The Wernicke-Korsakoff syndrome

The Wernicke-Korsakoff syndrome is a complex neurologic disorder caused by nutritional thiamine deficiency producing a characteristic, bilaterally symmetrical distribution of lesions within the medial diencephalon, brain stem, and cerebellum. The neuropathology of three clinically undiagnosed cases is described to illustrate the range of clinical presentation and associated neuropathology seen in acute, acute superimposed on chronic, and subacute chronic disease. The anatomically selective pathogenesis of these lesions is based on energy failure from blocked glucose metabolism because of regionally specific depletion of thiamine-diphosphate and alpha-ketoglutarate dehydrogenase. The energy failure ultimately contributes to increased histamine release, glutamate accumulation, and neuronal damage tia glutamate-mediated calcium channel excitotoxicity. The vascular damage that dominates the pathology of acute severe thiamine depletion is reversible. The more subtle parenchymal damage, once initiated, can progress onward to cause irreversible neurologic damage. It may also result from waxing and waning subacute levels of thiamine deficiency. In acute cases, the timing of treatment is critical in determining the extent of residual damage. Magnetic resonance imaging (MRI) may now help to achieve earlier clinical diagnosis.