MANGANESE AND CHRONIC HEPATIC-ENCEPHALOPATHY

Clinical observations and animal studies have raised the hypothesis th at increased concentrations of manganese (Mn) in whole blood might lea d to accumulation of this metal within the basal ganglia in patients w ith end-stage liver disease. We studied ten patients with liver failur e (and ten controls) by magnetic resonance imaging (MRI) and measureme nt of Mn in brain tissue of three patients who died of progressive liv er failure (and three controls) was also done. Whole blood Mn concentr ations in patients with liver cirrhosis were significantly increased ( median 34.4 mu g/L vs 10.3 mu g/L in controls; p=0.0004) and pallidal signal intensity indices correlated with blood Mn (R(s)=0.8, p=0.0058) . Brain tissue samples reveal highest Mn concentrations in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus. Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between Mn neurotoxicity and chronic hepatic encephalopathy suggest th at this metal may have a role in the pathogenesis of chronic hepatic e ncephalopathy. Further studies are warranted because the use of chelat ing agents could prove to be a new therapeutic option to prevent or re verse this neuropsychiatric syndrome.