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Objective: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM)., Methods: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength., Results: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients ( p = 0.015)., Conclusion: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes., Classification of Evidence: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes., (© 2018 American Academy of Neurology.)

The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, "The World of Pediatric MS: A Global Update," in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders. While these criteria currently identify clinical and MRI features for a particular diagnosis, advances in biomarkers may prove to be useful in the future. An update was also provided on environmental factors associated with pediatric MS risk and possibly outcomes, notably vitamin D deficiency. However, optimal vitamin D intake and its role in altering MS course in children have yet to be established. Regarding MS outcomes, our understanding of the cognitive consequences of early-onset MS has grown. However, further work is needed to define the course of cognitive function and its long-term outcome in diverse patient samples and to develop strategies for effective cognitive rehabilitation specifically tailored to children and adolescents. Finally, treatment strategies were discussed, including a need to consider additional drug treatment options and paradigms (escalation vs induction), although treatment should be tailored to the individual child. Of critical importance, clinical trials of newer MS agents in children are required. Although our understanding of childhood MS has improved, further research is needed to have a positive impact for children and their families., (© 2016 American Academy of Neurology.)

Many disease-modifying therapies are currently available for adults with relapsing-remitting multiple sclerosis (MS) but none of them has been tested in pediatric MS in randomized placebo-controlled trials. At present, as suggested by observational studies and experts' guidelines, interferon-β and glatiramer acetate continue to be the standard first-line treatments for pediatric MS. Observational studies and some controlled unblinded trials have shown a positive effect of these meditations in reducing relapse rate and delaying disease progression, with an acceptable safety profile. The goal of this article is to provide an overview of current knowledge with regard to safety, tolerability, and efficacy of first-line treatment options for MS in the pediatric age group, with the aim of providing guidance for planning first-line treatment of MS in children and adolescents., (© 2016 American Academy of Neurology.)