Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy

This study examines the effect of chronic alcohol consumption on the human cerebellum using operational criteria for case selection [Caine D, et nl, ( 1997) J. Neurol. Neurosurg. Psychiat. 62, 51-60] and unbiased stereological techniques. We describe, for the first time, structural changes in differe nt functional zones of the cerebellum of chronic alcoholics and correlate t hese changes with specific clinical symptoms. No consistent changes in the number of neurons or the structural volume for any cerebellar region were o bserved in the chronic alcoholics without the clinical signs of Wernicke's encephalopathy. In all cerebellar measures, these chronic alcoholics did no t differ significantly from the non-alcoholic controls, suggesting that chr onic alcohol consumption per se does not necessarily damage human cerebella r tissue. However, several cerebellar changes were noted in the thiamine-de ficient alcoholics studied. Their was a significant decrease in Purkinje ce ll density (reduced on average by 43%) and molecular layer volume (reduced by 32%) in the cerebellar vermis in all thiamine-deficient chronic alcoholi cs. A decrease in cell density and atrophy of the molecular layer, where th e dendritic trees of the Purkinje cells are found, without significant cell loss suggests loss of cellular dendritic structure and volume, These thiam ine-deficient alcoholics also had a significant decrease (36% loss) in the estimated Purkinje cell number of the flocculi, disrupting vestibulocerebel lar pathways. These results indicate that cerebellar Purkinje cells are selectively vulne rable to thiamine deficiency. There is evidence that this damage contribute s significantly to the clinical signs of Wernicke's encephalopathy. There w as a 36% loss of Purkinje cells in the lateral lobe in alcoholics with ment al state signs and 42% atrophy of vermal white matter in ataxic alcoholics. The finding of a 57% loss of Purkinje cells and a 43% atrophy of the molec ular layer of the vermis in alcoholics with cerebellar dysfunction supports previous findings highlighting the importance of spinocerebellar pathways to these symptoms. (C) 1999 IBRO, Published by Elsevier Science Ltd.