348. A 42-year-old man has had 6-to-15 drinks per day for the past 15 years. He is healthy overall, but has difficulty with tandem gait. Which of the following is the most common site of central nervous system (CNS) atrophy associated with chronic alcoholism?
a. The superior vermis
b. Wernicke area
c. The supraorbital gyrus
d. The angular gyrus
e. The flocculus
349. An 83-year-old man gives a history of being poisoned by “jake” when drinking illicit alcohol as a young man. After doing some research you learn that “jake” is actually triorthocresyl phosphate. Triorthocresyl phosphate is an organophosphate that may cause lethal neurological complications by which of the following means?
a. Eliciting massive intracerebral edema
b. Causing a severe motor polyneuropathy
c. Producing widespread CNS demyelination
d. Allowing CNS infections secondary to generalized immunosuppression
e. Inducing status epilepticus
350. A 1-year-old child is brought to the emergency room with an acute encephalopathy. It is determined that the etiology is lead intoxication. With severe lead poisoning, very young children may die of brain herniation secondary to which of the following?
a. Subdural hematomas
b. Epidural hematomas
c. Intracerebral hemorrhage
d. Obstructive hydrocephalus
e. Massive brain edema
351. A 30-year-old man takes a can of beer out of his refrigerator at the end of the day and rapidly swallows a mouthful of its contents before he realizes it is not beer. Within a few minutes he develops severe abdominal cramps, blurred vision, twitching, and loss of consciousness. His wife notifies emergency medical personnel that she had placed some roach spray in the beer can for storage and had left it in the refrigerator to deal with roaches that were nesting there and that she forgot to advise her husband of this. Emergency personnel check the insecticide brand and determine that it is an organophosphate. To counteract the cholinesterase-inhibiting activity of the organophosphate poison, the man should receive which of the following?
a. Methacholine
b. Pyridostigmine
c. Physostigmine
d. Edrophonium
e. Atropine
Questions 352 to 357
Choose the toxin that is most likely to produce each clinical scenario. Each lettered option may be used once, more than once, or not at all.
a. Lead
b. Arsenic
c. Manganese
d. Mercury
e. Carbon monoxide
f. Ergot
g. Nitrous oxide
352. A man working in a poorly regulated felt-processing plant develops tremors and memory disturbances over the course of months. He seeks medical help when tremors of his tongue and lips became embarrassing and he is injured during a fall. His family notes progressive irritability and depression. On neurological examination, he has prominent gait ataxia, limb and facial tremors, and decreased pain and temperature sense in his feet.
353. While vacationing in Latin America, a student buys a brightly painted glazed ceramic pitcher. He drinks orange juice from the pitcher every night while studying. Within 4 months of starting this practice, he develops weakness in both wrists. He consults a physician, who finds weakness on dorsiflexion of both hands, unassociated with any sensory deficits. An electromyography (EMG) reveals evidence of a peripheral motor neuropathy.
354. A 45-year-old woman reports to the police her discovery that her husband has added a suspicious material to her food. She has experienced matrimonial problems for several years and has developed progressive fatigue with frequent headache over the prior 3 months. She consulted a physician when she developed recurrent bouts of severe stomach pain and was told by neighbors that she had been talking to herself and attacking invisible assailants. The physician noted that she had an unexplained anemia and white lines running transversely across her fingernails. She also has had problems with her memory, excessive drowsiness, and a sensorimotor neuropathy with absent tendon reflexes. The physician sent a sample of her hair for analysis and found a neurotoxin present.
355. An Eastern European immigrant who recently arrived in the United States is brought to the emergency room after a seizure. He first developed seizures at the age of 30 and never received treatment. Neurological examination reveals fasciculations and occasional myoclonus. He is ataxic and has absent deep tendon reflexes. A sensory neuropathy is evident in his legs. Ulcers are evident on his fingers and toes. He acknowledges that his diet was very limited before he immigrated to the United States and states that most of his calories were derived from rye grains.
356. A 38-year-old miner develops a shuffling gait, tremor, and drooling. His speech is difficult to understand and trails off in volume until it is inaudible. He consults a physician because of easy fatigability and frequent falls. Cogwheel rigidity is evident in his arms and legs. His tremor is most evident when his limbs are at rest.
357. A 35-year-old woman is rescued from a burning building. She is comatose on arrival in the ER. Her skin is cyanotic. Computed tomography (CT) scan of her head shows mild cerebral edema. After intensive care in a burn unit, she recovers markedly, but 2 weeks later, she begins to develop dystonic posturing and bradykinesia. A CT scan now shows hypodensities in the globus pallidum bilaterally.
Questions 358 to 362
Choose the toxic substance most likely to produce each clinical scenario. Each lettered option may be used once, more than once, or not at all.
a. Ciguatoxin
b. Botulinum toxin
c. Saxitoxin
d. Tick paralysis
e. Ionizing radiation
f. Phencyclidine hydrochloride (PCP)
g. Cocaine
h. Lathyrus sativus
i. Ammonia
358. A 45-year-old Portuguese immigrant develops abdominal pain in the early evening after eating grouper for lunch. He later develops fatigue, headache, and paresthesias. He reports on examination that a cold tuning fork feels excessively hot to the touch.
359. A 30-year-old refugee from sub-Saharan Africa is malnourished. She has a subacute spastic paraparesis and gait instability. Cognition, sensory, and cerebellar functions are intact.
360. A 5-year-old girl with long hair is hospitalized during August with a rapidly ascending flaccid quadriparesis over 2 days. She had been camping in the woods with her family during the preceding week. She develops neck, eye, and bulbar paralysis over the 8 hours after admission, ultimately requiring mechanical ventilation. Spinal fluid protein and cell levels are entirely normal.
361. A 34-year-old schizophrenic man with a history of Hodgkin disease in remission since treatment 10 years ago presents with a right middle cerebral artery territory stroke. He is found to have bilateral carotid bruits. There is no history of hypertension, diabetes, or hypercholesterolemia. He smokes cigarettes.
362. A 27-year-old man with idiopathic cardiomyopathy and right heart failure is admitted to the intensive care unit. Over several days his mental status worsens. He is disoriented and inattentive, but able to follow commands. He has prominent asterixis bilaterally. He improves 24 hours later after lactulose is administered.
348. The answer is a. (Ropper, p 1124.) The superior vermis of the cerebellum loses Purkinje cells and exhibits atrophy of the molecular layer in alcoholic persons after years or decades of ethanol use. Alcoholic patients may have gait instability and limb ataxia associated with this injury, but the clinical signs are usually fairly mild considering the histologic damage done by ethanol. White matter in the cerebellum is relatively unaffected.
349. The answer is b. (Ropper, p 1275.) Triorthocresyl phosphate damages both upper and lower motor neurons. This damage is usually severe and likely to be permanent. Death may occur within a few days of severe exposure. This material is a common constituent of rat poisons, roach powders, and other insecticides. Oral ingestion is usually required for substantial toxicity. The acute symptoms of poisoning reflect the anticholinesterase activity of the poison. This produces headaches, vomiting, abdominal cramps, excessive sweating, wheezing, and twitching.
350. The answer is e. (Ropper, pp 1165-1167.) Lead poisoning may cause ataxia and tremor in children exposed to relatively low levels. Chronic exposure routinely impairs psychomotor development and may lead to substantial retardation in very young children. Brain edema develops with toxic lead exposure in infancy and may be lethal even with efforts to relieve the intracranial pressure. Children are exposed to lead in many forms in the environment, including lead-based paint chips from old construction and lead-tainted soil in areas with heavy vehicular traffic.
351. The answer is e. (Ropper, p 1169.) Methacholine is a cholinergic agent and would be expected to worsen the symptoms exhibited by this man. Pyridostigmine, physostigmine, and edrophonium are all cholinest-erase inhibitors used in the evaluation or treatment of myasthenia gravis, and they too would only hasten this man’s deterioration. Atropine is usually given in combination with pralidoxime. This man is at most immediate risk of severe bronchospasm and diaphragmatic paralysis with subsequent respiratory arrest. Even if the patient does survive the acute poisoning, he is at risk for a delayed deterioration of the motor system, which may itself prove fatal and which does not respond to atropine treatment.
352. The answer is d. (Ropper, pp 1168-1169.) The “Mad Hatter” of Alice in Wonderland was a familiar sight in the nineteenth century. Persons who cured felt (used in the manufacture of hats) with nitrate of mercury often developed pronounced personality changes, tremor, and ataxia. This type of poisoning is now more typically seen in paper, pulp, and electrochemical plants that use phenyl mercury as part of the manufacturing process. Pathologic changes in the CNS are usually prominent in the cerebellum and include extensive damage to the granular cell layer of the cerebellum. The calcarine cortex of the occipital lobe is also especially vulnerable, and damage to this tissue correlates with constriction of the visual fields.
353. The answer is a. (Ropper, pp 1165-1167.) Decorative paint and glazes manufactured and sold outside the United States may have very high lead levels. Even mildly acidic solutions, such as orange juice, may leach enough lead out of the paint to produce symptoms in persons exposed over a protracted period to fluids contaminated with the lead. Bilateral neuropathies may develop in adults exposed to lead, and the radial nerves are the most common sites of damage. This neuropathy at its most severe form will produce wrist and finger drops as well as occasionally very mild sensory abnormalities in the distribution of the radial nerves. Signs associated with the lead neuropathy may include abdominal pain, constipation, anemia, basophilic stippling of erythrocyte precursors, and a linear discoloration along the gingival margin (lead lines). Penicillamine is used as a chelating agent to reduce the body load of lead.
354. The answer is b. (Ropper, p 1167.) Acute poisoning with arsenic may cause tonic-clonic seizures or a less dramatic encephalopathy. Hemolysis may be substantial, and mucosal irritation may be evident. Death may develop with circulatory collapse if the dose of arsenic is substantial enough. The polyneuropathy that develops with chronic poisoning is resistant to treatment with chelating agents such as BAL. If the patient survives the poisoning, peripheral nerve damage resolves over the course of months or years.
355. The answer is f. (Ropper, p 1163.) This man’s history suggests a nutritional disorder rather than poisoning, but his clinical picture is consistent with chronic ergotism. Ergot is a potent vasoconstricting agent derived from the rye fungus, Claviceps purpurea. Currently, the contamination of bread with this material is unlikely in developed nations, but it is still a problem in areas with antiquated agricultural techniques. Chronic ergot poisoning is associated with histologic changes in the CNS, which include degeneration of the posterior columns and dorsal roots. A peripheral neuropathy is also evident, but persons at risk for this disorder are also at risk for other nutritional disturbances that may produce neuropathy.
356. The answer is c. (Ropper, pp 1167-1168.) Manganese inhalation by miners produces a clinical picture similar to that seen with hepatolenticular degeneration (Wilson disease). Parkinsonism is the most prominent feature, but axial rigidity and dystonia may also develop. Neuronal loss is evident in several areas of the brain, including the globus pallidus, putamen, caudate, hypothalamus, and cerebellum. Treatment with L-dopa is usually less effective with this heavy metal injury than it is with Parkinson disease. Agents more likely to produce parkinsonism in the general population include phenothiazines, butyrophenones, and metoclopramide. Metoclopramide is used increasingly after gastrointestinal surgery to manage nausea and other signs of gastrointestinal irritability. Although most physicians do ask about exposure to reserpine-like medications or phenothiazines, other drugs that may cause parkinsonism in susceptible persons are sometimes overlooked.
357. The answer is e. (Ropper, pp 1086-1087.) Carbon monoxide (CO) poisoning can be seen in victims of fires, in those who attempt suicide by carbon monoxide inhalation, or in those who are otherwise exposed to the gas in an unventilated setting. Because of its greater affinity for hemoglobin than oxygen, CO reduces oxygen in the blood and leads to prolonged hypoxia and acidosis. Symptoms may range from confusion and headache at carboxyhemoglobin levels of 20% to coma, posturing, and seizures at levels of 50% to 60%. Characteristic of CO poisoning is delayed neurological deterioration occurring 1-to-3 weeks after the initial event. Typically, this takes the form of an extrapyramidal disorder with parkinsonian gait and bradykinesia. Imaging may show the classic hypodensities in the globus pallidum bilaterally.
358. The answer is a. (Ropper, p 1164.) Ciguatera food poisoning occurs in the tropics but may affect parts of the southern coastal United States, including Florida and Hawaii. Many different toxins are produced by dinoflagellates, which are in turn consumed by reef fish. Ciguatoxin is the best known, and it acts on voltage-gated sodium channels, leading to increased permeability to sodium and increased excitability. Symptoms include abdominal discomfort, nausea, vomiting, and diarrhea, followed by neurological symptoms such as paresthesias, headache, fatigue, ataxia, and myalgias. About 80% of patients complain of a peculiar sensory phenomenon of temperature reversal, specifically characterized by a tendency for cold objects to feel uncomfortably hot. Occasionally, cardiovascular symptoms, including hypotension or shock, may occur due to the effects of the toxin on cardiac muscle cells. Intravenous mannitol appears to have some treatment benefit.
359. The answer is h. (Ropper, pp 163-1164.) Lathyrism is a condition characterized by slow or subacute onset of spastic paraparesis in the setting of excessive dietary reliance on the chickling pea (L sativus) or other members of the Lathyrus species. The syndrome typically occurs in epidemics in the setting of famine or war, in which people are forced to rely excessively on this legume. The toxin is thought to be β-N-oxalylamino-L-alanine, an excitatory neurotransmitter that can induce the disease in primate models. Damage in the CNS is primarily in spinal cord tracts, especially the corticospinal and spinocerebellar tracts. Demyelination is evident in some affected persons in the lateral and posterior columns of the spinal cord.
360. The answer is d. (Ropper, pp 1164-1165.) This girl has a clinical syndrome not unlike Guillain-Barré syndrome (GBS). The rapidity of progression, however, and the absence of an elevated spinal fluid protein level, make GBS less likely and tick paralysis more likely. Tick paralysis commonly affects young children, particularly those with long hair that may obscure the tick’s location. A careful search for the organism—either Ixodes holocyclus (Australia) or a Dermacentor tick (North America)—is required in cases of rapidly ascending paralysis of unclear etiology. Removal of the tick will produce dramatic improvement within hours. The responsible toxin of the Australian tick, called holocyclotoxin, interferes with the presynaptic release at the neuromuscular junction.
361. The answer is e. (Aminoff, p 541.) Ionizing radiation may cause accelerated atherosclerosis. Patients with Hodgkin disease undergoing mantle irradiation may present years later with carotid stenosis due to atherosclerosis. Surgical treatment is made more difficult by the radiation, which can cause scarring of the tissues surrounding the vessels, rendering dissection of the vessel more difficult.
362. The answer is i. (Aminoff, pp 265-276.) In its early stages, hepatic encephalopathy is characterized by a decrease in the level of alertness, irritability or depression, tremor, and asterixis. As it progresses, lethargy, paranoia, bizarre behavior, dysarthria, nystagmus, and pupillary dilatation may occur. There is good evidence that ammonia is an important factor in the development of encephalopathy, though other mechanisms, including disordered amino acids and neurotransmitters—particularly γ-aminobutyric acid and benzodiazepine metabolites—and short-chain fatty acids may play a role as well. Lactulose is the most effective agent in the treatment of hepatic encephalopathy. It appears to work by allowing bacteria in the gastrointestinal tract to assimilate ammonia. Hepatologists have recently updated previous recommendations regarding dietary restrictions on protein in patients with hepatic encephalopathy because it has been recognized that protein consumption is necessary to allow for recovery of liver function.