Multiple sclerosis (MS) is a chronic neuroinflammatory demyelinating disease that is a major cause of disability in young and middle-aged adults.1 Although it is clear that MS has a genetic component, several studies demonstrate that MS is indeed a complex disorder where multiple factors interact, such as genetics, sex, environment, and geography.2
Multiple Sclerosis Prevalence
Recent data has shown that multiple sclerosis prevalence is increasing worldwide, reaching 2.8 million in 2020, with a global prevalence of 35.9 per 100,000 people.3 MS prevalence is associated with geographical distribution, as it is known to increase with latitude4 and within temperate zones.2 Multiple sclerosis relapses have been linked to seasonal variation, with peaks in spring and troughs in winter, a trend observed in both the Northern and Southern Hemispheres.5,6 Such indication strongly suggests a correlation between MS prevalence and sunlight exposure,4 and low levels of vitamin D — which is produced during exposure to sunlight — have also been implicated in MS susceptibility.7
Regarding the prevalence of MS by world region, the latest 2020 World Health Organization report showed increases since 2013 of 87% in the Americas, 59% in Africa, 58% in South East Asia, 38% in the eastern Mediterranean, and 32% in both the western Pacific and Europe, with Europe having the highest number of MS cases per 100,000 people.3
Reports in 2020 have also shown increases in the Middle East and North Africa,8 the Russian Federation,9 Canada,10 Australia,11 and European countries, such as Denmark, Germany, Poland, and the United Kingdom.3 It was estimated that between 1990 and 2016, the prevalence rate increased by 95%, meaning that approximately 2,221,188 people were living with MS in 2016.12 The reason behind the increase in MS prevalence has been associated with earlier diagnosis, improved ascertainment, and longer survival.3
However, recent findings demonstrated there was inconsistency in the age of diagnosis between countries, suggesting that there is no evidence for a trend toward an earlier diagnosis effect at a global level for MS prevalence (2013: mean [range] of 30 [20–44] years; 2020: mean [range] of 32 [20–50] years).3 Nevertheless, the geographical distribution of MS has brought awareness to the various roles of endogenous and exogenous causes of the disorder and has led to an improvement in knowledge about MS.
Multiple Sclerosis Incidence
As observed with MS prevalence, regional variation in incidence (per 100,000 persons per year) follows the same pattern, suggesting that every 5 minutes a person is diagnosed with MS somewhere in the world.3 Europe remains the region with the highest incidence, reaching 6.8 per 100,000 people, while the Americas register 4.8 and Southeast Asia and Africa have the lowest rates of 0.4.3 However, there are strong suggestions that this gradient is decreasing in the Northern Hemisphere, with a particular impact in the United States.13
The age of MS onset again follows a similar pattern. The incidence in childhood is low but promptly increases after adolescence, where a peak is observed between 25 and 35 years of age, gradually declining after that.14 Multiple sclerosis incidence rates over the past 4 to 5 decades have remained stable or shown a slight increase among white populations while remaining higher in other racial groups.15
The increase in MS incidence worldwide has been attributed to the escalation of the disease among women.2,16 Current epidemiological studies demonstrate that MS is more common in women. While the sex ratio was almost equal in the early 1990s,4 currently the female-to-male ratio varies from 1.5:1 to 2.5:1, with recent data even suggesting higher values.17,18 Such sex-specific incidence has been linked to changes in smoking behavior in women,14 which can explain up to 40% of such growth, especially since smoking is a known risk factor for MS.4,19 This suggests that women could be more sensitive to environmental changes than men when it comes to developing particular neurodegenerative disorders, such as MS.
Undeniably, there is growing indication that environmental factors play a key role in MS development. Factors such as infections, including Epstein-Barr virus, the use of oral contraceptives, smoking, obesity in early life, dietary habits, and vitamin D (which is also correlated with the geographical distribution) are consistent environmental predictors for MS risk when combined with genetic background.1,4
While genetics probably contributes to the geographical differences observed in MS incidence, it does not elucidate the variances in MS risk among people with shared genetic backgrounds.14,20 In fact, taking into account the increased female-to-male incidence ratio, the decline in the latitude gradient of MS incidence, and the strong evidence for specific risk factors, suggests an environmental cause might play an important role in MS incidence and prevalence.
- Magyari M, Sorensen PS. The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis. Curr Opin Neurol. 2019;32(3):320-326. doi:10.1097/WCO.0000000000000695
- Magyari M. Gender differences in multiple sclerosis epidemiology and treatment response. Dan Med J. 2016;63(3):B5212.
- Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816-1821. doi:10.1177/1352458520970841
- Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019;26(1):27-40. doi:10.1111/ene.13819
- Jin Y, de Pedro-Cuesta J, Söderström M, Stawiarz L, Link H. Seasonal patterns in optic neuritis and multiple sclerosis: a meta-analysis. J Neurol Sci. 2000;181(1-2):56-64. doi:10.1016/s0022-510x(00)00408-1
- Spelman T, Gray O, Trojano M, et al. Seasonal variation of relapse rate in multiple sclerosis is latitude dependent. Ann Neurol. 2014;76(6):880-890. doi:10.1002/ana.24287
- Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther. 2018;7(1):59-85. doi:10.1007/s40120-017-0086-4
- Yamout BI, Assaad W, Tamim H, Mrabet S, Goueider R. Epidemiology and phenotypes of multiple sclerosis in the Middle East North Africa (MENA) region. Mult Scler J Exp Transl Clin. 2020;6(1):2055217319841881. doi:10.1177/2055217319841881
- Boyko A, Melnikov M. Prevalence and incidence of multiple sclerosis in Russian Federation: 30 years of studies. Brain Sci. 2020;10(5):305. doi:10.3390/brainsci10050305
- Kingwell E, Zhu F, Marrie RA, et al. High incidence and increasing prevalence of multiple sclerosis in British Columbia, Canada: findings from over two decades (1991-2010). J Neurol. 2015;262(10):2352-2363. doi:10.1007/s00415-015-7842-0
- Campbell JA, Simpson S Jr, Ahmad H, Taylor BV, van der Mei I, Palmer AJ. Change in multiple sclerosis prevalence over time in Australia 2010-2017 utilising disease-modifying therapy prescription data. Mult Scler. 2020;26(11):1315-1328. doi:10.1177/1352458519861270
- Wallin MT, Culpepper WJ, Nichols E, et al. Global, regional, and national burden of multiple sclerosis 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(3):269-285. doi:10.1016/S1474-4422(18)30443-5
- Koch-Henriksen N, Sorensen PS. Why does the north-south gradient of incidence of multiple sclerosis seem to have disappeared on the Northern hemisphere? J Neurol Sci. 2011;311(1-2):58-63. doi:10.1016/j.jns.2011.09.003
- Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention—an update. Semin Neurol. 2016;36(2):103-114. doi:10.1055/s-0036-1579693
- Wallin MT, Culpepper WJ, Campbell JD, et al. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology. 2019;92(10):e1029-e1040. doi:10.1212/WNL.0000000000007035
- Alonso A, Hernán 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
- Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol. 2006;5(11):932-936. doi:10.1016/S1474-4422(06)70581-6
Reviewed by Kyle Habet, MD, on 7/1/2021.