Marchiafava-Bignami1-3 disease is a demyelinating disorder affecting the corpus callosum and was first described in malnourished Italian men drinking cheap red wine. It has since been described in other countries and as occuring with other alcoholic beverages. Grossly, there is a discolored or partially cystic demyelinated region in the genu and body of the corpus callosum with sparing of the thin fibers along the dorsal and4 ventral surfaces of the corpus callosum. The optic chiasm and anterior commissures may also be involved. The lesion is bilateral and symmetric with sparing of the gray matter. Microscopically, there is demyelination sparing of the axon cylinders. The number of oligodendrocytes is reduced. Lipid-laden macrophages are often abundant.
Central pontine myelinolysis (CPM) is a demyelinating disorder of the central basis pontis that was first described in malnourished alcoholics by Adams.4 Patients with CPM have a sudden change in mental status, flaccid quadriparesis with hypereflexia, pseudobulbar palsy, and an extensor plantar response unless coma obscures these signs. CPM is associated with the rapid correction or overcorrection of hyponatremia5 and the symptoms appear a few days (ave.=6 days) after overcorrection with a serum sodium rise of at least 20 mmol/L. Grossly, victims have a discolored, finely granular demyelinated zone in the central basis pontis with sparing of the tegmentum, ventral pons, and corticospinal tracts (Figure 2.4.1 ).6 Extrapontine myelinolysis has become more recognized.7 The demyelinated area varies from a few millimeters to the entire basis pontis and may be triangular, diamond, or butterfly-shaped. Microscopically, there is demyelination with relative preservation of axon cylinders and neurons. Axonal spheroids are commonly observed. Acute lesions contain lipid-laden macrophages, but no
Figure 2.4.1 Discolored granular zone of myelinolysis in the central pons of this 28-year-old alcoholic who was treating aggressively for hyponatremia.
other inflammatory cells. Oligodendrocytes are reduced or absent and reactive astrocytes are present.
Cerebellar degeneration of alcoholics is clinically manifested by truncal instability, lower extremity ataxia, and wide-based gait, symptoms appearing gradually over months or years.3 The pathogenesis is still unknown and may be due to the direct toxic effect of alcohol or to thiamine deficiency, or from rapid correction or overcorrection of hyponatremia similar to central pontine myelinolysis. Grossly, the folia of the rostral vermis and anterosuperior cerebel-lar hemispheres are atrophic and shrunken with widened interfolial sulci. This is best demonstrated by a sagittal section through the vermis rather than the usual coronal sectioning. Microscopically, the folial crests are more severely affected than the depths of the interfolial sulci in contrast to anoxic-ischemic injury. There is Purkinje cell loss, patchy granular cell loss, molecular layer atrophy, and gliosis with Bregmann glial proliferation.
Acute alcohol intoxication can cause death due to central cardiopulmonary paralysis.3 While blood ethanol concentrations over 450 to 500 mg/dL are usually considered lethal, there is considerable variability due to tolerance. Children are considered more susceptible to the lethal effects than are adults. Cerebral edema may be present or the neuropathologic examination may be normal. Delirium tremens or withdrawal seizures are not associated with any specific neuropathologic abnormalities.8
Chronic alcohol use may be associated with cerebral atrophy, although this is a disputed effect of alcoholism.3 The cerebral atrophy involves the upper dorsolateral frontal lobes and may extend inferiorly to the inferior frontal gyri and posteriorly to the superior parietal lobule.1 There is mild ventricular enlargement. Microscopic changes are not specific. The cerebral atrophy may be associated with a dementia that is potentially reversible at its early stages.9
Fetal alcohol syndrome is a constellation of birth defects found in children of alcohol-abusing mothers. It is the most common cause of birth defect associated with mental retardation. Other clinical manifestations include irritability, seizures, hypotonia, and cerebellar dysfunction. The neuropathologic findings are non-specific and include microcephaly, compensatory hydrocephalus, neuroglial heterotopia of the ventricles or leptomeninges, and atrophy or hypoplasia of the cerebellum or centrum semiovale.3,10
Thiamine deficiency is responsible for the clinical manifestations (gaze paralysis, ataxia, nystagmus, and mental confusion) of Wernicke's encephalopathy and Korsakoff psychosis (retrograde amnesia, impaired short-term memory) seen in alcoholics.3 The morphologic features (seen in 1.7 to 2.7% of consecutive autopsies)11 include petechiae and pink discoloration of the mammillary bodies (Figure 2.4.2), hypothalamus, periventricular region of the thalamus, periaqueductal grey matter, and beneath the floor of the fourth ventricle.1 The lesions are bilateral and symmetric when present. These gross features are seen in only 50% of acute cases,12 therefore microscopic examination is essential. The lesions vary with the stage and severity of the deficiency. Acute lesions consist of dilated, congested capillaries with perivascular ball and ring hemorrhages and ischemic neuronal changes (Figure 2.4.3). Chronic lesions
have vascular endothelial cell swelling and proliferation and gliosis. Affected blood vessels may have irregular or bead-like swellings.
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