Alcohol-thiamine interactions: an update on the pathogenesis of Wernicke encephalopathy.
Wernicke encephalopathy is a neurological disorder commonly observed in chronic alcohol abuse, in patients with AIDS, and in other conditions of compromised nutritional status. The underlying cause of the disorder is thiamine deficiency. The present review highlights data focusing on alcohol-thiamine interactions and their relationship to the pathogenesis of Wernicke encephalopathy. Recent findings on the effects of alcohol on thiamine absorption and storage and on thiamine phosphorylation to the enzyme co-factor form (thiamine diphosphate) are discussed with regard to the postulated "biochemical lesion" of Wernicke encephalopathy. Also discussed are new findings on the molecular genetics of the thiamine-dependent enzyme transketolase in patients 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 acidosis, glutamate excitotoxicity, increased expression of immediate-early genes, free radicals and perturbations of the blood-brain barrier are presented. Finally, the possible role of thiamine deficiency in alcoholic peripheral neuropathy is reviewed.
Todd
K G
KG
Neuroscience Research Unit, University of Montreal (CHUM, Campus St Luc), Montreal, Quebec, Canada.
Hazell
A S
AS
Butterworth
R F
RF