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Background: Multiple sclerosis (MS) may occur before the age of 18. Differentiation between paediatric MS (PedMS) and other demyelinating syndromes (ODSs) is challenging. In adult with MS, the kappa free light chain (KFLC) index has proven to be a reliable marker of intrathecal Ig synthesis. Objective: To assess the diagnostic value of the KFLC index in a cohort of patients with paediatric-onset, inflammatory disorders of the CNS. Methods: We included 73 patients and divided them into four groups: PedMS (n = 16), ODS (n = 17), encephalitis and/or inflammatory epilepsy (EE, n = 15), and controls without inflammatory CNS diseases (n = 25). The KFLC index was calculated and compared with the results of the oligoclonal bands determination. Results: The KFLC index was higher in the PedMS group (median (interquartile range (IQR)): 150.9 (41.02–310.6)) than in the ODS (3.37 (2.22–8.11)), the EE (5.53 (2.31–25.81)) and the control group (3.41 (2.27–5.08)), respectively. The best KFLC index cut-off for differentiating between patients with PedMS and controls was 6.83 (sensitivity: 100%; specificity: 92%). A KFLC index over 93.77 indicated that the patient is very likely to have PedMS (sensitivity: 68%; specificity: 100%). Conclusion: The KFLC index is a reliable tool for the diagnosis of MS in a paediatric population. [ABSTRACT FROM AUTHOR]

Background Dural sinus malformations (DSMs) associated with high flow arteriovenous shunts are a challenging disease in babies that can lead to severe neurological damage or death. We report our treatment strategy in seven consecutive DSMs. Methods We performed a retrospective analysis of seven consecutive patients from four centres, treated with transarterial embolization and anticoagulants. Results Mean clinical and imaging follow-up was 2.8 years (IQR1-3 1.8-5.3). At baseline, the median size of the dilated venous pouch (giant lake) was 35 mm (IQR1-3 24-41) that decreased to a normal or near normal venous collector diameter of median size 11.5 mm (IQR1-3 8.5-13.8). This was achieved after a median of two embolization sessions targeted on dural feeders (IQR1-3 1.5-2.5), leaving associated pial feeders untreated. There were no cerebral hemorrhagic complications during the anticoagulation treatment. Median percentage of shunt remaining after embolization was 30% (IQR1-3 12-30), which spontaneously decreased with anticoagulation and even after discontinuation of anticoagulation, in parallel with the reduction in diameter of the dilated sinus, up to healing (or near healing). At the last clinical assessment, the modified Rankin Scale score was 0 in four patients, 1 in one patient, and 3 in two patients. Conclusions Anticoagulants may help to potentiate transarterial embolization in DSMs in babies by decreasing venous dilatation and reducing the remaining arteriovenous shunt, particularly the pial feeders. We did not observe recurrence of arteriovenous shunts after treatment, especially during anticoagulation treatment. Further studies are needed to support our findings. [ABSTRACT FROM AUTHOR]

Background: Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs. Objectives: This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Methods: Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5–6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child's health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6. Results: The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented. Conclusions: RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population. Study funding: EDMUS and ARSEP Foundation, Biogen, Roche. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To describe the impact of paediatric myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) on academic and cognitive outcomes.This was an observational, retrospective, and descriptive single‐centre study, carried out on a paediatric case series of children with MOGAD.A total of 51 patients were included (22 females); their median age was 8 years and the median follow‐up duration was 31.1 months (interquartile range 23.5). The most frequent clinical presentation was acute disseminated encephalomyelitis (54.9%), followed by optic neuritis (35.5%). At the last follow‐up, regardless of the clinical phenotype at disease onset, 39.5% of patients with MOGAD received academic and educational interventions (p < 0.05 compared to before disease onset), including academic accommodations (p < 0.05) or the need for a learning support assistant (p < 0.05). Ten patients were evaluated with the Wechsler Intelligence Scale for Children, Fifth Edition (WISC‐V). The overall IQ was calculated for six patients (mean = 92); two of these patients had an IQ lower than 85. No difference was found regarding prenatal and neonatal neurodevelopmental characteristics between this cohort and the general population.MOGAD was associated with a need for academic support; lower scores were found on the WISC‐V. Patients with MOGAD should receive cognitive and academic assessments to inform educational planning and support academic success. [ABSTRACT FROM AUTHOR]

Background: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity., Objective: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM., Patients and Methods: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test., Results: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001)., Conclusion: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD., Competing Interests: Declaration of competing interest Ines El Naggar: received travel grants from UCB. Eva-Maria Wendel: received travel grants from UCB. Annikki Bertolini: received travel grants from UCB. Markus Reindl: was supported by research grants from the Austrian Science Fund (FWF projects P32699 and IPN170), the Austrian Research Promotion Agency and Roche. Deiva Kumaran: received honoraria for invited talks for Biogen, Alexion, Sanofi and serves as consultant for Novartis and Horizon. Rinze Neuteboom: participated in pharmacological studies in demyelinating disorders with Roche, Horizon, Novartis and Sanofi-Genzym. Funding from Dutcht MS research foundation, Dreams Foundation, Postcode Loterij, Vrienden Sophia Foundation. Kevin Rostásy: received honoraria for invited talks from Horizon, UCB and serves as a consultant in the OperettaII study. Robert Cleaveland, Andreas Panzer, Sandy Molenaar, Laetitia Giorgi, Michael Karenfort, Charlotte Thiels, Zuzana Libá, Matthias Baumann, Steffen Leiz, Adela Della Marina, Jan G. Hengstler, members of the BIOMARKER study group (Steffen Berweck, Astrid Blaschek, Matthias Eckenweiler, Astrid Eisenkölbl, Tobias Geis, Annette Hackenberg, Verena Kraus, Heinz Lauffner, Daniela Pohl, Martin Pritsch, Michela Salandin, Torsten Sandrieser, Mareike Schimmel, Christoph von Kleist-Retzow, Gert Wiegand): no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis (MS) may occur before the age of 18. Differentiation between paediatric MS (PedMS) and other demyelinating syndromes (ODSs) is challenging. In adult with MS, the kappa free light chain (KFLC) index has proven to be a reliable marker of intrathecal Ig synthesis., Objective: To assess the diagnostic value of the KFLC index in a cohort of patients with paediatric-onset, inflammatory disorders of the CNS., Methods: We included 73 patients and divided them into four groups: PedMS ( n = 16), ODS ( n = 17), encephalitis and/or inflammatory epilepsy (EE, n = 15), and controls without inflammatory CNS diseases ( n = 25). The KFLC index was calculated and compared with the results of the oligoclonal bands determination., Results: The KFLC index was higher in the PedMS group (median (interquartile range (IQR)): 150.9 (41.02-310.6)) than in the ODS (3.37 (2.22-8.11)), the EE (5.53 (2.31-25.81)) and the control group (3.41 (2.27-5.08)), respectively. The best KFLC index cut-off for differentiating between patients with PedMS and controls was 6.83 (sensitivity: 100%; specificity: 92%). A KFLC index over 93.77 indicated that the patient is very likely to have PedMS (sensitivity: 68%; specificity: 100%)., Conclusion: The KFLC index is a reliable tool for the diagnosis of MS in a paediatric population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide., Objective: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension., Methods: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension., Results: The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflunomide, estimated clinical relapse risk was reduced by 38% (hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.39-0.98; p  = 0.11) and numbers of gadolinium-enhancing T1 and new/enlarging T2 lesions were reduced by 43% (relative risk (RR) 0.570; 95% CI 0.33-0.98; p  = 0.043) and 49% (RR 0.511; 95% CI 0.34-0.76; p  = 0.001), respectively, in the combined double-blind and open-label periods. There was a trend toward reduced risk of 24-week sustained disability progression for teriflunomide/teriflunomide versus placebo/teriflunomide (HR 0.47; 95% CI 0.23-0.96). During the open-label extension, incidences of safety-related discontinuations were 4.0% (teriflunomide/teriflunomide) and 13.5% (placebo/teriflunomide), including two children who developed pancreatitis in the teriflunomide/teriflunomide group., Conclusion: Teriflunomide reduced the long-term risk of focal inflammatory activity, with generally manageable tolerability and no new safety signals. Further evidence would strengthen clinical efficacy findings.ClinicalTrials.gov: NCT02201108., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kumaran Deiva: consulting fees and travel grants from Biogen, Merck, Novartis Pharmaceuticals, Roche, and Sanofi. Tanuja Chitnis: consulting fees from Biogen, Novartis Pharmaceuticals, Roche Genentech, and Sanofi; research support from National Institutes of Health, National MS Society, U.S. Department of Defense, EMD Serono, I-Mab Biopharma, Mallinckrodt ARD, Novartis Pharmaceuticals, Octave Bioscience, Genentech, and Tiziana Life Sciences. Brenda Banwell: consulting fees from Novartis Pharmaceuticals, Roche, Sanofi, and UCB; non-remunerated advisory input for Biogen, EMD Serono, Novartis Pharmaceuticals, and Teva. Ludwig Kappos: Dr Kappos’ institution (University Hospital Basel) has received in the past 3 years and used exclusively research support, steering committees, advisory boards, and consultancy fees from AbbVie, Actelion, AurigaVision AG, Biogen, Celgene, Desitin, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Japan Tobacco, Merck, Minoryx, Novartis, Roche, Sanofi, Santhera, Senda, Shionogi, Teva, and Wellmera; speaker fees from Celgene, Janssen, Merck, Novartis, and Roche; support for educational activities from Biogen, Desitin, Novartis, Sanofi, and Teva; license fees for Neurostatus products and grants from European Union, Innosuisse, Novartis, Roche Research Foundation, Swiss MS Society, and Swiss National Research Foundation. Douglas L Arnold: consulting fees from Alexion, Biogen, Celgene, Eli Lilly and Company, EMD Serono, Frequency Therapeutics, Genentech, Merck, Novartis, Roche, Sanofi, and Shionogi; equity interest in NeuroRx. Kivilcim Gücüyener: no competing interests. Stephane Saubadu: employee of Sanofi, with ownership interest. Wenruo Hu: employee of Sanofi, with ownership interest. Myriam Benamor: employee of Sanofi, with ownership interest. Annaig Le-Halpere: employee of Sanofi, with ownership interest. Philippe Truffinet: employee of Sanofi, with ownership interest. Marc Tardieu: research support from Novartis Pharmaceuticals and Sanofi.

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12-17) years) treated with RTX/OCR with 6 month standard-interval dosing ( n = 9) or early extended-interval dosing ( n = 12, median (range) interval 18 months (12-25)). Within a median (range) follow-up of 31 (12-63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Counseling on pregnancy is still challenging, particularly regarding the use of disease-modifying treatments (DMTs). We are lacking long-term outcomes in children exposed to DMTs., Objectives: This study aimed to set up a French pregnancy registry for women with multiple sclerosis (MS) and related disorders nested within the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort., Methods: Prospective, observational, multicentric, epidemiological study in France. Neurological visits are organized according to routine practice. Data are collected on the OFSEP minimal datasheet. Auto-questionnaires on pregnancy are completed by patients at Months 5-6 and 8 during pregnancy, and Months 3, 6, and 12 postpartum. A specific survey on analgesia is completed by anesthesiologists. Pediatric data are collected from the child's health book, where visits on Day 8, Month 9, and 24 are mandatory. Parents complete neurodevelopmental questionnaires at Year 1, Years 2 and 6., Results: The RESPONSE study started in August 2019. On 7 April 2023, 515 women were included. Baseline demographics are presented., Conclusions: RESPONSE will provide rich information on the global management of pregnancy in France and prospective data on children until the age of 6 years, exposed or not to a DMT, including data on neurodevelopment that can be compared to the general population., Study Funding: EDMUS and ARSEP Foundation, Biogen, Roche., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.V. has received consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Janssen, Merck, Novartis, Roche, Sandoz, and Sanofi. B.B. has received consulting and lecturing fees, travel grants, and unconditional research support from Alexion, Biogen, Horizon, Janssen, Merck, Novartis, Roche, Sandoz, and Sanofi. R.C. has no financial disclosure to declare. K.D. has received consulting and lecturing fees, travel grants, and consulting fees for advisory boards from Alexion, Biogen, Horizon, Novartis, Roche, and Sanofi. A.M.G. has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck, Sanofi, and Roche. F.R. and C.L.F. have no financial disclosure to declare. E.L. has received consulting and lecturing fees, and travel grants from Alexion, Merck, Novartis, Roche, and Sanofi. L.B. and C.G. have no financial disclosure to declare. R.M. has received personal fees from Horizon Therapeutics, Alexion, Roche, and UCB and non-financial support from Horizon Therapeutics, Merck, Biogen, and Roche, outside the submitted work. E.M. reports research support from Biogen and ARSEP foundation and personal fees for lectures and advisory boards from Biogen, Janssen, Merck, Novartis, Roche, Sanofi, and Teva.