Marchiafava-Bignami disease is more readily defined by its pathologic than its clinical features. The principal alteration, as mentioned, is usually in the middle portion of the corpus callosum, which on gross examination appears rarefied and sunken and reddish or gray-yellow in color, depending on its age. In the anterior portion of the corpus callosum, the lesion tends to be more severe in the midline than in its lateral parts; in the splenium, however, the opposite may pertain. The most chronic lesion takes the form of a centrally placed gray cleft or cavity, with collapse of the surrounding tissue and reduction in thickness of the corpus callosum. Microscopically, corresponding to the gross lesions, one observes clearly demarcated zones of demyelination, with variable involvement of the axis cylinders and an abundance of fatty macrophages with gliosis at the margins. Inflammatory changes are absent.
Infrequently, lesions of a similar nature are found in the central portions of the anterior and posterior commissures and the brachia pontis. These zones of myelin destruction are surrounded by a rim of intact white matter. The predilection of this disease process for commissural fiber systems has been stressed, but it is certainly not confined to these fibers. Symmetrically placed lesions have been observed in the columns of Goll, superior cerebellar peduncles, and cerebral hemispheres, involving the centrum semiovale and extending, in some cases, into the adjacent convolutional white matter. As a rule, the internal capsule and corona radiata, subcortical arcuate fibers, and cerebellum are spared. In several cases, the lesions of deficiency amblyopia (see earlier) have been added; in others, the lesions of Wernicke disease.
Many of the reported cases, as first pointed out by Jequier and Wildi, have involved cortical lesions of a special type: The neurons in the third layer of the frontal and temporal lobe cortices had disappeared and were replaced by a fibrous gliosis. Morel, who first described this cortical laminar sclerosis, did not observe its association with Marchiafava-Bignami disease. However, when Jequier and Adams reviewed his original cases (unpublished), all had Marchiafava-Bignami disease. In a subsequent report by Delay and colleagues comprising 14 cases of cortical laminar sclerosis, the cortical lesion was also consistently associated with a corpus callosum lesion. We believe the cortical lesions are best explained as secondary to the callosal degeneration.
The disease affects persons in middle and late adult life. With few exceptions, the patients have been males and severe chronic alcoholics. The clinical features of the illness are otherwise quite variable, and a clear-cut syndrome has not emerged. Many patients have presented in a state of terminal stupor or coma, precluding a detailed neurologic assessment. In others, the clinical picture was dominated by the manifestations of chronic inebriation and alcohol withdrawal, namely tremor, seizures, hallucinosis, and delirium tremens. In some of these patients, following the subsidence of the withdrawal symptoms, no signs of neurologic disease could be elicited, even in the end stage of the disease, which lasted for several days to weeks. In yet another group, a progressive dementia has been described, evolving slowly over a year before death. Emotional disorders, dysarthria, slowing and unsteadiness of movement, transient sphincteric incontinence, hemiparesis, and apractic or aphasic disorders have been reported. The last stage of the disease is characterized by physical decline, seizures, stupor, and coma. An impressive feature of these varied neurologic deficits in some patients has been their tendency toward remission when nutrition was restored.