We found that the incidence of pediatric MS and ADS was very low. In our cohort, black children were unexpectedly found to be at least twice as likely to develop pediatric ADS compared with white children. The incidence of pediatric ADS including pediatric MS was also higher in Asians compared with whites. In contrast, Hispanic children had a similar risk and incidence rate of pediatric ADS and MS compared with whites. While most of the children with ADS were Hispanic, this reflects the Hispanic predominance of our general pediatric cohort.
Based on our findings, we estimate that the age- and sex-adjusted US census standardized incidence rates for pediatric MS are 0.5 per 100,000 person-years or approximately 380 newly diagnosed cases per year in the United States and 1.63 per 100,000 person-years or approximately 1,250 newly diagnosed children with any acquired demyelinating syndrome per year.
We found a somewhat higher incidence of pediatric ADS than the 0.9 per 100,000 incidence rate previously reported in Canadian children.1
This modest discrepancy may be because we obtained more complete case capture than the Canadian study, which relied on questionnaires with response rates ranging from 78% to 82%1
or due to the increased racial and ethnic diversity of our population.
The increase of MS and ADS in black children is a novel finding and suggests that the prevalence of environmental or genetic risk factors may be more common in black compared with white or Hispanic children. It is tempting to speculate that this finding may be explained by the increased prevalence of vitamin D deficiency in dark-skinned individuals.13
However, our findings do not clearly follow the skin tone gradient associated with low vitamin D. Thus, it is unlikely that low vitamin D alone could explain why the risk of MS and ADS in Hispanic children is the same as in whites. Future studies should explore other environmental risk factors in addition to vitamin D.
As for candidate genetic factors that could explain our findings, HLA-DRB1*15
has been consistently associated with an increased risk of MS14–16
but the prevalence of HLA-DRB1
MS risk allele is lower in blacks than whites16
and unknown in Hispanics. The possibility remains that either non-HLA MS risk alleles may be more common in black compared with white and Hispanic children or that there is a synergistic interaction between low vitamin D and HLA-DRB1*1517
that is more common in blacks than Hispanics. Future studies of pediatric ADS should include non-MHC risk alleles and stratify analyses by race/ethnicity.
It is unclear whether our findings indicate that environmental or genetic risk factors are different in children compared with adults. There are no published studies comparing incidence rates or prevalence ratios from population-based multiethnic cohorts in either children or adults with MS or other forms of ADS. Blacks are believed to have a lower risk of adult-onset MS than whites but evidence for this comes predominantly from ecological studies and a prevalence study of US veterans published in 1979.18
Future studies of the incidence of MS in population-based multiethnic cohorts are needed to sort this out.
Consistent with the first pediatric ADS incidence study,1
we found that pediatric ADS is rare. In fact, the primary limitation of our study is the few incident cases particularly of pediatric MS despite the relatively long observation period. Another limitation of our study is the amount of missing self-reported race/ethnicity information. While we used a validated algorithm based primarily on birth certificates, language preference, and surnames,5
our results should be confirmed in future studies with more complete self-reported race/ethnicity information.
Similar to other studies, we found that ADEM is more likely to be a monophasic illness, occurring in young children,1,19,20
and that the female preponderance typically seen in adult MS was not present in younger children. In our cohort, none of the children with ADEM developed MS despite similar duration of follow-up with children who presented with ON, TM, and other types of CIS, of whom 34.5% converted to MS. It should be noted that this is one of the first studies reporting the conversion to MS after CIS using the 2007 International Pediatric MS Study Group definitions for ADEM. In the past, ADEM and multifocal CIS were often combined under a first demyelinating attack, which may explain why some authors reported higher conversion rates from ADEM to MS.21,22
Thus, our findings suggest that children with ADEM should be examined separately from CIS or MS cases in studies of pediatric MS susceptibility or prognosis as ADEM is often not a precursor to MS.
We found that black children have a higher risk of developing MS and other forms of ADS than white or Hispanic children. This finding is novel and highlights that inclusion of minorities in future studies of pediatric and adult MS incidence, susceptibility, and prognosis may reveal important insights into the etiology of MS and other forms of ADS.