Wernicke-Korsakoff syndrome

Overview

Wernicke-Korsakoff syndrome (also called wet brain, Korsakoff psychosis, alcoholic encephalopathy, Wernicke's disease, and encephalopathy - alcoholic)[1] is a manifestation of thiamine deficiency, or beri-beri. This is usually secondary to alcohol abuse. It mainly causes vision changes, ataxia and impaired memory. [2]

Causes

Wernicke-Korsakoff syndrome results from thiamine deficiency. It is generally agreed that Wernicke's encephalopathy results from severe acute deficiency of thiamine (Vitamin B1), whilst Korsakoff's psychosis is a chronic neurologic sequela after Wernicke's encephalopathy. The metabolically active form of thiamin is thiamin diphosphate which plays a major role as a cofactor Coenzyme in glucose metabolism. The enzymes which are dependent on thiamin diphosphate are associated with the TCA Cycle and catalyse the oxidation of pyruvate,alphaketoglutarate and branched chain amino acids. Thus, anything that encourages glucose metabolism will exacerbate an existing clinical or sub-clinical thiamine deficiency. As stated above, Wernicke-Korsakoff in the United States is usually found in malnourished chronic alcoholics, though it is also found in patients who undergo prolonged intravenous (IV) therapy without (Vitamin B1) supplementation, gastric stapling or intensive care unit (ICU) stays. In some regions, physicians have observed thiamin deficiency brought about by severe malnutrition, particularly in diets consisting mainly of polished rice, which is thiamine deficient. The resulting nervous system ailment is called Beriberi. In individuals with sub-clinical thiamine deficiency, a large dose of glucose (either as sweet food etc or glucose infusion), can precipitate the onset of overt encephalopathy. [3][4] Wernicke-Korsakoff syndrome in alcoholics especially is associated with atrophy of specific regions of the brain, especially the mamillary bodies. Other regions include the anterior region of the thalamus (accounting for amnesic symptoms), the medial dorsal thalamus, the basal forebrain, and median and dorsal raphe nuclei.[5] One as-yet-unreplicated study has associated susceptibility to this syndrome with a hereditary deficiency of transketolase, an enzyme involved in thiamine metabolism.[6]

Diagnosis

Diagnosis of Wernicke-Korsakoff syndrome is by clinical impression and can sometimes be confirmed with formal Neuropsychological assessment. Wernicke's encephalopathy typically presents with ataxia and nystagmus, and Korsakoff's psychosis with anterograde and retrograde amnesia and confabulation upon relevant lines of questioning. Frequently, for unknown reasons, patients with Korsakoff's psychosis will exhibit marked degeneration of the mamillary bodies. The mechanism of this degeneration is unknown, but it supports current neurological theory that the mamillary bodies play a role in various "memory circuits" within the brain. An example of a memory circuit is the Papez circuit.

Treatment

Treatment consists of reversing the thiamine deficiency by giving supplemental thiamine, usually by starting with an initial intravenous or intramuscular dose followed by supplemental oral doses. Some people think that it is important to start the thiamine treatment before giving any glucose as the encephalopathy will be worsened by the glucose, however this is based only on case reports. (Glucose administration promotes dehydrogenation of pyruvate, a biochemical reaction which requires thiamine.) By the time amnesia and psychosis have occurred, complete recovery is unlikely