Manganese parkinsonism in welders and miners

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Early descriptions: James Couper (1837, Scottish manganese-ore crushers), J. Rodier (1955, Moroccan miners) and Mena and colleagues (1967, chronic manganese poisoning), as cited in later reviews. Modern work: Brad Racette and colleagues, Washington University, St. Louis.

What happened

Manganese is inhaled as dust or fume in mining, steel work and welding. It reaches the bloodstream through the lungs and crosses into the brain.

• Historic miners: in Rodier's Moroccan mines exposures reached up to 926,000 µg per cubic metre of air; welding today is several orders of magnitude lower. (Racette's 2013 lecture calls these mines Chilean in one passage; the title of Rodier's paper and Racette's 2015 review say Moroccan.)
• Welders: in one worksite study, 15.6% of 716 welders had parkinsonism, against 0% in reference workers, with slowness and stiffness similar to newly diagnosed Parkinson's. In an earlier survey of Alabama welders, prevalence was about 10 times that of a general-population comparison (ratio 10.19, 95% CI 4.43–23.43).
• Differences from Parkinson's: MRI shows bright signal in the globus pallidus (a deeper movement structure), and in 20 active welders without symptoms fluorodopa PET showed the caudate hit most, the reverse of the Parkinson's pattern (Criswell et al. 2011), though earlier PET and SPECT reports in manganese-exposed people were conflicting. Levodopa has helped little in the small trials done (4 and 13 people), though one patient with liver-failure manganism improved on 900 mg a day. Autopsy data are very limited; the few old cases mostly show damage to the pallidum with a normal nigra, though one 1973 case had occasional Lewy bodies, and none of these studies used modern staining.
• Mechanism: proposed route is uptake by astrocytes (support cells), then oxidative stress, inflammation and neuron loss. This is a hypothesis.
• Population level: in a study of 29 million US Medicare beneficiaries (Willis et al. 2010, as summarised by Racette), counties with high industrial manganese release had Parkinson's incidence of 489 per 100,000 against 274 where release was low (RR 1.78). Counties are compared, not individuals.

Why it moved us toward a cure

It is a second, non-pesticide example, after MPTP (landmark 2), of an outside agent injuring dopamine circuits. Racette argues manganese may lower the age of onset rather than cause the disease: 15 welders with Parkinson's began at about 46, against about 63 in 100 non-welders.

Outcome

Open. Whether low-dose manganese causes ordinary Parkinson's is still argued.

Sources

• Racette BA, "Manganism in the 21st Century: The Hanninen Lecture", Neurotoxicology 2014;45:201-207 (author manuscript 2013), DOI 10.1016/j.neuro.2013.09.007, PMC3992192
• Andruska KM & Racette BA, "Neuromythology of Manganism", Curr Epidemiol Rep 2015;2:143-148, DOI 10.1007/s40471-015-0040-x (PMC4450773)
• Rodier J, "Manganese poisoning in Moroccan miners", Br J Ind Med 1955;12:21-35, DOI 10.1136/oem.12.1.21, PMID 14351643 (title and citation only)
• Mena et al., "Chronic manganese poisoning. Clinical picture and manganese turnover", Neurology 1967;17:128-136, DOI 10.1212/wnl.17.2.128, PMID 6066873 (citation only)
• Not yet verified: the Couper, Rodier and Mena papers (read only as cited in the reviews; Mena's country of study not confirmed); the primary welder and Willis Medicare papers; Criswell et al. 2011 (read only as summarised by Racette).