Color Atlas of Neurology

Neurodegenerative Diseases

Autonomic dysfunction (orthostatic hypotension, urinary incontinence, impotence, anhidrosis)

Asymmetrical parkinsonism, akinesia/rigidity, early postural/gait instability (falls)

Ataxia, dysarthria, dysphonia

Multiple system atrophy

Doll’s eyes phenomenon on vertical head movement

Vertical gaze palsy

(progressive supranuclear palsy)

Limb apraxia, dystonic arm position

Myoclonus

Corticobasal degeneration

Central Nervous System

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Neurodegenerative Diseases

Motor Neuron Diseases

These diseases involve a degeneration of the cerebral and/or spinal motor neurons (p. 44). They present with a wide variety of neurological syndromes of varying temporal course.

! Upper Motor Neuron Diseases

!Diseases Affecting Both the Upper and the Lower Motor Neuron

Hereditary. Amyotrophic lateral sclerosis (ALS) is familial in 5–10% of cases. Familial ALS with onset in childhood and adolescence (juvenile ALS) is transmitted either as an autosomal recessive trait (ALS2:2q33;ALS5:15q15.1−21.1) or as an autosomal dominant trait (9q34 linkage). Adult-onset familial ALS is transmitted as an autosomal dominant trait (ALS1:21q22.1; ALS3:18q21) associated with a mutation of the gene for superoxide dismutase 1 (SOD1). SOD1 plays a role in converting cytotoxic oxygen radicals to hydrogen peroxide. It remains unknown how the SOD1 defect causes motor neuron disease. Autosomal dominant inheritance has also been found for ALS plus frontotemporal dementia (9q21–22). ALS together with parkinsonism and dementia occurs among the Chamorro people of Guam.

Acquired. Sporadic ALS usually becomes ap-

304parent between the ages 50 and 70 (Table 47, p. 386). The presentation is typically with asym-

metric weakness of the limbs, either proximal

(difficulty raising the arms or standing up from a sitting position) or distal (frequent falls; difficulty grasping, turning a key in a lock), or else with bulbar dysfunction (dysarthria). These deficits are often accompanied by leg cramps and continuous, marked fasciculation in the proximal limb muscles. As the disease progresses, weakness, muscular atrophy, dysphagia, and dysarthria become increasingly severe. Respiratory weakness leads to respiratory insufficiency. Spasticity, hyperreflexia, pseudobulbar palsy, emotional lability, and Babinski reflex (inconsistent) are caused by dysfunction of the first motor neuron; muscular atrophy and fasciculation are caused by dysfunction of the second motor neuron; and dysarthria, dysphagia, and weakness are caused by both. About 10% of patients have paresthesiae, and some have pain in later stages of the disease. Bladder, rectal, and sexual dysfunction, impairment of sweating, and bed sores are not part of the clinical picture of ALS. The disease progresses rapidly and usually causes death in 3–5 years.

! Treatment

There is currently no effective primary treatment for motor neuron diseases. Treatment can be provided for the palliation of various disease manifestations, e. g., dysarthria (speech therapy, communication aids), dysphagia (swallowing training, percutaneous endoscopic gastrostomy, surgery), and drooling (medication to decrease salivary flow). Antispasmodic agents can be used to treat spasticity and muscle spasms, and psychiatric medications to treat emotional lability. Physical and occupational therapy are provided, including breathing exercises, contracture prophylaxis, and measures to increase mobility. Further measures include orthoses, breathing training (aspiration prophylaxis, secretolysis, ventilator for home use, tracheotomy), and psychosocial support. Riluzole (a glutamate antagonist) has been found to prolong survival in ALS.

Central Nervous System

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Central Nervous System

1 Other forms (p. 68) include Unverricht–Lundborg syndrome, myoclonus epilepsy with ragged red fibers (MERFF, p. 402), late forms of other lysosome defects (e. g., sialidosis type I, GM2-gangliosidosis). 2 Cytoplasmic inclusion bodies containing glycoprotein mucopolysaccharides in the brain, muscles, skin, and liver (also called Lafora disease). 3 Autosomal recessive trait, mutation at 13q14.3; serum ceruloplasmin, hepatic copper, free serum copper,

and urinary copper levels, rate of incorporation of 64Cu in ceruloplasmin, MRI signal changes (striatum, dentate nucleus, thalamus). 4 MRI shows bilaterally symmetric hypointensity of globus pallidus with central zone of hyperintensity (“tiger eye” sign). 5 Adrenomyeloneuropathy, p. 384. 6 Increased risk of stroke. 7 Most common form.

8 Formerly called Hallervorden-Spatz disease.

! Metabolic Encephalopathies of Adulthood

1 Tay–Sachs disease. 2 Westphal–Strümpell disease.

Central Nervous System

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Central Nervous System

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Encephalopathies

Acquired Metabolic Encephalopathies

Hypoxic–ischemic encephalopathy. An acute lack of oxygen (Pao2 !40 mmHg), severe hypotension (!70 mmHg systolic), or a combination of the two causes loss of consciousness within minutes. The most important causes of hypoxic and ischemic states are an inadequate pumping function of the heart (as in myocardial infarction, shock, and cardiac arrhythmia), suffocation, carbon monoxide poisoning, respiratory muscle paralysis (as in spinal trauma, Guil- lain–Barré syndrome, and myasthenia), and inadequate ventilation (as in opiate intoxication). Permanent damage usually does not occur if the partial pressure of oxygen and the blood pressure can be brought back to normal in 3–5 minutes. Longer periods of hypoxia and ischemia are rarely tolerated (except under conditions of hypothermia or barbiturate intoxication); brain damage usually ensues, and may be permanent. Persistent coma (p. 118) with absent brain stem reflexes (pp. 26, 118) once the circulation is restored indicates a poor prognosis; the probable outcome is then a persistent vegetative state or death (p. 120). Patients who regain consciousness may develop various postanoxic syndromes, e. g., dementia, visual agnosia, parkinsonism with personality changes, choreoathetosis, cerebellar ataxia, intention or action myoclonus (Lance–Adams syndrome), and Korsakoff syndrome. Delayed postanoxic syndrome occurs 1–4 weeks after the initial recovery from anoxia and is characterized by behavioral changes (apathy, confusion, restlessness) that may either regress or worsen, perhaps to coma. These changes may be accompanied by gait impairment and parkinsonism. Hypercapnia ( PaCO2) due to chronic hypoventilation (as in emphysema, fibrosing alveolitis, or central hypoventilation) causes headache, behavioral disturbances, impairment of consciousness (p. 116 ff), asterixis (p. 68), fasciculations, and bilateral papilledema.

Hypoglycemia. If the blood glucose concentration acutely falls below 40 mg/dl, behavioral changes occur (restlessness, hunger, sweating, anxiety, confusion). Any further decrease leads to unconsciousness (grand mal seizure, dilated pupils, pale skin, shallow breathing, bradycardia, decreased muscle tone). Glucose must be

given intravenously to prevent severe brain damage. Subacute hypoglycemia produces slowed thinking, attention deficits, and hypothermia. Chronic hypoglycemia produces behavioral changes and ataxia (p. 324); it is rarely seen (e. g., in pancreatic islet cell tumors).

Hyperglycemia (p. 324). Diabetic ketoacidosis is characterized by dehydration, headache, fatigue, abdominal pain, Kussmaul respiration (deep, rhythmic breathing at a normal or increased rate). Blood glucose " 350 mg/dl ( pH, pCO2, HCO3–). In hyperosmolar nonketotic hyperglycemia, the blood glucose concentration is "600 mg/dl and there is little or no ketoacidosis. The persons at greatest risk are elderly patients being treated with corticosteroids and/or hyperosmolar agents to reduce edema around a brain tumor.

Hepatic/portosystemic encephalopathy occurs by an unknown pathogenetic mechanism in patients with severe liver failure (hepatic encephalopathy) and/or intrahepatic or extrahepatic venous shunts (portosystemic encephalopathy). Venous shunts can develop spontaneously (e. g., hepatic cirrhosis) or be created surgically (portocaval anastomosis, transjugular intrahepatic stent). Clinical features (see Table 50, p. 387): Behavioral changes, variable neurological signs (increased or decreased reflexes, Babinski reflex, rigidity, decreased muscle tone, asterixis, dysarthrophonia, tremor, hepatic coma), and EEG changes (generalized symmetric delta/triphasic waves). The diagnosis is based on the clinical findings, the exclusion of other causes of encephalopathy (such as intoxication, sepsis, meningoencephalitis, and electrolyte disorders), and an elevated arterial serum ammonia concentration.

Repeated episodes of hepatic coma may lead to chronic encephalopathy (head tremor, asterixis, choreoathetosis, ataxia, behavioral changes); this can be prevented by timely liver transplantation.

Central Nervous System

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Central Nervous System

310

Central Nervous System

311

Encephalopathies

Wernicke–Korsakoff syndrome. Wernicke encephalopathy is characterized by gaze-evoked nystagmus or dissociated nystagmus, ophthalmoplegia (abducens palsy, conjugate gaze palsy or, rarely, miosis), postural and gait ataxia, and impairment of consciousness (p. 116; apathy, indifference, somnolence). Korsakoff syndrome is characterized by confabulatory amnesia (p. 134), disorientation, and decreased cognitive flexibility. Most patients have a combination of these two syndromes, which is then called Wer- nicke–Korsakoff syndrome. Polyneuropathy, autonomic dysfunction (orthostatic hypotension, tachycardia, exercise dyspnea), and anosmia may also be present. These syndromes are caused by a deficiency of thiamin (vitamin B1) due to alcoholism or malnutrition (malignant tumors, gastroenterologic disease, thiamin-free parenteral nutrition). This, in turn, causes dysfunction of thiamin-dependent enzymes (increase in transketolase, pyruvate decarboxylase, α-ketoglutarate dehydrogenase, and serum pyruvate and lactate; decrease in transketolase activity in erythrocytes). MRI reveals lesions in

312paraventricular areas (thalamus, hypothalamus, mamillary bodies) and periaqueductal areas

(mid brain, motor nucleus of X, vestibular nu-

clei, superior cerebellar vermis). Treatment: Immediate intravenous infusion of thiamin (50– 100 mg) in glucose solution. Note: glucose infusion without thiamin in a patient with latent or unrecognized thiamin deficiency may provoke or exacerbate Wernicke encephalopathy.

Encephalopathies Due to Substance Abuse

Alcohol. Acute alcohol intoxication (drunkenness, inebriation) may be mild (blood alcohol 0.1–1.5‰ dysarthria, incoordination, disinhibition, increased self-confidence, uncritical selfassessment), moderate (blood alcohol 1.5–2.5‰ataxia, nystagmus, explosive reactions, aggressiveness, euphoria, suggestibility), or severe (blood alcohol !2.5‰ loss of judgment, severe ataxia, impairment of consciousness, autonomic symptoms such as hypothermia, hypotension, or respiratory arrest). Concomitant intoxication with other substances (sedatives, hypnotics, illicit drugs) is not uncommon. The possibility of a traumatic brain injury (subdural or epidural hematoma, intracerebral hemorrhage) must also be considered. Pathological intoxication after the intake of relatively small quantities of alcohol is a rare disorder characterized by intense outbursts of emotion and destructive behavior, followed by deep sleep. The patient has no memory of these events.

Alcohol withdrawal syndrome. Reduction of alcohol intake or total abstinence from alcohol after chronic alcohol abuse causes acute autonomic disturbances (sweating, tachycardia, insomnia, nausea, vomiting), tremor, impairment of concentration, and behavioral changes. This initial stage of predelirium is followed by a stage of delirium (delirium tremens), in which all of the disturbances listed worsen and are accompanied by visual hallucinations. Epileptic seizures may occur. The course of delirium tremens can be complicated by systemic diseases that are themselves complications of alcoholism (hepatic and pancreatic disease, pneumonia, sepsis, electrolyte imbalances). Auditory alcoholic hallucinosis without autonomic symptoms or disorientation is an unusual form of alcohol withdrawal syndrome.