Pathophysiologic mechanisms responsible for the reversible (thiamine‐responsive) and irreversible (thiamine non‐responsive) neurological symptoms of Wernicke's encephalopathy

Abstract

Chronic alcoholism results in thiamine deficiency as a result of poor nutrition and impaired gastrointestinal absorption of the vitamin. Pyrithiamine-induced thiamine deficiency in the rat reproduces a neurological syndrome and ultimately neuropathological damage of a nature and distribution that is similar to that encountered in Wernicke's encephalopathy in humans. Pyrithiamine-induced thiamine deficiency results in selective reversible decreases in activity of the thiamine-dependent enzyme alpha-ketoglutarate dehydrogenase and concomitant reversible changes in brain amino acids. It is proposed that these changes constitute "the biochemical lesion" in thiamine deficiency encephalopathy. If sufficiently severe and prolonged, decreased activities of alpha-ketoglutarate dehydrogenase may result in compromised brain energy metabolism and in lactate accumulation in brain, both of which could be responsible for neuronal cell death in this condition. In addition, it has been suggested that cell death results from NMDA-receptor mediated excitotoxic damage. Similar pathophysiologic mechanisms could be responsible for brain cell death in Wernicke's encephalopathy in humans.