This article reviews the health effects of manganese (Mn) and introduces readers to recent issues in Mn neurotoxicity research.

An extensive Medline search that covered publications up to December 2008 was conducted and the relevant papers and their references were evaluated for review.

Exposure to excess levels of the essential trace element Mn produces cognitive, psychiatric, and motor abnormalities. The lungs and the gastrointestinal tract both absorb Mn, but homeostatic mechanisms limit the absorption of Mn by the gastrointestinal tract. Elimination of Mn occurs primarily by excretion into the bile. Average Mn levels in the blood reflect the total body burden on a group basis, but not on an individual basis. Previous studies have shown that blood Mn contributes to a high pallidal signal in a T1-weighted brain MRI and that the high signal is an effective predictor of neurobehavioral performance. Thus, a high pallidal signal on an MRI may offer clues concerning the target organ dose from Mn exposure in the spectrum of Mn symptomatology. Neuroimaging as well as a clinical evaluation with exposure history is very important in a differential diagnosis that can distinguish manganism from Parkinson disease (PD). Recent research on Mn neurotoxicity has focused on several issues. First, concerns about the interaction between manganism and PD have been raised, but further research is needed. Second, epidemiological studies on non-occupational Mn exposure have suggested that environmentally induced neurotoxicities may have features that are different from the classic features of occupational manganism, but, again, this requires further research. Third, liver cirrhosis could be used as a model of manganism. Finally, functional neuroimaging such as magnetic resonance spectroscopy, functional MRI, or diffusion tensor imaging appears to have promising applications in Mn research.

Reviewing the health effects of Mn and recent issues in Mn neurotoxicity research provides us with important suggestions for how to pursue other lines of toxicological research as well as for how best to develop a systematic understanding of Mn symptomatology.