The Examination in Coma

Workup of the patient with coma or altered mental status is often complex and always urgent. The neurologic examination is only one of several diagnostic methods that can be brought to bear in coma; and imaging, cerebrospinal fluid (CSF), and laboratory investigations play a vital role. However, the findings on examination often determine the early management, and the urgency with which imaging and CSF studies are obtained. Coma is a complicated topic, and this discussion will focus on what can be learned from the examination.

Consciousness has two dimensions: arousal and cognition. Arousal is a primitive function sustained by deep brainstem and medial thalamic structures. Cognitive functions require an intact cerebral cortex and major subcortical nuclei. In coma, stupor, and hypersomnia there is a lowering of consciousness; in confusion and delirium there is a clouding of consciousness.

THE ANATOMY OF CONSCIOUSNESS

The ascending reticular activating system (RAS) is a system of fibers which arises from the reticular formation of the brainstem, primarily the paramedian tegmentum of the upper pons and midbrain, and projects to the paramedian, parafascicular, centromedian, and intralaminar nuclei of the thalamus. Neurons in the reticular formation also receive collaterals from the ascending spinothalamic pathways and send projections diffusely to the entire cerebral cortex, so that sensory stimuli are involved not
only with sensory perception but—through their connections with the RAS—with the maintenance of consciousness. The fibers in the RAS are cholinergic, adrenergic, dopaminergic, serotonergic, and histaminergic. Experimentally, stimulation of the RAS produces arousal, and destruction of the RAS produces coma. The hypothalamus is also important for consciousness; arousal can be produced by stimulation of the posterior hypothalamic region.

Processes producing coma can be characterized as either structural or metabolic. Although restricted, focal lesions of the RAS can produce profound alterations in consciousness; hemispheric lesions cause coma only when extensive and bilateral, such as with head injury, meningitis, encephalitis, or bilateral cerebral infarction. The degree of alteration in consciousness is roughly proportional to the volume of brain tissue involved in the process. Focal lesions restricted to either hemisphere rarely produce significant alterations of consciousness. Metabolic processes produce coma by diffusely affecting the cerebral hemispheres or depressing the activity in the RAS, or both.

INITIAL MANAGEMENT OF COMA

Because of the dire consequences to the brain of lack of substrate, the initial management of coma, unless the cause is immediately apparent, is directed toward correction of possible deficiencies in glucose, oxygenation, and blood pressure; these emergency measures are necessary, even before a detailed history and examination. After initial determination of vital signs, attention should first be directed toward ensuring an adequate airway and oxygenation, blood pressure, and intravenous access. After obtaining emergency blood samples, 50 cc of 50% glucose should be given, followed quickly by 100 mg of thiamine IV in case the patient is alcoholic (Wernicke encephalopathy can be precipitated by IV glucose in such patients). Naloxone and flumazenil are often given empirically in case there has been an opiate or benzodiazepine overdose. A “coma cocktail,” consisting of dextrose, flumazenil, naloxone, and thiamine is sometimes used in the initial management of the comatose patient. Because the rapid reagent test strips used for glucose determination are not infallible, studies favor empirical administration of dextrose and thiamine to patients with altered consciousness, but naloxone should probably be reserved for patients with signs and symptoms of opioid intoxication, and flumazenil best left for reversal of therapeutic conscious sedation and rare select cases of benzodiazepine overdose. Preparations for intubation, respiratory support, and use of pressor agents must be made, should they become necessary. Always assume a cervical spine injury may be present, and immobilize the neck until a fracture can be ruled out.

DIAGNOSTIC ASSESSMENT

After ensuring adequate oxygenation and substrate for the central nervous system (CNS), a rapid neurologic examination should be performed to search for obvious signs, such as a dilated pupil, that may require urgent imaging and neurosurgical intervention. Otherwise, the initial emergent management should be followed by a history and general physical and neurologic examinations.

History

Though often difficult and sometimes impossible to obtain, historical information is extremely important and well worth pursuing vigorously. In the absence of family, a phone call to the neighbor, landlord, or companion may yield valuable details about the sequence of events leading to coma, the patient’s past health and illnesses, and current medications. A history of known seizure disorder, diabetes mellitus, hypertension, substance abuse, depression, or suicide attempts may emerge. Check the wallet or purse for medication lists, a doctor’s card or phone number, medical alert card, or other pertinent information. Talk with police or ambulance drivers if they are involved.

General Physical Examination

Findings on the general physical examination may be extremely helpful in elucidating the cause of altered consciousness (Table 35.1). The patient should always be examined carefully for bruises and hematomas, lacerations, fractures, and other signs of injury, especially about the head. It is essential to remember that two conditions may occur together (e.g., trauma and alcoholic intoxication). Simple vital signs may provide important clues. An elevated temperature suggests infection or serious intracranial disease. Extremely elevated blood pressure suggests hypertensive encephalopathy or subarachnoid hemorrhage. Hypotension suggests impaired CNS perfusion due to some systemic process, such as hemorrhage or myocardial disease. Hypotension rarely occurs because of primary CNS disease, except in the terminal phase. Either tachycardia or bradycardia may impair CNS perfusion. The combination of hypertension and bradycardia suggests brainstem dysfunction, often because of increased intracranial pressure (Cushing reflex).

Abnormalities of respiration are important in the evaluation of patients with depressed consciousness. Abnormal respiratory patterns due to neurologic disease include Cheyne-Stokes respirations (CSR), central neurogenic hyperventilation, ataxic breathing, and apneustic breathing. In CSR, periods of hyperpnea alternate with periods of hypopnea. Respirations increase in depth and volume up to a peak, and then decline until there is a period of apnea, after which the cycle repeats. In posthyperventilation apnea, a brief period of hyperventilation is followed by apnea lasting 15 to 30 seconds or longer. The mechanisms underlying CSR and posthyperventilation apnea are likely similar. Cheyne-Stokes respirations may be due to bilateral hemisphere lesions, as well as to increased intracranial pressure and cardiopulmonary dysfunction. In respiratory ataxia, the pattern of breathing is irregular, with erratic shallow and deep respiratory movements. Ataxic breathing occurs with dysfunction of the medullary respiratory centers, and may signify impending agonal respirations and apnea. Central neurogenic hyperventilation refers to sustained, rapid, and regular hyperpnea. It is primarily associated with disease affecting the paramedian reticular formation in the low midbrain and upper pons, but it may also occur with lesions in other brainstem locations, either intra-axial or extra-axial. Apneustic breathing, which is rare, causes a prolonged inspiratory phase, and occurs in pontine lesions just rostral to the trigeminal motor nuclei, or cervicomedullary compression. Abnormal respiratory patterns may occur because of systemic disease, such as diabetic ketoacidosis (Table 35.1). Slow, regular respirations are noted with a variety of substance or drug intoxications and in severe myxedema.

Note the patient’s appearance and behavior, apparent age, grooming, and signs of acute or chronic illnesses such as fever, cyanosis, jaundice, pallor, and signs of dehydration and loss of weight. Assess responses to noises, verbal commands, visual stimuli, threats, and tactile and painful stimulation, and whether there has been incontinence. Note whether the patient, even in coma, appears to be comfortable and natural or assumes unnatural positions. Carefully observe spontaneous movements, and the reaction to various stimuli. Note general activity (immobile, underactive, restless, or hyperkinetic), tone (limp, relaxed, rigid, or tense), and the presence of abnormal movements (tremors, twitches, tics, grimaces, and spasms). Motor unrest and excessive activity are seen in both organic and psychogenic states. If there is seizure activity, note the distribution and pattern of spread of the convulsive movements, and any associated manifestations such as the degree of impairment of consciousness, frothing at the mouth, tongue biting, and incontinence.

The behavior of the patient should be observed closely and as often as necessary until the diagnosis is established. Note the patient’s reactions to physicians, nurses, and relatives. Do the eyes follow people? Is there some awareness of what is happening in the immediate environment? The conduct may be constant or may vary from time to time. For instance, the patient may appear to be completely unconscious and fail to respond to any type of stimulation while the observer is in the room, yet when not aware of being watched, may open the eyes, make furtive glances, and move around.

TABLE 35.1 Findings on General Physical Examination that May Provide a Clue to the Etiology of Coma or Altered Mental Status

System	Finding	Possible Implications
Blood pressure	Hypotension	Hypovolemia, Ml, intoxication (especially ETOH and barbiturates), Wernicke encephalopathy, sepsis
	Hypertension	Stroke, intracranial hemorrhage, increased ICP, hypertensive encephalopathy, renal disease
Heart rate	Bradycardia	Heart disease, intoxication, increased ICP
	Tachycardia	Hypovolemia, cocaine overdose, infection
Respiration	Breath odor	Acetone (DKA), ETOH (intoxication), fetor hepaticus, uriniferous (uremia), garlic odor (arsenic poisoning), household gas (carbon monoxide)
	Hyperventilation	Hypoxia, hypercapnia, acidosis, fever, liver disease, sepsis, pulmonary emboli, toxins or drugs producing metabolic acidosis, central neurogenic hyperventilation, salicylism
	Hypoventilation	Overdose, myxedema
	Cheyne-Stokes	Bilateral cerebral disease, impending transtentorial herniation, upper brainstem lesions, metabolic encephalopathy, CHF
	Cluster breathing	Increased ICP, posterior fossa lesion
	Apneustic breathing	Pontine lesion, transtentorial herniation, metabolic coma
	Ataxic breathing	Medullary lesion
	Ondine’s curse	Medullary lesion
Temperature	Fever	Infection, inflammation, neoplasms (rare), anticholinergics, SAH, hypothalamic lesion, heatstroke, thyroid storm, malignant hyperthermia
	Hypothermia	Exposure, sepsis, shock, myxedema coma, Wernicke encephalopathy, drug intoxication (especially barbiturates), hypothalamic lesion, hypoglycemia
Head and neck	Scalp laceration or edema, Battle sign, raccoon eyes	Trauma
	Stiff neck	Meningitis, SAH, cerebellar tonsillar herniation
	Unilateral, fixed dilated pupil	Uncal herniation, aneurysm
	Small, reactive pupils	Metabolic coma, early transtentorial herniation
	Bilateral, large, fixed pupils	Midbrain or pretectal lesion (tectal pupils)
	Midposition, fixed pupils	Midbrain stage of transtentorial herniation
	Pinpoint pupils	Pontine hemorrhage or infarct, opiate overdose
	Fundus exam	Papilledema (increased ICP), hypertensive or diabetic retinopathy, subhyaloid hemorrhages, Roth spots
Skin	Needle tracks	Drug overdose
	Cyanosis	Hypoxia, cardiac disease, cyanide
	Cherry red	Carbon monoxide intoxication
	Jaundice	Hepatic encephalopathy, hemolysis
	Pallor	Anemia, hemorrhage, shock, vasomotor syncope
	Petechiae	DIC, TTP, meningococcemia, drugs, fat embolism
	Purpuric rash	Meningococcemia, RMSF, and others
	Maculopapular rash	Toxic shock syndrome, SBE, SLE, and others
	Bruises	Trauma, coagulopathy
	Bullous lesions	Drug overdose, especially barbiturates
	Sweating	Fever, hypoglycemia
	Flushing, erythema	Polycythemia, fever, alcohol intoxication
Heart	Arrhythmia	Cerebral embolism
	Murmur	SBE, embolism
Lungs	Pulmonary edema	Neurogenic pulmonary edema, CHF, anoxic encephalopathy
Gl	Fecal incontinence	Seizure with post-ictal coma
	+ stool blood	Hepatic encephalopathy, Gl hemorrhage
GU	Urinary incontinence	Seizure with post-ictal coma
	Hematuria	Cerebral embolism
Extremities	Subtle twitching	Subclinical status epilepticus
CHF, congestive heart failure; DIC, disseminated intravascular coagulation; DKA, diabetic ketoacidosis; ETOH, ethanol; Gl, gastrointestinal; GU, genitourinary; ICP, intracranial pressure; MI, myocardial infarction; RMSF, Rocky Mountain spotted fever; SAH, subarachnoid hemorrhage; SBE, subacute bacterial endocarditis; SLE, systemic lupus erythematosus; TTP, thrombotic thrombocytopenic purpura.

After the general physical exam, a focused neurologic exam may help characterize the pathologic process. Specific attention should be paid to the level of responsiveness, pupils, eye movements, and motor responses.

Neurologic Examination

The details of the neurologic examination in the various states of disordered consciousness necessarily vary with the degree of impairment and depth of coma. As a minimum, the following must be assessed: level of consciousness, pupils, eye movements (including reflex movements), fundoscopic, motor status, reflexes, and meningeal signs. Other portions of the examination then follow as necessary. Coma is most often due to a metabolic process. With rare exception, metabolic
encephalopathies are characterized by reactive pupils and a symmetric neurologic examination. Any asymmetry in motor or sensory responses and any pupillary or eye movement abnormality should prompt an immediate, vigorous search for structural disease.

Level of Responsiveness

Coma is a state of complete loss of consciousness from which the patient cannot be aroused by ordinary stimuli. There is complete unresponsiveness to self and the environment. The patient in coma has no awareness of herself, makes no voluntary movements, and has no sleep-wake cycles. Stupor is a state of partial or relative loss of response to the environment in which the patient’s consciousness may be impaired to varying degrees. The patient is difficult to arouse, and although brief stimulation may be possible, responses are slow and inadequate. The patient is otherwise oblivious to what is happening in the environment, and promptly falls back into the stuporous state. The lethargic patient can usually be aroused or awakened and may then appear to be in complete possession of her senses, but promptly falls asleep when left alone. In a confusional state patients may be alert, but are confused and disoriented. Patients with delirium are confused, disoriented, and often agitated; the best example is delirium tremens. Terminologic description of the differences between various states of impaired altered consciousness is at best ambiguous. Because of imprecision and inconsistency in usage, such terms as semi-coma and semi-stupor, all describing changes across a spectrum of altered awareness, are best avoided. It is preferable to describe the patient’s state of responsiveness, or use an objective and well-defined scheme, such as the Glasgow coma scale (GCS), which has gained wide acceptance in the evaluation of patients with impaired consciousness, particularly in head injury. In the GCS, scores are obtained for ocular, verbal, and motor functions (Table 35.2). An alert person with normal eye and motor responses would score 15 points; a patient in profound coma would score 3 points. Other coma scales are available. Coma must be distinguished from the persistent vegetative state, locked-in syndrome, and mutism.

TABLE 35.2 The Glasgow Coma Scale

Eye opening
	Open spontaneously	4
	Open only to verbal stimuli	3
	Only to pain	2
	Never open	1
Best verbal response
	Oriented and converses	5
	Converses, but disoriented, confused	4
	Uses inappropriate words	3
	Makes incomprehensible sounds	2
	No verbal response	1
Best motor response
	Obeys commands	6
	Localizes pain	5
	Exhibits flexion withdrawal	4
	Decorticate rigidity	3
	Decerebrate rigidity	2
	No motor response	1