Jun. 30 2010

Doctors have known for more than 150 years that exposure to the metal manganese can cause tremors and other neurological symptoms that closely resemble Parkinson’s Disease.  In a review of the recent scientific literature, including PET scan studies, Tomás Guilarte, PhD, Leon Hess Professor of Environmental Health Sciences at Columbia University’s Mailman School of Public Health, clarifies how manganese-induced parkinsonism differs from the classic form of the disease both in terms of its biology and its treatment. The review paper appears in the July issue of Environmental Health Perspectives.

Manganese neurotoxicity is a concern in occupational settings especially for those working in the welding, steel-making, and mining industries. In Eastern Europe, addicts injecting the psycho-stimulant ephedrone have been afflicted with manganese-related parkinsonism, because the illicit drug is often prepared with potassium permanganate and high doses of manganese are injected. From a public health perspective, manganese has been approved for use in gasoline in the U.S. and many parts of the world with the potential for increased exposure to the general population.

The symptoms of manganese-induced parkinsonism are often mistaken for Parkinson’s Disease, but the underlying biology is somewhat different and so is the treatment, according to Dr. Guilarte, who chairs the Department of Environmental Health Sciences at the Mailman School but was previously at Johns Hopkins.

In classic or idiopathic Parkinson’s Disease, many of the dopamine-producing cells in the substantia nigra region of the brain degenerate, resulting in a deficiency in the key neurotransmitter dopamine. In this case giving patients L-dopa, a precursor of dopamine, helps alleviate the shortage and resulting symptoms.

In manganese-induced parkinsonism, however, the problem is not with dopamine production or supply but rather in the brain’s ability to release available dopamine into synapses. Consequently, L-dopa is far less effective.

“This latest evidence based on our review and studies from our laboratory led us to the finding that movement abnormalities associated with manganese exposure are due to dysfunction but not degeneration of the dopaminergic system,” says Dr. Guilarte. “These latest results, indicating that manganese-induced motor dysfunction is a problem of the ability to release the available dopamine, provide an invaluable starting point and a new avenue of research to explain a recognized mechanism of these movement abnormalities.” Neuroimaging studies, he notes, are particularly likely to provide additional new information.