Incidence and prevalence of multiple sclerosis in Europe: a systematic review

Elaine Kingwell, James J Marriott, Nathalie Jetté, Tamara Pringsheim, Naila Makhani, Sarah A Morrow, John D Fisk, Charity Evans, Sarah Gabrielle Béland, Sophie Kulaga, Jonathan Dykeman, Christina Wolfson, Marcus W Koch, Ruth Ann Marrie, Elaine Kingwell, James J Marriott, Nathalie Jetté, Tamara Pringsheim, Naila Makhani, Sarah A Morrow, John D Fisk, Charity Evans, Sarah Gabrielle Béland, Sophie Kulaga, Jonathan Dykeman, Christina Wolfson, Marcus W Koch, Ruth Ann Marrie

Abstract

Background: Multiple sclerosis (MS) is the most common cause of neurological disability in young adults worldwide and approximately half of those affected are in Europe. The assessment of differential incidence and prevalence across populations can reveal spatial, temporal and demographic patterns which are important for identifying genetic and environmental factors contributing to MS. However, study methodologies vary and the quality of the methods can influence the estimates. This study aimed to systematically review European studies of incidence and prevalence of MS and to provide a quantitative assessment of their methodological quality.

Methods: A comprehensive literature search was performed to obtain all original population-based studies of MS incidence and prevalence in European populations conducted and published between January 1985 and January 2011. Only peer-reviewed full-text articles published in English or French were included. All abstracts were screened for eligibility and two trained reviewers abstracted the data and graded the quality of each study using a tool specifically designed for this study.

Results: There were 123 studies that met the inclusion criteria. The study estimates were highly heterogeneous, even within regions or countries. Quality was generally higher in the more recent studies, which also tended to use current diagnostic criteria. Prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. With rare exceptions, prevalence and incidence estimates were higher in women with ratios as high as 3:1. Few studies examined ethnicity. Epidemiological data at the national level was uncommon and there were marked geographical disparities in available data, with large areas of Europe unrepresented and other regions well-represented in the literature. Only 37% of the studies provided standardized estimates.

Conclusions: Despite the breadth of the literature on the epidemiology of MS in Europe, inter-study comparisons are hampered by the lack of standardization. Further research should focus on regions not yet studied and the evaluation of ethnic differences in MS prevalence and incidence. National-level studies using current diagnostic criteria, validated case definitions and similar age- and sex-standardization would allow better geographical comparisons.

Figures

Figure 1
Figure 1
Flow diagram of selection of MS incidence and prevalence studies January 1 1985 – January 31, 2011.
Figure 2
Figure 2
Heterogeneity of prevalence estimates from included studies, stratified by region.

References

    1. World Health Organization. Atlas multiple sclerosis resources in the world 2008. Geneva: WHO Press; 2008.
    1. Poser CM, Brinar VV. The accuracy of prevalence rates of multiple sclerosis: a critical review. Neuroepidemiology. 2007;29(3–4):150–155.
    1. Ebers GC. Environmental factors and multiple sclerosis. The Lancet Neurology. 2008;7(3):268–277. doi: 10.1016/S1474-4422(08)70042-5.
    1. Koch-Henriksen N, Sørensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9:520–532. doi: 10.1016/S1474-4422(10)70064-8.
    1. Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2):129–135. doi: 10.1212/01.wnl.0000316802.35974.34.
    1. Orton S-M, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5:932–936. doi: 10.1016/S1474-4422(06)70581-6.
    1. Ramagopalan SV, Byrnes JK, Orton SM, Dyment DA, Guimond C, Yee IM, Ebers GC, Sadovnick AD. Sex ratio of multiple sclerosis and clinical phenotype. Eur J Neurol. 2010;17(4):634–637. doi: 10.1111/j.1468-1331.2009.02850.x.
    1. Trojano M, Lucchese G, Graziano G, Taylor BV, Simpson SJ, Lepore V, Grand’maison F, Duquette P, Izquierdo G, Grammond P. et al.Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One. 2012;7(10):348078.
    1. Kurtzke JF. Multiple sclerosis in time and space–geographic clues to cause. J Neurovirol. 2000;6(Suppl 2):S134–S140.
    1. Evans C, Beland SG, Kulaga S, Wolfson C, Kingwell E, Marriott J, Koch M, Makhani N, Morrow S, Fisk J. et al.Incidence and Prevalence of Multiple Sclerosis in the Americas: a systematic review. Neuroepidemiology. 2013;40(3):195–210. doi: 10.1159/000342779.
    1. Becuș T, Popoviciu L. Epidemiologic survey of multiple sclerosis in Mureș County, Romania. Rom J Neurol Psychiat. 1994;32(2):115–122.
    1. Garcia JR, Rodriguez S, Sosa Henriquez M, Batista E, Corujo E, Font De Mora Turon A, Hernandez Hernandez D, Betancor Leon P. Prevalence of multiple sclerosis in Lanzarote (Canary Islands) Neurology. 1989;39:265–267. doi: 10.1212/WNL.39.2.265.
    1. Grasso AA, Regio A, Marano P, Florio S, Scordino N, Cappello S, Nicoletti F. Epidemiological survey of multiple sclerosis in Catania city. Ital J Neurol Sci. 1992;13:301–309. doi: 10.1007/BF02223094.
    1. Matias-Guiu J, Bolumar F, Martin R, Insa R, Casquero P, Moltó JM, Calatayud EJA. Multiple sclerosis in Spain: an epidemiological study of the Alcoy health region, Valencia. Acta Neurol Scand. 1990;6:479–493.
    1. Dean G, Elian M, Galea De Bono A, Pace Asciak R, Vella N, Mifsud V, Aquilina J. Multiple sclerosis in Malta in 1999: an update. J Neurol Neurosurg Psychiatry. 2002;73:256–260. doi: 10.1136/jnnp.73.3.256.
    1. Milanov I, Topalov N, Kmetska T. Prevalence of Multiple Sclerosis in Gypsies and Bulgarians. Neuroepidemiology. 1999;18:218–222. doi: 10.1159/000026214.
    1. Smestad C, Sandvik L, Holmoy T, Harbo HF, Celius EG. Marked differences in prevalence of multiple sclerosis between ethnic groups in Oslo, Norway. J Neurol. 2008;255(1):49–55. doi: 10.1007/s00415-007-0659-8.
    1. Binzer M, Forsgren L, Holmgren G, Drugge U, Fredrikson S. Familial clustering of multiple sclerosis in a northern Swedish rural district. J Neurol Neurosurg Psychiatry. 1994;57:497–499. doi: 10.1136/jnnp.57.4.497.
    1. Tienari PJ, Sumelahti ML, Rantamaki T, Wikstrom J. Multiple sclerosis in western Finland: evidence for a founder effect. Clin neurol neurosur. 2004;106(3):175–179. doi: 10.1016/j.clineuro.2004.02.009.
    1. Nicoletti A, Lo Fermo S, Reggio E, Tarantello R, Liberto A, Le Pira F, Patti F, Reggio A. A possible spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa, Sicily. J Neurol. 2005;252(8):921–925. doi: 10.1007/s00415-005-0781-4.
    1. Rothwell PM, Charlton D. High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition. J Neurol Neurosurg Psychiatry. 1998;64:730–735. doi: 10.1136/jnnp.64.6.730.
    1. Sumelahti ML, Tienari PJ, Wikström J, Palo J, Hakama M. Regional and Temporal Variation in the Incidence of Multiple Sclerosis in Finland 1979–1993. Neuroepidemiology. 2000;19:67–75. doi: 10.1159/000026241.
    1. Dean G, Aksoy H, Akalin T, Middleton L, Kyriallis K. Multiple sclerosis in the Turkish- and Greek-speaking communities of Cyprus: a United Nations (UNHCR) Bicommunal Project. J Neurol Sci. 1997;145:163–168. doi: 10.1016/S0022-510X(96)00255-9.
    1. Middleton L, Dean G. Multiple sclerosis in Cyprus. J Neurol Sci. 1991;103:29–36. doi: 10.1016/0022-510X(91)90279-G.
    1. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13(3):227–231. doi: 10.1002/ana.410130302.
    1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC. et al.Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol. 2001;50:121–127. doi: 10.1002/ana.1032.
    1. Rose AS, Ellison GW, Myers LW, Tourtellotte WW. Criteria for the clinical diagnosis of multiple sclerosis. Neurology. 1976;26:20–22. doi: 10.1212/WNL.26.6_Part_2.20.
    1. Schumaker GA, Beebe G, Kibler RF, Kurland LT, Kurtzke JF, McDowell F, Nagler B, Sibley WA, Tourtellotte WW, Willmon TL. Problems of experimental trials of therapy in multiple sclerosis. Ann NY Acad Sci. 1965;122:552–568.
    1. McAlpine D, Lumsden CE, Acheson ED. Multiple sclerosis: a reappraisal. Edinburgh: Churchill Livingstone; 1972.
    1. McDonald WI, Halliday AM. Diagnosis and classification of multiple sclerosis. Br Med Bull. 1977;33:4–9.
    1. Grimaldi LM, Palmeri B, Salemi G, Giglia G, D’Amelio M, Grimaldi R, Vitello G, Ragonese P, Savettieri G. High prevalence and fast rising incidence of multiple sclerosis in Caltanissetta, Sicily, southern Italy. Neuroepidemiology. 2007;28(1):28–32. doi: 10.1159/000097853.
    1. Grimaldi LME, Salemi G, Grimaldi G, Rizzo A, Marziolo R, Lo Presti C, Maimone D, Savettieri G. High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy. Neurology. 2001;57:1891–1893. doi: 10.1212/WNL.57.10.1891.
    1. Nicoletti A, Lo Bartolo ML, Lo Fermo S, Cocuzza V, Panetta MR, Marletta C, Ciancio MR, Cataldi ML, Patti F, Reggio A. Prevalence and incidence of multiple sclerosis in Catania, Sicily. Neurology. 2001;56:62–66. doi: 10.1212/WNL.56.1.62.
    1. Nicoletti A, Patti F, Lo Fermo S, Sorbello V, Reggio E, Maimone D, Zappia M, Reggio A. Possible increasing risk of multiple sclerosis in Catania, Sicily. Neurology. 2005;65:1259–1263. doi: 10.1212/01.wnl.0000180628.38786.85.
    1. Ragonese P, Salemi G, D’Amelio M, Gammino M, Aridon P, Savettieri G. Multiple sclerosis in southern Europe: Monreale City, Italy. A twenty-year follow-up incidence and prevalence study. Neuroepidemiology. 2004;23(6):306–309. doi: 10.1159/000080097.
    1. Salemi G, Ragonese P, Aridon P, Scola G, Saporito V, Conte S, Savettieri G. Incidence of multiple sclerosis in Bagheria City, Sicily, Italy. Neurol Sci. 2000;21:361–365. doi: 10.1007/s100720070051.
    1. Savettieri G, Salemi G, Ragonese P, Aridon P, Scola G, Randisi G. Prevalence and incidence of multiple sclerosis in the city of Monreale, Italy. J Neurol. 1998;245:40–43.
    1. Bergamaschi R, Montomoli C, Candeloro E, Monti MC, Cioccale R, Bernardinelli L, Fratino P, Cosi V, Group P. Bayesian mapping of multiple sclerosis prevalence in the province of Pavia, northern Italy. J Neurol Sci. 2006;244(1–2):127–131.
    1. Granieri E, Economou NT, De Gennaro R, Tola MR, Caniatti L, Govoni V, Fainardi E, Casetta I. Multiple sclerosis in the province of Ferrara: evidence for an increasing trend. J Neurol. 2007;254(12):1642–1648. doi: 10.1007/s00415-007-0560-5.
    1. Granieri E, Malagu S, Casetta I, Tola MR, Govoni V, Paolino E, Monetti VC. Multiple sclerosis in Italy: a reappraisal of incidence and prevalence in Ferrara. Arch Neurol. 1996;53:793–798. doi: 10.1001/archneur.1996.00550080115019.
    1. Guidetti D, Cavalletti S, Merelli E, Zanoni P, Simonazzi P, Sola P, Solime F. Epidemiological survey of multiple sclerosis in the provinces of Reggio Emilia and Modena, Italy. Neuroepidemiology. 1995;14:7–13. doi: 10.1159/000109772.
    1. Ranzato F, Perini P, Tzintzeva E, Tiberio M, Calabrese M, Ermani M, Davetag F, De L, Garbin E, Verdelli F. et al.Increasing frequency of multiple sclerosis in Padova, Italy: a 30 year epidemiological survey. Multiple sclerosis. 2003;9(4):387–392. doi: 10.1191/1352458503ms920oa.
    1. Sironi L, Mamoli A, D’Alessandro G, Camerlingo M, Bottacchi E. Frequency of multiple sclerosis in Valle d’Aosta, 1971-1985. Neuroepidemiology. 1991;10:66–69. doi: 10.1159/000110249.
    1. Solaro C, Allemani C, Messmer Uccelli M, Canevari E, Dagnino N, Pizio R, Regesta G, Tanganelli P, Battaglia MA, Mancardi GL. The prevalence of multiple sclerosis in the north-west Italian province of Genoa. J Neurol. 2005;252(4):436–440. doi: 10.1007/s00415-005-0670-x.
    1. Casetta I, Granieri E, Marchi D, Murgia SB, Tola MR, Ticca A, Lauria G, Govoni V, Murgia B, Pugliatti M. An epidemiological study of multiple sclerosis in central Sardinia, Italy. Acta Neurol Scand. 1998;98:391–394. doi: 10.1111/j.1600-0404.1998.tb07319.x.
    1. Granieri E, Casetta I, Govoni V, Tola MR, Marchi D, Murgia SB, Ticca A, Pugliatti M, Murgia B, Rosati G. The increasing incidence and prevalence of MS in a Sardinian province. Neurology. 2000;55:842–847. doi: 10.1212/WNL.55.6.842.
    1. Montomolia C, Allemania C, Solinasa G, Mottaa G, Bernardinellia L, Clementeb S, Murgiac BS, Ticcac AF, Musuc L, Pirasc ML. et ecologic study of geographical variation in multiple sclerosis risk in central Sardinia, Italy. Neuroepidemiology. 2002;21:187–193. doi: 10.1159/000059522.
    1. Pugliatti M, Riise T, Sotgiu MA, Sotgiu S, Satta WM, Mannu L, Sanna G, Rosati G. Increasing incidence of multiple sclerosis in the province of Sassari, northern Sardinia. Neuroepidemiology. 2005;25(3):129–134. doi: 10.1159/000086677.
    1. Pugliatti M, Sotgiu S, Solinas G, Castiglia P, Pirastru M, Murgia B, Mannu L, Sanna G, Rosati G. Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk. Acta Neurol Scand. 2001;103:20–26. doi: 10.1034/j.1600-0404.2001.00207.x.
    1. Rosati G, Aiello I, Mannu L, Pirastru MI, Agnetti V, Sau G, Garau M, Gioia R, Sanna G. Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease. Neurology. 1988;38:384–388. doi: 10.1212/WNL.38.3.384.
    1. Rosati G, Aiello I, Pirastru MI, Mannu L, Sanna G, Sau GF, Sotgiu S. Epidemiology of multiple sclerosis in northwestern Sardinia: further evidence for higher frequency in Sardinians compared to other Italians. Neuroepidemiology. 1996;15:10–19. doi: 10.1159/000109884.
    1. Millefiorini E, Cortese A, Di Rezze S, Barletta G, Bellantonio P, Batocchi AP, Di Battista G, Fiore S, Gasperini C, Grasso MG. et al.The prevalence of multiple sclerosis in central Italy. Multiple sclerosis. 2010;16(12):1432–1436. doi: 10.1177/1352458510373263.
    1. Totaro R, Marini C, Cialfi A, Giunta M, Carolei A. Prevalence of multiple sclerosis in the L’Aquila district, central Italy. J Neurol Neurosurg Psychiatry. 2000;68:349–352. doi: 10.1136/jnnp.68.3.349.
    1. Iuliano G, Napoletano R. Prevalence and incidence of multiple sclerosis in Salerno (southern Italy) and its province. Eur J Neurol. 2008;15(1):73–76.
    1. Granieri E, Monaldini C, De Gennaro R, Guttmann S, Volpini M, Stumpo M, Fazio P, Casetta I. Multiple sclerosis in the Republic of San Marino: a prevalence and incidence study. Multiple sclerosis. 2008;14(3):325–329. doi: 10.1177/1352458507084114.
    1. Sotgiu S, Pugliatti M, Sanna A, Sotgiu A, Castiglia P, Solinas G, Dolei A, Serra C, Bonetti B, Rosati G. Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy. Eur J Neurol. 2002;9:329–341. doi: 10.1046/j.1468-1331.2002.00412.x.
    1. Allen KW. The prevalence of multiple sclerosis in the health district of Bassetlaw. Public Heal. 1990;104:37–43. doi: 10.1016/S0033-3506(05)80344-0.
    1. Ford HL, Gerry E, Airey CM, Vail A, Johnson MH, Williams DRR. The prevalence of multiple sclerosis in the Leeds Health Authority. J Neurol Neurosurg Psychiatry. 1998;64:605–610. doi: 10.1136/jnnp.64.5.605.
    1. Ford HL, Gerry E, Johnson M, Williams R. A prospective study of the incidence, prevalence and mortality of multiple sclerosis in Leeds. J Neurol. 2002;249:260–265. doi: 10.1007/s004150200002.
    1. Fox CM, Bensa S, Bray I, Zajicek JP. The epidemiology of multiple sclerosis in Devon: a comparison of the new and old classification criteria. J Neurol Neurosurg Psychiatry. 2004;75:56–60.
    1. Lockyer MJ. Prevalence of multiple sclerosis in five rural Suffolk practices. BMJ. 1991;303:347–348. doi: 10.1136/bmj.303.6798.347.
    1. MacDonald BK, Cockerell OC, Sander JWAS, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain. 2000;123:665–676. doi: 10.1093/brain/123.4.665.
    1. Mumford CJ, Fraser MB, Wood NW, Compston DAS. Multiple sclerosis in the Cambridge health district of East Anglia. J Neurol Neurosurg Psychiatry. 1992;55:877–882. doi: 10.1136/jnnp.55.10.877.
    1. Roberts MHW, Martin JP, McLellan DL, McIntosh-Michaelis SA, Spackman AJ. The prevalence of multiple sclerosis in the Southampton and South West Hampshire Health Authority. J Neurol Neurosurg Psychiatry. 1991;54:55–59. doi: 10.1136/jnnp.54.1.55.
    1. Robertson N, Deans J, Fraser M, Compston DAS. Multiple sclerosis in the north Cambridgeshire districts of East Anglia. J Neurol Neurosurg Psychiatry. 1995;59:71–76. doi: 10.1136/jnnp.59.1.71.
    1. Robertson N, Deans J, Fraser M, Compston DAS. Multiple sclerosis in south Cambridgeshire: incidence and prevalence based on a district register. J Epidemiol Community Health. 1996;50:274–279. doi: 10.1136/jech.50.3.274.
    1. Shepherd DI, Summers A. Prevalence of multiple sclerosis in Rochdale. J Neurol Neurosurg Psychiatry. 1996;61:415–417. doi: 10.1136/jnnp.61.4.415.
    1. Williams ES, McKeran RO. Prevalence Of Multiple Sclerosis In A South London Borough. BMJ. 1986;293(6541):237–239. doi: 10.1136/bmj.293.6541.237.
    1. Rice-Oxley M, Williams ES, Rees JE. A prevalence survey of multiples clerosis in Sussex. J Neurol Neurosurg Psychiatry. 1995;58:27–30. doi: 10.1136/jnnp.58.1.27.
    1. Cook SD, MacDonald J, Tapp W, Poskanzer D, Dowling PC. Multiple sclerosis in the Shetland Islands: an update. Acta Neurol Scand. 1988;77:148–151. doi: 10.1111/j.1600-0404.1988.tb05885.x.
    1. Donnan PT, Parratt JDE, Wilson SV, Forbes RB, O’Riordan JI, Swingler RJ. Multiple sclerosis in Tayside, Scotland: detection of clusters using a spatial scan statistic. Multiple sclerosis. 2005;11(4):403–408. doi: 10.1191/1352458505ms1191oa.
    1. Forbes RB, Wilson SV, Swingler RJ. The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist? J Neurol. 1999;246:1033–1040. doi: 10.1007/s004150050509.
    1. Grant RM, Carver AD, Sloan RL. Multiple sclerosis in Fife. Scot Med J. 1998;42:44–47.
    1. Murray S, Bashir K, Penrise G, Womersley SJ. Epidemiology of multiple sclerosis in Glasgow. Scot Med J. 2004;49:100–104.
    1. Hennessy A, Swingler RJ, Compston DAS. The incidence and mortality of multiple sclerosis in southeast Wales. J Neurol Neurosurg Psychiatry. 1989;52:1085–1089. doi: 10.1136/jnnp.52.9.1085.
    1. Hirst C, Ingram G, Pickersgill T, Swingler R, Compston DA, Robertson NP. Increasing prevalence and incidence of multiple sclerosis in South East Wales. J Neurol Neurosurg Psychiatry. 2009;80(4):386–391.
    1. Swingler RJ, Compston DAS. The prevalence of multiple sclerosis in South East Wales. J Neurol Neurosurg Psychiatry. 1988;51:1520–1524. doi: 10.1136/jnnp.51.12.1520.
    1. Gray OM, McDonnell GV, Hawkins SA. Factors in the rising prevalence of multiple sclerosis in the north-east of Ireland. Multiple sclerosis. 2008;14(7):880–886. doi: 10.1177/1352458508090663.
    1. Hawkins SA, Kee K. In: Recent advances in multiple sclerosis therapy: proceedings of the Vth Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Brussels, 16-18 March 1989. Gonsette RE, Delmotte P, editor. Amsterdam: Excerpta Medica; 1989. The changing prevalence of multiple sclerosis in Northern Ireland with reference to benign multiple sclerosis; pp. 357–358.
    1. McDonnell GV, Hawkins SA. An epidemiologic study of multiple sclerosis in Northern Ireland. Neurology. 1998;50:423–428. doi: 10.1212/WNL.50.2.423.
    1. McGuigan C. Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity. J Neurol Neurosurg Psychiatry. 2004;75(4):572–576. doi: 10.1136/jnnp.2003.012666.
    1. Sharpe G, Price SE, Last A, Thompson RJ. Multiple sclerosis in island populations: prevalence in the Bailiwicks of Guernsey and Jersey. J Neurol Neurosurg Psychiatry. 1995;58:22–26. doi: 10.1136/jnnp.58.1.22.
    1. Alonso A, Jick SS, Olek MJ, Hernan MA. Incidence of multiple sclerosis in the United Kingdom : findings from a population-based cohort. J Neurol. 2007;254(12):1736–1741. doi: 10.1007/s00415-007-0602-z.
    1. Celius EG, Vandvik B. Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period. Eur J Neurol. 2001;8:463–469. doi: 10.1046/j.1468-1331.2001.00269.x.
    1. Dahl OP, Aarseth JH, Myhr KM, Nyland H, Midgard R. Multiple sclerosis in Nord-Trøndelag County, Norway: a prevalence and incidence study. Acta Neurol Scand. 2003;109:378–384.
    1. Grønlie SA, Myrvoll E, Hansen G, Grønning M, Mellgren SI. Multiple sclerosis in North Norway, and first appearance in an indigenous population. J Neurol. 2000;247:129–133. doi: 10.1007/PL00007793.
    1. Grønning M, Riise T, Kvåle G, Nyland H, Larsen JP, Aarli JA. Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern. Neuroepidemiology. 1991;10:53–61. doi: 10.1159/000110247.
    1. Grytten N, Glad SB, Aarseth JH, Nyland H, Midgard R, Myhr K-M. A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway. Neurology. 2006;66:182–186. doi: 10.1212/01.wnl.0000195549.95448.b9.
    1. Harbo HF, Utsi E, Lorentzen AR, Kampman MT, Celius EG, Myhr KM, Lie BA, Mellgren SI, Thorsby E. Low frequency of the disease-associated DRB1*15-DQB1*06 haplotype may contribute to the low prevalence of multiple sclerosis in Sami. Tissue antigens. 2007;69(4):299–304. doi: 10.1111/j.1399-0039.2007.00803.x.
    1. Midgard R, Riise T, Nyland H. Epidemiologic trends in multiple sclerosis in Møre and Romsdal, Norway: a prevalence/incidence study in a stable population. Neurology. 1991;41:887–892. doi: 10.1212/WNL.41.6.887.
    1. Midgard R, Riise T, Svanes C, Kvåle G, Nyland H. Incidence of multiple sclerosis in M0re and Romsdal, Norway from 1950 to 1991: an age-period-cohort analysis. Brain. 1996;119:203–211. doi: 10.1093/brain/119.1.203.
    1. Sundström P, Nyström L, Forsgren L. Prevalence of multiple sclerosis in Västerbotten County in northern Sweden. Acta Neurol Scand. 2001;103:214–218. doi: 10.1034/j.1600-0404.2001.103004214.x.
    1. Sundström P, Nyström L, Forsgren L. Incidence (1988–97) and prevalence (1997) of multiple sclerosis in Västerbotten County in northern Sweden. J Neurol Neurosurg Psychiatry. 2003;74:29–32. doi: 10.1136/jnnp.74.1.29.
    1. Svenningsson A, Runmarker B, Lycke J, Andersen O. Incidence of MS during two fifteen-year periods in the Gothenburg region of Sweden. Acta Neurol Scand. 1990;82:161–168. doi: 10.1111/j.1600-0404.1990.tb04483.x.
    1. Bostrom I, Callander M, Kurtzke JF, Landtblom AM. High prevalence of multiple sclerosis in the Swedish county of Varmland. Multiple sclerosis. 2009;15(11):1253–1262. doi: 10.1177/1352458509345909.
    1. Bentzen J, Flachs EM, Stenager E, Bronnum-Hansen H, Koch-Henriksen N. Prevalence of multiple sclerosis in Denmark 1950–2005. Multiple sclerosis. 2010;16(5):520–525. doi: 10.1177/1352458510364197.
    1. Eaton WW, Pedersen MG, Atladottir HO, Gregory PE, Rose NR, Mortensen PB. The prevalence of 30 ICD-10 autoimmune diseases in Denmark. Immunol Res. 2010;47(1–3):228–231.
    1. Eaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB. Epidemiology of autoimmune diseases in Denmark. J Autoimmun. 2007;29(1):1–9. doi: 10.1016/j.jaut.2007.05.002.
    1. Koch-Henriksen N. The Danish Multiple Sclerosis Registry: a 50-year follow-up. Multiple sclerosis. 1999;5(4):293–296.
    1. Sarasoja T, Wikstrom J, Paltamaa J, Hakama M, Sumelahti ML. Occurrence of multiple sclerosis in central Finland: a regional and temporal comparison during 30 years. Acta Neurol Scand. 2004;110(5):331–336. doi: 10.1111/j.1600-0404.2004.00326.x.
    1. Benedikz J, Magnússon H, Guõmundsson G. Multiple sclerosis in Iceland, with observations on the alleged epidemic in the Faroe Islands. Ann Neurol. 1994;36(S2):S175–S179. doi: 10.1002/ana.410360804.
    1. Benedikz J, Magnússon H, Poser CM, Benedikz E, Olafsdottir G, Gudmundsson G. Multiple sclerosis in Iceland 1900-1985. J Trop and Geogr Neurol. 1991;1:16–22.
    1. Benedikz J, Stefánsson M, Guõmundsson J, Jónasdóttir A, Fossdal R, Gulcher J, Stefánsson K. The natural history of untreated multiple sclerosis in Iceland. A total population-based 50 year prospective study. Clin Neurol Neurosurg. 2002;104:208–210. doi: 10.1016/S0303-8467(02)00040-9.
    1. Joensen P. Multiple sclerosis incidence in the Faroe Islands 1986-2007. Acta Neurol Scand. 2010;121(5):348–353. doi: 10.1111/j.1600-0404.2009.01252.x.
    1. De Sa J, Paulos A, Mendes H, Becho J, Marques J, Roxo J. The prevalence of multiple sclerosis in the District of Santarem, Portugal. J Neurol. 2006;253(7):914–918. doi: 10.1007/s00415-006-0132-0.
    1. Ares B, Prieto JM, Lema M, Dapena D, Arias M, Noya M. Prevalence of multiple sclerosis in Santiago de Compostela (Galicia, Spain) Mult Scler. 2007;13:262–264. doi: 10.1177/1352458506069540.
    1. Benito-Léon J, Martin E, Vela L, Villar ME, Felgueroso B, Marrero C, Guerrero A, Ruiz-Galiana J. Multiple sclerosis in Mbstoles, central Spain. Acta Neurol Scand. 1998;98:238–242. doi: 10.1111/j.1600-0404.1998.tb07302.x.
    1. Bufill E, Blesa R, Galan I, Dean G. Prevalence of multiple sclerosis in the region of Osona, Catalonia, northern Spain. J Neurol Neurosurg Psychiatry. 1995;58:577–581. doi: 10.1136/jnnp.58.5.577.
    1. Fernandez O, Fernandez V, Martinez-Cabrera V, Mayorga C, Alonso A, Leon A, Arnal C, Hens M, Luque G, de Ramon E. et al.Multiple sclerosis in Gypsies from southern Spain: prevalence, mitochondrial DNA haplogroups and HLA class II association. Tissue Antigens. 2008;71(5):426–433. doi: 10.1111/j.1399-0039.2008.01016.x.
    1. Fernandez O, Luque G, San Román C, Bravo M, Dean G. The prevalence of multiple sclerosis - in the Sanitary District of Vélez-Malaga, southern Spain. Neurology. 1994;44:425–429. doi: 10.1212/WNL.44.3_Part_1.425.
    1. Modrego Pardo PJ, Pina Latorre MA, López A, Errea JM. Prevalence of multiple sclerosis in the province of Teruel, Spain. J Neurol. 1997;244:182–185. doi: 10.1007/s004150050070.
    1. Modrego PJ, Pina MA. Trends in prevalence and incidence of multiple sclerosis in Bajo Aragón, Spain. J Neurol Sci. 2003;216(1):89–93. doi: 10.1016/j.jns.2003.07.007.
    1. Pina MA, Ara JR, Modrego PJ, Morales F, Capablo JL. Prevalence of multiple sclerosis in the sanitary district of Calatayud, Northern Spain: is Spain a zone of high risk for this disease? Neuroepidemiology. 1998;17:258–264. doi: 10.1159/000026178.
    1. Tola MA, Yugueros MI, Fernández-Buey N, Fernández-Herranz R. Prevalence of multiple sclerosis in Valladolid, northern Spain. J Neurol. 1999;246:170–174. doi: 10.1007/s004150050329.
    1. Uria DF, Calatayud MT, Virgala P, Diaz A, Chamizo C, Dean G. Multiple sclerosis in Gijon health district, Asturias, northern Spain. Acta Neurol Scand. 1997;96:375–379.
    1. Aladro Y, Alemany MJ, Perez-Vieitez MC, Amela R, Conde M, Reyes MP, Alamo F, Angel-Moreno A. Prevalence and incidence of multiple sclerosis in Las Palmas, Canary Islands, Spain. Neuroepidemiology. 2005;24(1–2):70–75.
    1. Hernandez MA. Epidemiology of multiple sclerosis in the Canary Islands (Spain): a study on the island of La Palma. J Neurol. 2002;249(10):1378–1381. doi: 10.1007/s00415-002-0841-y.
    1. Casqueroa P, Villosladac P, Montalbán X, Torrent M. Frequency of multiple sclerosis in Menorca, Balearic Islands, Spain. Neuroepidemiology. 2001;20:129–133. doi: 10.1159/000054772.
    1. van Ooteghem P, D’Hooghe MB, Vlietinck R, Carton H. Prevalence of multiple sclerosis in Flanders, Belgium. Neuroepidemiology. 1994;13:220–225. doi: 10.1159/000110383.
    1. Debouverie M, Pittion-Vouyovitch S, Louis S, Roederer T, Guillemin F. Increasing incidence of multiple sclerosis among women in Lorraine, Eastern France. Multiple sclerosis. 2007;13(8):962–967. doi: 10.1177/1352458507077938.
    1. Moreau T, Manceau E, Lucas B, Lemesle M, Urbinelli R, Giroud M. Incidence of multiple sclerosis in Dijon, France: a population-based ascertainment. Neurol Res. 2000;22:156–159.
    1. Sagnes-Raffy C, Gourraud P-A, Hannon V, Bourrel R, Laffontan M-A, Gaulene M-C, Viala F, Clanet M. La SEP en Haute-Garonne: une sous-estimation importante du nombre de cas. Rev Epidemiol Sante Publique. 2010;59:23–31.
    1. Fromont A, Binquet C, Sauleau EA, Fournel I, Bellisario A, Adnet J, Weill A, Vukusic S, Confavreux C, Debouverie M. et al.Geographic variations of multiple sclerosis in France. Brain. 2010;133(Pt 7):1889–1899.
    1. Beer S, Kesselring J. High prevalence of multiple sclerosis in Switzerland. Neuroepidemiology. 1994;13:14–18. doi: 10.1159/000110353.
    1. Poser S, Stickel B, Krtsch U, Burckhardt D, Nordman B. Increasing incidence of multiple sclerosis in south lower Saxony, Germany. Neuroepidemiology. 1989;8:207–213. doi: 10.1159/000110184.
    1. Fasbender P, Kolmel HW. Incidence of multiple sclerosis in the urban area of Erfurt, Thuringia, Germany. Neuroepidemiology. 2008;30(3):147–151. doi: 10.1159/000122331.
    1. Baumhackl U, Eibl G, Ganzinger U, Hartung HP, Mamoli B, Pfeiffer KP, Fazekas F, Vass K, Committee AMS. Prevalence of multiple sclerosis in Austria; results of a nationwide survey. Neuroepidemiology. 2002;21:226–234. doi: 10.1159/000065640.
    1. Bencsik K, Rajda C, Füvesi J, Klivényi P, Járdánházy T, Török M, Vécsei L. The prevalence of multiple sclerosis, distribution of clinical forms of the disease and functional Status of patients in Csongrád County, Hungary. Eur Neurol. 2001;46:206–209. doi: 10.1159/000050806.
    1. Bencsik K, Rajda C, Klivényi P, Járdánházy T, Vécsei L. The prevalence of multiple sclerosis in the Hungarian city of Szeged. Acta Neurol Scand. 1998;97:315–319.
    1. Sepcic J, Antonelli L, Materljan E, Sepic-Grahovac D. In: Multiple sclerosis research: proceedings of the International Multiple Sclerosis Conference-an update on Multiple Sclerosis. Battaglia MA, editor. Amsterdam: Excerpta Medica; 1989. Multiple sclerosis cluster in Gorski Kotar, Croatia, Yugoslavia; pp. 165–169.
    1. Pekmezovic T, Jarebinski M, Drulovic J, Stojsavljevic N, Levic Z. Prevalence of multiple sclerosis in Belgrade, Yugoslavia. Acta Neurol Scand. 2001;104:353–357. doi: 10.1034/j.1600-0404.2001.00064.x.
    1. Dobec-Meić B, Puljić I. Incidence of multiple sclerosis in the Varaždin County. Neurol Croat. 2007;56(1–2):17–24.
    1. Dobec-Meić B, Puljić I, Kalousek M. Prevalence of multiple sclerosis in Varaždin Region. Neurol Croat. 2008;57(1–2):3–9.
    1. Peterlin B, Ristic S, Sepcic J, Vracko BK, Rako A, Lovrecic L, Brajenovic-Milic B, Rudez J, Materljan E, Kapovic M. Region with persistent high frequency of multiple sclerosis in Croatia and Slovenia. J Neurol Sci. 2006;247(2):169–172. doi: 10.1016/j.jns.2006.04.002.
    1. Klupka-Sarić I, Galić M. Epidemiology of multiple sclerosis in Western Herzegovina and Herzegovina – Neretva Canton, Bosnia and Herzegovina. Coll Antropol. 2010;34(S1):189–193.
    1. Klupka-Saric I, Ristic S, Sepcic J, Kapovic M, Peterlin B, Materljan E, Jurisic T, Mamic DM, Burina A, Sulentic V. Epidemiology of multiple sclerosis in western Herzegovina. Clin Neurol Neurosurg. 2007;109(9):779–783. doi: 10.1016/j.clineuro.2007.07.014.
    1. Milanov I, Georgiev D, Kmetska K, Jordanova L, Topalov N. Prevalence of multiple sclerosis in Bulgaria. Neuroepidemiology. 1997;16:304–307. doi: 10.1159/000109701.
    1. Papathanasopoulos P, Gourzoulidou E, Messinis L, Georgiou V, Leotsinidis M. Prevalence and incidence of multiple sclerosis in western Greece: a 23-year survey. Neuroepidemiology. 2008;30(3):167–173. doi: 10.1159/000122334.
    1. Piperidou HN, Heliopoulos IN, Maltezos ES, Milonas IA. Epidemiological Data of Multiple Sclerosis in the Province ofEvros, Greece. Eur Neurol. 2003;49(1):8–12. doi: 10.1159/000067020.
    1. Gross K, Kokk A, Kaasik A-E. Prevalence of MS in South Estonia. Evidence of a new border of the Fennoscandian Iocus. Acta Neurol Scand. 1993;88:241–246.
    1. Koutsouraki E, Costa V, Baloyannis S. Epidemiology of multiple sclerosis in Europe: a review. Int Rev Psychiatry. 2010;22(1):2–13. doi: 10.3109/09540261003589216.
    1. Pugliatti M, Rosati G, Carton H, Riise T, Drulovic J, Vecsei L, Milanov I. The epidemiology of multiple sclerosis in Europe. Eur J Neurol. 2006;13(7):700–722. doi: 10.1111/j.1468-1331.2006.01342.x.
    1. Rosati G. Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: a critical overview. Ann Neurol. 1994;36(S2):S164–S174. doi: 10.1002/ana.410360803.
    1. Culpepper W, Ehrmantraut M, Wallin M, Flannery K, Bradham D. Veterans Health Administration multiple sclerosis surveillance registry: the problem of case-finding from administrative databases. J Rehabil Res Dev. 2006;43:17–24. doi: 10.1682/JRRD.2004.09.0122.
    1. Marrie R, Yu N, Blanchard J, Leung S, Elliot L. The rising prevalence and changing age distribution of multiple sclerosis in Manitoba. Neurology. 2010;74:465–471. doi: 10.1212/WNL.0b013e3181cf6ec0.
    1. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry. 2011;82:1132–1141. doi: 10.1136/jnnp.2011.240432.
    1. Esbjerg S, Keiding N, Koch-Henriksen N. Reporting delay and corrected incidence of multiple sclerosis. Stat Med. 1999;18(13):1691–1706. doi: 10.1002/(SICI)1097-0258(19990715)18:13<1691::AID-SIM160>;2-D.
    1. Marrie RA, Cutter G, Tyry T, Hadjimichael O, Campagnolo D, Vollmer T. Changes in the ascertainment of multiple sclerosis. Neurology. 2005;65(7):1066–1070. doi: 10.1212/01.wnl.0000178891.20579.64.
    1. Kingwell E, Leung AL, Roger E, Duquette P, Rieckmann P, Tremlett H, The MS. Clinic Neurologists: Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts. J Neurol Sci. 2010;292:57–62. doi: 10.1016/j.jns.2010.02.007.
    1. Zivadinov R, Iona L, Monti-Bragadin L, Bosco A, Jurjevic A, Taus C, Cazzato G, Zorzon M. The use of standardized incidence and prevalence rates in epidemiological studies in multiple sclerosis: a meta-analysis study. Neuroepidemiology. 2003;22:65–74. doi: 10.1159/000067107.

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