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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.<\/jats:p>","DOI":"10.1155\/2015\/817238","type":"journal-article","created":{"date-parts":[[2015,1,31]],"date-time":"2015-01-31T21:00:41Z","timestamp":1422738041000},"page":"1-11","source":"Crossref","is-referenced-by-count":93,"title":["Risk Factors Associated with the Onset of Relapsing-Remitting and Primary Progressive Multiple Sclerosis: A Systematic Review"],"prefix":"10.1155","volume":"2015","author":[{"given":"Kyla A.","family":"McKay","sequence":"first","affiliation":[{"name":"Faculty of Medicine (Neurology), Vancouver Coastal Health Research Institute, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 2B5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Kwan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), Vancouver 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