Related Experiment Videos
Manganese toxicity, dopaminergic dysfunction and hepatic encephalopathy
R F Butterworth1, L Spahr, S Fontaine
1Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
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.
Insights
Chronic liver disease causes manganese buildup in the brain, leading to abnormal MRI signals and movement disorders. Liver transplants can reverse these manganese-related brain changes.
Area of Science:
- Neurology
- Hepatology
- Radiology
Background:
- Chronic liver disease frequently causes pallidal signal hyperintensity on T1-weighted MRI (>75% incidence).
- This hyperintensity correlates with blood manganese levels and extrapyramidal symptoms.
- Manganese deposition is a primary cause of pallidal hyperintensity in T1-weighted MRI.
Purpose of the Study:
- To investigate the role of manganese deposition in pallidal hyperintensity in chronic liver disease patients.
- To explore the relationship between manganese, dopaminergic function, and extrapyramidal symptoms.
- To assess the effects of liver transplantation on these parameters.
Main Methods:
- Analysis of T1-weighted Magnetic Resonance Imaging (MRI) findings.
- Measurement of blood manganese levels.
- Autopsy studies measuring pallidal manganese and dopamine D2 binding sites.
- Evaluation of patients before and after liver transplantation.
Main Results:
- Patients with chronic liver disease show significant pallidal manganese deposition (2-7 fold increase) and reduced dopamine D2 binding sites.
- Pallidal MR signal hyperintensity correlates with blood manganese levels.
- Liver transplantation led to normalization of pallidal MR signals and blood manganese levels.
Conclusions:
- Pallidal MR signal hyperintensity in chronic liver disease is attributed to manganese deposition.
- Manganese-induced alterations in dopaminergic function may contribute to extrapyramidal symptoms in these patients.
- Liver transplantation effectively reverses manganese-related neurological changes.