Neuropathology

Early neuropathological studies of the alcoholic brain described fairly uniform cerebral atropy, mainly over the dorsolateral frontal regions, widened sulci, a narrowed cortical ribbon, and enlargement particularly of the anterior horns of the lateral ventricles. (D Air encephalographic studies indicated that between half and three-quarters of subjects showed cortical changes or ventricular enlargement.(56) In comparison with controls, brain weights of alcoholics are reduced at autopsy. (7B) Brain volume, estimated by the volume of the pericerebral space—the cerebrospinal fluid-filled region between the brain and the skull—is also reduced. (9) This indirect measure of cerebral atrophy is, however, mostly described in alcoholics with liver disease or Wernicke's encephalopathy.

The reduction in cerebral volume seen in the alcoholic brain is due mainly to the loss of white matter in the cerebral hemispheres. (1. !!) The corpus callosum, in particular, is reduced in thickness. (12> Cortical grey matter appears also to be affected, although the evidence is more equivocal. The selective neuronal loss in the superior frontal cortex reported in one study(13) was not confirmed in another/11 However, there is evidence that individual neurones are shrunken in regions where neuronal numbers are normal, such as the superior frontal, cingulate, and motor cortices. (13,14)

Animal research suggests that alcohol has a direct neurotoxic effect on the brain. Chronic ingestion of ethanol by well-nourished rats has been shown to be toxic to cholinergic projection neurones(15,> and to reduce the complexity of dendritic arborization in hippocampal pyramidal neurones. (!6> In the former study, transplantation of cholinergic neurones into the hippocampus and neocortex corrected the cholinergic deficits and memory abnormalities. In the latter, abstinence led to an increase in dendritic arborization.

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