Multiple Sclerosis in the Mount Etna Region: Possible Role of Volcanogenic Trace Elements

Background: Trace elements have been hypothesised to be involved in the pathogenesis of Multiple Sclerosis and volcanic
degassing is the major natural sources of trace elements. Both incidence of Multiple Sclerosis in Catania and volcanic activity
of Mount Etna have been significantly increased during the last 30 years. Due to prevailing trade winds direction, volcanic
gases from Etna summit craters are mostly blown towards the eastern and southern sectors of the volcano.
Objective: To evaluate the possible association between Multiple Sclerosis and exposure to volcanogenic trace elements.
Methods: We evaluated prevalence and incidence of Multiple Sclerosis in four communities (47,234 inhabitants) located in
the eastern flank and in two communities (52,210 inhabitants) located in the western flank of Mount Etna, respectively the
most and least exposed area to crater gas emissions.
Results: A higher prevalence was found in the population of the eastern flank compared to the population of the western
one (137.6/100,000 versus 94.3/100,000; p-value 0.04). We found a borderline significantly higher incidence risk during the
incidence study period (1980–2009) in the population of the eastern flank 4.6/100,000 (95% CI 3.1–5.9), compared with the
western population 3.2/100,000 (95% CI 2.4–4.2) with a RR of 1.41 (95% CI 0.97–2.05; p-value 0.06). Incidence risks have
increased over the time in both populations reaching a peak of 6.4/100,000 in the eastern flank and of 4.4/100.000 in the
western flank during 2000–2009.
Conclusion: We found a higher prevalence and incidence of Multiple Sclerosis among populations living in the eastern flank
of Mount Etna. According to our data a possible role of TE cannot be ruled out as possible co-factor in the MS pathogenesis.
However larger epidemiological study are needed to confirm this hypothesis.

1. Poser CM (1994) The epidemiology of multiple sclerosis: a general overview.
Ann Neurol 34: S180–193.
2. Alonso A, Hernan MA (2008) Temporal trends in the incidence of multiple
sclerosis. A systematic review. Neurology 71: 129–135.
3. Pugliatti M, Rosati G, Cartonc H (2006) The epidemiology of multiple sclerosis
in Europe. Eur J of Neurol 13: 700–722.
4. Ranzato F, Perini P, Tzintzeva E, Tiberio M, Calabrese M, et al. (2003)
Increasing frequency of multiple sclerosis in Padova: a 30 year epidemiological
survey. Mult Scler 9: 387–392.
5. Iuliano G, Napoletano R (2008) Prevalence and incidence of multiple sclerosis in
Salerno (southern Italy) and its province. Eur J Neurol 15: 73–76.
6. Cocco E, Sardu C, Massa R, Mamusa E, Musu L, et al. (2011) Epidemiology of
multiple sclerosis in south-western Sardinia. Mult Scler 17: 1282–1289.
7. Savettieri G, Ragonese P, Aridon P, Salemi G (2001) Epidemiology of multiple
sclerosis in Sicily. Neurol Sci 22: 175–177.
8. Puthenparampil M, Seppi D, Rinaldi F, Federle L, Calabrese M, et al. (2013)
Increased incidence of multiple sclerosis in the Veneto region, Italy. Multiple
Sclerosis Epidemiology Veneto Study Group (MuSEV).Mult Scler 19(5):601–604.
9. Guidetti D, Cavalletti S, Merelli E, Zanoni P, Simonazzi P et al. (1995)
Epidemiological survey of multiple sclerosis in the provinces of Reggio Emilia
and Modena, Italy. Neuroepidemiology 14: 7–13.
10. Granieri E, Economou NT, De Gennaro R, Tola MR, Caniatti L, et al. (2007)
Multiple sclerosis in the province of Ferrara: evidence for an increasing trend.
J Neurol 254: 1642–1648.
11. Pugliatti M, Riise T, Sotgiu A, Sotgiu S, Satta WM, et al. (2005) Increasing
incidence of multiple sclerosis in the province of Sassari, Northern Sardinia.
Neuroepidemiology 25: 29–134.
12. Nicoletti A, Lo Bartolo ML, Lo Fermo S, Cocuzza V, Panetta MR, et al. (2001)
Prevalence and incidence of multiple sclerosis in Catania, Sicily. Neurology 56:
62–66.
13. Nicoletti A, Patti F, Lo Fermo S, Sorbello V, Reggio E, et al. (2005) Possible
increasing risk of multiple sclerosis in Catania, Sicily. Neurology 65: 1259–1263.
14. Nicoletti A, Patti F, Lo Fermo S, Messina S, Bruno E, et al. (2011) Increasing
frequency of multiple sclerosis in Catania, Sicily: a 30-year survey. Mult Scler
17:273–280.
15. Handel AE, Giovannoni G, Ebers GC, Ramagopalan SV (2010) Environmental
factors and their timing in adult-onsetmultiple sclerosis.Nat RevNeurol 6: 156–166.
16. Alimonti A, Ristori G, Giubilei F, Stazi MA, Pino A, et al. (2007)
Serumchemical elements and oxidative status in Alzheimer’s disease, Parkinson
disease andmultiple sclerosis. Neurotoxicology 28: 450–456.
17. Ristori G, Brescianini S, Pino A, Visconti A, Vittori D, et al. (2011)
Serumelements and oxidative status in clinically isolated syndromes: Imbalance
andpredictivity Neurology 76: 549–555.
18. Hansell AL, Horwell CJ, Oppenheimer C (2006) The health hazards of
volcanoes and geothermal areas. Occup Environ Med 63: 149–156.
19. Calabrese S, Aiuppa A, Allard P, Bagnato E, Bellomo S, et al. (2011)
Atmospheric sources ad sinks of volcanogenic elements in a basaltic volcano
(Etna, Italy). Geochi et Cosmoch Acta 75: 7401–7425.
20. Aiuppa A, Allard P, D’Alessandro W, Giammanco S, Parello F, et al. (2004)
Magmatic gas leakage at Mount Etna (Sicily, Italy): Relationships with the
volcano-tectonic structures, the hydrological pattern and the eruptive activity.
Geophys Monogr Ser 143: 129–145.
21. Behncke B, Neri M (2003) Cycles and trends in the recent eruptive behaviour of
Mount Etna (Italy). Can J Earth Sci 40: 1405–1411.
22. Branca S, Del Carlo P (2005) Types of eruptions of Etna volcano AD 16702003:
implications for short-term eruptive behaviour. Bull Volcanol 67: 732–742.
23. Martin RS, Mather TA, Pyle DM, Watt SFL, Day JA, et al. (2009) Sweet
chestnut (Castanea sativa) leaves as a bio-indicator of volcanic gas, aerosol and
ash deposition onto the flanks of Mt Etna in 2005–2007. J Volcanol Geoth Res
179: 107–119.
24. Giammanco S, Ottaviani M, Valenza M, Veschetti E, Principio E, et al. (1998)
Major and trace elements geochemistry in the ground waters of a volcanic area:
Mount Etna (Sicily). Wat Res 32: 9–30.
25. Aiuppa A, Bellomo S, Brusca L, D’Alessandro W, Federico C, et al. (2003)
Natural and anthropogenicfactors affecting groundwater quality of an active
volcano (Mt. Etna, Italy). Applied Geochemistry 18: 863–882.
26. Istituto Centrale di Statistica (2011) 15u Censimento generale della popolazione.
27. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, et al. (1983)
New diagnostic criteria for multiple sclerosis: guidelines for research protocols.
Ann Neurol 13: 227–231.
28. Giovannoni G, Ebers G (2007) Multiple sclerosis: the environment and
causation. Curr Opin Neurol 20(3):261–268.
29. Riise T, Moen BE, Kyvik KR (2002) Organic solvents and the risk of multiple
sclerosis. Epidemiology 6: 718–720.
30. Grønning M, Albrektsen G, Kva° le G, Moen B, Aarli JA, et al. (1993) Organic
solvents and multiple sclerosis: a case-control study. Acta Neurol Scand 88: 247–
250.
31. Schiffer RB, Mcdermott MP, Copley C (2001) A Multiple Sclerosis Cluster
Associated with a Small, North-Central Illinois Community. Arch Environ
Health 56: 389–395.
32. Purdey M (2004) Chronic barium intoxication disrupts sulphated proteoglycan
synthesis: a hypothesis for the origins of multiple sclerosis. Med Hypotheses 62:
746–754.
33. Johnson S (2000) The possible role of gradual accumulation of copper,
cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium,
vitamins B2, B6, D and E and essential fatty acids in multiple sclerosis. Med
Hypotheses 55: 239–241.
34. Kapaki E, Segditsa J, Papageorgiou C (1989) Zinc, copper and magnesium
concentration in serum and CSF of patients with neurological disorders. Acta
Neurol Scand 79: 373–378.
35. Larsen C, White LR, Aasly J, Sjøbakk TE, Flaten TP, et al. (2003) Manganese,
copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis. Biol
Trace Elem Res 93: 1–8.
36. Sayre LM, Perry G, Atwood CS, Smith MA (2000) The role of metals in
neurodegenerative diseases. Cell Mol Biol (Noisy-le-grand) Jun;46(4):731–741.
37. Dhib-Jalbut S, Arnold DL, Cleveland DW, Fisher M, Friedlander RM, et al.
(2006) Neurodegeneration and neuroprotection in multiple sclerosis and other
neurodegenerative diseases. J Neuroimmunol Jul;176(1–2):198–215.
38. Gellein K, Skogholt JH, Aaseth J, Thoresen GB, Lierhagen S, et al. (2008)Trace
elements in cerebrospinal fluid and blood from patients with a rare progressive
central and peripheral demyelinating disease. J Neurol Sci; 266:70–78.
39. Klein R, Schwenk M, Templeton DM (2006) Cytokine Profiles In Human
Exposure To Metals (Iupac Technical Report). Pure Appl Chem;78 (11):2155–
2168.
40. Denkhaus E, Salnikow K (2002) Nickel essentiality, toxicity, and carcinogenicity.
Crit Rev Oncol Hematol 42:35–56.
41. Gauthier PJ, Le Cloarec MF (1998) Variability of alkali and heavy metal fluxes
released by Mt. Etna volcano, Sicily, between 1991 and 1995. J Volcanol
Geotherm Res 81: 311–326.
42. Nicoletti A, Lo Fermo S, Reggio E, Tarantello R, Liberto A, et al. (2005) A
possible spatial and temporal cluster of multiple sclerosis in the town of
Linguaglossa, Sicily. J Neurol 252: 921–5.
43. Nicoletti A, Patti F, Lo Fermo S, Messina S, Bruno E, et al. (2009) A possible
spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa,
Sicily: an update. Mult Scler 15:129–130.