Manganese neurotoxicity: connecting the dots along the continuum of dysfunction.

Three different manifestations of manganese neurotoxicity have been described. The first, and historically most prominent, is often termed manganism: a dramatic extrapyramidal syndrome following acute, overwhelming exposure. While resembling Idiopathic Parkinson's Disease (IPD), most authorities have regarded the two conditions as clinically and pathophysiologically distinct. The second manifestation, reported by several investigators starting in the 1980s, consisted of subclinical and subfunctional declines in the performance of specialized neuropsychological tests. The implication of these cross-sectional findings was that, when superimposed upon age-related attritional effects, increased rates of clinical disease could result. In this decade, it has been proposed that manganese exposure may play a role in the development of IPD itself. Investigating the relationship between these three manifestations should be a priority for future research.