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Background and Objectives: Although the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice., Methods: Eleven medical centers retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF using live cell-based assays. Comparisons were performed using parametric or nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression., Results: The cohort included 255 patients: 139 (55%) women and 132 (52%) children (i.e., <18-year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n = 14, 45%) and sensory symptoms (n = 13, 42%), and all but 4 (2 multiple sclerosis, 1 polyradiculoneuritis, and 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [IQR] 3.0-7.5 vs 3.0, IQR 2.0-6.8, p = 0.007) and presented more commonly with sensory (45.5% vs 24%, p = 0.002), motor (33.6% vs 19%, p = 0.021), and sphincter symptoms (26.9% vs 7.8%, p = 0.001) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008) . Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up ( p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0., Discussion: Paired serum and CSF MOG-Abs positivity are common in MOGAD and are associated with a more severe clinical presentation. CSF-only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus., (© 2022 American Academy of Neurology.)

Objective: The impetus for this consensus discussion was to recommend clinical trial designs that can deliver high-quality data for effective therapies for pediatric patients, in a reasonable timeframe, with a key focus on short- and long-term safety., Methods: The International Pediatric Multiple Sclerosis Study Group convened a meeting of experts to review the advances in the understanding of pediatric-onset multiple sclerosis (MS) and the advent of clinical trials for this population., Results: In the last few years, convincing evidence has emerged that the biological processes involved in MS are largely shared across the age span. As such, treatments proven efficacious for the care of adults with MS have a biological rationale for use in pediatric MS given the relapsing-remitting course at onset and high relapse frequency. There are also ethical considerations on conducting clinical trials in this age group including the use of placebo owing to highly active disease. It is imperative to reconsider study design and implementation based on what information is needed. Are studies needed for efficacy or should safety be the primary goal? Further, there have been major recruitment challenges in recently completed and ongoing pediatric MS trials. Phase 3 trials for every newly approved therapy for adult MS in the pediatric MS population are simply not feasible., Conclusions: A primary goal is to ensure high-quality evidence-based treatment for children and adolescents with MS, which will improve our understanding of the safety of these agents and remove regulatory or insurance-based limitations in access to treatment., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS)., Methods: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study., Results: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age ( p = 0.0001), diagnosis of ADEM ( p = 0.005), increased CSF cell counts ( p = 0.011), and negative OCB ( p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers ( p = 0.0003) and older age at onset ( p = 0.024). MS was predicted by MS-like MRI ( p < 0.0001) and OCB ( p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%., Conclusions: Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course., (© 2017 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.)