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Dessalegn Y Melesse,1,2 Ruth Ann Marrie,2,3 James F Blanchard,1 Bo Nancy Yu,1,4 Charity Evans5 1Centre for Global Public Health, 2Department of Community Health Sciences, 3Department of Internal Medicine, University of Manitoba, 4Public Health, Manitoba Health Seniors and Active Living, Winnipeg, Manitoba, 5College of Pharmacy & Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Purpose: To examine the long-term persistence to the first-line injectable disease-modifying therapies (DMTs) for multiple sclerosis (MS) and to identify the factors associated with nonpersistence. Patients and methods: We used population-based administrative data from Manitoba, Canada. All adult subjects who were diagnosed with MS and dispensed a first-line injectable DMT (beta-interferon-1b, beta-interferon-1a, and glatiramer acetate) between 1996 and 2011 and had a minimum of 1 year of follow-up were included. The primary outcome was the median time to discontinuation of any DMT. The associations between potential predictors and persistence were estimated using multivariable Cox-proportional hazard models. Results: Overall, 721 subjects were followed for a median of 7.8 years (interquartile range 6.1). The median time to discontinuation of all first-line DMTs was 4.2 years (25th and 75th percentile: 1.7, 10.6 years). Of the 451 (62.6%) subjects who discontinued their DMT during the study period, 259 (57.4%) eventually resumed or restarted a DMT. Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy. Conclusion: Over half of the individuals receiving a DMT for MS in Manitoba remained on therapy for at least 4 years. DMT discontinuation occurred in 60% of the cohort, but most restarted a DMT within 1 year. While not all of the factors identified with discontinuing DMT are modifiable, they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation. Keywords: drug utilization, discontinuation, adherence, administrative data

Amber R Salter,1 Ruth Ann Marrie,2,3 Neetu Agashivala,4 Daniel A Belletti,4 Edward Kim,4 Gary R Cutter,1 Stacey S Cofield,1 Tuula Tyry51Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Internal Medicine, 3Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; 4Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 5Division of Neurology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USAIntroduction: The evolving landscape of disease-modifying therapies (DMTs) for multiple sclerosis raises important questions about why patients change DMTs. Physicians and patients could benefit from a better understanding of the reasons for switching therapy. Purpose: To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch.Method: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry conducted a supplemental survey among registry participants responding to the 2011 update survey. The supplemental survey investigated reasons for switching DMT, origin of the discussion of DMT change, and which factors influenced the decision. Chi-square tests, Fisher’s exact tests, and logistic regression were used for the analyses. Results: Of the 691 eligible candidates, 308 responded and met the inclusion criteria (relapsing disease course, switched DMT after September 2010). The responders were 83.4% female, on average 52 years old, with a median (interquartile range) Patient-Determined Disease Steps score of 4 (2–5). The most recent prior therapy included first-line injectables (74.5%), infusions (18.1%), an oral DMT (3.4%), and other DMTs (4.0%). The discussion to switch DMT was initiated almost equally by physicians and participants. The primary reason for choosing the new DMT was based most frequently on physician’s recommendation (24.5%) and patient perception of efficacy (13.7%). Conclusion: Participants frequently initiated the discussion regarding changing DMT, although physician recommendations regarding the specific therapy were still weighed highly. Long-term follow-up of these participants will provide valuable information on their disease trajectory, satisfaction with, and effectiveness of their new medication. Keywords: multiple sclerosis, health communication

Objective To assess the relationship between the 5 min Apgar score and developmental vulnerability at 5 years of age. Design Population-based retrospective cohort study. Setting Manitoba, Canada. Participants All children born between 1999 and 2006 at term

Background: Families are the primary source of support and care for most children. In Western societies, 4 to 12% of children live in households where a parent has a chronic illness. Exposure to early-life stressors, including parenting stress, parental de

Objective: To assess the feasibility of collaboration and retrospective data harmonization among three multiple sclerosis (MS) registries by investigating employment status. Methods: We used the Maelstrom guidelines to facilitate retrospective harmonization of data from three MS registries, including the NARCOMS (North American Research Committee on MS) Registry, German MS Register (GMSR), and United Kingdom MS (UK-MS) Register. A protocol was developed based on the guidelines, and summary-level data were used to combine results. Employment status and a limited set of factors associated with employment (age, sex, education, and disability level) were harmonized. A meta-analytic approach was used to pool estimates using a weighted average of logistic regression estimates and their variances in a random effects model. Results: Employment status, age, sex, education, and disability were mapped. The overall employment rate was 57% (11,143 employed out of 19,562 persons with MS) with the GMSR having the highest proportion of participants employed (66.2%), followed by the UK-MS (55.2%) and NARCOMS (43.0%) registries. As disability level increased, the odds of not being employed increased. Conclusion: Harmonization across registries was feasible. The Maelstrom guidelines provide a valuable roadmap for conducting high-quality harmonization projects. The pooling of data sources has the potential to be an important mechanism for conducting research in MS. [ABSTRACT FROM AUTHOR]

Water is one of the food products analyzed in water chemistry and environmental laboratories. One of the parameters analyzed are organic substances. The number of samples that were not comparable with the analytical skills can cause delays in test results. Analytical Hierarchy Process applied to evaluate the analytical methods used. Alternative methods tested include titrimetric method, spectrophotometry, and total organic carbon (TOC). Respondents consisted of deputy technical manager, laboratory coordinator, and two senior analysts. Alternative results obtained are methods of TOC. Proposed improvements alternative analytical method based on the results obtained, the method of the TOC with a 10-15 minute analysis time and use of CRM to the validity of the analysis results.

Background and Objectives: Recent studies suggest that the choroid plexus (CP) may function as a site of access of inflammatory cells into the CNS in multiple sclerosis (MS). Pediatric-onset MS (POMS) is characterized by a high inflammatory burden, as evidenced by a high relapse rate and volume of T2 lesions, making patients with POMS an informative population to evaluate choroid plexus volume (CPV). The objectives of the study were (1) to evaluate CPV at symptom onset in participants with POMS compared with healthy controls (HCs); (2) to evaluate changes in CPV in the first year of disease in participants with POMS; and (3) to evaluate associations between CPV, brain volumes, relapse activity, and disability in participants with POMS., Methods: Baseline 1.5T MRI scans were acquired from 23 participants with POMS and 23 age-matched and sex-matched HCs; 18 participants with POMS also had 12-month follow-up MRI scans. The CP of the lateral ventricles was segmented manually. CP and brain structure volumes were normalized for total intracranial volume. The number of relapses, T2 and gadolinium-enhancing T1 lesion counts, and Expanded Disability Status Scale (EDSS) scores at 12 months were also analyzed. Baseline CPVs were compared between groups using the Wilcoxon exact test, and CPV change from baseline to 12 months in participants with POMS was compared using the Wilcoxon signed-rank test. The relationship between CPV and brain volumetric measures, T2 lesion volumes, lesion count, number of relapses, and EDSS scores was assessed through Spearman correlation., Results: The median normalized CPV was 1.51 × 10 -3 (interquartile range [IQR]: 1.32-1.76) in POMS baseline scans and 1.21 × 10 -3 (IQR: 1.1-1.47) in HC scans ( p = 0.001). CPV did not significantly change at 12 months in the 18 participants with POMS with follow-up scans ( p = 0.352). CPV in participants with POMS and HCs correlated with lateral ventricular volume ( p = 0.012 for both groups) but did not correlate with brain and T2 lesion volumes or lesion count at baseline, nor with relapse activity or EDSS scores at 12 months in participants with POMS., Discussion: CPV measured at baseline is greater in participants with POMS than in HCs. Baseline CPV did not predict higher disease activity or worse neurologic outcomes over 1 year. While higher CPV may be an early feature of inflammation in MS, its strong correlation with ventricular volumes could also reflect enlargement secondary to the mechanical attachment of CP to the ventricular wall.

Background: Depression is common and phenotypically heterogenous in multiple sclerosis (MS). MS may increase risk of some but not all affective symptoms or certain symptoms may predispose individuals to higher MS risk., Objective: To assess the existence and direction of causality between distinct depressive symptoms and MS using two-sample Mendelian randomization (MR)., Methods: Using summary data from genome-wide association studies, we selected genetic instrument variables (IV) for MS (n = 115,776) and IVs for depressive symptoms (average n = 117,713): anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems and suicidality. We performed two-sample MR in either direction using inverse-variance models. Sensitivity analyses included weighted-median and MR-Egger regression. Obesity is a known risk factor for MS and depression; we adjusted for body mass index in multivariable-MR., Results: Genetic liability to MS was associated with anhedonia (IVW estimate per 10 2 : 0.69; 95 % CI: 0.24-1.13; p = 0.002), concentration difficulty (0.66; 0.19-1.13; p = 0.006) and psychomotor changes (0.37; 0.08-0.65; p = 0.01). Results were similar in sensitivity analyses. In the opposite direction, we found no evidence of a causal relationship for any affective symptom on MS risk., Conclusions: Genetic susceptibility to MS was associated with anhedonia, concentration, and psychomotor-related symptoms, suggesting a specific phenotype of depression in MS., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Multiple sclerosis (MS) has a high comorbidity burden. Despite known associations with adverse outcomes, a comprehensive evaluation of the specific associations between individual comorbidities and disability, treatment initiation, and mortality remains underexplored. This study aimed to review and summarize existing evidence on the association between comorbidities and these three MS outcomes., Methods: A rapid review spanning the period from January 2002 to October 2023 was conducted following the Cochrane Rapid Review Methods Group recommendations. MEDLINE, Embase, and the grey literature were searched to identify studies examining the effects of comorbidities on disability, treatment initiation, and mortality among individuals with MS. Data extraction and risk of bias assessments were systematically performed, with the Newcastle-Ottawa scale and A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) criteria for observational studies and systematic reviews respectively., Results: The review included 100 primary studies, encompassing 88 different comorbidities. Most study populations were between 60-80% female, with an average age of 30-45 years at study start. The majority of included studies were conducted in Europe, North America, and Asia (specifically the Middle East). Over half (66%) of specific comorbidity-outcome relationships were examined within a single study only, and just two studies examined treatment initiation as an outcome. Methods used to assess comorbidities and outcomes varied widely and included self-report measures, medical records and diagnostic codes, and standardized clinical assessments. Depression was consistently associated with greater disability (adjusted hazard ratio (aHR): 1.50-3.59) and mortality (aHR: 1.62-3.55). Epilepsy was similarly associated with increased disability (aOR: 1.13-1.77) and increased mortality (aHR: 2.23-3.85). Diabetes was generally associated with increased mortality (aHR: 1.39-1.47), but results for disability were inconsistent. Most other conditions were examined in one or two studies only or findings varied across studies, unable to collectively indicate a clear association. Although the anxiety-disability relationship was assessed by 24 studies, the findings varied in terms of the presence, direction, and strength of a possible association, requiring nuanced interpretation., Conclusions: This study identifies relationships between various comorbidities and three outcomes in MS, providing a foundation for future research and clinical guidelines. People with psychiatric, metabolic, and neurological conditions may be at a higher risk of MS disease progression and may therefore benefit from the targeted treatment of their comorbidities. Overall, comorbidities have varying associations with MS outcomes and individual associations require further exploration. However, there is evidence that some comorbidities indicate worse disability and higher mortality risk, and present barriers to initiating MS treatment, making the prevention and management of comorbidities an integral piece of MS patient care., Protocol: The protocol for this rapid review was registered on PROSPERO (ID: CRD42023475565) and published on Protocol Exchange (https://doi.org/10.21203/rs.3.pex-2438/v1)., Competing Interests: Declaration of competing interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HT has, in the last five years, received research support from the Canada Research Chair Program, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, MS Canada, the Multiple Sclerosis Scientific Research Foundation and the EDMUS Foundation (‘Fondation EDMUS contre la sclérose en plaques’). In addition, in the last five years, HT has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences or attend meetings (as a member of the International Advisory Committee on Clinical Trials in Multiple Sclerosis) from the Consortium of MS Centres (2023), the Canadian Neurological Sciences Federation (2023), National MS Society (2022, 2023, 2024), ECTRIMS/ ACTRIMS (2017–2024), American Academy of Neurology (2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT's research group. RAM receives research funding from: CIHR, MS Canada, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society, Pfizer Foundation and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. LML receives research funding from CIHR, the Arthritis Society, and the Canadian Agency for Drugs and Technology in Health. She holds a Canada Research Chair. KAM receives research funding from StratNeuro and has received speaker honoraria from Biogen Inc and Sanofi. MEK is supported by the Michael Smith Foundation for Health Research Scholar award. Over the past 3 years, MEK has received consulting fees from Biogen Inc. for consulting unrelated to this current work. HAF, MC, YF, and FZ have no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: People with multiple sclerosis (PwMS) have an increased cardiovascular and cerebrovascular disease burden, but this could be mitigated by vascular risk factor management., Objectives: We compared the trajectories of vascular risk factors, vascular comorbidities and clinical management in PwMS against the general population post-MS diagnosis while controlling for frailty., Methods: Retrospective longitudinal analysis using English data from the Clinical Practice Research Datalink between 1987 and 2018 comprising PwMS matched with up to six controls without MS by age, sex and general practice., Results: We compared 12,251 PwMS with 72,572 matched controls; 3.8% of PwMS had mild-moderate frailty, 1.2% more than matched controls. Compared to controls, PwMS had an elevated incidence of Type 2 diabetes (HR 1.18, 95% CI (1.04, 1.34)), and starting antihypertensive medications (HR 1.40, 95% CI (1.33, 1.47)). Among those with hypertension at baseline, blood pressure trajectories did not differ between PwMS and controls. PwMS had increased rates of meeting targets for hypertension management (HR 1.25, 95% CI (1.12, 1.41))., Conclusion: The observation that PwMS with hypertension are more likely to meet treatment targets than matched controls is encouraging, but the elevated rates of vascular comorbidities suggest that tighter vascular management may be needed in this population., 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: In the last 3 years, R.P. has received support from the UK MS Society and has taken part in advisory boards/consultancy for MSD and Sanofi. In the last 3 years, J.C. has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society, and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS society. A local principal investigator for commercial trials funded by Ionis, Novartis and Roche, and has taken part in advisory boards/consultancy for Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis and Roche. R.A.M. receives research funding from the Canadian Institutes of Health Research (CIHR), Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Research Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defence, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada.

Background: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease., Aim: To develop an algorithm to reliably identify MS cases within a national health data bank., Method: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry., Results: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population., Discussion: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis. Neuromyelitis optica, systemic lupus erythematous, neurosarcoidosis, infections, and cerebrovascular conditions (eg, hypertension) should be considered in the differential diagnosis of multiple sclerosis for people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia. The diagnosis of multiple sclerosis in people from a minority ethnic or racial background in these regions requires a comprehensive approach that considers the complex interplay of immigration, diagnostic inequity, and social determinants of health., Competing Interests: Declaration of interests LA has received research support from the National Multiple Sclerosis Society, National Institutes of Health National Institute of Neurological Disorders and Stroke, Bristol Myers Squibb Foundation, Race to Erase MS Foundation, and Biogen Idec; is a local Principal Investigator for commercial trials funded by Genentech, Sanofi, and Genzyme; and declares consulting fees from Biogen Idec, Novartis, Genentech, and EMD Serono. DR has received research support from MS Canada, the National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, University of Toronto Division of Neurology, and Roche Canada; and has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Horizon Therapeutics, Novartis, Roche, and Sanofi Aventis. OC is a member of the data and safety monitoring board for Novartis, has served on one advisory board for Biogen, and has received a speaker honorarium from Merck. DO has received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis; and has received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Genzyme, Janssen, Novartis, and Merck. MM has served on scientific advisory boards for Sanofi, Novartis, and Merck; and received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. VR has received honoraria from the Autonomous University of Barcelona, Roche, Corne Neurosciences, and the Multiple Sclerosis Association of America; and is a consultant (Expert Opinion Program) for Teladoc Health International. DK has served as a consultant for CVS Health. RD has received research support from the UK MS Society, National Multiple Sclerosis Society, BMA Foundation, Horne Family Charitable Foundation, Biogen, and Merck; and has received honoraria for advisory boards and educational activities from Biogen, Novartis, Sandoz, Roche, Janssen, and Merck. MW is a co-investigator for a study funded by Genentech; has received honoraria and consulting fees from Alexion, Biogen Idec, Novartis, Genentech, Horizon Therapeutics, EMD Serono, Octave Biosciences, TG Therapeutics, and Sanofi/Genzyme; and has participated in speakers bureau for Biogen Idec, Genentech, EMD Serono, and TG Therapeutics. RAM is a co-investigator on a study funded in part by Biogen and Roche (no funds to her or her institution). JAC has received personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI; and serves as an Editor for Multiple Sclerosis. BB served as a consultant for Novartis, Roche, and UCB; and is funded by the National Multiple Sclerosis Society and National Institutes of Health for work unrelated to this paper. BH served on scientific advisory boards for Novartis; and has served as a data and safety monitoring board member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; and his institution has received institutional research grants from Roche. BH has received honoraria for counselling for the Gerson Lehrmann Group; and holds part of two patents: (1) the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, and (2) genetic determinants of neutralising antibodies to interferon. SDN reports grants or contracts from Biogen, Roche, Genentech, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; reports personal compensation for consulting for Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and participates on a data safety monitoring board and advisory board for MedDay Pharmaceuticals; and reports support from the Stiff Person Syndrome Research Foundation. AJS reports grant funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Bristol Myers Squibb; is contracted for research with Sanofi, Biogen, Novartis, Actelion, and Genentec; has received personal compensation for consulting from EMD Serono and Octave Bioscience; has received payment or honoraria for lectures for EMD Serono; has been called for expert testimony by The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; participates on a data safety monitoring board for Patient Centered Outcomes Research Institute and Yale University; participates on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is content Chair for the American Academy of Neurology Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. WR3rd has research grant support from the National Institutes of Health and the Veterans Administration; reports honoraria, consulting fees, and support for advisory activities for the Consortium of Multiple Sclerosis Centers, the University of Maryland, the University of Calgary, Temple University, Thomas Jefferson University, the Chan Zuckerberg Initiative, the American Association for Cancer Research, and the Alzheimer's Association of Georgia; and receives compensation for serving as Director of specialty programming for Mediflix. AS and BT declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe., Competing Interests: Declaration of interests JC declares receiving grants or research contracts from Biogen and Merck; personal compensation for consulting from Merck; payment or honoraria for lectures from Biogen, Merck, Bristol Myers Squibb, Novartis, and Roche; and support for attending meetings and travel from Merck. JC is a deputy chair International Medical and Scientific Board of Multiple sclerosis International Federation (MSIF), unpaid; and has received equipment, materials, drugs, medical writing, gifts, or other services from Novartis (Investigator initiated award). AJS declares receiving grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health and Bristol Myers Squibb (investigator initiated award); has done contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech; has received personal compensation for consulting from Emmanuel Merck, Darmstadt, Serono and Octave Bioscience; has received payments or honoraria for lectures from Emmanuel Merck, Darmstadt, Serono; has received expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; is a participant on a Data Safety Monitoring Board for the Patient Centered Research Institute, and Yale University; declares participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is a content Chair for the American Academy of Neurology (AAN) Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. JAC declares personal compensation for consulting from Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an editor of Multiple Sclerosis Journal. BLB is funded by the National Multiple Sclerosis Society, and National Institute of Health; is a consultant for Roche, and Sanofi; and is a Board Director AAN (unpaid). TG has served as a consultant and received compensation from Genentech, Horizon, Sanofi, Alexion, and Greenwich Biosciences. BH declares grants from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; received personal compensation for consulting from Sandoz, Novartis, and GLG consulting; holds patents for antibodies against KIR4·1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralising antibodies to interferon (filed 2010); and participated in a Data Safety and Monitoring Board for Novartis, Allergy Care DSMB, TG Therapeutics, and Polpharma, and Advisory Board for Novartis. HJK declares a research grant from the National Research Foundation of Korea and research support from Aprilbio, UCB, and Eisai; has received consultancy fees from Altos Biologics, AstraZeneca, Biogen, Daewoong, Kaigene, Kolon Life Science, MDimune, Merck Serono, and Roche; declares honoraria for lectures from Alexion, Eisai, GCPharma, Handok, Mitsubishi Tanabe Pharma, and Sanofi Genzyme; has received personal compensation for participation on a Data Safety Monitoring Board from Sanofi-Genzyme; has received compensation as Co-editor for the Multiple Sclerosis Journal and Associate Editor for the Journal of Clinical Neurology; and is a Vice President of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (unpaid). RAM declares grants or contracts from Biogen, Idec, and Roche. FM has received research funding to her institution from Sumaira Foundation, Genentech, Biogen, Horizon Therapeutics, US National Histitute Institute of Health, US Department of State, Foundation Pierre Fabre, and Novartis; has received consulting fees from Alexion, EMD Serono, Genentech, TG Therapeutics, and Horizon Therapeutics; and declares shares of the startup company Brain Capture (not related to the content of this manuscript). SDN declares grants or contracts (paid directly to institution) from Biogen, Roche, Genentech, National MS Society, Department of Defense, and Patient Centered Outcomes Research Institute; has received personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and is a study lead principal investigator for a Roche clinical trial programme. MAS declares personal honoraria for lectures from Roche, Biogen, Cinnagen, NanoAlvand, Merck, Novartis, and Abidi. DKS declares grants or research contracts from CNPq / Brazil 425331/2016–4 and 308636/2019–8, and Brazilian National Council for Scientific and Technological Development; has received investigator initiated awards from TEVA, Merck, and Biogen; has received personal compensation for consulting from Roche, and Alexion; declares personal honoraria for lectures from Roche, Alexion, Horizon, Merck, Americas Health Foundation; and is a member of International Society of Neuroimmunology, International Advisory Board (unpaid), and Academia Brasileira de Neurologia, Educational Committee (unpaid). DS declares a pilot research grant from the National MS Society paid to the Institution; declares receipt of personal honoraria for lecturing from Roche Pharmaceuticals; declares travel support from Roche Pharmaceutical; and is a Committee member and chair of Multiple Sclerosis International Federation (unpaid). AS has received grants or contracts from the Turkish MS Society, Istanbul University-Cerrahpasa Research Support Funds, and The Scientific and Technological Research Council of Türkiye Health Sciences Research Grants; has received consulting fees from Roche, Merck-Serono, Biogen Idec/Gen Pharma of Turkey , Sanofi-Genzyme, Novartis, and Alexion; has received honoraria for lectures from Sanofi-Genzyme, Novartis, TEVA, and Roche; and has received support for attending meetings from Sanofi-Genzyme, Roche, Merck-Serono, and Alexion. KT declares personal consulting fees from Merck and Eisai; declares payment for lectures from Merck, Eisai, Roche, and Terumo Blood and Cell Technology; and is a member of the Organizing Committee Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid). MW has received publication royalties from Springer and Elsevier; has received consultancy honoraria from Icometrix, Imcyse, Novartis, Sanofi, Merck, and Biologix; declares personal compensation for lectures or presentations from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, Icometrix, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; and declares support for attending meetings from Merck-Serono. BGW declares royalties from RSR, Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR , and Oxford University; declares personal consulting fees from Roche, Horizon Therapeutics, Cambridge Pharmaceuticals, and Mitsubishi Tanabe; has received payments for lecture presentations from Roche and Horizon; has a patent planned for NMO-IgG for diagnosis of neuromyelitis optica; and declares participation on a Data Safety Monitoring Board and Advisory borads for Alexion MedImmune/VielaBio/Horizon, and UCB Biosciences. KF declares grants from Ministry of Education, Culture, Sports, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan; has received personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; has received payment or honoraria forlectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; declares participation in an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB; serves as President of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid), President of the Japanese Society of Neuroimmunology (unpaid), is a Board Member of the Japan Multiple Sclerosis Society (unpaid), is a board member of theEuropean Charcot Foundation (unpaid), and is a Member of the International Medical and Scientific Board, MSIF (unpaid). All other authors declared no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)