What causes pediatric multiple sclerosis (MS)?

Updated: Jan 30, 2019
  • Author: Alice K Rutatangwa, DO, MSc; Chief Editor: Amy Kao, MD  more...
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Answer

Several environmental factors have been shown to play a role in MS susceptibility in adults. In children, very few studies have addressed these issues. Studying the role of common viruses in the pediatric MS population provides a unique opportunity given the close temporal relationship between the infection and MS onset and the fact that exposure to those viruses is lesser in children than in adults. Several studies examining viral exposures in pediatric MS have consistently identified significantly increased frequencies of Epstein-Barr virus (EBV) seropositivity in children with MS compared to matched controls. [10, 11, 12, 13] This association is independent of age at blood draw, sex, race, ethnicity, and HLA-DRB1 status. [14]

The novel observations in this study are that in HLA-DRB1–positive individuals, a remote infection with herpes simplex virus-1 (HSV-1) decreased the MS risk by 90%. In contrast, in HLA-DRB1–negative individuals, HSV-1 seropositivity increased the MS risk fourfold.

Concern over the use of vaccinations, most recently hepatitis B vaccine, and the subsequent development of MS has been raised. Mikaeloff et al found no increased risk of developing a first episode of childhood MS up to 3 years postvaccination in the French population. [15]

Interestingly, the same group evaluated the risk of childhood-onset MS as related to exposure to passive smoking. [16] The relative risk for a first episode of MS was found to be over twice that in the control population and was even higher in those with prolonged exposure (≥10 years).

Finally, unlike in adult MS, the effect of vitamin D status on MS susceptibility is unknown, although levels of 25(OH) vitamin D have been found to be independently associated with subsequent relapse rate in patients with pediatric MS (for each 10 ng/mL increment of 25(OH) vitamin D3, risk of subsequent MS relapse was decreased by 34%). [17]

A few studies have evaluated genetic risk factors in pediatric MS. The US Pediatric MS Network has also reported that HLA-DRB1, as in adult MS, may be a risk factor for pediatric MS. In multivariate models adjusted for age, race, ethnicity, and remote viral exposures, the risk of developing MS if carrying at least one HLA-DRB1 allele was increased by 2- to 4-fold, depending on the model used. [4, 14]

Further studies on genetic and environmental risk factors are ongoing to explore the precise mechanisms that lead to disease onset. The discovery of gene-environment interactions may also shed new light on the understanding of molecular mechanisms involved in disease processes and might lead to the development of new therapeutic strategies.


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