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Reuters Health Information (2004-03-24): Brain manganese deposits may contribute to fatigue in primary biliary cirrhosis


Brain manganese deposits may contribute to fatigue in primary biliary cirrhosis

Last Updated: 2004-03-24 16:26:03 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Accumulation of manganese in the globus pallidus may contribute to the sensation of fatigue in patients with primary biliary cirrhosis (PBC) long before the development of cirrhosis and hepatic encephalopathy, according to a report in the April issue of Gut.

Significant fatigue affects a substantial percentage of patients with PBC, the authors explain, but the mechanism behind the fatigue is unclear.

Based on postmortem evidence from patients dying with PBC, Dr. Daniel M. Forton from Imperial College London, London, UK and colleagues hypothesized that the fatigue in patients with PBC in the absence of cirrhosis could derive from increased globus pallidus manganese concentrations resulting from impaired biliary excretion. They studied 14 women with stage I-II PBC and 4 women with advanced PBC in order to investigate the hypothesis.

Blood manganese levels were significantly higher in early-stage PBC patients with high fatigue than in similar patients with less fatigue, the investigators report.

Using MRI and MR spectroscopy, magnetization transfer ratios (MTR) -- a sensitive measure of brain parenchymal changes -- were significantly reduced in the globus pallidus of stage I-II PBC patients compared with healthy controls, the authors report, but such changes were not seen in other brain regions of interest.

Among the PBC patients, globus pallidus MTR indices were significantly lower in patients with high fatigue than in patients with low fatigue, the report indicates. Globus pallidus MTR indices were inversely related to blood manganese concentrations, the researchers note, and there was a significant correlation between patient age and globus pallidus MTR index in PBC patients.

"Fatigue is often a major symptom in patients in the early stages of PBC and should be taken seriously," Dr. Forton told Reuters Health. "Manganese may be an etiological factor in some patients but not all, since fatigue is a multidimensional and multifactorial complaint."

"Further large cohort studies are required to investigate the relationship between blood manganese levels and fatigue," Dr. Forton said. "However, blood manganese may not be an accurate representation of brain manganese levels, and further brain MR imaging studies are planned using higher field strengths."

"Advice to restrict manganese would be premature at present," Dr. Forton concluded.

Gut 2004;53:587-592.

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