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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.

Background: Because common viruses are encountered during childhood, pediatric multiple scle-

The purpose of this study was to compare the clinical and quantitative magnetic resonance imaging metrics of paediatric-onset multiple sclerosis to adult-onset multiple sclerosis. It was a prospective comparison of clinical and magnetic resonance imaging characteristics of two paediatric onset multiple sclerosis and two adult onset multiple sclerosis groups that were matched for disease duration. The paediatric-onset-C group consisted of children with paediatric-onset multiple sclerosis with mean disease duration of 2.7 years, whereas the paediatric onset-A group consisted of adults with mean disease duration of 20 years. The adult onset multiple sclerosis-1 and adult onset multiple sclerosis-2 groups were matched to the paediatric onset-C and paediatric onset-A groups. The brain magnetic resonance imaging measures included: T(1)-, T(2)- and gadolinium contrast-enhancing volumes and the T(2)-lesion volume relative magnetization transfer ratio, global and tissue specific white and grey matter brain atrophy and normal appearing grey and white matter magnetization transfer ratio. Regression analyses were employed for magnetic resonance imaging measures. The paediatric onset multiple sclerosis-C (n = 17) and adult onset multiple sclerosis-1 (n = 81) groups had mean disease duration values of 2.7 +/- standard deviation 2.0 and 2.6 +/- 1.1 years, respectively. The paediatric onset multiple sclerosis-A group (n = 33) and adult onset multiple sclerosis-2 group (n = 300) had mean disease durations of 20 +/- standard deviation 10.9 and 20 +/- 9.3 years, respectively. In regression analysis, the T(2)- lesion volume of the paediatric onset multiple sclerosis-C and adult onset multiple sclerosis-1 groups were similar but there was a trend toward higher T(1)- lesion volume (P = 0.028) in the paediatric onset group. The brain parenchymal fraction and grey matter fraction in the paediatric-onset multiple sclerosis-C group were higher than those for the adult onset multiple sclerosis-1 group (both P < 0.001). The frequency of progressive multiple sclerosis in the paediatric onset multiple sclerosis-A group (27.3%) trended lower (odds ratio = 0.43, P = 0.042) than that in the adult onset multiple sclerosis-2 group (46.3%). The Expanded Disability Status Scale (median; inter-quartile range) in the paediatric onset multiple sclerosis-A group (2.25; 2.5) trended lower (P = 0.058) compared with the adult onset multiple sclerosis-2 group (3.5; 4.0). There was a trend toward lower magnetization transfer ratio values in T(2)-lesions, normal appearing grey matter and normal appearing white matter and higher grey matter fraction in the paediatric onset multiple sclerosis-A group compared with the adult onset multiple sclerosis-2 group. There was no evidence for differences on T(2)-lesion volume, T(1)-lesion volume, brain parenchymal fraction or white matter fraction. Paediatric-onset multiple sclerosis is characterized by a significant disease burden both early and later in the disease course. Despite this, disability is slower to accrue i...

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Background: Currently available disease-modifying therapies (DMTs) are known to be only partially effective in adults with multiple sclerosis (MS). Little is known about pediatric patients with MS who experience refractory disease while receiving first-line DMTs. Objective: To assess the occurrence and management of refractory disease in a group of pediatric patients with MS treated with first-line DMTs approved for adult patients within a network of pediatric MS centers in the United States. Design, Setting, and Patients: A multicenter, retrospective, longitudinal, open-label study design involving record review of 258 patients with pediatric-onset MS (68.6% female; mean [SD] age at disease onset, 13.2 [3.5] years; range of age at onset, 2.0-17.9 years) who were seen at 6 pediatric MS centers in the United States. Intervention: We evaluated medication changes owing to refractory disease in cases of pediatric-onset MS. Main Outcome Measure: Disease stability as represented by lack of medication change for breakthrough disease. Results: Records of 258 children with a confirmed diagnosis of MS and exposure to DMTs were reviewed. Interferon beta (prescribed to 200 of 258 children [77.5%]) and glatiramer acetate (prescribed to 53 of 258 children [20.5%]) were the 2 most frequently used first-line DMTs. Overall, 144 children (55.8%) continued receiving 1 therapy, while 65 (25.2%), 29 (11.2%), and 20 (7.8%) received 2, 3, or 4 or more sequential therapies, respectively, during a mean (SD) observation period of 3.9 (2.8) years. Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%). Hispanic children were more likely to experience breakthrough disease while receiving first-line DMTs than non-Hispanic children. Conclusion: Although switching between first-line DMTs may be effective in pediatric patients with disease that is refractory to initial treatment, a subset of patients may require second-line therapeutic interventions.

Objective:To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.Methods:To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms “quantitative” and “optical coherence tomography” from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts, and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.Results:One hundred sixteen authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point-checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans; we suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants’ consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.Conclusions:The modified Delphi method resulted in an expert-led guideline (evidence class III, GRADE criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, fundoscopic imaging, post-acquisition data selection, post-acquisition analysis, nomenclature and abbreviations, and statistical approach. It will still be essential to update these recommendations to new research and practices regularly.

Summary:Multiple sclerosis (MS) occurs at all ages of the pediatric population. Childhood MS may represent up to 10% of all MS cases. Establishing the diagnosis of MS in a child is complicated by the limited diagnostic criteria and the possibility of significant clinical and magnetic resonance imaging (MRI) overlap with acute disseminated encephalomyelitis and other pediatric diseases. Although the clinical profile of MS appears similar to that seen in adults, several features may differ and specific issues arise in children. Sex ratios are different between young children with MS and adolescentsimplicating a role for sex hormones in disease pathogenesis and/or modification of disease expression. Younger patients with MS are more likely to have seizures, brainstem, and cerebellar symptoms than adults. Children with MS may have fewer T2 hyperintense areas on MRI scans, therefore not meeting MRI criteria established for adults. It is possible that the pediatric MS course is more indolent than in adult patients but the disease may lead to significant disability at a younger age, e.g., while patients are students, young professionals, or want to start a family. There has been no controlled clinical trial in children with disease modifying therapies approved for adult MS due to the limited number of patients under the age of 18 years compared with the adult contingent. As a result, children are receiving adult therapies in an arbitrary manner and our understanding of pediatric treatment effect and tolerability is limited. Available data on tolerability of approved drugs for adults is reviewed.