Manganese deposition in basal ganglia structures results from both postal-systemic shunting and liver dysfunction

Background & Aims: Manganese(Mn) deposition could be responsible for the T- 1-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specifici ty of the Mn increases as well as their relationship to portal-systemic shu nting or hepatobiliary dysfunction. Methods: Mn concentrations were measure d in (1) brain samples from basal ganglia structures (pallidum, putamen, ca udate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma an d from 12 matched controls; and from (2) brain samples (caudate/putamen, gl obus pallidus, frontal cortex) from groups (n = 8) of rats either with end- to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant h epatic failure as well as from sham-operated and normal rats. Results: Mn c ontent was significantly increased in frontal cortex (by 38%), occipital co rtex (by 55%), pallidum (by 186%), putamen (by 66%), and caudate (by 54%) o f cirrhotic patients compared with controls. Brain Mn content did not corre late with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was i ncreased in pallidum (by 27% and 57%, respectively) and in caudate/putamen (by 57%. and 67%, respectively) compared with control groups. Mn concentrat ion in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were obs erved in rats with acute liver failure. Conclusions: These findings suggest that brain Mn deposition results both from portal-systemic shunting and fr om liver dysfunction.