Background. MS incidence has increased among females, suggesting the presence of environmental effect. Object. Regional differences and temporal changes in gender-specific MS incidence were studied in Finland. Methods. Cases from Jan 1, 1981 to Dec 31, 2010 in Pirkanmaa, Sein？joki and Vaasa districts were included. The standardized incidence rates (SIR), incidences per 105 person years with 95% confidence intervals (CI), and female-to-male ratios (F/M) were determined by district. Results. 1617 cases were included. Compared to Pirkanmaa, the MS risk was 1.9-fold (95% CI: 1.7–2.0) greater in Sein？joki and 1.2-fold (95% CI: 1.1–1.4) in Vaasa, and the risk was high for both genders. The incidence trend stabilized in Sein？joki and Vaasa, accompanied by an increase in the F/M ratio. A steady increase in Pirkanmaa was accompanied by a high F/M ratio. Conclusion. A high female preponderance accompanied a general increase in incidence since the 1990s, suggesting the influence of environmental factors. In high-risk districts, increased MS risk prevailed in both genders. High risk reflects both genetic and environmental effects. These effects may be shared with autoimmune diseases such as type 1 diabetes mellitus; the incidence of which follows MS in Finland. Population-based case-control studies are needed to identify these factor effects. 1. Introduction MS incidence has increased, particularly among females [1–4], indicating the influence of environmental factors. The integration of magnetic resonance imaging (MRI) in diagnostic criteria since the 1990s and progress in immunomodulatory drug treatments have contributed to these increasing rates [5, 6]. Epidemiologically, MS is characterized by an uneven geographical distribution [7]. Studies performed since 1964 confirm this observation in Finland [8–10], which is located in Northern Europe between the latitudes 60 and 70°N. High-risk areas in the western districts, Sein？joki and Vaasa, are characterized by an irregular incidence pattern, and an increased male risk was observed in Sein？joki in 1979–1993 [10]. We aimed to analyze the gender-specific incidence in high- and medium-risk areas in 1981–2010 to make inferences on the etiological factors correlated with high-risk groups. The incidence in the former medium-risk area Pirkanmaa [8] is studied for the first time. Incidence is regarded as the most important indicator of disease frequency, and changes in incidence reflect environmental factors in genetically stable populations. 2. Materials and Methods The districts examined in this study are shown in Figure
References
[1]
N. Koch-Henriksen and P. S. S？rensen, “The changing demographic pattern of multiple sclerosis epidemiology,” The Lancet Neurology, vol. 9, no. 5, pp. 520–532, 2010.
[2]
O. M. Gray, G. V. McDonnell, and S. A. Hawkins, “Factors in the rising prevalence of multiple sclerosis in the North-East of Ireland,” Multiple Sclerosis, vol. 14, no. 7, pp. 880–886, 2008.
[3]
S. Simpson Jr., L. Blizzard, P. Otahal, I. van der Mei, and B. Taylor, “Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 82, no. 10, pp. 1132–1141, 2011.
[4]
A. Alonso and M. A. Hernán, “Temporal trends in the incidence of multiple sclerosis: a systematic review,” Neurology, vol. 71, no. 2, pp. 129–135, 2008.
[5]
M. Tintoré, A. Rovira, J. Río et al., “New diagnostic criteria for multiple sclerosis: application in first demyelinating episode,” Neurology, vol. 60, no. 1, pp. 27–30, 2003.
[6]
M. Filippi and M. A. Rocca, “MR imaging of multiple sclerosis,” Radiology, vol. 259, no. 3, pp. 659–681, 2011.
[7]
A. Compston, “Genetic epidemiology of multiple sclerosis,” Journal of Neurology Neurosurgery and Psychiatry, vol. 62, no. 6, pp. 553–561, 1997.
[8]
J. Wikstr？m, “Studies on the clustering of multiple sclerosis in Finland. II: microepidemiology in one high risk county with special reference to familial cases,” Acta Neurologica Scandinavica, vol. 51, no. 3, pp. 173–183, 1975.
[9]
E. Kinnunen, “Multiple sclerosis in Finland: evidence of increasing frequency and uneven geographic distribution,” Neurology, vol. 34, no. 4, pp. 457–461, 1984.
[10]
M. L. Sumelahti, P. J. Tienari, J. Wikstr？m, J. Palo, and M. Hakama, “Regional and temporal variation in the incidence of multiple sclerosis in Finland 1979–1993,” Neuroepidemiology, vol. 19, no. 2, pp. 67–75, 2000.
C. M. Poser, D. W. Paty, L. Scheinberg et al., “New diagnostic criteria for multiple sclerosis: guidelines for research protocols,” Annals of Neurology, vol. 13, no. 3, pp. 227–231, 1983.
[13]
P. Armitage and G. Berry, “Standardization,” in Statistical Methods in Medical Research, P. Armitage and G. Berry, Eds., pp. 436–443, Blackwell Science, Oxford, UK, 1994.
[14]
C. Hirst, G. Ingram, T. Pickersgill, R. Swingler, D. A. S. Compston, and N. P. Robertson, “Increasing prevalence and incidence of multiple sclerosis in South East Wales,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 80, no. 4, pp. 386–391, 2009.
[15]
S. M. Orton, B. M. Herrera, I. M. Yee et al., “Sex ratio of multiple sclerosis in Canada: a longitudinal study,” The Lancet Neurology, vol. 5, no. 11, pp. 932–936, 2006.
[16]
E. G. Celius and C. Smestad, “Change in sex ratio, disease course and age at diagnosis in Oslo MS patients through seven decades,” Acta Neurologica Scandinavica, no. 189, pp. 27–29, 2009.
[17]
E. Kinnunen, S. Koskimies, A. Lagerstedt, and J. Wikstrom, “Histocompatibility antigens in familial multiple sclerosis in a high-risk area of the disease,” Journal of the Neurological Sciences, vol. 65, no. 2, pp. 147–155, 1984.
[18]
P. J. Tienari, J. Wikstr？m, A. Sajantila, J. Palo, and L. Peltonen, “Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene,” The Lancet, vol. 340, no. 8826, pp. 987–991, 1992.
[19]
H. R. Nevanlinna, “The Finnish population structure. A genetic and genealogical study,” Hereditas, vol. 71, no. 2, pp. 195–236, 1972.
[20]
E. Salmela, T. Lappalainen, I. Fransson et al., “Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe,” PLoS ONE, vol. 3, no. 10, Article ID e3519, 2008.
[21]
U. Hannelius, E. Salmela, T. Lappalainen et al., “Population substructure in Finland and Sweden revealed by the use of spatial coordinates and a small number of unlinked autosomal SNPs,” BMC Genetics, vol. 9, article 54, 2008.
[22]
W. I. McDonald, A. Compston, G. Edan et al., “Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis,” Annals of Neurology, vol. 50, no. 1, pp. 121–127, 2001.
[23]
C. H. Polman, S. C. Reingold, G. Edan et al., “Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald criteria’,” Annals of Neurology, vol. 58, no. 6, pp. 840–846, 2005.
[24]
D. S. Goodin, E. M. Frohman, G. P. Garmany Jr. et al., “Disease modifying therapies in multiple sclerosis: report of the therapeutics and technology assessment subcommittee of the American academy of neurology and the MS council for clinical practice guidelines,” Neurology, vol. 58, no. 2, pp. 169–178, 2002.
[25]
“NICE guideline for management of multiple sclerosis,” 2003, http://www.nice.org/.
[26]
Working Group Appointed by the Finnish Medical Society Duodecim and the Finnish Neurological Society, “Current care guideline: multiple sclerosis,” The Finnish Medical Society Duodecim and the Finnish Neurological Society, 2009 and 2012.
[27]
M. S. Freedman, E. J. Thompson, F. Deisenhammer et al., “Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement,” Archives of Neurology, vol. 62, no. 6, pp. 865–870, 2005.
[28]
G. Soltesz, C. C. Patterson, and G. Dahlquist, “Worldwide childhood type 1 diabetes incidence—what can we learn from epidemiology?” Pediatric Diabetes, vol. 8, no. 6, pp. 6–14, 2007.
