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Manganese toxicity, dopaminergic dysfunction and hepatic encephalopathy

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Abstract

Patients with chronic liver disease manifest a high incidence (>75%) of pallidal signal hyperintensity on T1-weighted Magnetic Resonance Imaging (MRI), the intensity of which correlates with blood manganese levels and the presence of extrapyramidal symptoms. A major cause of pallidal hyperintensity on T1-weighted MRI is manganese deposition; chronic manganese intoxication in the absence of liver disease results in pallidal MR signal hyperintensity, in extrapyramidal symptoms and in selective effects on the dopaminergic neurotransmitter system in basal ganglia. Direct measurements in globus pallidus obtained at autopsy from patients with chronic liver disease who died in hepatic coma reveal 2 to 7-fold increases of pallidal manganese and a concomitant loss of dopamine D2 binding sites. Liver transplantation results in normalization of pallidal MR signals and of blood manganese levels. These findings suggest that (1) pallidal MR signal hyperintensity in patients with chronic liver disease is the result of manganese deposition and (2) alterations of dopaminergic function due to the toxic effects of manganese may contribute to the extrapyramidal symptoms in these patients.

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Authors and Affiliations

  1. Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), 1058 St-Denis, H2X 3J4, Montreal, Quebec, Canada

    Roger F. Butterworth

  2. Liver Unit, Hôpital Saint-Luc (University of Montreal), Montreal, Quebec

    Laurent Spahr & Gilles Pomier Layrargues

  3. Radiology Department, Hôpital Saint-Luc (University of Montreal), Montreal, Quebec

    Suzanne Fontaine

Authors
  1. Roger F. Butterworth
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  2. Laurent Spahr
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  3. Suzanne Fontaine
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  4. Gilles Pomier Layrargues
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Butterworth, R.F., Spahr, L., Fontaine, S. et al. Manganese toxicity, dopaminergic dysfunction and hepatic encephalopathy. Metab Brain Dis 10, 259–267 (1995). https://doi.org/10.1007/BF02109357

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