 72 h should be added to the times above because hypothermia slows recovery. If none of the above criteria is met, outcome is usually (but not always) poor; thus, whether to withdraw life support may be a difficult decision.


  • Immediate stabilization (airway, breathing, circulation, or ABCs)
  • Supportive measures, including, when necessary, control of ICP
  • Admission to an ICU
  • Treatment of underlying disorder

Airway, breathing, and circulation must be ensured immediately. Hypotension must be corrected (see Shock and Fluid Resuscitation: Cardiogenic shock). Patients are admitted to the ICU so that respiratory and neurologic status can be monitored.

Because some patients in coma are undernourished and susceptible to Wernicke encephalopathy, thiamin 100 mg IV or IM should be given routinely. If plasma glucose is low, patients should be given 50 mL of 50% dextrose IV. If opioid overdose is suspected,naloxone

2 mg IV is given. If trauma is involved, the neck is immobilized until damage to the cervical spine is ruled out. If a recent (within about 1 h) drug overdose is possible, gastric lavage can be done through a large-bore orogastric tube (eg, ≥ 32 Fr) after endotracheal intubation. Activated charcoal can then be given via the orogastric tube.

Endotracheal intubation: Patients with any of the following require endotracheal intubation to prevent aspiration and ensure adequate ventilation:

  • Infrequent, shallow, or stertorous respirations
  • Low O2 saturation (determined by pulse oximetry or ABG measurements)
  • Impaired airway reflexes
  • Severe unresponsiveness (including most patients with a Glasgow Coma Scale score ≤ 8

If increased ICP is suspected, intubation should be done via rapid-sequence oral intubation (using a paralytic drug) rather than via nasotracheal intubation; nasotracheal intubation in a patient who is breathing spontaneously causes more coughing and gagging, thus increasing ICP, which is already increased because of intracranial abnormalities.

To minimize the increase in ICP that may occur when the airway is manipulated, some clinicians recommend giving lidocaine

1.5 mg/kg IV 1 to 2 min before giving the paralytic. Patients are sedated before the paralytic is given. Etomidate

is a good choice in hypotensive or trauma patients because it has minimal effects on BP; IV dose is 0.3 mg/kg for adults (or 20 mg for an average-sized adult) and 0.2 to 0.3 mg/kg for children. Alternatively, if hypotension is absent and unlikely and if propofol

is readily available, propofol

0.2 to 1.5 mg/kg may be used. Succinylcholine

1.5 mg/kg IV is typically used as a paralytic. However, use of paralytics is minimized and, whenever possible, avoided because they can mask neurologic findings and changes.

Pulse oximetry and ABGs (if possible, end-tidal CO2) should be used to assess adequacy of oxygenation and ventilation.

ICP control: If ICP is increased, intracranial and cerebral perfusion pressure should be monitored (see Approach to the Critically Ill Patient: Intracranial Pressure Monitoring), and pressures should be controlled. The goal is to maintain ICP at ≤ 20 mm Hg and cerebral perfusion pressure at 50 to 70 mm Hg. Cerebral venous drainage can be enhanced (thus lowering ICP) by elevating the head of the bed to 30° and by keeping the patient’s head in a midline position.

Control of increased ICP involves several strategies:

  • Sedation: Sedatives may be necessary to control agitation, excessive muscular activity (eg, due to delirium), or pain, which can increase ICP. Propofol

    is often used in adults (contraindicated in children) because onset and duration of action are quick; dose is 0.3 mg/kg/h by continuous IV infusion, titrated gradually up to 3 mg/kg/h as needed. An initial bolus is not used. The most common adverse effect is hypotension. Prolonged use at high doses can cause pancreatitis. Benzodiazepines (eg, midazolam


    ) can also be used. Because sedatives can mask neurologic findings and changes, their use should be minimized and, whenever possible, avoided. Antipsychotics should be avoided if possible because they can delay recovery. Sedatives are not used to treat agitation and delirium due to hypoxia; O2 is used instead.

  • Hyperventilation: Hyperventilation causes hypocapnia, which causes vasoconstriction, thus decreasing cerebral blood flow globally. Reduction in Pco2 from 40 to 30 mm Hg can reduce ICP about 30%. Hyperventilation that reduces Pco2 to 28 to 33 mm Hg decreases ICP for only about 30 min and is used by some clinicians as a temporary measure until other treatments take effect. Aggressive hyperventilation to < 25 mm Hg should be avoided because it may reduce cerebral blood flow excessively and result in cerebral ischemia. Other measures may be used to control increased ICP (see Traumatic Brain Injury (TBI): Increased intracranial pressure).
  • Hydration: Isotonic fluids are used. Providing free water through IV fluids (eg, 5% dextrose, 0.45% saline) can aggravate cerebral edema and should be avoided. Fluids may be restricted to some degree, but patients should be kept euvolemic. If patients have no signs of dehydration or fluid overload, IV fluids with normal saline can be started at 50 to 75 mL/h. The rate can be increased or decreased based on serum Na, osmolality, urine output, and signs of fluid retention (eg, edema).
  • Diuretics: Serum osmolality should be kept at 295 to 320 mOsm/kg. Osmotic diuretics (eg, mannitol

    ) may be given IV to lower ICP and maintain serum osmolality. These drugs do not cross the blood-brain barrier. They pull water from brain tissue across an osmotic gradient into plasma, eventually leading to equilibrium. Effectiveness of these drugs decreases after a few hours. Thus, they should be reserved for patients whose condition is deteriorating or used preoperatively for patients with hematomas. Mannitol

    20% solution is given 0.5 to 1 g/kg IV (2.5 to 5 mL/kg) over 15 to 30 min, then given as often as needed (usually q 6 to 8 h) in a dose ranging from 0.25 to 0.5 g/kg (1.25 to 2.5 mL/kg). Mannitol

    must be used cautiously in patients with severe coronary artery disease, heart failure, renal insufficiency, or pulmonary vascular congestion because mannitol

    rapidly expands intravascular volume. Because osmotic diuretics increase renal excretion of water relative to Na, prolonged use of mannitol

    may result in water depletion and hypernatremia.Furosemide

    1 mg/kg IV can decrease total body water, particularly when transient hypervolemia associated with mannitol

    is to be avoided. Fluid and electrolyte balance should be monitored closely while osmotic diuretics are used. A 3% saline solution is being studied as another potential osmotic agent to control ICP.

  • BP control: Systemic antihypertensives are needed only when hypertension is severe (>180/95 mm Hg). How much BP is reduced depends on the clinical context. Systemic BP needs to be high enough to maintain cerebral perfusion pressure even when ICP increases. Hypertension can be managed by titrating a nicardipine

    drip (5 mg/h, increased by 2.5 mg q 5 min to a maximum of 15 mg/h) or by boluses of labetalol

    (10 mg IV over 1 to 2 min, repeated q 10 min to a maximum of 150 mg).

  • Corticosteroids: These drugs are usually helpful for patients with a brain tumor or brain abscess, but they are ineffective for patients with head trauma, cerebral hemorrhage, ischemic stroke, or hypoxic brain damage after cardiac arrest. Corticosteroids increase plasma glucose; this increase may worsen the effects of cerebral ischemia and complicate management of diabetes mellitus. After an initial dose of dexamethasone

    20 to 100 mg, 4 mg once/day appears to be effective while minimizing adverse effects. Dexamethasone

    can be given IV or po.

If ICP continues to increase despite other measures to control it, the following may be used:

  • Pentobarbital coma: Pentobarbital

    can reduce cerebral blood flow and metabolic demands. However, its use is controversial because the effect on clinical outcome is not consistently beneficial. Coma is induced by giving pentobarbital

    10 mg/kg IV over 30 min, followed by 5 mg/kg/h for 3 h, then 1 mg/kg/h. The dose may be adjusted to suppress bursts of EEG activity, which is continuously monitored. Hypotension is common and is managed by giving fluids and, if necessary, vasopressors. Other possible adverse effects include arrhythmias, myocardial depression, and impaired uptake or release of glutamate.

  • Decompressive craniotomy: Craniotomy with duraplasty can be done to provide room for brain swelling. This procedure can prevent deaths, but overall functional outcome may not improve much. It may be most useful for large cerebral infarcts with impending herniation, particularly in patients < 50 yr.

Long-term care: Patients require meticulous long-term care. Stimulants, sedatives, and opioids should be avoided.

Enteral feeding is started with precautions to prevent aspiration (eg, elevation of the head of the bed); a percutaneous endoscopic jejunostomy tube is placed if necessary.

Early, vigilant attention to skin care, including checking for breakdown especially at pressure points, is required to prevent pressure ulcers. Topical ointments to prevent desiccation of the eyes are beneficial.

Passive range-of-motion exercises done by physical therapists and taping or dynamic flexion splitting of the extremities may prevent contractures. Measures are also taken to prevent UTIs and deep venous thrombosis.

Key Points

  • Coma and impaired consciousness require dysfunction of both cerebral hemispheres or dysfunction of the reticular activating system.
  • Manifestations include abnormalities of the eyes (eg, abnormal conjugate gaze, pupillary responses, and/or oculocephalic or oculovestibular reflexes), vital signs (eg, abnormal respirations), and motor function (eg, flaccidity, hemiparesis, asterixis, multifocal myoclonus, decorticate or decerebrate posturing).
  • Taking a complete history of prior events is critical; ask witnesses and relatives about the time course for the change in mental status and about possible causes (eg, recent travel, ingestion of unusual meals, exposure to possible infections, drug or alcohol use, possible trauma).
  • Do a general physical examination, including thorough examination of the head and face, skin, and extremities and a complete neurologic examination (focusing on level of consciousness, the eyes, motor function, and deep tendon reflexes), followed by appropriate blood and urine tests, toxicology screening, and fingerstick plasma glucose measurements.
  • Do noncontrast CT immediately as soon as the patient has been stabilized.
  • Ensure adequate airways, breathing, and circulation.
  • Give IV or IM thiamin and IV glucose if plasma glucose is low and IV naloxone

    if opioid overdose is suspected.

  • Control ICP using various strategies, which may include sedatives (as needed) to control agitation, temporary hyperventilation, fluids and diuretics to maintain euvolemia, and antihypertensives to control BP.

Vegetative state: Patients show no evidence of awareness of self or environment and cannot interact with other people. Purposeful responses to external stimuli are absent, as are language comprehension and expression.

Signs of an intact reticular formation (eg, eye opening) and an intact brain stem (eg, reactive pupils, oculocephalic reflex) are present. Sleep-wake cycles occur but do not necessarily reflect a specific circadian rhythm and are not associated with the environment. More complex brain stem reflexes, including yawning, chewing, swallowing, and, uncommonly, guttural vocalizations, are also present. Arousal and startle reflexes may be preserved; eg, loud sounds or blinking with bright lights may elicit eye opening. Eyes may water and produce tears. Patients may appear to smile or frown. Spontaneous roving eye movements—usually slow, of constant velocity, and without saccadic jerks—may be misinterpreted as volitional tracking and can be misinterpreted by family members as evidence of awareness.

Patients cannot react to visual threat and cannot follow commands. The limbs may move, but the only purposeful motor responses that occur are primitive (eg, grasping an object that contacts the hand). Pain usually elicits a motor response (typically decorticate or decerebrate posturing) but no purposeful avoidance. Patients have fecal and urinary incontinence. Cranial nerve and spinal reflexes are typically preserved.

Rarely, brain activity, detected by functional MRI or EEG, indicates a response to questions and commands even though there is no behavioral response. The extent of patients’ actual awareness is not yet known. In most patients who have such brain activity, the vegetativestate resulted from brain trauma, not hypoxic encephalopathy.

Minimally conscious state: Fragments of meaningful interaction with the environment are preserved. Patients may establish eye contact, purposefully grasp at objects, respond to commands in a stereotypic manner, or answer with the same word.


  • Clinical criteria after sufficient observation
  • Neuroimaging

A vegetative state is suggested by characteristic findings (eg, no purposeful activity or comprehension) plus signs of an intact reticular formation. Diagnosis is based on clinical criteria. However, neuroimaging is indicated to rule out treatable disorders.

The vegetative state must be distinguished from the minimally conscious state. Both states can be permanent or temporary, and the physical examination may not reliably distinguish one from the other. Sufficient observation is needed. If observation is too brief, evidence of awareness may be overlooked, resulting in a false-positive diagnosis. Some patients with severe Parkinson disease are misdiagnosed as being in a vegetative state.

CT or MRI can differentiate an ischemic infarct, an intracerebral hemorrhage, and a mass lesion involving the cortex or the brain stem. MR angiography can be used to visualize the cerebral vasculature after exclusion of a cerebral hemorrhage. Diffusion-weighted MRI is becoming the preferred imaging modality for following ongoing ischemic changes in the brain. PET and SPECT can be used to assess cerebral function (rather than brain anatomy). If the diagnosis of persistent vegetative state is in doubt, PET or SPECT should be done. EEG is useful in assessing cortical dysfunction and identifying occult seizure activity.


Vegetative state: Prognosis varies somewhat by cause and duration of the vegetative state. Prognosis may be better if the cause is a reversible metabolic condition (eg, toxic encephalopathy) than if the cause is neuronal death due to extensive hypoxia and ischemia or another condition. Also, younger patients may recover more motor function than older patients but not more cognition, behavior, or speech.

Recovery from a vegetative state is unlikely after 1 mo if brain damage is nontraumatic and after 12 mo if brain damage is traumatic. Even if some recovery occurs after these intervals, most patients are severely disabled. Rarely, improvement occurs late; after 5 yr, about 3% of patients recover the ability to communicate and comprehend, but even fewer can live independently; no patients regain normal function.

Most patients in a persistent vegetative state die within 6 mo of the original brain damage. The cause is usually pulmonary infection, UTI, or multiple organ failure, or death may be sudden and of unknown cause. For most of the rest, life expectancy is about 2 to 5 yr; only about 25% of patients live > 5 yr. A few patients live for decades.

Minimally conscious state: Most patients tend to recover consciousness but to a limited extent depending on how long minimally conscious state has lasted. The longer it has lasted, the less chance of patients recovering higher cortical function. Prognosis may be better if the cause is traumatic brain injury. Rarely, patients regain clear but limited awareness after years of coma, called awakenings by the news media.


  • Supportive care

Supportive care is the mainstay of treatment and should include the following:

  • Preventing systemic complications due to immobilization (eg, pneumonia, UTI, thromboembolic disease)
  • Providing good nutrition
  • Preventing pressure ulcers
  • Providing physical therapy to prevent limb contractures

Vegetative state has no specific treatment. Decisions about life-sustaining care should involve social services, the hospital ethics committee, and family members. Maintaining patients, especially those without advanced directives to guide decisions about terminating treatment (see Medicolegal Issues: Advance Directives), in a prolonged vegetative state raises ethical and other (eg, resource utilization) questions.

Most patients in a minimally conscious state do not respond to specific treatments. However, rarely, treatment with zolpidem

can cause dramatic and repeated improvement in neurologic responsiveness for as long as the drug is continued.

Key Points

  • Vegetative state is typically characterized by intact brain stem function and sometimes the simulation of awareness despite its absence.
  • Minimally conscious state differs from vegetative state in that patients have some interaction with the environment and tend to improve over time.
  • Diagnosis requires exclusion of other disorders and often prolonged observation, particularly to differentiate vegetative state, minimally conscious state, and Parkinson disease.
  • Prognosis tends to be poor, particularly for patients in a vegetative state.
  • Treatment is mainly supportive.

Last full review/revision September 2012 by Kenneth Maiese, MD

Content last modified November 2012

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