Progress and Prospects in Parkinson's Research/Causes/Toxins/Manganese

Evidence
The first person to link manganese (Mn) toxicity to the onset of Parkinson’s Disease symptoms was Couper (1837). .

He described the effects of exposure to manganese oxide on workers at the chemical factory of Charles Tennant and Co.(staggering, drooling, impassive expression and low audibility}.

These observations were confirmed by subsequent researchers, who added that, in contrast to other PD cases, manganese toxicity was marked by a lack of a resting tremor and a poor repose to L-dopa therapy. The condition has also been named manganism and has been extensively evaluated by Guilarte (2010). It is believed that manganese induces Parkinsonism by inhibiting the production of tyrosine hydroxylation, which is an essential metabolic step in the formation of dopamine.

2007

Santamaria et al reviwed the neurological risks associated with welding and concluded;-

"Existing exposure data indicate that, in general, Mn exposures in welders are less than those associated with the reports of clinical neurotoxicity (e.g., 'manganism') in miners and smelter workers. It was also found that although manganism was observed in highly exposed workers, the scant exposure-response data available for welders do not support a conclusion that welding is associated with clinical neurotoxicity."

2012

Butterworth decribes a form of Parkinsonism arising from cirrhosis of the liver.

"Acquired hepatolenticular degeneration, also known as 'Parkinsonism in cirrhosis' is characterized by extrapyramidal symptoms including hypokinesia, dystonia and rigidity that are rapidly progressive and may be independent of the severity of cognitive dysfunction..... The cause of Parkinsonism in cirrhosis has been attributed to manganese deposition in basal ganglia structures, leading to the dysfunction of the dopaminergic neurotransmitter system. "

Ephedrone
Several reports from Eastern Europe have recorded MnPD arising from the intravenous injection of a homemade psychostimulant drug called “ephedrone” or “Russian cocktail,” a drug in which ephedrine is oxidized using potassium permanganate and acetic acid

(2007)

Sanotsky et al. Normal Mn concentrations in whole blood are ≤ 10–12 μg/L, but the blood Mn concentrations in ephodrone addicts have been measured at levels as high as 2,000–3,000 μg/L.

MnPD has not been observed among ephedrone users in North America. Here, however, chromate is used as the oxidizing agent rather than potassium permanganate.

Liver Disease
Patients with chronic liver disease excrete manganese into their bile and this too can lead to MnPD. Welders are prone to MnPD from the inhalation of manganese fumes and, atypically, show a positive response to L-dopa therapy.

There is scope for more research into the natural occurrence of manganese compounds in the environment and its production as a by-product of industrial processes.