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New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.

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Recently, a novel leukoencephalopathy syndrome was described in eight patients with a distinct pattern of MRI abnormalities. Here we describe the clinical, laboratory, and MRI findings in five new, unrelated patients. The clinical picture was homogeneous with onset in childhood, a slowly progressive course, variable mental deficits, signs of pyramidal and cerebellar dysfunction and sometimes dorsal column dysfunction. In two patients, a minor head trauma was followed by neurological deterioration and fever. No underlying metabolic defect was found. In two patients serum lactate was elevated, but no evidence of a mitochondrial defect was found. MRI showed variably extensive, diffuse, or spotty cerebral white matter abnormalities and a selective involvement of particular brainstem tracts. The tracts involved included the pyramidal tracts, sensory tracts, superior and inferior cerebellar peduncles, and intraparenchymal trajectories of the trigeminal nerve. In four patients spinal MRI was performed and revealed involvement of tracts over the entire length depicted. Single voxel proton MRS in three patients revealed increased lactate within the abnormal white matter. The uniform and highly characteristic MRI findings, in combination with the similarities in clinical and MRS findings, provide evidence for a distinct nosological entity.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p  =  0.02 andp  =  0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.