BACKGROUND:Diets are increasingly dominated by ultra-processed foods, which have been linked to several chronic diseases. Emerging evidence suggests an association between ultra-processed food consumption and inflammatory diseases, including multiple sclerosis (MS). OBJECTIVE:To assess associations between consumption of ultra-processed foods and paediatric-onset MS (PoMS). METHODS:We used data from the microbiome sub-study of the Canadian Pediatric Demyelinating Disease Network Study for PoMS cases (symptom onset aged <18 years) and unaffected controls. Data on consumption of ultra-processed foods (defined within the Nova system) were derived from dietary intake data collected using the Block Kids Food Screener. Dietary contribution of ultra-processed foods (% of total grams consumed per day) was estimated. Logistic regression models were used to examine associations between ultra-processed food consumption (continuous and tertiles) and likelihood of PoMS. Models were adjusted for age at dietary data collection, sex, race, region of residence, and total energy intake. RESULTS:Dietary data were collected from PoMS participants (females=57, males=23) aged 5-28 years and controls (females=30, males=16) aged 8-26 years. Each additional 10% in ultra-processed food consumption was associated with a 35% higher odds of being a PoMS participant (adjusted odds ratio [aOR]=1.35, 95% CI 1.05, 1.73). Participants in the highest (versus lowest) tertile for ultra-processed food consumption had over five times higher odds of being a PoMS participant (aOR=5.30, 95% CI 1.36, 20.70). CONCLUSION:Participants with PoMS reported greater consumption of ultra-processed foods compared to unaffected peers. More comprehensive longitudinal dietary histories are required to better understand this observation.

While the multiple sclerosis (MS) prodrome may be prolonged, healthcare use by sex >5 years pre-onset remains underexplored. We examined healthcare use up to 29 years pre-MS onset, stratified by sex. Using administrative data from Ontario, Canada (1991-2020), we compared annual physician visit rates by diagnostic chapter between MS and matched non-MS cohorts, stratified by sex. Quasi Poisson models estimated rate ratios (RRs) with 95% confidence intervals (CI). Included were 35,018 MS and 136,007 matched non-MS individuals (mean onset age ∼43 years; standard deviation ∼14 years; ∼69% female in both cohorts). Sex differences were observed for nervous system-related visits; males exhibited higher RRs from 10 years pre-onset ('year -10'), peaking in year -1 for both sexes (RRs: males=28.60;95%CI:24.10-34.00, females=13.60;95%CI:12.56-14.70). This was followed by mental disorders, being higher for males from year -4, peaking in year -1 (RRs: males=2.98;95%CI:2.73-3.25; females=2.09;95%CI:1.99-2.21), then ill-defined signs/symptoms and injury-related visits from year -3 to -1 (e.g., ill-defined signs/symptoms, RRs range: males=1.85-4.26 and females=1.67-3.27). Additionally, males had higher RRs in the 1-2 years pre-onset for respiratory, genitourinary, musculoskeletal, circulatory, digestive, and infection-related visits. Sex differences in healthcare use were evident up to 10 years pre-MS onset across multiple diagnostic chapters. Findings suggest that prodromal MS patterns differ by sex, potentially reflecting differences in symptom presentation, health-seeking behaviour, or diagnostic recognition before MS onset.

BackgroundDegree of rurality and neighbourhood deprivation are important factors in understanding variation in mental illness across populations, but epidemiological data on their relevance to mental illness in home care (HC) clients are limited. We estimated the prevalence of several mental illnesses by these characteristics and their interaction effects among HC clients and matched community comparators in Ontario, Canada.MethodWe conducted a repeated cross-sectional study using linked health administrative data. HC recipients aged ≥18 years were matched to community comparators on demographics, dementia, and comorbidity. Within each study sample, prevalence estimates were calculated and compared across urban/rural residence and binary measures of the 4 dimensions of the Canadian Index of Multiple Deprivation (CIMD). Outcomes were derived with validated case definitions for any mental illness, mood/anxiety disorders, depression and anxiety (with/without drug claims), schizophrenia, bipolar disorder, and suicide attempt. Prevalence ratios (PRs: 95% CIs) were estimated with modified Poisson regression models adjusted for relevant covariates.ResultsWe included 479,064 urban- and 72,862 rural-residing HC clients (mean age 73.2 and 72.4 years, respectively). Mental illnesses were less common in rural than urban clients (e.g., any mental illness 31.3% vs. 39.4%), with adjusted PRs between 0.80 and 0.87. Prevalence estimates were significantly higher among clients in areas more marginalized in residential instability and ethno-cultural composition, with more pronounced adjusted PRs for clients in urban than rural settings (e.g., PR [more vs. less marginalized residential instability] for any mental illness: 1.12 (1.12, 1.13) for urban and 1.07 (1.04, 1.10) for rural clients, P < 0.001). In matched community comparators, we observed similar patterns by urban/rural and deprivation measures though mental illness prevalence was significantly lower overall.ConclusionsMental illnesses are common among HC clients and vary regionally. Incorporating geographic and socioeconomic indicators into mental health surveillance systems offers insight into mental health disparities that may warrant more targeted interventions.

OBJECTIVES:To compare mental illness prevalence, and agreement between mental illness measures, in home care (HC) and long-term care (LTC) using administrative definitions and Resident Assessment Instrument (RAI)-diagnoses. METHODS:Applying a common protocol to linked administrative-RAI datasets in Alberta, Manitoba, and Ontario, Canada, we selected adults receiving HC or LTC between 2012 and 2023. Cross-sectionally, we compared administrative definitions with RAI-diagnoses (depression, anxiety, bipolar disorder and schizophrenia) using kappa, sensitivity, specificity, positive and negative predictive value. We examined discordance-associated factors using multivariable logistic regression. RESULTS:Depression was the most prevalent mental illness (administrative data, HC: 29%-34% of 493,895 people; LTC: 21%-51% of 357,117 people). Prevalence estimates were consistently lower using RAI-diagnoses than administrative definitions. Agreement between data sources was moderate for depression (k = 0.33-0.57) and anxiety disorders (k = 0.35-0.63). Younger age, dementia, and more physician visits were associated with higher likelihood of discordance between data sources; male sex had a lower likelihood. CONCLUSION:While mental illness prevalence is high in HC and LTC populations, RAI-based estimates are lower than administrative data estimates. Discordance between data sources differs by individual characteristics. Concurrent comparison of RAI-diagnoses and administrative data to a gold standard clinical interview would clarify the optimal surveillance strategy.

This cohort study examines data for a large population-based cohort to identify and characterize any cases of primary Epstein-Barr virus infection that occurred after the onset of multiple sclerosis.

While adults with rheumatic diseases often visit doctors more frequently before a formal diagnosis, it is unclear if children with juvenile arthritis (JA) follow the same trend. In this paper, we present a data science solution to discover common patterns and trends from historical JA patient healthcare trajectories (birth-to-diagnosis medical histories) for early detection of future JA patients. To elaborate, the solution aims to identify healthcare visit patterns in JA patients before their diagnosis and compare them to children without the condition. Evaluation results on real-world digital health records-with 386 JA patients and 1,930 healthy peers-from a Canadian province reveal 456 frequently occurring patterns, among which 12 were unique to JA patients. As key indicators, the most common sign was visiting a doctor for joint issues within six months before the official JA diagnosis. Children with these joint-related patterns were over 135 times more likely to be diagnosed with JA than the control group. Ultimately, these unique medical “fingerprints” are expected to help doctors identify JA earlier, leading to faster treatment and better long-term health for affected children.

BACKGROUND:Few studies assessed drug dispensations for periods >5 years pre-multiple sclerosis (MS) onset or examined the time pre-MS symptom onset. OBJECTIVE:The objective of this study was to examine prescription drug dispensations up to 15 years pre-MS symptom onset. METHODS:Matched cohort study linking prescription, clinical and administrative data, 1996-2018. RESULTS:Among 1243/6212 MS/non-MS persons, those with MS had higher dispensation rate ratios (RRs) pre-onset for systemic antibacterials up to 15 years (RR (range) = 1.15-1.30; q-values (range) = 0.11-0.31), airway drugs up to 8 years (RR (range) = 1.49-1.71; q-values (range) = 0.26-0.35), sex hormones (females only) up to 7 years (RR (range) = 1.19-1.46; q-values (range) = 0.26-0.39) and psychoanaleptics up to 6 years (RR (range) = 1.36-1.59; q-values (range) = 0.09-0.31), but lower beta-blockers (years 13-14 pre-onset, RRs = 0.10; q-values (range) = <0.00001-0.31). After multiple-comparison adjustment, beta-blockers remained significant. CONCLUSION:Drug dispensations differed up to 15 years pre-MS onset and may reflect early disease.

In immune-mediated inflammatory diseases (IMID), females report elevated depressive symptoms more frequently than males. We examined clinical and sociodemographic factors associated with elevated depressive symptoms in IMID and whether endorsement of individual depressive symptoms differed by sex. This study included 652 individuals with an IMID from Manitoba, Canada. Depressive symptoms were measured using the PHQ-9 and HADS-D, with IMID-specific cut-offs to identify elevated depression. Elevated depressive symptoms were present in 234 participants (36%). Females did not show higher odds of elevated depression than males. Males were more likely to endorse the HADS-D item on cheerfulness. Smoking and anxiety symptoms, but not sex, were associated with elevated depressive symptoms. These findings may help identify high-risk individuals with an IMID and comorbid elevated depressive symptoms and guide intervention.

Background and ObjectivesThe 2024 McDonald criteria allow diagnosis of multiple sclerosis (MS) in individuals presenting with symptoms not specific for MS or incidental imaging findings suggestive of demyelination when supported by biomarker evidence, reflecting a shift toward diagnostic definitions increasingly grounded in biological mechanisms of disease. The diagnostic yield of these criteria in such populations has not been evaluated in multicenter cohorts. We aimed to determine the proportion of individuals with nonspecific or incidental imaging presentations who meet the 2024 McDonald criteria and describe the contribution of central vein sign and CSF oligoclonal bands (OCBs) to diagnostic classification.MethodsThis cross-sectional post hoc analysis used data from the Central Vein Sign in Multiple Sclerosis study, a multicenter observational cohort. Adults aged 18-65 years referred for diagnostic evaluation of possible MS were adjudicated by an expert panel. This analysis focused on participants with symptoms not specific for MS or incidental imaging findings suggestive of demyelination. Dissemination in space (DIS) and dissemination in time (DIT) were assessed using 2017 MRI criteria. Fulfillment of the 2024 McDonald criteria at baseline-the primary outcome-was determined using the Select-6 CVS and CSF OCBs. Select-6 assessment was available for all participants, whereas OCB data were available for a subset based on prior clinical evaluation.ResultsOf 420 participants enrolled, 191 (45%) presented with either nonspecific symptoms (n = 166) or incidental imaging findings (n = 25). The mean age was 42 years, and 78% were female. Thirty-six (19%) met the 2024 McDonald criteria at baseline, including 28 (17%) in the nonspecific symptom cohort and 8 (32%) in the incidental imaging cohort. Among 51 participants meeting 2017 DIS, 22 (43%) were Select-6 positive, 17 (33%) had positive OCBs, and 4 (8%) met 2017 DIT. Nonspecific sensory symptoms, visual disturbances, and subacute cognitive decline were most associated with a diagnosis of MS.DiscussionApplication of the 2024 McDonald criteria identified nearly one-fifth of individuals without typical presentations as meeting diagnostic criteria for MS at baseline. Biomarker incorporation-particularly the CVS-accounted for a substantial proportion of diagnostic yield. Interpretation is limited by availability of CSF data and absence of longitudinal follow-up.

BACKGROUND:Findings conflict regarding the risk of peripartum mental illness in women with multiple sclerosis (MS) and how this compares to the risk among women with other chronic diseases. We compared the incidence and prevalence of peripartum mental illness among women with MS, epilepsy, inflammatory bowel disease (IBD), diabetes, and women without any of these diseases (comparators). METHODS:Using population-based Swedish administrative health data we selected women with MS, epilepsy, IBD, diabetes, and comparators who had deliveries between 2002 and 2019. Using validated case definitions for peripartum mental illness we estimated the incidence and prevalence of mental illness during the period encompassing pregnancy and the first post-partum year. We compared incidence and prevalence between cohorts using crude estimates and unadjusted Poisson regression. RESULTS:We included 1096,814 women (1936 MS; 7709 epilepsy; 7731 IBD; 7182 diabetes; 1072,256 comparators). Mean (SD) age at conception was 30.1 (5.1) years. Compared to comparators, mothers with MS had a higher incidence of any mental illness (incidence rate ratio [IRR] 1.36; 1.04-1.78), as did mothers with epilepsy (1.78; 1.58-2.00), IBD (1.46; 1.28-1.66) and diabetes (1.61; 1.41-1.83). Mothers with MS, epilepsy, IBD and diabetes also had a higher incidence and prevalence of depression and bipolar disorder than comparators. Mothers with epilepsy had higher incidence rates of anxiety, and higher prevalence ratios of any mental illness and anxiety than mothers with MS. CONCLUSIONS:Women with MS, epilepsy, IBD and diabetes have a similarly elevated incidence and prevalence of peripartum mental illness as compared to mothers without these conditions.

BACKGROUND:People with multiple sclerosis (PwMS) have an elevated risk of macrovascular disease that may be underestimated by vascular risk calculators (VRCs) validated in the general population. OBJECTIVES:This study evaluated, recalibrated and externally validated five commonly used VRCs for PwMS using population-based data from England, 1987-2023. METHODS:PwMS and matched controls were identified from Clinical Practice and Research Datalink (CPRD) GOLD (calibration) and CPRD Aurum (validation). Exposure variables included multiple sclerosis (MS) status and risk factors as defined in Atherosclerotic Cardiovascular Disease, Framingham Risk Score (FRS), FRS-BMI (body mass index), QRESEARCH risk estimator version 3 score and Systematic Coronary Risk Evaluation version 2 score (SCORE2). Model performance was assessed using Somers' D statistic, area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow chi-square test. VRCs with ROC < 0.70 in PwMS were recalibrated using Cox regression, incorporating MS status. Ten-fold cross-validation was used to estimate Somers' D. RESULTS:Calibration: 9411 PwMS and 57,805 controls; validation: 45,934 PwMS and 278,452 controls. Discrimination declined with standard thresholds (e.g. SCORE2 sensitivity in PwMS, 30.0%). Only FRS-BMI retained all significant predictors and was successfully recalibrated, improving discrimination (Somers' D = 0.815 vs. 0.792; Δ = 0.023) and showing good calibration. External validation showed modest gain (Somers' D = 0.716; Δ = 0.003). CONCLUSION:These findings underscore the limitations of general-population VRCs in PwMS and support the development of MS-specific vascular risk models.

BACKGROUND:The Expanded Disability Status Scale (EDSS) is routinely used to evaluate disability in Neuromyelitis Optica Spectrum Disorder (NMOSD), although it has only been validated in multiple sclerosis (MS) and may not capture important aspects of the patient experience in NMOSD. OBJECTIVE:To evaluate the relationship between Patient-Reported Outcomes (PROs), including for pain, fatigue, anxiety, and depression, and EDSS scores in NMOSD. METHODS:This cross-sectional study used baseline visit data from participants with aquaporin-4 antibody positive NMOSD who were enrolled in the multi-centre Canadian NMOSD cohort study CANOPTICS and had consented to the PROs substudy. Participants completed the following PROs: the short-form McGill Pain Questionnaire (sf-MPQ), Modified Fatigue Impact Scale (MFIS), Generalized Anxiety Disorder Assessment 7-item scale (GAD-7), and Beck Depression Inventory II (BDI-II). We evaluated PRO scores overall and stratified by demographic factors including sex, age, and ethnicity. We assessed the correlation among PROs and between each PRO and the EDSS. Multivariable linear regression models were used to identify the association between demographic and clinical characteristics (including EDSS) and two key symptom domains, pain and fatigue, given their high prevalence and impact in NMOSD. RESULTS:Out of 69 included participants, 57 (82.6%) were female and median (IQR) age was 50 years (40-61). Median (IQR) scores were: sf-MPQ 7 (1-16), MFIS 39 (22-50), GAD-7 5 (2-8), BDI-II 11 (4-19), and EDSS 3.0 (1.5-4.0). Depression and fatigue (r=0.71), fatigue and pain (r=0.62), and depression and anxiety (r=0.69) were correlated, but correlations between EDSS and PROs were weak (r<0.25). No significant differences in PROs were observed by sex, age and ethnicity, although female sex was associated with a higher fatigue score in multivariable models (beta = 12.69, 95% CI 0.33-25.04). CONCLUSIONS:There was a substantial burden of fatigue, pain, and mood disorders in this NMOSD cohort; however, these outcomes were weakly correlated with EDSS scores, suggesting that the EDSS may not capture important aspects of the patient experience in NMOSD.

Contemporary management of multiple sclerosis is based on the clinical course descriptors of relapsing-remitting, secondary progressive and primary progressive. However, recognition is growing in the field that these clinical course descriptors do not capture the full disease spectrum of multiple sclerosis or reflect the underlying biological mechanisms of disease, and that biologically informed course descriptors are needed. In this Roadmap, participants in an International Advisory Committee on Clinical Trials in Multiple Sclerosis workshop discuss the problems with the existing course descriptors, highlight considerations for developing new course descriptors and propose a roadmap for transitioning towards a more dynamic, biologically informed description of the multiple sclerosis disease course.

BackgroundDiversity of the multiple sclerosis (MS) population in Canada is unknown, yet demographic and diversity-related characteristics influence health outcomes.ObjectiveTo determine “What strategy would best address the information gaps regarding diversity of the MS population in Canada?”MethodsThe virtual nominal group technique involved silent idea generation, recording and discussion of items, preliminary voting, discussion and final ranking.ResultsEight participants proposed 10 strategies; two were dropped before final voting, after which the top options (tied) were: a national standardized clinic form, novel applications of administrative data, and novel data linkages.ConclusionWe identified strategies to characterize the diversity of the MS population in Canada.

OBJECTIVE:This qualitative study explored the impact of comorbidities on multiple sclerosis (MS) management, integrating perspectives from individuals with lived MS experience and healthcare professionals who have direct experience in treating and managing MS. METHODS:Semi-structured interviews were conducted with five individuals living with MS and five clinicians recruited through professional networks and advocacy groups. Interviews were conducted online between February 26th to March 15th, 2024. A thematic analysis was used to identify the main themes emerging from the interviews, focusing on the influence of comorbidities on MS progression, treatment decisions, and daily experiences. RESULTS:Comorbidities were found to significantly complicate MS management by exacerbating symptoms and influencing clinical decision-making. Individuals with lived MS experience and clinicians emphasized the need for enhanced coordination between healthcare providers and more comprehensive, interdisciplinary care models. Additionally, participants highlighted gaps in existing research on the relationship between comorbidities such as insomnia and substance use and their effects on MS outcomes. CONCLUSIONS:Comorbidities add a significant layer of complexity to MS management, both for individuals living with the disease and for clinicians providing care. Our findings suggest a need for integrated care models that address the unique needs of individuals with MS and comorbidities. Enhanced communication between specialists, comprehensive education for the individuals living with MS, and research that further explores the links between MS and comorbidities are critical steps toward improving outcomes. TRIAL REGISTRATION:Not applicable.

IntroductionL’utilisation de données administratives sur la santé pour recenser les cas de maladies chroniques peut entraîner des biais de classification. Des règles de sortie basées sur la reclassification pourraient réduire ces biais de classification. MéthodologieNous avons utilisé les données administratives du Manitoba sur la santé (1995-2022) pour mesurer la prévalence de la sclérose en plaques (SP) et du diabète insulino-dépendant (DID). Nous avons élaboré des algorithmes basés sur un modèle de régression logistique multivarié et utilisé une règle de sortie de probabilité prédite par le modèle pour reclasser chaque année les cas de DID et de SP. Nous avons estimé la sensibilité, la spécificité, la valeur prédictive positive (VPP), la valeur prédictive négative (VPN) et les taux de reclassification. La régression linéaire a permis de tester les différences dans les estimations de prévalence entre un algorithme basé sur un modèle avec règle de sortie et un algorithme existant du Système canadien de surveillance des maladies chroniques (SCSMC) sans règle de sortie. RésultatsLa cohorte de la SP comprenait 60 228 personnes (608 cas, 59 620 non-cas) et la cohorte du DID 44 125 personnes (2 506 cas, 41 619 non-cas). La sensibilité de l’algorithme basé sur un modèle était comprise entre 0,62 et 0,85 pour la SP et entre 0,87 et 0,95 pour le DID. La VPP était comprise entre 0,21 et 0,60 pour la SP et entre 0,92 et 0,95 pour le DID. La spécificité et la VPN étaient systématiquement élevées (0,98 à 1,00). Les non-cas ont souvent été mal classés et les taux de reclassification des non-cas ont été plus élevés que ceux des cas à la fois pour la SP (0,22 à 0,33 c. 0,14 à 0,28) et pour le DID (0,18 à 0,65 c. 0,13 à 0,15). L’algorithme basé sur un modèle avec règle de sortie a produit une augmentation plus lente de la prévalence que l’algorithme du SCSMC pour la SP, mais pas pour le DID. ConclusionLes algorithmes de vérification des cas avec règle de sortie peuvent résoudre les biais de classification erronée lors de l’estimation de la prévalence des maladies chroniques à l’aide de données administratives sur la santé. Les améliorations dépendent de la maladie.

Background and Objectives We aimed to assess the feasibility and acceptability of self-collected saliva for genetics from participants of a registry and determine whether responses to hypothetical questions regarding sharing of genetic information reflected observed behaviors. Methods We conducted a cross-sectional study collecting saliva for a genetic study in the North American Research Committee on MS (NARCOMS) registry. We linked participants to a prior survey for a subset of participants with responses, to examine factors associated with concordance between consent status and hypothetical willingness to share genetic information using logistic regression. Results Of ∼6200 participants contacted, 1227 expressed interest in the genetic study, 763 consented (62.2% of interested, ∼10% of those contacted) and most returned saliva samples (>80% of those consented). We found low agreement between the genetic study response and willingness to link genetic data (adjusted kappa = 0.186, standard error = 0.029). Multivariable regression identified no factors significantly associated with concordance between consent status and hypothetical willingness to share genetic information, though findings may reflect limited power. Conclusion Among participants who expressed interest, most were willing to provide saliva for genetics studies, though hypothetical sharing of genetic information did not reflect actual behaviors, and overall participation represented a minority of those contacted.

BACKGROUND:Increased healthcare use precedes classical multiple sclerosis (MS) symptom onset. Limited evidence exists on sex and age variation. We assessed physician visit patterns pre-MS onset by sex and age. METHODS:Using data from British Columbia, Canada, we compared annual physician visit rates (overall, by reason and specialty) in the 15 years before the neurologist-determined MS symptom onset date (index) and a matched non-MS cohort, stratified by sex and age (<30, 30-49, ≥50). RESULTS:We included 2038 MS and 10 182 non-MS persons (74% female). Mean age (years) at index was 37.6 (females) and 38.7 (males). Compared with matched non-MS persons, females with MS showed earlier and more consistent elevations in physician visits (years -14 to -1), while males had sporadic elevations (years -5, -3 and -1). Females also had longer periods of elevated rate ratios (RRs) for ill-defined signs/symptoms (years -15 to -1), mental disorders (years -14 to -1 except year -7) and musculoskeletal conditions (years -6 to -1). Females exhibited sustained elevated visits by specialty, including general practice (all years; RR ≥1.1), psychiatry (years -12 to -1 except -8 to -6; RRs ≥1.6) and ophthalmology (years -9 to -1 except -2; RRs ≥1.4). Compared with matched non-MS counterparts, those aged 30-49 years had sustained higher RRs for psychiatry visits (years -12 to -1 except -8 and -6; RRs ≥1.9) and ophthalmology (years -9 to -1; RRs ≥1.4). Other age groups had fewer elevated RRs preindex. Across comparisons, RRs were of similar magnitude across sex and age groups. CONCLUSIONS:Sex-specific and age-specific differences in physician visits extended up to 15 years pre-MS onset, suggesting a durable prodromal signature, most evident in females and those aged 30-49 years.

BACKGROUND AND OBJECTIVES:Little is known about glucagon-like peptide-1 receptor agonists (GLP1RAs) use in multiple sclerosis. We described the frequency and characteristics associated with use. METHODS:A cross-sectional survey of NARCOMS Registry participants captured use of GLP1RAs semaglutide and tirzepatide. Multivariable logistic regression explored factors associated with use. RESULTS:Among 4181 eligible participants, 7.4% had ever and 5.5% currently used these GLP1RAs. Ever users were younger and had more cardiometabolic conditions. 37.3% of never users had an indication for GLP1RAs. DISCUSSION:Despite 40% having an indication for taking GLP1RAs, a small percentage of surveyed persons with multiple sclerosis used them.

Background Alterations of the gut microbiome have been reported in central nervous system demyelinating diseases. While the gut microbiome in pediatric multiple sclerosis (MS) has been studied, the role of the gut microbiome in other pediatric-onset acquired demyelinating syndromes (ADS) remains unknown. We compared the gut microbiome composition between myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-) participants with pediatric-onset ADS. Methods Participants aged ≤21 years enrolled in the Canadian Pediatric Demyelinating Disease Network microbiome study (2015-2018) with a single episode or relapsing non-MS, non-neuromyelitis optica spectrum disease attacks of demyelination with symptom onset <18 years were included. Stool sample-derived DNA underwent 16S rRNA (V4) sequencing. Serum MOG-IgG antibodies were tested within 30 days of first attack onset. Alpha-diversity (Shannon, Margalef’s index, Chao1) and beta-diversity (weighted UniFrac) were analysed. Phylum/genus-level taxa were assessed using negative binomial models with false discovery rate correction. Rate ratios were sex- and age-adjusted (aRR). Results Forty-six participants (18 MOG+/28 MOG-) were included. Mean age at stool sample collection (MOG+/MOG-) was 14.7/17.2 years. Alpha-/beta-diversities did not differ between MOG+/MOG- participants (p>0.3). At the phylum level, the relative abundance of Proteobacteria was lower in MOG+ than MOG- participants (aRR:0.22;95%CI:0.07-0.69;q=0.03). At the genus level, the relative abundance of Escherichia/Shigella was lower in MOG+ than MOG- participants (aRR:0.01;95%CI:0.001-0.07;q=0.001), Conclusions While alpha/beta-diversities did not differ between MOG+/MOG- participants, taxa-level differences were observed. Our findings suggest that the gut microbiome composition may differ by MOG serostatus among pediatric-onset ADS participants. Future work is warranted, utilizing larger cohorts and longitudinal follow-up.