Inger Boström

Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg).

Background: Sex ratio in multiple sclerosis has been reported from several geographical areas. The disease is more common in women. In Europe the female-to-male ratio varies from 1.1 to 3.4. A recent study from Canada has reported a significant increase, with time, in female-to-male ratio in multiple sclerosis over the last 100 years. Objective: The aim of this study was to analyse any change in sex ratio in multiple sclerosis in the Swedish population. Methods: Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset. Results: In the analysis of sex ratio by year of birth there were 8834 patients (6271 women and 2563 men) born between 1931 and 1985. The mean women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p = 0.298, n = 11). The number of patients analysed by year of onset was 9098 during the time period 1946 until 2005. The mean women-to-men ratio was 2.57. No significant change in women-to-men ratio (Spearman’s rho = −0.007, p = 0.983, n = 12) with time was observed. Conclusion: There is no evidence for an increasing women-to-men ratio with time amongst Swedish multiple sclerosis patients.

High prevalence of multiple sclerosis in the Swedish county of Värmland.

Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991—1995, 1996—2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

New data identify an increasing sex ratio of multiple sclerosis in Sweden

Background: An increasing women-to-men ratio in later birth cohorts of patients with multiple sclerosis (MS) has been observed in several populations and has been hypothesised to be due to one or several environmental factors of importance for disease aetiology. However, in a study based on data from the Swedish MS registry (SMSreg) this ratio was recently reported to be rather stable during the 20th century. Objective: The purpose of this study was to reinvestigate the women-to-men ratio in Sweden based on data from all available data sources, including deceased patients. Method: We combined data from the SMSreg with data from national patient registers. Results: In total we obtained information on 19,510 MS patients born 1931–1985, 13,321 women and 6189 men. The women-to-men ratio increased from 1.70 for patients born in the 1930s to 2.67 for patients born in the 1980s. When comparing the coverage of SMSreg to the full data set, a significantly higher proportion of women born 1931–1935 compared to men born in the same period were found in SMSreg, resulting in a sampling bias hiding the increasing sex ratio in the full material. Conclusion: The women-to-men ratio in MS has increased in Sweden during the 20th century similarly to observations in other western countries.

Mortality statistics for multiple sclerosis and amyotrophic lateral sclerosis in Sweden.

Background: Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic neurologic diseases for which distinct explanations of the pathogenesis are lacking. Two large Swedish register studies have rather unexpectedly detected a correlation between MS and ALS. The aim of this study was to investigate if an association between ALS and MS could be demonstrated as has been shown earlier. Material and Methods: Data on mortality from ALS and MS, 1990–2010, were collected from the Swedish National Statistics Office. In all there were 5,696 deaths due to ALS and 3,941 deaths due to MS. Age- and sex-adjusted mortality rates were calculated. Results: There was no correlation between the mortality rates of ALS and MS in the 21 counties of Sweden for the period 1990–2010 (Spearman’s rho = –0.052; p = 0.822; n = 21). The national mean mortality rate for ALS throughout the period of 1990–2010 was 2.98 per 100,000 person-years (95% CI 2.87–3.08). For MS the national mean mortality rate was 2.04 per 100,000 person-years (95% CI 1.95–2.12). Conclusion: This study did not confirm the previously shown association between MS and ALS in Sweden.

Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study:

Background: The lifestyle factors smoking and obesity have been associated with the risk of multiple sclerosis (MS). Physical activity (PA) may also be of importance. Objective: To examine the association between PA and MS risk in Italy, Norway, and Sweden and to evaluate the possible influence by established risk factors. Methods: In this case–control study, 1904 cases and 3694 controls were asked to report their average weekly amounts of light and vigorous PA during adolescence on a scale ranging from none to more than 3 hours activity. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for potential confounders. Results: Vigorous PA was inversely associated with MS risk in the pooled analysis (p-trend < 0.001) with an age- and sex-adjusted OR of 0.74 (95% CI: 0.63–0.87) when comparing the highest and lowest levels. Adjusting for outdoor activity, infectious mononucleosis, body size, and smoking yielded similar results. The association was present in all countries and was not affected by exclusion of patients with early disease onset. Light PA was not associated with the risk of MS. Conclusion: Our findings suggest that vigorous PA can modify the risk of developing MS independent of established risk factors.

Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study

Background: Results from previous studies on a possible interaction between smoking and Epstein–Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. Objectives: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. Methods: Within the case–control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM. We examined the interaction between the two exposures on the additive and multiplicative scale. Results: Smoking and IM were each found to be associated with an increased MS risk in all three countries, and there was a negative multiplicative interaction between the two exposures in each country separately as well as in the pooled analysis (p = 0.001). Among those who reported IM, there was no increased risk associated with smoking (odds ratio (OR): 0.95, 95% confidence interval (CI): 0.66–1.37). The direction of the estimated interactions on the additive scale was consistent with a negative interaction in all three countries (relative excess risk due to interaction (RERI): −0.98, 95% CI: −2.05–0.15, p = 0.09). Conclusion: Our findings indicate competing antagonism, where the two exposures compete to affect the outcome.

Does the changing sex ratio of multiple sclerosis give opportunities for intervention

In several international studies, an increasing women‐to‐men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age‐specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.

Age-specific sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg)

In several countries, an increase in the women-to-men ratio in multiple sclerosis (MS) has been observed but, interestingly, this trend has not been confirmed in Sweden1 as was quoted in the editorial of Multiple Sclerosis Journal, 2012; 19: 3–4. Important observations on the potential influence of environmental factors were introduced in the editorial, e.g. an older age at first birth or fertility rates. The increase of the women-to-men ratio seems to be correlated to a reduced number of child births in the populations from Canada and Denmark, but not from Sweden. This is in spite of the fact, that the changes in fertility rates during 1940– 2000 in Sweden are quite similar to the Danish (editorial). It is intriguing that the Nordic countries differ regarding the changes in sex ratio in MS with time, and the cause of this difference is not clear, although hormonal factors are of interest. A Swedish study2 revealed that combined oral contraceptives and childbirth delayed MS onset and a recent study from Denmark3 showed that childbirths and pregnancies may have a protective effect in women. It may also be, like the authors in the editorial mentioned, that Sweden already for a long time had a higher women-to-men ratio compared to Canada and Denmark. On the other hand, Sweden may demonstrate an increasing women-to-men ratio in the future. Our results on sex ratio, discussed in the editorial, were calculated on the total of MS patients, by year of birth and by year of onset. If hormonal factors have an effect on the tendency to develop MS, it is logical to suspect that changes of such factors may affect the sex ratio in the fertile subgroup of women. Therefore we stratified our data and added an analysis of the age-specific sex ratio. This gives more information about the trends in the fertile age groups in Swedish women with MS. Our previous results regarding the sex ratio in MS in Sweden1 were reused to analyse the age-specific sex ratio by year of onset (n=9098). The study period was divided into six time periods and into six age groups. For these time periods the ageand sex-adjusted incidence rates were calculated, thereafter the sex ratios were analysed. There was a variation of the women-to-men ratio in all groups during 1951–2005, but no significant changes were found. The age-specific sex ratios in MS from 21 to 50 years are shown in Figure 1. In conclusion, when the sex ratio of MS in Sweden was calculated to give an age-specific women-to-men ratio, the result did not show any significant increase of the womento-men ratio in the fertile age-groups. One may speculate that the short peak (presented in the editorial) in fertility rates in the Swedish women during the time period 1985– 1995 actually prevented an increased women-to-men ratio of MS 1990–2005. Follow-up studies are needed to determine whether the women-to-men ratio in Sweden has increased after 2005, which has now been noticed in the Netherlands.4 One should also adjust for the latitude, since differences regarding sunshine exposure and effects of vitamin D intake may be present.

An ecological study of industry in a high-risk region of multiple sclerosis

The county of Värmland, Sweden, has shown a high frequency of multiple sclerosis in several investigations. It has been presented in three studies; a period prevalence study in 1925-1934, a mortality study during 1952-1992 and a prevalence investigation in 2002. The aim of this study was to investigate the pattern of industry in this high-risk area for multiple sclerosis. The three investigations were correlated with industry in 1913 and in the 1950s, all analyzed by the Kruskall-Wallis test. Select industries from wood-pulp, paper and iron/mechanical sectors were tested also in whole Sweden. The Spearman rank correlation was used for these data and forestry data in Värmland. In Värmland, industrial data from 1913 revealed that large sawmills were associated with the period prevalence in 1925-1934 and there was a possible correlation with the prevalence for 2002. Wood-pulp factories showed a possible association with the prevalence 1925-1934 and the mortality 1952-1992. Some industries in the 1950s were correlated with the prevalence 2002. Wood and paper industries in Sweden 1913 showed an association with the MS mortality 1952-1992. In summary, data on MS prevalence in Värmland and mortality both in Värmland and all Sweden from the past 100 years suggest an association with wood-related industries in 1913 and in the 1950s, whereas no consistent association was found for other industries.

Contents Vol. 38, 2012

196 Regional North American Annual Meeting of the World Federation of Neurology – Research Group on Neuroepidemiology Louisiana State University, New Orleans, La., April 27, 2012 Guest Editors: England, J. (New Orleans, La.); Franklin, G. (Seattle, Wash.) Leimpeter, A. (Oakland, Calif.) Van Den Eeden, S.K. (Oakland, Calif.) (available online only)