Objective To investigate the clinical and MRI features of MOG seropositive pediatric demyelinating syndromes. Methods Serum samples collected from 74 children with suspected demyelinating disorders followed at Massachusetts General Hospital, were incubated with MOG-GFP and GFP control transfected Jurkat cell clones. Binding ratios were calculated using flow cytometry. Statistical analysis compared demographic, clinical and radiological features in seropositive and seronegative patients. Results 13/74 (17.5%) patients were seropositive for MOG. MOG seropositive patients were younger than seronegatives (p=0.049). No single disease category predominated amongst seropositives, nor was one group more likely to have a polyphasic course. 2/4 NMO patients had MOG antibodies; both were serognegative for AQP4. One had monophasic disease, and the other had frequent relapses. There was a bimodal distribution of MOG seropositive patients by age at onset, with a distinct younger group (4–8 years) having high prevalence of encephalopathy and an older group who presented almost exclusively with optic neuritis (13–18 years). MRI analysis demonstrated absence of corpus callosum lesions in seropositive patients (p=0.012). Annualized relapse-rate and EDSS at 2 years did not differ between seropositive and seronegative patients. Conclusion MOG antibodies are found across a variety of pediatric demyelinating syndromes with some distinct clinical and MRI features.

To assess the effects and mechanisms of a CD200R1 agonist administered during the progressive stage of a multiple sclerosis model, we administered CD200R1 agonist (CD200Fc) or control IgG2a during the chronic phase of disease (days 10 -30) in mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) peptide. We found that administration of CD200Fc during the chronic stages of EAE reduced disease severity, demyelination, and axonal damage, through the modulation of several key disease mechanisms. CD200Fc treatment suppressed macrophage and microglial accumulation within the CNS, in part through downregulation of adhesion molecules VLA-4 and LFA-1, which are necessary for macrophage migration. Additionally, expression of activation markers MHC-II and CD80 and production of proinflammatory cytokines IL-6, tumor necrosis factor-␣, and nitric oxide by CD11bϩ cells were decreased in both the spleen and CNS in CD200Fc-treated animals. Antigen-presenting cell function in the spleen and CNS was suppressed in CD200Fc-treated mice, but there were no significant alterations on T cell activation or phenotype. CD200Fc increased apoptosis of CD11b ϩ cells but not astrocytes. In contrast, addition of CD200Fc treatment protected oligodendrocytes from apoptosis in vitro and in vivo. Our results demonstrate that CD200R1 agonists modulate both myeloid-and non-myeloid-related mechanisms of chronic disease in the EAE model and may be effective in the treatment of progressive multiple sclerosis and other neurodegenerative diseases.

Onset of multiple sclerosis in childhood occurs in 3-5% of patients. There is limited, but growing knowledge about the underlying pathobiology of pediatric MS. It is crucial to better understand this area in order to address central questions in the field: 1) Can pediatric multiple sclerosis inform us about factors related to disease initiation and propagation? 2) What are the biomarkers of disease course in pediatric multiple sclerosis; 3) Does pediatric multiple sclerosis pathogenesis differ from adult-onset multiple sclerosis; 4) How can we optimize treatment in pediatric demyelinating diseases? 5) Can pediatric multiple sclerosis provide insights into the environmental risk factors for multiple sclerosis in general? Here we review the current knowledge of the pathogenesis of multiple sclerosis in children, and address the five questions raised above.

BackgroundLeptin and adipocyte-fatty acid binding protein (A-FABP) are produced by white adipose tissue and may play a role in chronic inflammation in Multiple Sclerosis (MS). To assess leptin and A-FABP in relapsing and progressive forms of MS.MethodsAdipokine levels were measured in untreated adult relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and Healthy control (HC). Pediatric-onset MS (POMS) and pediatric healthy controls (PHC) were also assessed. Leptin and A-FABP levels were measured in serum by ELISA. Groups were compared using linear mixed-effects model.ResultsExcluding two patients with Body Mass Index (BMI) > 50, a significant difference in leptin level was found between RRMS and HC controlling for age (p = 0.007), SPMS and HC controlling for age alone (p = 0.002), or age and BMI (p = 0.007). A-FABP levels were higher in SPMS than HC (p = 0.007), controlling for age and BMI. Differences in A-FABP levels between POMS and PHC was observed after controlling for age (p = 0.019), but not when BMI was added to the model (p = 0.081).ConclusionLeptin and A-FABP levels are highest in SPMS compared to HC, suggesting a role in pathogenesis of this disease subtype. A-FABP levels are increased in POMS patients and may play a role in the early stages of disease.

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