Alcohol-thiamine interactions: an update on the pathogenesis of Wernicke encephalopathy

Wernicke encephalopathy is a neurological disorder commonly observed in chr onic alcohol abuse, in patients with AIDS, and in other conditions of compr ised nutritional status. The underlying cause of the disorder is thiamine d eficiency. The present review highlights data focusing on alcohol-thiamine interactions and their relationship to the pathogenesis of Wernicke encepha lopathy. Recent findings on the effects of alcohol on thiamine absorption a nd storage and on thiamine phosphorylation to the enzyme co-factor form (th iamine diphosphate) are discussed with regard to the postulated "biochemica l lesion" of Wernicke encephalopathy. Also discussed are new findings on th e molecular genetics of the thaimine-dependent enzyme transketolase in pati ents with Wernicke encephalopathy. A discussion of the hypotheses regarding the mechanisms underlying the phenomenon of selective neuronal cell death observed in this disorder including cerebral energy deficit, focal lactic a cidosis, glutamate excitotoxicity, increased expression of immediate-early genes, free radicals and perturbations of the blood-brain barrier are prese nted. Finally, the possible role of thiamine deficiency In alcoholic periph eral neuropathy is reviewed.