Multiple sclerosis (MS) is a chronic central nervous system disease with a highly heterogeneous course. The aetiology of MS is not well understood but is likely a combination of both genetic and environmental factors. Approximately 85% of patients present with relapsing-remitting MS (RRMS), while 10–15% present with primary progressive MS (PPMS). PPMS is associated with an older onset age, a different sex ratio, and a considerably more rapid disease progression relative to RRMS. We systematically reviewed the literature to identify modifiable risk factors that may be associated with these different clinical courses. We performed a search of six databases and integrated twenty observational studies into a descriptive review. Exposure to Epstein-Barr virus (EBV) appeared to increase the risk of RRMS, but its association with PPMS was less clear. Other infections, such as human herpesvirus-6 and chlamydia pneumoniae, were not consistently associated with a specific disease course nor was cigarette smoking. Despite the vast literature examining risk factors for the development of MS, relatively few studies reported findings by disease course. This review exposes a gap in our understanding of the risk factors associated with the onset of PPMS, our current knowledge being predominated by relapsing-onset MS.
ObjectiveTo gain a better understanding of the complex patterns of causes that contribute to death due to multiple sclerosis (MS) by assessing the relationship between MS and other causes of death listed on death certificates.MethodsMultiple cause of death data for all adult deaths (aged ≥18 years) in British Columbia, Canada, between 1986 and 2013 were accessed. All causes, as listed on the death certificate, whether underlying or contributing, were considered “any mention” causes. The associations between mention of MS on the death certificate and mention of other causes of death were examined by logistic regression, adjusted for age, sex, and calendar year (Bonferroni-corrected α level = 0.002). Findings were also sex-stratified.ResultsAmong 771,288 deaths, MS was mentioned on 2,153 certificates. If MS was mentioned (versus not mentioned), there was a greater chance that specific conditions contributed to the death: respiratory infection (adjusted odds ratio [aOR], 3.03 [95% confidence interval (CI), 2.73–3.36]), aspiration pneumonia (aOR, 7.15 [95% CI, 6.23–8.22]), urinary tract infection (UTI) (aOR, 10.2 [95% CI, 8.7–12.0]), other infection including sepsis (aOR, 1.34 [95% CI, 1.15–1.56]), and skin disease (aOR, 5.06 [95% CI, 3.96–6.46]). Sex differences existed for urinary tract infection (men: aOR, 14.9 [95% CI, 11.5–19.3]; women: aOR, 8.00 [95% CI, 6.53–9.81]) and chronic respiratory disease (men = aOR, 1.36 [95% CI, 1.14–1.63]; women = aOR, 0.97 [95% CI, 0.84–1.13]).ConclusionsDeaths attributed to MS were commonly caused by infection (especially respiratory and urinary tract–related); conditions associated with advanced disability and immobility, such as aspiration pneumonia; and chronic respiratory disease in men. All are potentially modifiable; interventions that reduce the frequency or severity of these complications could improve survival in MS.
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