The onset of
multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is
HLA DRB1*1501 In addition to genetic factors, a large part of
disease susceptibility in adults is conferred by environmental risk factors such as low
vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (
EBV) infection. In children, both exposure to cigarette smoking and prior
EBV infection have been reported consistently as risk factors for MS. The role of
vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene-environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(
OH)
vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric
neuromyelitis optica spectrum disorders and
acute disseminated encephalomyelitis and only collaborative studies will answer those questions.