Blood Manganese Correlates with Brain Magnetic Resonance Imaging Changes in Patients with Liver Disease

Abstract

Background: Chronic liver failure is associated with high signal abnormalities in the basal ganglia on Tl-weighted magnetic resonance imaging of the brain. These abnormalities are strikingly similar to those seen following manganese intoxication. As dietary manganese is normally cleared by the liver, we hypothesize that hepatic dysfunction could lead to manganese overload and account for the MR1 abnormalities seen in patients with chronic liver disease. Methods: We measured blood manganese concentrations in eleven patients with biopsy-proven hepatic cirrhosis and eleven healthy age and sex-matched controls. We also performed semi-quantitative measures of Tl signal abnormalities on MRI in the patients with chronic liver disease. Results: Patients with cirrhosis had significantly higher blood manganese concentrations (20.6 ± 10.2 mcg/L) than controls (7.2 ± 2.7, p = .0013). In addition, semi-quantitative scores of TI-weighted signal hyperintensity on MRI correlated with blood manganese concentration in patients with cirrhosis (r = .65, p = .029). Conclusions: These findings demonstrate that chronic liver disease is associated with manganese overload and suggest that manganese is responsible for the Tlweighted signal hyperintensity seen on MRI of patients with liver disease. As manganese intoxication is known to cause parkinsonism and an encephalopathy similar to those which occur with chronic liver disease, it is possible that manganese toxicity contributes to the development of these symptoms in liver damaged patients and that therapies which prevent or reduce manganese overload may have clinical benefit. RESUME: Le taux de manganese sanguin est en correlation avec les changements observes a I'imagerie par resonance magnetique chez les patients avec atteinte hepatique. Introduction: L'insuffisance hdpatique chronique est associde a des anomalies du signal dans le noyau lenticulaire, le noyau caudd, I'avant-mur et le noyau amygdalien a I'imagerie par resonance magndtique avec ponddration Tl du cerveau. Ces anomalies sont dtonnammant semblables a celles observdes dans l'intoxication au manganese. Comme le manganese de la diete est normalement dlimind par le foie, nous avons dmis l'hypothese qu'une dysfonction hdpatique pourrait engendrer une surcharge en manganese et etre responsable des anomalies observdes a I'IRM chez les patients atteints de maladie hdpatique chronique. Methodes: Nous avons mesurd la concentration de manganese sanguin chez onze patients avec cirrhose hdpatique prouvde par biopsie et onze controles sains, apparids pour I'Sge et le sexe. Nous avons dgalement rdalisd des mesures semi-quantitatives des anomalies de signal Tl a I'IRM chez les patients atteints de maladie hdpatique chronique. Rdsultats: Les patients atteints de cirrhose avaient des concentrations sanguines de manganese significativement plus dlevdes (20.6 ± 10.2 mcg/L) que les controles (7.2 ± 2.7, p=.0013). De plus, les scores semi-quantitatifs de l'hyperintensitd du signal ponddrd Tl a I'IRM etaient corrdlds avec les conce...

Neuroimaging in Manganese-Induced Parkinsonism

“…Nelson et al (1993) were the first to report increased signal intensities in a patient with occupational Mn neurointoxication. A similar MRI pattern has also been observed in patients receiving total parenteral nutrition (TPN) by direct intravenous administration (Ejima et al, 1992;Mirowitz et al, 1991) and in patients with portal systemic shunts such as individuals with liver cirrhosis, leading to an inability to clear Mn via biliary excretion (Butterworth et al, 1995;Hauser et al, 1994Hauser et al, , 1996Krieger et al, 1995;Park et al, 2003;Spahr et al, 1996). A high pallidal signal is very frequently observed in patients with established liver cirrhosis, but who lack exposure to Mn .…”

“…This is very important when the similarities and differences between idiopathic Parkinson's disease (IPD) and manganism are considered. Many reports have shown that blood Mn concentration is highly correlated with PI in liver cirrhotics (Hauser et al, 1996;Krieger et al, 1995;Spahr et al, 1996). In Mn-exposed workers, blood Mn concentration was also found to correlate with PI (Chang et al, 2009a;Dietz et al, 1999;Jiang et al, 2007;Kim et al, 1999a).…”

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“…Only 1-3% of this normally reaches the systemic circulation because manganese is rapidly cleared by the liver and excreted into the bile (Papavasiliou et al, 1966). Increases in blood manganese levels have been reported previously in cirrhotic patients (Spahr et al, 1996;Versieck et al, 1974;Hauser et al, 1994;Hauser et al, 1996) and it was shown that blood manganese correlated with brain MRI changes in patients with chronic liver disease (Figure 3). …”

Early Primary Biliary Cholangitis is Characterised by Brain Abnormalities on Cerebral Magnetic Resonance Imaging

“…Several investigators report correlations between measures of MRI T 1 hyperintensity in the basal ganglia and blood manganese levels in patients with cirrhosis of any cause, but not always associated with hepatic encephalopathy. 26,33,34 In the context of established cirrhosis of any cause, reductions in have been attributed to low-grade cerebral oedema, which is thought to occur in hepatic encephalopathy. 35 While associations between reduced magnetisation transfer ratios and the Child-Pugh score have been found by some, 36 this is not a consistent finding in the literature.…”