Manganese and Parkinson's disease: a critical review and new findings.
BACKGROUND
Excess accumulation of manganese (Mn) in the brain results in a neurological syndrome with cognitive, psychiatric, and movement abnormalities. The highest concentrations of Mn in the brain are achieved in the basal ganglia, which may precipitate a form of parkinsonism with some clinical features that are similar and some that are different to those in Parkinson's disease (PD). Recently, scientists have debated the possibility that Mn may have an etiological role in PD or that it may accelerate the expression of PD.


OBJECTIVE
The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation.


METHODS
I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations.


METHODS
Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism.


RESULTS
Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD.


CONCLUSIONS
The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.
Guilarte
Tomás R
TR
Neurotoxicology and Molecular Imaging Laboratory, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. trguilarte@columbia.edu
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D003937:Diagnosis, Differential; D004781:Environmental Exposure; D006801:Humans; D008345:Manganese / Q000378:metabolism / Q000633:toxicity*; D020149:Manganese Poisoning / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology; D011323:Primates
D008345:Manganese
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