Wernicke disease and Korsakoff amnesia are not separate diseases, but that the ocular and ataxic signs and the transformation of the global confusional state into an amnesic syndrome are successive stages in a single disease process. In the series of Victor et al (1989), of 186 patients who survived the acute illness, 157 (84 percent) showed this sequence of clinical events. As a corollary, a survey of alcoholic patients with Korsakoff amnesia in a psychiatric hospital disclosed that in most patients the illness had begun with the symptoms of Wernicke disease and that approximately 60 percent of them still showed some ocular or cerebellar stigmata of Wernicke disease many years after the onset. The same continuum cannot be invoked to explain alcoholic-nutritional cerebellar degeneration that arises as an independent illness rather than the persistent ataxia of Wernicke disease (see further on and Victor and Adams [1961] and monograph by Victor and Adams).
Patients who die in the acute stages of Wernicke disease show symmetrical lesions in the paraventricular regions of the thalamus and hypothalamus, mammillary bodies, periaqueductal region of the midbrain, floor of the fourth ventricle (particularly in the regions of the dorsal motor nuclei of the vagus and vestibular nuclei), and superior cerebellar vermis. Lesions are consistently found in the mammillary bodies and less consistently in other areas. The microscopic changes are characterized by varying degrees of necrosis of parenchymal structures. Within the area of necrosis, nerve cells are lost, but usually some remain; some of these are damaged but others are intact. Myelinated fibers are more affected than neurons. These changes are accompanied by a prominence of the blood vessels, although in some cases there appears to be a primary endothelial proliferation and evidence of recent or old petechial hemorrhage. In the areas of parenchymal damage there is astrocytic and microglial proliferation. Discrete hemorrhages were found in only 20 percent of Victor’s (1989) cases, and many appeared to be agonal rather than acquired earlier during the acute illness. The cerebellar changes consist of degeneration of all layers of the cortex, particularly of the Purkinje cells; usually this lesion is confined to the superior parts of the vermis, but in advanced cases the most anterior parts of the anterior lobes are involved as well. Of interest is the fact that the lesions of Leigh encephalomyelopathy, a mitochondrial disorder implicating pyruvate metabolism, bear a resemblance to those of Wernicke disease but have a slightly different distribution and histologic characteristics.
The ocular muscle and gaze palsies are attributable to lesions of the sixthand third-nerve nuclei and adjacent tegmentum, and the nystagmus to lesions in the regions of the vestibular nuclei. The latter are also responsible for the loss of caloric responses and probably for the gross disturbance of equilibrium that characterizes the initial stage of the disease. The lack of significant destruction of nerve cells in these lesions accounts for the rapid improvement and the high degree of recovery of oculomotor and vestibular functions. The persistent ataxia of stance and gait is caused by the lesion of the superior vermis of the cerebellum; ataxia of individual movements of the legs is attributable to an extension of the lesion into the anterior parts of the anterior lobes. Hypothermia, which occurs sometimes as an early feature of Wernicke disease, is probably attributable to lesions in the posterior and posterolateral nuclei of the hypothalamus (experimentally placed lesions in these parts have been shown to cause hypothermia or poikilothermia in monkeys).