Acute depression in level of consciousness is a critical, life-threatening emergency that requires a systematic approach for evaluation of etiology. The variety of causes of coma are myriad. Therefore, a reliable history should be obtained from family, witnesses, or medical personnel, and examination should seek representative localizing neurological and general physical findings.
Clues can be ascertained from the onset of coma. An acute onset in a previously healthy individual may indicate a cerebral vascular etiology (i.e., subarachnoid hemorrhage, intracerebral hemorrhage, or hemispheric or brain stem stroke), generalized epileptic activity, traumatic brain injury, or drug overdose. Likewise, a subacute deterioration may point to systemic illness, evolving intracranial mass, or a degenerative infectious or paraneoplastic neurologic disorder. Moreover, the duration of a comatose state should be documented because it may have predictive value for prognosis in certain causes.
General Clinical Features and Protocol
Frequently the etiology of acute depression in consciousness in the hospitalized patient includes sepsis, acid-base and electrolyte disorders, or hepatic, renal, or cardiac failure. Therefore careful physical examination is performed with attention to vital signs, spontaneous breathing pattern, and careful auscultation of the lungs and heart (Table 67-3). Airway patency and protective reflexes should be assessed. Emergency measures should be taken to ensure vital functions continue despite an obscure diagnosis. Furthermore, laboratory studies should be obtained to exclude metabolic and endocrine causes.
Table 67–3. Useful Physical Examination Findings in Comatose Patients ||Download (.pdf)
Table 67–3. Useful Physical Examination Findings in Comatose Patients
|Exam Focus||Specific Features||Suggested Condition|
|Skin||Petechiae, splinter hemorrhage||Coagulopathy; SBE|
|Needle tracks||Drug overdose or withdrawal|
|Lymph nodes||Adenopathy||Infectious etiologies; immunocompromised hosts|
|Head||Contusion; postauricular ecchymosis (Battle's sign)||Trauma|
|VP shunt||Hydrocephalus; shunt malfunction|
|Eyes||Periorbital ecchymosis (raccoon eyes)||Trauma|
|Papilledema||Increased intracranial pressure|
|Neck||Stiff||Subarachnoid hemorrhage, infection|
|Cardiovascular||Arrhythmia, etc.||Hypoxic/iechemic encephalopathy|
|Abdomen||Small hard liver||Hepatic encephalopathy|
|Misc.||Acetone, alcohol breath||Ketoacidosis; alcohol intoxication|
|Tongue laceration; incontinence||Postictal state|
During evaluation, core body temperature is an important clue. Hypothermia can be seen in drug overdose, brain death, or acute spinal cord transection. Moreover, hyperthermia can be seen in infection; traumatic brain injury; subarachnoid, intracerebral, or pontine hemorrhage; and hypothalamic dysfunction.
The neurologic exam in a patient with depressed level of consciousness can be a valuable tool to localize the etiology. The important neurologic features include (Table 67-4): (1) respiratory pattern, (2) pupillary size and reactivity, (3) eye position and movements, (4) corneal reflexes, and (5) motor function.
Table 67–4. Neurologic Assessment of the Comatose Patient ||Download (.pdf)
Table 67–4. Neurologic Assessment of the Comatose Patient
|Level of consciousness|
|Brain stem function|
| Respiratory rate and pattern|
| Blood pressure and heart rate|
| Pupil size and reactivity|
| Eye position and movements|
| Doll's eyes maneuver|
| Cold caloric testing|
| Corneal reflexes|
| Facial symmetry|
| Spontaneous movements|
| Withdrawal to noxious stimulus|
| Deep tendon reflexes|
Assessment of Consciousness
The determination of the level of consciousness depends on analyzing arousability and content (see Table 67-1). Initially, observe whether the patient appears asleep or wakeful with spontaneous eye opening. In a sleeping patient, quantify how much stimulation is required to arouse the patient. Attempts should be made to elicit a behavioral response by verbal command alone. If no response is obtained, then physical stimulation should be used, first by shaking the patient. Then noxious stimulation can be applied by digital pressure to the supraorbital nerves or nailbeds of the fingers or toes. Purposeful attempts by the patient to remove the offending stimulus indicate preservation of brain stem function and intact connections to the appropriate cerebral hemisphere. Eye opening, either spontaneous or in response to stimulation, indicates preserved function of the RAS in the upper brain stem and hypothalamus. Once aroused, the patient's ability to remain wakeful and respond coherently is determined.
Lethargy (or drowsiness), stupor, and coma represent different points on a continuum of decreasing levels of consciousness. Patients in these states appear to be sleeping with eyes closed. In contrast, patients with akinetic mutism and locked-in syndrome appear to be awake with eyes opened.
The Glasgow Coma Scale (Table 67-5) is used to assign a numerical description of consciousness. The scale was devised to evaluate patients with head injury and is most reliable and reproducible in trauma patients.16,17 Its application in nontraumatic conditions is less reliable, but it is still the most widely used clinical scale to evaluate the level of consciousness. Furthermore, it provides a reproducible tool to monitor progression.
Table 67–5. The Glascow Coma Scalea ||Download (.pdf)
Table 67–5. The Glascow Coma Scalea
| To speech||3|
| To pain||2|
|Best verbal response|
|Best motor response|
| Obeys commands||6|
| Localizes pain||5|
| Abnormal flexion||3|
The cerebral cortex and forebrain are important in the control of regular respiration. Patients with isolated brain injury uncomplicated by other critical medical illnesses may have characteristic breathing patterns that aid in neuroanatomic localization (Fig. 67-1). However, these patterns are not reliable in patients with multiple organ system failure who are receiving mechanical ventilation. Nevertheless, a discussion is warranted.
Respiratory patterns in coma.
Cheyne-Stokes respiration is a periodic breathing pattern in which periods of hyperpnea regularly alternate with apnea in a smooth crescendo-decrescendo pattern. This neurogenic respiratory alteration occurs with damage to the cortex and forebrain bilaterally, or secondary to cardiac or respiratory failure. It is the result of the loss of frontal lobe control over respiratory patterns with excessive dependence on blood CO2 levels to trigger brain stem respiratory centers.
Midbrain and upper pontine lesions may cause a central neurogenic hyperventilation syndrome with persistent deep hyperventilation. It can only be diagnosed with arterial blood gas measurements, since hyperventilation also occurs secondary to hypoxemia and acidemia. Likewise, metabolic disorders, especially the early stages of hepatic coma, cause central neurogenic hyperventilation.
Lesions of the middle or lower pons are characterized by deep prolonged inspiration followed by a long pause referred to as apneustic breathing. Most patients with this respiratory pattern require early intubation and mechanical ventilation.
Ataxic and irregular periodic breathing occurs with lesions in the dorsomedial medulla and may be accompanied by hypersensitivity to respiratory depressants. These patterns are not compatible with sustained life.
When assessing a comatose patient, the rate and pattern of respiration should be observed. In addition, vomiting and hiccups should be noted because they may result from intrinsic brain stem pathology or transmitted pressure on the brain stem. Furthermore, spontaneous yawning may occur in comatose patients. The neurogenic networks for this complex respiratory response are integrated in the lower brain stem.
Pupillary Size and Reactivity
In one study of 346 comatose patients, the pupillary reflex was shown to be the strongest prognostic variable for awakening when compared with evoked-potential studies.18 Pupillary size is controlled by the autonomic nervous system and is dictated by the balance between sympathetic and parasympathetic input to the pupillary dilators and constrictors, respectively. The parasympathetic efferents to the pupil originate from the Edinger-Westphal nucleus in the upper midbrain and travel with the ipsilateral third cranial nerve (oculomotor). Dysfunction within this pathway will produce unopposed sympathetic input to the pupil and relative pupillary dilation ipsilateral to the lesion. The sympathetic efferents to the pupil originate in the hypothalamus, descend through the brain stem and cervical spinal cord, and exit the upper thoracic spinal cord (T1 to T3 levels). From this point they ascend the carotid sheath and follow the vasculature to the pupil. Any disruption of the sympathetic fibers along this loop can lead to unopposed parasympathetic pupillary activity and subsequently an ipsilateral small (miotic) pupil.
A light stimulus to one eye produces constriction of the ipsilateral pupil (direct response) and contralateral pupil (consensual response), through a network of connections. Table 67-6 summarizes the pupillary changes commonly seen in coma and their significance.
Table 67–6. Pupillary Changes in Coma ||Download (.pdf)
Table 67–6. Pupillary Changes in Coma
| Normal or small||Normal||Toxic-metabolic disturbance|
| Midposition (3–5 mm)||Poor||Midbrain dysfunction; drugs (glutethimide [Doriden])|
| Small (pinpoint)||Poor||Pontine dysfunction; drugs (narcotics)|
| Large||Poor||Toxic-metabolic disturbance (anoxia); drugs (anticholinergics)|
| Large||Unreactive||Ipsilateral midbrain pathology or compression of ipsilateral CN III:
uncal herniation, posterior communicating artery aneurysm|
| Small||Minimal||Ipsilateral sympathetic dysfunction|
Small reactive pupils may be due to a toxic-metabolic disturbance. Very small pupils (pinpoint) that react to naloxone are characteristic of narcotic overdose. Pinpoint pupils that are poorly reactive are characteristic of pontine dysfunction. Lesions rostral or caudal to the midbrain may disrupt descending sympathetics and produce small pupils.
Bilateral, widely dilated, fixed pupils are due to sympathetic overactivity from an endogenous cause (seizures or severe anoxic ischemia) or exogenous catecholamines (dopamine or norepinephrine) or atropine-like drugs.
Since the midbrain is the one location in the brain stem where parasympathetic and sympathetic pupillary fibers are adjacent, a midbrain lesion classically results in intermediate pupil size. Such pupils are seen in brain death and severe midbrain injuries.
A unilaterally dilated, unreactive pupil in a comatose patient may be caused by herniation of the ipsilateral temporal uncus through the tentorium, which compresses the ipsilateral oculomotor nerve and its parasympathetic fibers. In this setting, the large pupil is eventually accompanied by other evidence of cranial nerve (CN) III disruption (i.e., ipsilateral eye deviation inferolaterally). In the setting of head trauma, this implies an ipsilateral epidural, subdural, or intracerebral hematoma. In nontraumatic conditions, it usually occurs with large cerebral infarcts, spontaneous intracerebral hematoma, or supratentorial brain tumors.
Eye Position and Movement
The eye muscles are controlled by three sets of cranial nerves, CN III, CN IV (trochlear), and CN VI (abducens), their nuclei being located in the upper midbrain, lower midbrain, and pontomedullary junction, respectively. Proper eye movement control requires a network of interconnections between these nuclei so that the eyes move conjugately. This interconnection is referred to as the medial longitudinal fasciculus (MLF), which is also integrated with the vestibular nuclei and allows for reflex conjugate eye movement in response to positional head changes.
Figure 67-2 displays the relevant anatomy accounting for horizontal conjugate eye movements. Each frontal eye field controls gaze to the contralateral side by stimulating the contralateral pontine paramedian reticular formation (PPRF) at the pontomedullary junction. Lesions of the frontal eye fields or the PPRFs lead to conjugate eye deviation, provided that the MLF is intact. Therefore, a lesion of the right frontal eye field or left PPRF impairs leftward gaze, and thus the eyes conjugately deviate to the right. In short, the eyes turn toward the lesion with frontal eye field dysfunction and away from the lesion with PPRF dysfunction. In contrast, MLF lesions are manifested as poor adduction of the eye ipsilateral to the MLF lesion. Spontaneous “roving” eye movements in all directions in the comatose patient demonstrate integrity of a significant portion of the brain stem. If no spontaneous eye movements are observed, the intactness of the interconnections responsible for eye control is in question. Since comatose patients are unable to follow commands, maneuvers that take advantage of vestibular input to ocular control must be utilized.
Schematic representation of the neurologic pathways controlling horizontal conjugate gaze. PPRF, pontine paramedian reticular formation; MLF, median longitudinal fasciculus; CN III, third cranial nerve; 1–4, sites of possible pathologic lesions (see text).
An oculocephalic reflex (doll's eye maneuver) is performed by rapidly rotating the head from side to side and observing the patient's eye positional changes (Fig. 67-3). The normal response in the comatose patient with intact brain stem is for the eyes to remain fixed on the same point in space. Thus when the head is turned rightward, the eyes move to the left. When the head is turned leftward, the eyes move conjugately to the right. If a comatose patient does not have normal doll's eyes, a disruption of brain stem ocular and vestibular connections may be present. Of course, in the setting of trauma, the head should not be rotated due to the possibility of cervical spine injury. In this situation or when doll's eye maneuvers are inconclusive, cold water calorics are helpful.
Eye positions in the doll's eye maneuver and with cold caloric testing in coma. MLF, median longitudinal fasciculus; PPRF, pontine paramedian reticular formation.
Oculovestibular reflexes (cold water caloric testing) depend on vestibular system stimulation by altering endolymphatic flow in the semicircular canals. The change in endolymphatic flow is achieved by instilling ice-cold water in the external auditory canal, thereby cooling the mastoid process, and in turn the semicircular canal. Prior to performing this test, the external auditory canal should be examined to confirm intactness of the tympanic membrane and remove any impacted cerumen. The head should then be elevated 30 degrees. A functional apparatus for instilling the water is a butterfly catheter (with the needle removed) connected to a syringe containing approximately 100 mL of cold water.
The responses to cold water in patients with various lesions are summarized in Fig. 67-3. In normal wakeful patients the response is horizontal nystagmus, with the slow phase toward and the fast phase away from the stimulated side and with minimal eye movement from the midline. With diminishing consciousness in patients without structural brain stem damage, the fast phase of the nystagmus disappears, and the eyes tend to deviate conjugately toward the stimulated side. Structural brain stem disease eliminates the caloric response, as does inner ear disease, deep drug coma, and anticonvulsant drug overdose. In order to ensure proper interpretation of cold water caloric testing, the opposite side should not be stimulated until 5 minutes after the initial side.
The corneal reflex is an important protective mechanism for the cornea. it is a blinking reflex triggered when the cornea is presented with a noxious stimulus. The afferent limb is via the trigeminal nerve (CN V), and the efferent limb is via the facial nerve (CN VII). Although corneal reflexes assess brain stem function, they have limited localizing value.
The corticospinal tract predominantly originates from the frontal cortex and descends ipsilaterally through the corona radiata, the posterior limb of the internal capsule, and the cerebral peduncle of the midbrain and consolidates in the pyramids, the ventral swellings of the medulla. The pyramidal fibers decussate to the contralateral side at the junction of the medulla and spinal cord to form the lateral corticospinal tract.
Observation is the key to the motor examination in the comatose patient. The patient is observed for spontaneous movements or maintenance of particular postures. Lesions involving the corticospinal tract generally lead to diminished contralateral spontaneous activity. Upper midbrain or more rostral lesions may lead to decorticate posturing characterized by flexion of the contralateral arm at the elbow and hyperextension of the leg. Central midbrain and high pontine lesions, with a relatively intact brain stem inferiorly, may lead to decerebrate posturing characterized by contralateral arm and leg extension. Such posturing may also be caused by structural lesions or metabolic insults and it is often mistaken for seizure activity. The patient should be observed for the presence of tremor, myoclonus, or asterixis, because these may be associated with toxic-metabolic encephalopathies.
After observing for spontaneous movements and posturing, motor tone should be assessed by passive flexion and extension of the extremities. Tone may be increased or decreased, depending on the location of the motor system involvement. Afterward, noxious stimuli should then be applied to each limb and the supraorbital regions. Purposeful movement upon noxious stimulation suggests intactness of motor tracts to that limb, whereas decorticate or decerebrate posturing in response to noxious stimuli has the localizing significance mentioned above.
Acute corticospinal tract lesions may cause hyporeflexia because hyperreflexia may not occur for days to weeks after the injury. However, a Babinski sign, which is characterized by extension of the great toe and fanning of the other toes upon lateral plantar stimulation, may be present acutely with corticospinal tract lesions. Complete bilateral paralysis without any response to noxious stimuli usually indicates a grave prognosis. However, spinal cord injury and neuromuscular transmission blockade must be excluded because they may produce a similar state of complete paralysis.