MANGANESE TOXICITY, DOPAMINERGIC DYSFUNCTION AND HEPATIC-ENCEPHALOPATHY

Patients with chronic liver disease manifest a high incidence (>75%) o f pallidal signal hyperintensity on T-1-weighted Magnetic Resonance Im aging (MRI), the intensity of which correlates with blood manganese le vels and the presence of extrapyramidal symptoms. A major cause of pal lidal hyperintensity on T-1-weighted MRI is manganese deposition; chro nic manganese intoxication in the absence of liver disease results in pallidal MR signal hyperintensity, in extrapyramidal symptoms and in s elective effects on the dopaminergic neurotransmitter system in basal ganglia. Direct measurements in globus pallidus obtained at autopsy fr om patients with chronic liver disease who died in hepatic coma reveal 2 to 7-fold increases of pallidal manganese and a concomitant loss of dopamine D-2 binding sites. Liver transplantation results in normaliz ation of pallidal MR signals and of blood manganese levels. These find ings suggest that (1) pallidal MR signal hyperintensity in patients wi th chronic liver disease is the result of manganese deposition and (2) alterations of dopaminergic function due to the toxic effects of mang anese may contribute to the extrapyramidal symptoms in these patients.