Neuromythology of Manganism

Manganese is an essential trace element with neurotoxicant properties at high levels that were first described in the mid-nineteenth century. The largest sources of occupational and environmental exposures are mining, fossil fuel combustion, and iron and steel industries. Manganese neurotoxicity has been described in many workers with high levels of occupational manganese exposure and can cause a distinct neurologic phenotype known as manganism. Recently, our understanding of the clinical syndrome and pathophysiology of manganese toxicity has shifted. Modern day manganese exposures, which are an order of magnitude lower than previously described in cases of manganism, result in different clinical, imaging, and pathologic phenotypes. Here we will review three neurologic "myths" of manganism in the twenty-first century and will provide evidence that Mn is associated with a clinical syndrome of parkinsonism that resembles Parkinson disease, dopaminergic dysfunction on molecular imaging, and an inflammatory neuropathology in the striatum.