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Study supports link between pediatric MS and remote viral infections


– Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

Photo of a clipboard with the words multiple sclerosis lying next to pills, an injection needle, and stethoscope copyright Zerbor/Thinkstock
HSV-1 and -2 seropositivity was also associated significantly with pediatric onset MS (OR, 1.5), said Dr. Nourbakhsh, who was a clinical fellow at the University of California, San Francisco, when he conducted the research but is now at Johns Hopkins University, Baltimore.

“We didn’t see an association between CMV and the risk of developing pediatric MS,” he said, noting that prior studies had shown a protective effect of prior CMV.

There was a trend toward an association between lower serum vitamin D levels and the risk of developing pediatric MS, but the findings are questionable because of vitamin D supplementation started after diagnosis in most patients, he noted.

Further, analysis showed that race also played a role in the relationships between prior infections and MS.

The association between HSV-1 and -2 infection was significant only among white patients, the association between prior EBV and MS was much stronger in whites than non-whites, and the association between EBV and MS was stronger in non-Hispanics than in Hispanics, he said.

The MS risk variant HLA DRB1*1501 also played a role in the associations. The association between prior HSV-1 and -2 infection and MS risk was apparent only in DRB1-negative individuals, and, conversely, the association between prior EBV and MS risk was much stronger in those who were DRB1-positive, he said.

Patients included in the study had a mean age of 15.2 years, 64% were girls, and the mean disease duration was 354 days. Controls had a mean age of 14.3 years.

“Remote viral infections have been known as one of the most commonly cited risk factors for adult and pediatric MS,” Dr. Nourbakhsh said, noting that a prior case-control study showed these associations and that other studies suggested associations with vitamin D deficiency.

The current study was conducted in an attempt to replicate those prior findings, he said.

The results of this large study support an association between prior EBV and HSV infections and MS risk and a possible association between vitamin D deficiency and MS risk but are limited by lack of testing before disease development and by vitamin D supplementation in almost all patients after diagnosis, he said.

“In the future, hopefully, we can look further at the interaction of genes and environment and the heterogeneity of the effect of risk factors in different subpopulations,” he concluded.

Dr. Nourbakhsh reported having no disclosures.

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