PATHOPHYSIOLOGY OF ALCOHOLIC BRAIN-DAMAGE - SYNERGISTIC EFFECTS OF ETHANOL, THIAMINE-DEFICIENCY AND ALCOHOLIC LIVER-DISEASE

Chronic alcoholism results in brain damage and dysfunction leading to a constellation of neuropsychiatric symptoms including cognitive dysfu nction, the Wernicke-Korsakoff Syndrome, alcoholic cerebellar degenera tion and alcoholic dementia. That these clinically-defined entities re sult from independent pathophysiologic mechanims is unlikely. Alcohol and its metabolite acetaldehyde are directly neurotoxic. Alcoholics ar e thiamine deficient as a result of poor diet, gatrointestinal disorde rs and liver disease. In addition, both alcohol and acetaldehyde have direct toxic effects on thiamine-related enzymes in liver and brain. A lcoholics frequently develope severe liver disease and liver disease p er se results in altered thiamine homeostasis, in cognitive dysfunctio n and in neuropathologic damage to astrocytes. The latter may result i n the loss of neuron-astrocytic trafficking of neuroactive amino acids and thiamine esters, essential to CNS function. The present review ar ticle proposes mechanisms whereby the effects of alcohol, thiamine def iciency and liver disease combine synergistically to contribute to the phenomena of cognitive dysfunction and ''alcoholic brain damage''.