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Abstract
Multiple sclerosis (MS) is a chronic disease of the central nervous system with an
unidentified etiology. We systematically reviewed the literature on the possible risk
factors associated with MS disease onset, relapses and progression from 1960 to 2012
by accessing six databases and including relevant systematic reviews, meta-analyses,
case-control or cohort studies. The focus was on identifying modifiable risk factors.
Fifteen systematic reviews and 169 original articles were quality assessed and integrated
into a descriptive review. Best evidence, which included one or more prospective studies,
suggested that lower exposure to sunlight and/or lower serum vitamin D levels were
associated with an increased risk of developing MS onset and subsequent relapses,
but a similar quality of evidence was lacking for disease progression. Prospective
studies indicated that cigarette smoking may increase the risk of MS as well as accelerate
disease progression, but whether smoking altered the risk of a relapse was largely
unknown. Infections were implicated in both risk of developing MS and relapses, but
data for progression were lacking. Specifically, exposure to the Epstein-Barr virus,
particularly if this manifested as infectious mononucleosis during adolescence, was
associated with increased MS risk. Upper respiratory tract infections were most commonly
associated with an increase in relapses. Relapse rates typically dropped during pregnancy,
but there was no strong evidence to suggest that pregnancy itself altered the risk
of MS or affected long-term progression. Emerging research with the greatest potential
to impact public health was the suggestion that obesity during adolescence may increase
the risk of MS; if confirmed, this would be of major significance.