What causes multiple sclerosis? Getting closer to the answers

Bruce V Taylor
Med J Aust 2022; 217 (4): . || doi: 10.5694/mja2.51645
Published online: 15 August 2022

MS risk is becoming less of a mystery as we gain a better understanding of its causes

Multiple sclerosis (MS) is a complex neuroinflammatory/neurodegenerative disease of the central nervous system. Recent work1,2 has significantly advanced our understanding of the aetiology of MS, emphasising the importance of infection with Epstein–Barr virus as a significant driver of MS risk. MS manifests clinically as neurological dysfunction affecting any area of the central nervous system, in particular the optic nerves, spinal cord, and brainstem. Most people with MS (90%) present with relapse onset MS where episodes of neurological dysfunction are followed by partial or full recovery but over time, disability almost invariably accumulates (secondary progressive MS).3 In contrast, 10% of people present with progression from disease onset, termed progressive onset MS.3 In the developed world, MS is one of the leading causes of neurological disability in young adults, and as the median age of onset in Australia is between 35 and 40 years,4 it affects people in their most productive years. Consequently, the economic and social costs to individuals and the wider community are high. In 2017, we estimated the cost of MS to Australia was $1.7 billion annually and increasing significantly each year.5 Currently, there is no cure for MS, but significant gains have been made in its treatment, particularly the use of highly effective disease‐modifying therapies and the development of comprehensive care through specialised MS clinics. However, no current treatment can stop or reverse the neurodegenerative component of the disease.3

  • Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia



I receive National Health and Medical Research Council Leadership Fellow salary support.

Competing interests:

No relevant disclosures.

  • 1. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein‐Barr virus associated with multiple sclerosis. Science 2022; 375: 296‐301.
  • 2. Wekerle H. Epstein‐Barr virus sparks brain autoimmunity in multiple sclerosis. Nature 2022; 603: 230‐232.
  • 3. Thompson AJ, Baranzini SE, Geurts J, et al. Multiple sclerosis. Lancet 2018; 391: 1622‐1636.
  • 4. Taylor BV, Lucas RM, Dear K, et al. Latitudinal variation in incidence and type of first central nervous system demyelinating events. Mult Scler 2010; 16: 398‐405.
  • 5. Ahmad H, Campbell JA, van der Mei I, et al. The increasing economic burden of multiple sclerosis by disability severity in Australia in 2017: results from updated and detailed data on types of costs. Mult Scler Relat Disord 2020; 44: 102247.
  • 6. Belbasis L, Bellou V, Evangelou E, et al. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta‐analyses. Lancet Neurol 2015; 14: 263‐273.
  • 7. Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol 2019; 6: 1905‐1922.
  • 8. Rothman KJ, Greenland S. Causation and causal inference in epidemiology. Am J Public Health 2005; 95 Suppl 1: S144‐S150.
  • 9. Trojano M, Lucchese G, Graziano G, et al. Geographical variations in sex ratio trends over time in multiple sclerosis. PLoS One 2012; 7: e48078.
  • 10. Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler 2014; 20: 520‐526.
  • 11. O'Gorman C, Freeman S, Taylor BV, et al. Familial recurrence risks for multiple sclerosis in Australia. Neurol Neurosurg Psychiatry 2011; 82: 1351‐1354.
  • 12. International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 2019; 365: eaav7188.
  • 13. Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Acta Neurol Scand 1975; 51: 137‐157.
  • 14. Amezcua L, McCauley JL. Race and ethnicity on MS presentation and disease course. Mult Scler 2020; 26: 561‐567.
  • 15. Taylor BV, Pearson JF, Clarke G, et al. MS prevalence in New Zealand, an ethnically and latitudinally diverse country. Mult Scler 2010; 16: 1422‐1431.
  • 16. Simpson S, Jr, Wang W, Otahal P, et al. Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta‐analysis. J Neurol Neurosurg Psychiatry 2019; 90: 1193‐1200.
  • 17. Lucas RM, Ponsonby AL, Dear K, et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011; 76: 540‐548.
  • 18. van der Mei IA, Ponsonby AL, Blizzard L, Dwyer T. Regional variation in multiple sclerosis prevalence in Australia and its association with ambient ultraviolet radiation. Neuroepidemiology 2001; 20: 168‐174.
  • 19. Sabel CE, Pearson JF, Mason DF, et al. The latitude gradient for multiple sclerosis prevalence is established in the early life course. Brain 2021; 144: 2038‐2046.
  • 20. Kimlin MG, Lucas RM, Harrison SL, et al. The contributions of solar ultraviolet radiation exposure and other determinants to serum 25‐hydroxyvitamin D concentrations in Australian adults: the AusD Study. Am J Epidemiol 2014; 179: 864‐874.
  • 21. Campbell JA, Simpson S, Jr, Ahmad H, et al. Change in multiple sclerosis prevalence over time in Australia 2010‐2017 utilising disease‐modifying therapy prescription data. Mult Scler 2020; 26: 1315‐1328.
  • 22. Pakpoor J, Schmierer K, Cuzick J, et al. Estimated and projected burden of multiple sclerosis attributable to smoking and childhood and adolescent high body‐mass index: a comparative risk assessment. Int J Epidemiol 2021; 49: 2051‐2057.
  • 23. van der Mei I, Lucas RM, Taylor BV, et al. Population attributable fractions and joint effects of key risk factors for multiple sclerosis. Mult Scler 2016; 22: 461‐469.
  • 24. Simpson S, Jr, van der Mei I, Lucas RM, et al. Sun exposure across the life course significantly modulates early multiple sclerosis clinical course. Front Neurol 2018; 9: 16.
  • 25. Michaelsson K, Baron JA, Snellman G, et al. Plasma vitamin D and mortality in older men: a community‐based prospective cohort study. Am J Clin Nutr 2010; 92: 841‐848.
  • 26. Holick MF. Sunlight, UV radiation, vitamin D, and skin cancer: how much sunlight do we need? Adv Exp Med Biol 2020; 1268: 19‐36.
  • 27. Alfredsson L, Armstrong BK, Butterfield DA, et al. Insufficient sun exposure has become a real public health problem. Int J Environ Res Public Health 2020; 17: 5014.


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