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

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          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.

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          Most cited references134

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          Sex ratio of multiple sclerosis in Canada: a longitudinal study.

          Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change. Since environmental risk factors seem to act early in life, we calculated sex ratios by birth year in 27 074 Canadian patients with multiple sclerosis identified as part of a longitudinal population-based dataset. The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3.2:1 in Canada. Year of birth was a significant predictor for sex ratio (p<0.0001, chi(2)=124.4; rank correlation r=0.84). The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene-environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed pound1 million per case in the UK.
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            Environmental factors and multiple sclerosis.

            Studies in Canada have provided strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of multiple sclerosis (MS). However, the available data accommodate more than one type of environmental effect. Migration studies show that changes to early environment can greatly affect risk, and there are recent indications that risk can be altered in situ. The rising incidence rates of MS in Canada implied by longitudinal increases in sex ratio place this effect in temporal context and narrow the candidates for mediating the effect of environment. Similarly, geographical patterns in Australia imply that modifiable environmental factors hold the key to preventing some 80% of cases. Genetic epidemiology provides overwhelming evidence that genetic background has an important complementary role. If genetic factors are held constant, the environment sets the disease threshold. Although these could be independent additive risk factors, it seems more likely that susceptibility is mediated by direct interactions between the environment and genes.
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              Temporal trends in the incidence of multiple sclerosis: a systematic review.

              Multiple sclerosis (MS) has been traditionally considered to be more frequent in women and in regions more distant from the equator. However, recent reports suggest that the latitude gradient could be disappearing and that the female-to-male ratio among patients with MS has increased in the last decades. We have conducted a systematic review of incidence studies of MS to assess the overall incidence of MS and explore possible changes in the latitude gradient and the female-to-male ratio over time. Systematic review of incidence studies of MS published in Medline between 1966 and February 2007. Age- and sex-specific incidence rates were collected from eligible publications. We computed age-adjusted rates using the world population as standard, and assessed differences in rates according to latitude and period of case ascertainment. Additionally, we evaluated the association between period of case ascertainment and the female-to-male ratio. The overall incidence rate of MS was 3.6 cases per 100,000 person-years (95% CI 3.0, 4.2) in women and 2.0 (95% CI 1.5, 2.4) in men. Higher latitude was associated with higher MS incidence, though this latitude gradient was attenuated after 1980, apparently due to increased incidence of MS in lower latitudes. The female-to-male ratio in MS incidence increased over time, from an estimated 1.4 in 1955 to 2.3 in 2000. The latitude gradient present in older incidence studies of multiple sclerosis (MS) is decreasing. The female-to-male MS ratio has increased in the last five decades.
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                Author and article information

                Contributors
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central
                1471-2377
                2013
                26 September 2013
                : 13
                : 128
                Affiliations
                [1 ]Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
                [2 ]Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
                [3 ]Department of Community Health Sciences, University of Calgary, Calgary, Canada
                [4 ]Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
                [5 ]Institute for Public Health, University of Calgary, Calgary, Canada
                [6 ]Department of Pediatrics, University of Calgary, Calgary, Canada
                [7 ]Division of Neurology and Department of Pediatrics, University of Toronto, Toronto, Canada
                [8 ]Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada
                [9 ]Departments of Psychiatry and Medicine, Dalhousie University, Halifax, Canada
                [10 ]College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada
                [11 ]Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
                [12 ]Department of Epidemiology & Biostatistics and Occupational Health, McGill University, Montreal, Canada
                Article
                1471-2377-13-128
                10.1186/1471-2377-13-128
                3856596
                24070256
                33d8a85e-839a-48ab-84db-db3c63e908ca
                Copyright © 2013 Kingwell et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 May 2013
                : 17 September 2013
                Categories
                Research Article

                Neurology
                multiple sclerosis,epidemiology,europe,incidence,prevalence
                Neurology
                multiple sclerosis, epidemiology, europe, incidence, prevalence

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