Accumulation of manganese and copper in pallidum of cirrhotic patients: role in the pathogenesis of hepatic encephalopathy?

Abstract

Concentrations of zinc, copper and manganese were measured by atomic absorption spectrometry in samples of globus pallidus obtained at autopsy from 9 patients with chronic liver disease and an equal number of age-matched controls. Manganese concentrations were significantly increased several fold (p < 0.01) in globus pallidus of liver disease patients accompanied by smaller but significant 2-fold increases of copper. Zinc concentrations, on the other hand, were within normal limits. Increased pallidal manganese offers a cogent explanation for the observed T1-weighted MRI signal hyperintensity in pallidum of cirrhotic patients. Increased copper content in brain suggests the existence of common pathophysiologic mechanisms in inherited (Wilson Disease) and acquired hepatocerebral disorders.

Dopamine Transporter SPECT of a Liver Cirrhotic with Atypical Parkinsonism

“…Our case without occupational history of exposure to Mn showed high level of blood Mn level and T1 hyperintensities in the basal ganglia on MRI. Previous studies 21,22) demonstrated increased Mn concentrations in pallidum of cirrhotic patients, and suggested that increased Mn concentrations are responsible for T1 hyperintensities in the basal ganglia on MRI. Increased blood Mn level and T1 hyperintensities in the globus pallidus are the principal findings shown in manganism in industrial settings.…”

Nutrition in the Management of Cirrhosis and its Neurological Complications

“…[64][65][66] Manganese deposition in basal ganglia structures of the brain has been proposed as the cause of T1-weighted magnetic resonance signal hyperintensities 65 and cirrhosisrelated Parkinsonism. 67 Recent reports describe dysfunction of the nigrostriatal dopaminergic neuronal pathway related to manganese toxicity in patients with end-stage liver disease.…”

Acute-on-Chronic Liver Failure: Pathophysiological Basis of Therapeutic Options

“…Increased manganese concentrations have been found in the basal ganglia of patients with HE and good correlation occurs between the MRI abnormalities and the blood manganese levels [65].…”