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Pathophysiology of Cerebellar Dysfunction in the Wernicke-Korsakoff Syndrome

Published online by Cambridge University Press:  18 September 2015

F. BuutterWoth Roger
F. BuutterWoth Roger*
Affiliation:
Neuroscience Research Unit, Andre-Viallet Clinical Research Centre, Hopital St-Luc (University of Montreal), Montreal
*
Neuroscience Research Unit, Andre-Viallet Clinical Research Centre, Hopital St-Luc, 1058 St-Denis, Montreal, PQ, Canada H2X 3J4
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Abstract:

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Cerebellar ataxia is a common presenting sign in the Wernicke-Korsakoff syndrome (WKS). Recovery from ataxia following thiamine treatment is rarely complete, suggesting the existence of both a reversible (“biochemical”) lesion as well as irreversible, neuropathological damage. Cerebellar pathology in WKS includes severeloss of Purkinje cells in superior cerebellar vermis as well as neuronal loss from the granular layer. In addition, damage to inferior olivary nucleus could result in loss of climbing fibre input to cerebellum in this condition. Experiments using an animal model of WKS, the pyrithiamine-treated rat, reveal selective reversible decreases of α-ketoglutarate dehydrogenase (αKGDH) in cerebellum. Decreased enzyme activities are associated with decreased cerebellar content of GABA and aspartate. Thiamine reversal of neurological symptoms results in normalization of cerebellar enzyme activities and GABA content suggesting that reduced activities of αKGDH constitute “the biochemical lesion” in these animals. Possible mechanisms implicated in neuronal cell death in cerebellum include impaired cellular energy metabolism, focal lactic acidosis and excitotoxic damage resulting from excess glutamate release mediated by Nmethyl-D-aspartate (NMDA) receptors. Similar mechanisms could be involved in the reversible and irreversible neurological symptoms of WKS in humans.

Type
Abstract
Information
Canadian Journal of Neurological Sciences , Volume 20 , Issue S3 , May 1993 , pp. S123 - S126
Copyright
Copyright © Canadian Neurological Sciences Federation 1993

References

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