Fast track — ArticlesClinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study
Introduction
HLA-DRB1*15 genotype, remote infection with Epstein-Barr virus, and vitamin D insufficiency are possible predisposing factors to multiple sclerosis,1, 2 but have not previously been assessed in one cohort. Such an investigation would allow their interrelations and relative contributions to be established. Because risk of multiple sclerosis is strongly affected by country of residence during childhood,3 the contribution of environmental factors to development of this disease can be uniquely explored in children living in an area of high prevalence who have incident demyelination during the time of risk factor acquisition. In addition to consideration of these predisposing factors, clinical, MRI, and laboratory findings at presentation provide predictive information about the likelihood of subsequent disease—although the relative contribution of these features in prediction of multiple sclerosis outcomes in the paediatric population is less well defined than it is for the adult population. Improved identification of children who are very likely to be diagnosed with multiple sclerosis would justify clinical and MRI monitoring for diagnostic confirmation and would enable prompt initiation of targeted treatment. Conversely, identification of children in whom multiple sclerosis is unlikely would substantially reduce concern for the patients, parents, and care providers. We aimed to assess the contribution of predisposing environmental factors and clinical and laboratory findings on development of multiple sclerosis in a national cohort of children in Canada.
Section snippets
Participants and study design
In our prospective national cohort study of incident demyelination in children, we obtained comprehensive clinical, laboratory, and MRI data to examine the contribution and interrelations of HLA-DRB1*15, remote Epstein-Barr-virus infection, and vitamin D status as predisposing factors and clinical features, MRI images, and oligoclonal bands as predictors of multiple sclerosis. We developed a decision tree to aid in counselling regarding multiple sclerosis risk.
All 16 Canadian paediatric
Results
Between Sept 1, 2004, and June 30, 2010, we enrolled 332 children (figure 1), of whom 302 were eligible and followed up for more than 3 years (table 1). Six (2%) participants withdrew from the study after a median of 93 days (IQR 85–187) of follow-up, and data were censored at time of withdrawal.
Of 302 eligible patients with acute demyelinating syndrome, 63 (21%) were diagnosed with multiple sclerosis (24 by MRI evidence of dissemination in time only). Median time to a second clinical event or
Discussion
In our nationwide prospective cohort study of children with incident demyelination, the presence of HLA-DRB1*15 alleles, remote Epstein-Barr-virus infection, and low 25-hydroxyvitamin D concentrations predisposed to multiple sclerosis. Our findings add to those of previous studies5, 15, 16, 17, 18 comparing the frequency of these exposures between paediatric and adult patients with established multiple sclerosis with healthy controls (panel). We show that the three exposures are present in
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