Книги по МРТ КТ на английском языке / PLUM AND POSNER S DIAGNOSIS OF STUPOR AND COM-1

memory loss that is proportional to other losses of cognitive functions. When the maximal pathologic changes involve the medial temporal lobe, however, recent memory loss outstrips other intellectual impairments. Thus, memory loss and an inability to form new associations can be a sign of either diffuse or bilateral focal brain disease.

AFFECT AND COMPORTMENT

Patients may appear apathetic and withdrawn, in which case they are often believed by their relatives to be depressed, or they may be ebullient and outgoing, particularly when hyperaroused. Inappropriate comments and behavior are common and often embarrassing to friends and relatives. Patients are usually unaware that their behavior is inappropriate.

PERCEPTION

Patients with metabolic brain disease frequently make perceptual errors, mistaking the members of the hospital staff for old friends and relatives and granting vitality to inanimate objects. Illusions are common and invariably involve stimuli from the immediate environment. Quiet and apathetic patients suffer illusory experiences, but these must be asked about since they are rarely volunteered. Anxious and fearful patients, on the other hand, frequently express concern about their illusions and misperceptions to the accompaniment of loud and violent behavior. Unlike patients with psychiatric disorders, visual or combined visual and

auditory hallucinations are more common than pure auditory ones.10,11

Pathogenesis of the Mental

Changes

Both global and focal cerebral functional abnormalities can cause the mental symptoms of metabolic brain disease. The global symptoms result from alterations of arousal that in turn interfere with attention, comprehension, and cognitive synthesis. Well-recognized focal cerebral abnormalities include specific abnormalities in language recognition and synthesis, in recent memory storage and recall, in gnosis (recognition of persons and/or objects [from

the Greek for knowledge]) and praxis (ability to preform an action [from the Greek for action]), and perhaps in the genesis of hallucinations. Focal lesions may mimic more diffuse causes of delirium. Perhaps the best example is the florid delirium that sometimes accompanies cerebral infarcts of the nondominant parietal lobe,12 an area implicated in selective attention13 that, as indicated above, may be the primary abnormality in delirium.

A combination of diffuse and focal dysfunction probably underlies the cerebral symptoms of most patients with metabolic encephalopathy. The extensive corticocortical physiologic connectivity of the human brain discussed in Chapter 1 implies that large focal abnormalities inevitably will cause functional effects that extend well beyond their immediate confines. Furthermore, the more rapidly the lesion develops, the more extensive will be the acute functional loss. Thus, the general loss of highest integrative functions in metabolic diseases is compatible with a diffuse dysfunction of neurons and, as judged by measurements of cerebral metabolism, the severity of the clinical signs is directly related to the mass of neurons affected. However, certain distinctive clinical signs in different patients and in different diseases probably reflect damage to more discrete areas having to do with memory and other selective aspects of integrative behavior. An example is the encephalopathy resulting from thiamine deficiency (Wernicke-Korsakoff syndrome; see page 223). In this illness, patients show acutely the clinical signs of delirium and, rarely, coma.14 All neuronal areas are deprived of thiamine to the same extent, but certain cell groups such as the mamillary bodies, the mediodorsal nucleus of the thalamus, the periaqueductal gray matter, and the oculomotor nuclei are pathologically more sensitive to the deficiency and show the greatest anatomic evidence of injury. The final common pathway to neuronal destruction, as in many other disorders, is probably glutamate-induced excitotoxicity.15,16 Thus, a diffuse disease may have a focal maximum. Clinically, eye movements, balance, and recent memory are impaired more severely than are other mental functions, and indeed, memory loss may persist to produce a permanent Wernicke-Korsakoff syndrome after other mental functions and overall cerebral metabolism have improved to a near-normal level.

RESPIRATION

Sooner or later, metabolic brain disease nearly always results in an abnormality of either the depth or rhythm of breathing. Most of the time, this is a nonspecific alteration and simply a part of a more widespread brainstem depression. Sometimes, however, the respiratory changes stand out separately from the rest of the neurologic defects and are more or less specific to the disease in question. Some of these specific respiratory responses are homeostatic adjustments to the metabolic process causing encephalopathy. The others occur in illnesses that particularly affect the respiratory mechanisms. Either way, proper evaluation and interpretation of the specific respiratory changes facilitate diagnosis and often suggest an urgent need for treatment.

As a first step in appraising the breathing of patients with metabolically caused coma, increased or decreased respiratory efforts must be confirmed as truly reflecting hyperventilation or hypoventilation. Increased chest efforts do not indicate hyperventilation if they merely overcome obstruction or pneumonitis, and conversely, seemingly shallow breathing can fulfill the reduced metabolic needs of subjects in deep coma. Although careful clinical evaluation usually avoids those potential deceptions, the bedside observations are most helpful when anchored by direct determinations of the arterial blood gases.

Neurologic Respiratory Changes

Accompanying Metabolic

Encephalopathy

Lethargic or slightly obtunded patients have posthyperventilation apnea, probably resulting from loss of the influence of the frontal lobes in causing continual if low-volume ventilation, even when there is no metabolic need to breathe.17 Those in stupor or light coma commonly exhibit Cheyne-Stokes respiration. With more profound brainstem depression, transient neurogenic hyperventilation can ensue either from suppression of brainstem inhibitory regions or from development of neurogenic pulmonary edema.18,19 As an illustration, poisoning with shortor intermediate-acting barbiturate preparations often induces brief episodes of hyperventilation and motor hy-

pertonus, either during the stage of deepening coma or as patients reawaken. Hypoglycemia and anoxic damage are even more frequent causes of transient hyperpnea. Diabetic ketoacidosis and other causes of coma that cause a metabolic acidosis may produce slow, deep (Kussmaul) respirations. Both hepatic encephalopathy and systemic inflammatory states cause persistent hyperventilation, resulting in a primary respiratory alkalosis. In these instances, the increased breathing sometimes outlasts the immediate metabolic perturbation, and if the subject also has extensor rigidity, the clinical picture may superficially resemble structural disease or severe metabolic acidosis. However, attention to other neurologic details usually leads to the proper diagnosis, as the following case illustrates.

Patient 5–1

A 28-year-old man was brought unconscious to the emergency department. Fifteen minutes earlier, with slurred speech, he had instructed a taxi driver to take him to the hospital, then ‘‘passed out.’’ His pulse was 100 per minute, and his blood pressure was 130/90 mm Hg. His respirations were 40 per minute and deep. The pupils were small (2 mm), but the light and ciliospinal reflexes were preserved. Oculocephalic reflexes were present. Deep tendon reflexes were hyperactive; there were bilateral extensor plantar responses, and he periodically had bilateral extensor spasms of the arms and legs. His blood glucose was 20 mg/dL. After 25 g of glucose was given intravenously, respirations quieted, the extensor spasms ceased, and he withdrew appropriately from noxious stimuli. After 75 g of glucose, he awoke and disclosed that he was diabetic, taking insulin, and had neglected to eat that day.

Comment: This man’s hyperpnea and decerebrate rigidity initially suggested structural brainstem disease to the emergency department physicians. Normal oculocephalic responses, normal pupillary reactions, and the absence of other focal signs made metabolic coma more likely, and the diagnosis was confirmed by the subsequent findings.

The effectiveness of respiration must be evaluated repeatedly when metabolic disease depresses the brain, because the brainstem

reticular formation is especially vulnerable to chemical depression. Anoxia, hypoglycemia, and drugs all are capable of selectively inducing hypoventilation or apnea while concurrently sparing other brainstem functions such as pupillary responses and blood pressure control.

Acid-Base Changes Accompanying

Hyperventilation During

Metabolic Encephalopathy

Respiration is the first and most rapid defense against systemic acid-base imbalance. Chemoreceptors located in the carotid body and aortic arterial wall, as well as in the lower brainstem, quickly respond to alterations in the blood of either hydrogen ion concentration or PCO2. Hypoxia sensitizes peripheral chemoreceptors and activates central chemoreceptors, but under most circumstances carbon dioxide levels, which are linked to blood pH, are more important in determining respiration (see Chapter 2). Table 5–3 lists some causes of abnormal ventilation in unresponsive patients.

HYPERVENTILATION

In a stuporous or comatose patient, hyperventilation is a danger sign meaning one of two things: either compensation for metabolic acidosis or a response to primary respiratory stimulation (respiratory alkalosis). Metabolic acidosis and respiratory alkalosis are differentiated by blood biochemical analyses. In the first instance, the arterial blood pH is low (less than 7.30 if hyperpnea is to be attributed to acidosis) and the serum bicarbonate is also low (usually below 10 mEq/L). In the second case, the arterial pH is high (over 7.45) and the serum bicarbonate is normal or reduced. In both primary respiratory alkalosis and metabolic acidosis with respiratory compensation, the arterial carbon dioxide tension (PaCO2) is reduced, usually below 30 mm Hg. Respiratory compensation for metabolic acidosis is a normal brainstem reflex response and, hence, occurs in most cases of metabolic acidosis. Mixed primary metabolic acidosis and primary respiratory alkalosis (which persists after the acidotic load is removed) also occurs in several conditions, particularly salicylate toxicity and hepatic coma. A diagnosis of mixed metabolic abnormality can be made when the degree of

Table 5–3 Some Causes of Abnormal

Ventilation in Unresponsive Patients

I.Hyperventilation

A.Metabolic acidosis

1.Anion gap

Diabetic ketoacidosis* Diabetic hyperosmolar coma*

Lactic acidosis Uremia*

Alcoholic ketoacidosis Acidic poisons*

Ethylene glycol Propylene glycol Methyl alcohol Paraldehyde

Salicylism (primarily in children)

2.No anion gap Diarrhea Pancreatic drainage

Carbonic anhydrase inhibitors

NH4Cl ingestion Renal tubular acidosis Ureteroenterostomy

B.Respiratory alkalosis

Hepatic failure*

Sepsis*

Pneumonia

Anxiety (hyperventilation syndrome)

C.Mixed acid-base disorders (metabolic acidosis and respiratory alkalosis)

Salicylism Sepsis*

Hepatic failure* II. Hypoventilation

A.Respiratory acidosis

1.Acute (uncompensated) Sedative drugs*

Brainstem injury Neuromuscular disorders Chest injury

Acute pulmonary disease

2.Chronic pulmonary disease*

B.Metabolic alkalosis

Vomiting or gastric drainage Diuretic therapy

Adrenal steroid excess (Cushing’s syndrome)

Primary aldosteronism Bartter’s syndrome

*Common causes of stupor or coma.

respiratory or metabolic compensation is excessive. Table 5–4 lists some of the causes of hyperventilation in patients with metabolic encephalopathy.

Table 5–4 Pathophysiology of

Metabolic Acidosis

From Swenson,20 with permission.

Metabolic acidosis sufficient to produce coma and hyperpnea has four important causes: uremia, diabetes, lactic acidosis (anoxic or spontaneous), and the ingestion of poisons that are acidic or have acidic breakdown products (Table 5–4).

In any given patient, a quick and accurate selection can and must be made from among these disorders. Diabetes and uremia are diagnosed by appropriate laboratory tests, and diabetic acidosis is confirmed by identifying serum ketonemia. It is important to remember that severe alcoholics without diabetes occasionally can develop ketoacidosis after prolonged drinking bouts.21 An important observation is that diabetics, especially those who have been treated with the oral hypoglycemic agent metformin, are subject to lactic acidosis as well as to diabetic ketoacidosis, but in the former condition ketonemia is lacking.22 If diabetes and uremia are eliminated in a patient as causes of acidosis, it can be inferred either that he or she has spontaneous lactic acidosis or has been poisoned with an exogenous toxin such as ethylene glycol, propylene glycol (which is metabolized to a racemic mixture of lactate), methyl alcohol, or decomposed paraldehyde. Anoxic lactic acidosis would be suspected only if anoxia or shock was present, and even then severe anoxic acidosis is relatively uncommon. Although laboratory tests can identify and quantify the ingested agents, these tests are not usually immediately available (see Chapter 7). However, the toxins are osmotically active and measurement of serum osmolality can detect the presence of an osmotically active substance, indicating exposure to a toxic agent.23 Severe toxic alcohol poisonings can be treated with fomepizole and, if necessary in patients with renal failure, hemodialysis.24 One report suggests that diethylene glycol poisoning can cause delayed neurologic sequelae including cranial neuropathies and bulbar palsy.25

The treatment of metabolic acidosis depends first on treating the inciting factor. Intravenous bicarbonate is indicated to treat hyperkalemia and to help clear acidic toxins from cells. Bicarbonate does not appear helpful in treating diabetic ketoacidosis.20

Sustained respiratory alkalosis has five important causes among disorders producing the picture of metabolic stupor or coma: salicylism, hepatic coma, pulmonary disease, sepsis, and psychogenic hyperventilation (Table 5–5).

Table 5–5 Pathophysiology of

Respiratory Alkalosis

Hypoxia

Parenchymal lung disease Pneumonia

Bronchial asthma

Diffuse interstitial fibrosis Pulmonary embolism Pulmonary edema

Medications and mechanical ventilation Medications

Salicylate

Nicotine

Xanthine Catecholamines Analeptics

Mechanical ventilation Central nervous system disorders

Meningitis, encephalitis Cerebrovascular disease Head trauma Space-occupying lesion Anxiety

Metabolic

Sepsis Hormonal Pyrexia Hepatic disease

Hyperventilation syndrome

From Foster et al.,26 with permission.

Neurogenic pulmonary edema and central neurogenic hyperventilation may also cause respiratory alkalosis in patients with metabolic stupor or coma. As is true with metabolic acidosis, these usually can be at least partially separated by clinical examination and simple laboratory measures.

Salicylate poisoning causes a combined respiratory alkalosis and metabolic acidosis that lowers the serum bicarbonate disproportionately to the degree of serum pH elevation. Salicylism should be suspected in a stuporous hyperpneic adult if the serum pH is normal or alkaline, there is an anion gap, and the serum bicarbonate is between 10 and 14 mEq/L. Salicylism in children lowers serum bicarbonate still more and produces serum acidosis. A bedside laboratory test can rapidly establish a diagnosis of salicylate intoxication,27 although usually in an awake patient the positive history and the presence of respiratory alkalosis are sufficient. A single serum salicylate measurement may be somewhat misleading, particularly if

the patient has taken enteric-coated tablets that may delay absorption. Therefore, in a patient with a suspected salicylate overdose, careful measurements should be done every 3 hours until levels have peaked. The ingestion of sedative drugs in addition to salicylates may blunt the hyperpnea and lead to metabolic acidosis, a picture that may mislead the examiner.

Salicylates directly activate the respiratory centers of the brainstem, although the mechanism is not known. Acetaminophen poisoning, more common than salicylate poisoning, may cause either metabolic acidosis (lactic acidosis)

or respiratory alkalosis resulting from its hepatic toxicity (see below).28,29

The treatment includes, where appropriate, gastric lavage and activated charcoal. Urinary alkalization helps promote excretion of the drug; hemodialysis may be necessary if there is renal failure.30 Acetylcysteine may limit the degree of hepatic toxicity by acetaminophen (see Chapter 7).

Hepatic coma, producing respiratory alkalosis, rarely depresses the serum bicarbonate below 16 mEq/L, and the diagnosis usually is betrayed by other signs of liver dysfunction. The associated clinical abnormalities of liver disease are sometimes minimal, particularly with fulminating acute liver failure or when gastrointestinal hemorrhage precipitates coma in a chronic cirrhotic patient. Liver function tests and measurement of arterial ammonia must be relied upon in such instances.

Sepsis is always associated with hyperventilation, probably a direct central effect of the cascade of cytokines and prostaglandins initiated by endotoxinemia. In fact, a respiratory rate of more than 20 breaths per minute, or a PCO2 of less than 30 torr, is part of the definition of sepsis.31 Early in the course of the illness the acid-base defect is that of a pure respiratory alkalosis (HCO3 greater than 15 mEq/L), but in critically ill patients, lactic acid later accumulates in the blood and the stuporous patient usually presents a combined acid-base defect of respiratory alkalosis and metabolic acidosis (HCO3 less than 15 mEq/L). Fever, or in severe cases hypothermia and hypotension, may accompany the neurologic signs and suggest the diagnosis.

Respiratory alkalosis caused by pulmonary congestion, fibrosis, or pneumonia rarely depresses the serum bicarbonate significantly. This diagnosis should be considered in hyp-

oxic, hyperpneic comatose patients who have normal or slightly lowered serum bicarbonate levels and no evidence of liver disease.

Psychogenic hyperventilation does not cause coma, but may cause delirium, and may be present as an additional symptom in a patient with psychogenic ‘‘coma.’’ Severe alkalosis, by itself, has been reported to cause seizures and coma. The decreased ionizable calcium complicating alkalosis may lead to muscle twitching, muscle spasms, and tetany, as well as positive Chvostek and Trousseau’s signs.32

Acid-Base Changes Accompanying

Hypoventilation During

Metabolic Encephalopathy

In an unconscious patient, hypoventilation means either respiratory compensation for metabolic alkalosis or respiratory depression with consequent acidosis. The differential diagnosis is outlined in Table 5–3. In metabolic alkalosis the arterial blood pH is elevated (greater than 7.45), as is the serum bicarbonate (greater than 35 mEq/L). In untreated respiratory acidosis with coma, the serum pH is low (less than 7.35) and the serum bicarbonate is either normal or

high, depending on prior treatment and how rapidly the respiratory failure has developed. The PaCO2 is always elevated in respiratory acidosis (usually greater than 55 mm Hg) and is often elevated in metabolic alkalosis as well because of respiratory compensation in metabolic alkalosis. In respiratory acidosis, the pH

of the cerebrospinal fluid (CSF) is always low if artificial ventilation has not been used.33,34 The

PCO2 is elevated in respiratory acidosis, and in metabolic alkalosis with respiratory compensation, but is usually less than 50 mm Hg in primary metabolic alkalosis and almost invariably rises considerably higher than this when primary respiratory acidosis causes stupor or coma. In both disorders, the oxygen tension is reduced due to hypoventilation. A normal serum bicarbonate level is consistent with untreated respiratory acidosis of short duration but not with metabolic alkalosis.

Metabolic alkalosis results from (1) excessive loss of acid via gastrointestinal or renal routes, (2) excessive bicarbonate load, or (3) failure to fully correct the posthypocapnic state (Table 5–6).32 To find the specific cause often requires exhaustive laboratory analyses, but delirium and obtundation owing to metabolic alkalosis are rarely severe and never life threatening, so that

From Epstein and Singh,36 with permission.

time exists for careful diagnostic considerations. Respiratory compensation from metabolic alkalosis leads to hypocapnia, but the PCO2 rarely is higher than 50 torr. Higher levels suggest coexistent pulmonary disease.35

Respiratory acidosis is a more pressing problem,36 caused by either severe pulmonary or neuromuscular disease (peripheral respiratory failure) or by depression of the respiratory center (central respiratory failure) (Table 5–7).

Both causes induce hypoxia as well as CO2 retention. Chest examinations almost always can differentiate neuromuscular from pulmonary disease, and the presence of tachypnea distinguishes pulmonary or peripheral neuromuscular failure from central failure with its irregular or slow respiratory patterns. Severe respiratory acidosis of any origin is best treated

by artificial ventilation. Acute respiratory acidosis causes encephalopathy, sometimes associated with headache, which may reflect intracranial vasodilation. If the PCO2 exceeds 70 torr, the patient may become stuporous or comatose. If awake, there may be asterixis, myoclonus, and sometimes papilledema, the last resulting from increased intracranial pressure (ICP) due to the carbon dioxide-induced cerebral vasodilation.

PUPILS

Among patients in deep coma, the state of the pupils becomes the single most important criterion that clinically distinguishes between metabolic and structural disease. The presence

of preserved pupillary light reflexes, despite concomitant respiratory depression, vestibuloocular caloric unresponsiveness, decerebrate rigidity, or motor flaccidity, suggests metabolic coma. Conversely, if asphyxia, anticholinergic or glutethimide ingestion, or pre-existing pupillary disease can be ruled out, the absence of pupillary light reflexes strongly implies that the disease is structural rather than metabolic.

Pupils cannot be considered conclusively nonreactive to a light stimulus unless care has been taken to examine them with magnification using a very bright light and maintaining the stimulus for several seconds. Infrared pupillometry is more reliable than the flashlight.38 Ciliospinal reflexes are less reliable than light reflexes but, like them, are usually preserved in metabolic coma even when motor and respiratory signs signify lower brainstem dysfunction.37

OCULAR MOTILITY

The eyes usually rove randomly with mild metabolic coma and come to rest in the forward position as coma deepens. Although almost any eye position or random movement can be observed transiently when brainstem function is changing rapidly, a maintained conjugate lateral deviation or dysconjugate positioning of the eyes at rest suggests structural disease. Conjugate downward gaze, or occasionally upward gaze, can occur in metabolic as well as in structural disease and by itself is not helpful in the differential diagnosis.39

HISTORICAL VIGNETTE

Patient 5–2

A 63-year-old woman with severe hepatic cirrhosis and a portacaval shunt was found in coma. She groaned spontaneously but otherwise was unresponsive. Her respirations were 18 per minute and deep. The pupillary diameters were 4 mm on the right and 3 mm on the left, and both reacted to light. Her eyes were deviated conjugately downward and slightly to the right. Oculocephalic responses were conjugate in all directions. Her muscles were flaccid, but her stretch reflexes were brisk

and more active on the right with bilateral extensor plantar responses. No decorticate or decerebrate responses could be elicited. Her arterial blood pH was 7.58, and her PaCO2 was 21 mm Hg. Two days later she awoke, at which time her eye movements were normal. Four days later she again drifted into coma, this time with the eyes in the physiologic position and with sluggish but full oculocephalic responses. She died on the sixth hospital day with severe hepatic cirrhosis. No structural central nervous system (CNS) lesion was found at autopsy.

Comment: This patient was seen prior to the availability of computed tomography (CT) scanning, but the later autopsy confirmed the clinical impression that these focal abnormalities were due to her liver failure, not a structural lesion. The initial conjugate deviation of the eyes downward and slightly to the right had suggested a deep, right-sided cerebral hemispheric mass lesion. But the return of gaze to normal with awakening within 24 hours and nonrepetition of the downward deviation when coma recurred ruled out a structural lesion. At autopsy, no intrinsic cerebral pathologic lesion was found to explain the abnormal eye movements. We have observed transient downward as well as transient upward deviation of the eyes in other patients in metabolic coma.

Because reflex eye movements are particularly sensitive to depressant drugs, cold caloric stimulation often provides valuable information about the depth of coma in patients with metabolic disease. The ocular response to passive head movement is less reliable than the caloric test, as absence of oculocephalic responses may imply purposeful inhibition of the reflex and does not dependably distinguish psychogenic unresponsiveness from brainstem depression. Cold caloric stimulation produces tonic conjugate deviation toward the irrigated ear in patients in light coma and little or no response in those in deep coma. If caloric stimulation evokes nystagmus, cerebral regulation of eye movements is intact and the impairment of consciousness is either very mild or the ‘‘coma’’ is psychogenic. If the eyes spontaneously deviate downward following lateral deviation, one should suspect drug-induced coma.39 Finally, if caloric stimulation repeatedly produces dysconjugate eye movements, structural brainstem disease should be suspected (but see Chapter 2).

Patient 5–3

A 20-year-old woman became unresponsive while riding in the back seat of her parents’ car. There was no history of previous illness, but her parents stated that she had severe emotional problems. On examination, her vital signs and general physical examination were normal. She appeared to be asleep when left alone, with quiet shallow respiration and no spontaneous movements. Her pupils were 3 mm and reactive. Oculocephalic responses were absent. She lay motionless to noxious stimuli but appeared to resist passive elevation of her eyelids. Cold caloric testing elicited tonic deviation of the eyes with no nystagmus. Blood and urine toxicology screens were positive for barbiturates, and she awoke the next morning and admitted ingesting a mixture of sedative drugs to frighten her mother.

Comment: The coma in this patient initially appeared light or even simulated. However, tonic deviation of the eyes in response to cold caloric irrigation signified that normal cerebral control of eye movements was impaired and indicated that her unresponsiveness was the result of organic, but probably toxic or metabolic, and not structural brain dysfunction. Toxicology screening discovered at least one cause, but drug overdosages are often mixed, and not all of the components may be picked up on screening.

MOTOR ACTIVITY

Patients with metabolic brain disease generally present two types of motor abnormalities: (1) nonspecific disorders of strength, tone, and reflexes, as well as focal or generalized seizures, and(2)certaincharacteristicadventitiousmovements that are almost diagnostic of metabolic brain disease.

‘‘Nonspecific’’ Motor Abnormalities

Diffuse motor abnormalities are frequent in metabolic coma and reflect the degree and distribution of CNS depression (Chapter 1). Paratonia and snout, suck, or grasp reflexes may be seen in dementia, as well as in patients in light coma. With increasing brainstem depres-

sion, flexor and extensor rigidity and sometimes flaccidity appear. The rigid states are sometimes asymmetric.

Patient 5–4

A 60-year-old man was found in the street, stuporous, with an odor of wine on his breath. No other history was obtainable. His blood pressure was 120/80 mm Hg, pulse rate 100 per minute, and respirations 26 per minute and deep. After assessing radiographically for cervical spine injury, his neck was found to be supple. There was fetor hepaticus and the skin was jaundiced. The liver was palpably enlarged. He responded to noxious stimuli only by groaning. There was no response to visual threat. His left pupil was 5 mm, the right pupil was 3 mm, and both reacted to light. The eyes diverged at rest, but passive head movement elicited full conjugate ocular movements. The corneal reflexes were decreased but present bilaterally. There was a left facial droop. The gag reflex was present. He did not move spontaneously, but grimaced and demonstrated extensor responses to noxious stimuli. The limb muscles were symmetrically rigid and stretch reflexes were hyperactive. The plantar responses were extensor. An emergency CT scan was normal. The lumbar spinal fluid pressure was 120 mm/CSF and the CSF contained 30 mg/dL protein and one white blood cell. The serum bicarbonate was 16 mEq/L, chloride 104 mEq/L, sodium 147 mEq/L, and potassium 3.9 mEq/L. Liver function studies were grossly abnormal.

The following morning he responded appropriately to noxious stimulation. Hyperventilation had decreased, and the extensor posturing had disappeared. Diffuse rigidity, increased deep tendon reflexes, and bilateral extensor plantar responses remained. Improvement was rapid, and by the fourth hospital day he was awake and had normal findings on neurologic examination. However, on the seventh hospital day his blood pressure declined and his jaundice increased. He became hypotensive on the ninth hospital day and died. The general autopsy disclosed severe hepatic cirrhosis. An examination of the brain revealed old infarcts in the frontal lobes and the left inferior cerebellum. There were no other lesions.

Comment: In this patient, the signs of liver disease suggested the diagnosis of hepatic coma. At first, however, anisocoria and decerebrate rigidity

hinted at a supratentorial mass lesion such as a subdural hematoma. The normal pupillary and oculocephalic reactions favored metabolic disease and the subsequent CT scan and absence of signs of rostral-caudal deterioration supported that diagnosis.

Focal weakness is surprisingly common with metabolic brain disease. Several of our patients with hypoglycemia or hepatic coma were transiently hemiplegic, and several patients with uremia or hyponatremia had focal weakness of upper motor neuron origin. Others have reported similar findings.40,41

HISTORICAL VIGNETTE

Patient 5–5

A 37-year-old man had been diabetic for 8 years. He received 35 units of protamine zinc insulin each morning in addition to 5 units of regular insulin when he believed he needed it. One week before admission he lost consciousness transiently upon arising, and when he awoke, he had a left hemiparesis, which disappeared within seconds. The evening before admission the patient had received 35 units of protamine zinc and 5 units of regular insulin. He awoke at 6 a.m. on the floor and was soiled with feces. His entire left side was numb and paralyzed. His pulse was 80 per minute, respirations 12, and blood pressure 130/80 mm Hg. The general physical examination was unremarkable. He was lethargic but oriented. His speech was slurred. There was supranuclear left facial paralysis and left flaccid hemiplegia with weakness of the tongue and the trapezius muscles. There was a left extensor plantar response but no sensory impairment. The blood sugar was 31 mg/ dL. EEG was normal with no slow-wave focus. He was given 25 g of glucose intravenously and recovered fully in 3 minutes.

Comment: This patient, who was seen prior to the availability of CT scanning, provides a closer look at the range of physical signs and EEG phenomena that may occur in hypoglycemia. Today, fingerstick glucose testing would have occurred much earlier, often before reaching the hospital, and the physician rarely gets to see such cases. In this man, the occurrence of a similar brief attack of left hemiparesis a week previously suggested right

carotid distribution infarction initially.41 However, the patient was a little drowsier than expected with an uncomplicated unilateral carotid stroke in which the damage was apparently rather limited. The fact that his attack might have begun with unconsciousness and the fecal staining made his physicians suspect a seizure. However, hypoglycemia also can cause unconsciousness as well as focal signs in conscious patients. After treatment of the low glucose, the hemiplegia cleared rapidly.

Patients with metabolic brain disease may have either focal or generalized seizures that can be indistinguishable from the seizures of structural brain disease. However, when metabolic encephalopathy causes focal seizures, the focus tends to shift from attack to attack, something that rarely happens with structural seizures. Such migratory seizures are especially common and hard to control in uremia.

Motor Abnormalities Characteristic

of Metabolic Coma

Tremor, asterixis, and multifocal myoclonus are prominent manifestations of metabolic brain disease; they are less commonly seen with focal structural lesions unless these latter have a toxic or infectious component.

The tremor of metabolic encephalopathy is coarse and irregular and has a rate of 8 to 10 per second. Usually these tremors are absent at rest and, when present, are most evident in the fingers of the outstretched hands. Severe tremors may spread to the face, tongue, and lower extremities, and frequently interfere with purposeful movements in agitated patients such as those with delirium tremens. The physiologic mechanism responsible for this type of tremor is unknown. It is not seen in patients with unilateral hemispheric or focal brainstem lesions.

First described by Adams and Foley42 in patients with hepatic coma, asterixis is now known to accompany a wide variety of metabolic brain diseases and even some structural lesions.43 Asterixis was originally described as a sudden palmar flapping movement of the outstretched hands at the wrists.44 It is most easily elicited in lethargic but awake patients by directing them to hold their arms outstretched with hands dorsiflexed at the wrist and fingers extended