Background & Aims: Manganese (Mn) deposition could be responsible for the T1-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. Methods: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. Results: Mn content was significantly increased in frontal cortex (by 38%), occipital cortex (by 55%), pallidum (by 186%), putamen (by 66%), and caudate (by 54%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27% and 57%, respectively) and in caudate/putamen (by 57% and 67%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. Conclusions: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction.

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1 long-term parenteral nutrition, 3 and after occupational manIncreasing evidence suggests that manganese deposiganese exposure sufficient to cause Parkinson's-like extrapytion is responsible for the T 1 -weighted magnetic resoramidal symptoms. 4 MRI signal hyperintensities may disapnance imaging (MRI) signal hyperintensity consistently pear after the cessation of manganese administration during observed in pallidum of cirrhotic patients. However, the parenteral nutrition 5 or after liver transplantation. 1 More relationship between blood manganese and the etiology recently, we demonstrated that pallidal manganese concenor severity of liver disease, as well as the neurological trations were markedly elevated in cirrhotic patients who symptomatology in these patients, has not been well esdied in hepatic coma. tablished. In the present study, blood manganese conHepatic encephalopathy (HE) is a spectrum of neuropsychicentrations were measured by atomic absorption specatric disturbances occurring in patients with chronic liver trometry together with MRI and neurological evaluation disease. Variable degrees of impairment of mental function in 57 cirrhotic patients with various etiologies and seare observed, and close clinical examination may disclose exverity of liver disease. Blood manganese concentrations trapyramidal signs. Recent reports evaluating the relationwere elevated in 67% of cirrhotic patients and were sigship between pallidal hyperintensity and neurological sympnificantly higher in patients with previous portacaval toms provide conflicting results. 7-12 Because manganese anastomoses or transjugular intrahepatic portosystemic toxicity may result in both pallidal hyperintensity and in shunt (TIPS). Pallidal signal hyperintensity was ob-Parkinson's-like extrapyramidal symptoms, and because served in 88% of patients, and significant correlations similar symptoms have been described in patients with were demonstrated between blood manganese and palchronic liver disease, we evaluated and attempted to correlidal index (PI) (a measure of pallidal signal hyperintenlate, in the same cirrhotic patients, neurological status, T 1 -sity), as well as Child-Pugh score. Assessment of extrapyweighted pallidal MRI signal intensity, and blood manganese ramidal symptoms using the Columbia rating scale concentrations. revealed a significant incidence of tremor, rigidity, or akinesia in up to 89% of cirrhotic patients. However, PATIENTS AND METHODSthere was no significant correlation between blood manPatients. Fifty-seven patients with biopsy-proven cirrhosis were ganese and extrapyramidal symptoms, although severincluded in the present study. None of them had clinically overt ity of akinesia was significantly greater in Child-Pugh encephalopathy. Clinical and biochemical characteristics are shown C patients. Extrapyramidal symptoms could result from in Table 1. a toxic effect of manganese on basal ganglia dopaminerNeurological evaluation was performed by the same neurologist gic function. These findings further support a rol...