Metabolic Encephalopathies: Opportunities and Challenges

For the clinical neuroscientist, the metabolic en cephalopathies are a source of both optimism and frustration. This group of disorders is caused by failure of organs other than the brain that results in one of three basic mechanisms producing brain dysfunction: the presence of a toxin or accumula tion of a metabolic waste product, as in hyperam monemia or liver failure; deficiency of a necessary metabolic substrate, as in hypoglycemia and hyp oxia; or disruption of the internal milleau of the brain, as seen during water intoxication. When con sidering the mechanisms that are likely causes of the symptoms exhibited by patients, it is easy to feel optimistic, since restoration of the normal physiological and biochemical state should lead to a resolution of symptoms. Unfortunately, despite our best theories concerning the pathophysiology of this group of disorders, the results of treatment may be discouraging. The development of new tools for clinical investigation that are specifically designed to facilitate in vivo studies of cerebral me tabolism and physiology, such as positron-emission tomography (PET), should make it possible to ac celerate progress in the study and treatment of this group of disorders. Liver disease, according to recent morbidity and mortality data in the United States, is the sixth ranked cause of lost years of life in adults (CDC, 1984). Hepatic encephalopathy is very common in patients with fulminant hepatic failure and chronic cirrhosis, where neurological symptoms may lead