Manganism

Manganism
Classification and external resources
Specialty Occupational medicine
ICD-10 T57.2
ICD-9-CM 985.2
MeSH D020149

Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese.[1] It was first identified in 1837 by James Couper.[2]

Signs and symptoms

Chronic exposure to excessive manganese levels can lead to a variety of psychiatric and motor disturbances, termed manganism. Generally, exposure to ambient manganese air concentrations in excess of 5 micrograms Mn/m3 can lead to Mn-induced symptoms.[3]

In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.[4] Upon protracted exposure symptoms are more prominent and resemble those of idiopathic Parkinson's disease, as which it is often misdiagnosed, although there are particular differences in both the symptoms (nature of tremors, for example), response to drugs such as levodopa, and affected portion of the basal ganglia. Symptoms are also similar to Lou Gehrig's disease and multiple sclerosis.

Causes

Manganism has become an active issue in workplace safety as it has been the subject of numerous product liability lawsuits against manufacturers of arc welding supplies. In these lawsuits, welders have accused the manufacturers of failing to provide adequate warning that their products could cause welding fumes to contain dangerously high manganese concentrations that could lead welders to develop manganism. Companies employing welders are also being sued, for what colloquially is known as "welders' disease." However, studies fail to show any link between employment as a welder and manganism (or other neurological problems).[5][6][7]

Manganism is also documented in reports of illicit methcathinone manufacturing.[8] This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser.[9] Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.[10]

Reports also mention such sources as contaminated drinking water,[11] and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT),[12] which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust,[13][14][15] and manganese ethylene-bis-dithiocarbamate (Maneb), a pesticide.[16]

Pathophysiology

Manganese may affect liver function, but the threshold of acute toxicity is very high. On the other hand, more than 95 percent of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma.[17] The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron,[18][19][20][21] zinc,[22] aluminum,[18][22] and copper.[22] Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.[23]

It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders.[24] A study of the exposed workers showed that they have significantly fewer children.[25] This may indicate that long-term accumulation of manganese affects fertility. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls.[26] It is found in large quantities in paint and steelmaking.

Treatment

The current mainstay of manganism treatment is levodopa and chelation with EDTA. Both have limited and at best transient efficacy. Replenishing the deficit of dopamine with levodopa has been shown to initially improve extrapyramidal symptoms,[27][28][29] but the response to treatment goes down after 2 or 3 years,[30] with worsening condition of the same patients noted even after 10 years since last exposure to manganese.[31] Enhanced excretion of manganese prompted by chelation therapy brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.[32][33]

Increased ferroportin protein expression in human embryonic kidney (HEK293) cells is associated with decreased intracellular manganese concentration and attenuated cytotoxicity, characterized by the reversal of Mn-reduced glutamate uptake and diminished lactate dehydrogenase (LDH) leakage.[3]

Epidemiology

The Red River Delta near Hanoi has high levels of manganese or arsenic in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium, and barium.[34]

References

  1. ↑ Silva Avila, Daiana; Luiz Puntel, Robson; Aschner, Michael (2013). "Chapter 7. Manganese in Health and Disease". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences 13. Springer. pp. 199–227. doi:10.1007/978-94-007-7500-8_7.
  2. ↑ Couper, J. (1837). "Sur les effets du peroxide de manganèse". Journal de chimie médicale, de pharmacie et de toxicologie 3: 223–225.
  3. 1 2 Yin, Zhaobao; Jiang, Haiyan; Lee, Eun-Sook Y.; Ni, Mingwei; Erikson, Keith M.; Milatovic, Dejan; Bowman, Aaron B.; Aschner, Michael (2010). "Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation" (PDF). Journal of Neurochemistry 112 (5): 1190–8. doi:10.1111/j.1471-4159.2009.06534.x. PMC 2819584. PMID 20002294.
  4. ↑ Roth JA (2006). "Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination". Biol. Res. 39 (1): 45–57. doi:10.4067/S0716-97602006000100006. PMID 16629164.
  5. ↑ Fryzek JP, Hansen J, Cohen S, Bonde JP, Llambias MT, Kolstad HA, Skytthe A, Lipworth L, Blot WJ, Olsen JH. A cohort study of Parkinson's disease and other neurodegenerative disorders in Danish welders. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 2005 May;47(5):466-72.
  6. ↑ Fored, C M; Fryzek, JP; Brandt, L; Nise, G; Sjögren, B; McLaughlin, JK; Blot, WJ; Ekbom, A (2006). "Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders". Occupational and Environmental Medicine 63 (2): 135–40. doi:10.1136/oem.2005.022921. PMC 2078076. PMID 16421393.
  7. ↑ Marsh GM, Gula MJ. Employment as a welder and Parkinson disease among heavy equipment manufacturing workers. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 2006 Oct;48(10):1031-46.
  8. ↑ de Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE (June 2007). "Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse". Arch. Neurol. 64 (6): 886–9. doi:10.1001/archneur.64.6.886. PMID 17562938.
  9. ↑ Sanotsky, Y., Lesyk, R., Fedoryshyn, L., Komnatska, I., Matviyenko, Y. and Fahn, S. (June 2007). "Manganic encephalopathy due to "ephedrone" abuse". Movement Disorders 22 (9): 1337–1343. doi:10.1002/mds.21378. PMID 17566121.
  10. ↑ Ensing,, J. G. (1985). "Bazooka: Cocaine-Base and Manganese Carbonate". Journal of Analytical Toxicology 9 (1): 45–46. doi:10.1093/jat/9.1.45. PMID 3981975.
  11. ↑ Kondakis, Xenophon G.; Makris, Nicolas; Leotsinidis, Michael; Prinou, Mary; Papapetropoulos, Theodore (1989). "Possible Health Effects of High Manganese Concentration in Drinking Water". Archives of Environmental Health 44 (3): 175–178. doi:10.1080/00039896.1989.9935883.
  12. ↑ Hudnell, HK (1999). "Effects from environmental manganese exposures: A review of the evidence from non-occupational exposure studies". Neurotoxicology 20 (2–3): 379–397. PMID 10385898.
  13. ↑ Lynam, DR; Roos, JW; Pfeifer, GD; Fort, BF; Pullin, TG (1999). "Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline". Neurotoxicology 20 (2–3): 145–150. PMID 10385878.
  14. ↑ Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AK, 1997.
  15. ↑ Lynam, D.R.; Pfeifer, G.D.; Fort, B.F.; Gelbcke, A.A. (1990). "Environmental assessment of MMT™ fuel additive". Science of the Total Environment 93: 107–114. doi:10.1016/0048-9697(90)90098-F. PMID 2113712.
  16. ↑ Ferraz, H. B.; f. Bertolucci, P. H.; Pereira, J. S.; Lima, J.G.C.; f. Andrade, L. A. (1988). "Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication". Neurology 38 (4): 550–553. doi:10.1212/WNL.38.4.550. PMID 3352909.
  17. ↑ Ballatori N. Molecular mechanisms of hepatic metal transport. In Molecular Biology and Toxicology of Metals, Zalups RK, Koropatnick J (eds). Taylor & Francis: New York, 2000; 346-381.
  18. 1 2 Verity, MA (1999). "Manganese neurotoxicity: A mechanistic hypothesis". Neurotoxicology 20 (2–3): 489–497. PMID 10385907.
  19. ↑ Zheng, Wei; Zhao, Qiuqu (2001). "Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells". Brain Research 897 (1–2): 175–179. doi:10.1016/S0006-8993(01)02049-2. PMID 11282372.
  20. ↑ Zheng, Wei; Zhao, Qiuqu; Slavkovich, Vesna; Aschner, Michael; Graziano, Joseph H (1999). "Alteration of iron homeostasis following chronic exposure to manganese in rats". Brain Research 833 (1): 125–132. doi:10.1016/S0006-8993(99)01558-9. PMID 10375687.
  21. ↑ Zheng, Wei (2001). "Neurotoxicology of the Brain Barrier System: New Implications" (PDF). Clinical Toxicology 39 (7): 711–719. doi:10.1081/CLT-100108512. PMC 4111935. PMID 11778669.
  22. 1 2 3 Lai, JC; Minski, MJ; Chan, AW; Leung, TK; Lim, L (1999). "Manganese mineral interactions in brain". Neurotoxicology 20 (2–3): 433–444. PMID 10385902.
  23. ↑ Zheng, Wei; Ren, Sean; Graziano, Joseph H. (1998). "Manganese inhibits mitochondrial aconitase: A mechanism of manganese neurotoxicity". Brain Research 799 (2): 334–342. doi:10.1016/S0006-8993(98)00481-8. PMID 9675333.
  24. ↑ Li G, Zhang L, Lu L, Wu P, Zheng W. Occupational exposure to welding fume among welders: alterations of manganese, iron, zinc, copper, and lead in body fluids and the oxidative stress status. J. Occup. Environ. Med. 2004; 46(3): 241-248.
  25. ↑ Lauwerys, Robert (1985). "Fertility of male workers exposed to mercury vapor or to manganese dust: A questionnaire study". American Journal of Industrial Medicine 7 (2): 171–176. doi:10.1002/ajim.4700070208. PMID 3976664.
  26. ↑ Treinen, Kimberley A.; Gray, Tim J. B.; Blazak, William F. (1995). "Developmental toxicity of mangafodipir trisodium and manganese chloride in Sprague-Dawley rats". Teratology 52 (2): 109–115. doi:10.1002/tera.1420520207. PMID 8588182.
  27. ↑ Lee, J.-W. (2000). "Manganese Intoxication". Archives of Neurology 57 (4): 597–599. doi:10.1001/archneur.57.4.597. PMID 10768639.
  28. ↑ Mena I, Court J, Fuenzalida S, Papavasiliou PS, Cotzias GC. Modification of chronic manganese poisoning. Treatment with Ldopa or 5-OH tryptophane. New Engl. J. Med. 1970; 282(1): 5-10.
  29. ↑ Rosenstock, Harvey A. (1971). "Chronic Manganism<subtitle>Neurologic and Laboratory Studies During Treatment with Levodopa</subtitle>". JAMA: the Journal of the American Medical Association 217 (10): 1354–1358. doi:10.1001/jama.1971.03190100038007.
  30. ↑ Huang, C.-C.; Lu, C.-S.; Chu, N.-S.; Hochberg, F.; Lilienfeld, D.; Olanow, W.; Calne, D. B. (1993). "Progression after chronic manganese exposure". Neurology 43 (8): 1479–1483. doi:10.1212/WNL.43.8.1479. PMID 8351000.
  31. ↑ Huang, C.-C.; Chu, N.-S.; Lu, C.-S.; Chen, R.-S.; Calne, D. B. (1998). "Long-term progression in chronic manganism: Ten years of follow-up". Neurology 50 (3): 698–700. doi:10.1212/WNL.50.3.698. PMID 9521259.
  32. ↑ Ono, Kenjiro; Komai, Kiyonobu; Yamada, Masahito (2002). "Myoclonic involuntary movement associated with chronic manganese poisoning". Journal of the Neurological Sciences 199 (1–2): 93–96. doi:10.1016/S0022-510X(02)00111-9. PMID 12084450.
  33. ↑ Calne, DB; Chu, NS; Huang, CC; Lu, CS; Olanow, W (1994). "Manganism and idiopathic parkinsonism: Similarities and differences". Neurology 44 (9): 1583–1586. doi:10.1212/WNL.44.9.1583. PMID 7936278.
  34. ↑ http://www.watertechonline.com/news.asp?N_ID=75635

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