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Background: Extrapyramidal syndrome and alterations in brain magnetic resonance images are described in patients undergoing long-term home parenteral nutrition (HPN) and in cholestatic patients. These abnormalities have been correlated to basal ganglia manganese (Mn) accumulation., Methods: A longitudinal 1-year study was conducted on 15 patients undergoing HPN (median duration, 3.8 years; range, 1.7-10; median Mn parenteral supplementation, 0.1 mg/d). Whole-blood, plasma, intra-erythrocytes, and urinary Mn concentrations were measured and brain magnetic resonance was performed at the beginning (time 0) and after 1 year of Mn intravenous supplementation withdrawal (time 1). No patients showed psychosis, extrapyramidal syndrome, or cholestasis., Results: At time zero, 10 of 15 patients (67%) showed paramagnetic accumulation on cerebral magnetic resonance images; at time 1 there was a reduction of cerebral Mn accumulation. In all patients, blood-Mn levels were significantly reduced after 1 year of Mn intravenous supplementation withdrawal., Conclusions: Patients receiving long-term HPN showed an elevated incidence of alterations in brain magnetic resonance images with a median Mn intravenous supplementation of 0.1 mg/d. Mn supplementation withdrawal significantly decreased metal levels in blood and brain storage. We noticed that the intra-erythrocyte Mn level was a good index of Mn status.