Wernicke-Korsakoff encephalopathy and the endorphin system.

Sir, We read with interest the recent paper of Gibb et al. (1985) in which reversible coma in Wernicke's encephalopathy was reported. Treatment with thiamine was successful in that the patient regained consciousness but unsuccessful in preventing the residual amnestic defect of Korsakoff's encephalopathy. In a similar report (Wallis et al., 1978) four comatose patients with the Wernicke syndrome also experienced improvement in their level of consciousness with thiamine administration. However, three of these patients died and one remained disabled despite thiamine administration, due to complications, some of which were related to Korsakoff's residuals. While the acute phase of Wernicke-Korsakoff syndrome has been attributed to a specific thiamine deficiency, the neurological basis of the specific regions of pathology in Wernicke's patients and the memory deficits and other residuals associated with Korsakoffis psychosis are yet to be fully explained. Thus, we speculate that another factor other than thiamine deficiency may be important in the pathophysiology of the Korsakoff syndrome. The pathological lesions in Wernicke-Korsakoff syndrome involve areas rich in endorphin-containing neurones (Cuello, 1983). Furthermore, chronic ethanol intake is known to be associated with depletion of central nervous system endorphins as evidenced by reduced concentrations of opioid-like substances in the basal ganglia (Chernick & Craig, 1982) and betaendorphin levels in cerebrospinal fluid (Borg et al., 1982). Also endogenous opioids have been implicated in memory mechanisms (Izquierdo, 1982) and clonidine (a specific alpha-2 adrenoreceptor agonist which may enhance endorphin activity) was reported to improve memory in Korsakoff psychosis patients (McEntee & Mair, 1980). It is therefore conceivable that damage to endorphin systems may be the key factor in the pathophysiology of Wernicke-Korsakoff syndrome. The extent of damage to the endorphin system may dictate the degree to which the patient may recover or remain with the sequelae of Korsakoff's encephalopathy.