ABSTRACT Objective Little is known about shifting from pediatric to adult‐focused multiple sclerosis (MS) care. This study aims to explore transition of care and follow‐up in the US pediatric‐onset MS (POMS) population. Methods Surveys were distributed to 10 sites in the US Network of Pediatric MS Centers (US NPMSC) about transition‐of‐care practices. A cohort of POMS/clinically isolated syndrome (CIS) at 12 US NPMSC sites was analyzed. The primary comparison was between < 18 and ≥ 18‐years of age. The primary outcome was 1‐ and 2‐year lapse in last follow‐up visit, measured from last recorded database visit to data lock date or, if ≥ 18 years of age, up to 1 year after a patient reached their site's typical transition age, if earlier. Secondary outcomes were baseline factors associated with follow‐up lapse. The model was adjusted for preidentified confounders. Results Compared with < 18 years, age ≥ 18 was associated with greater hazard of 1‐ and 2‐year follow‐up lapse. In POMS/CIS, the estimated hazard was 1.61 for 1‐year lapse (95% confidence interval [CI] 1.32–1.97, p < 0.001) and 1.40 for 2‐year lapse (95% CI 1.11–1.76, p = 0.004). In POMS‐only, the estimated hazard was 1.70 for 1‐year lapse (95% CI 1.33–2.18, p < 0.001) and 1.49 for 2‐year lapse (95% CI 1.11–1.99, p = 0.007). Platform injectable disease‐modifying therapy was associated with greater and intravenous with lesser hazard of lapse in follow‐up, while MS was associated with lower hazard than CIS. Conclusion Variable transition‐of‐care practices and barriers were reported by major US POMS centers. Before typical transition age, age ≥ 18 was associated with greater hazard of 1‐ and 2‐year follow‐up lapse than < 18. Developing standardized, targeted transition‐of‐care practices in POMS may be important.

BACKGROUND:De novo tumefactive demyelination (TD) poses a diagnostic challenge, with lower rates of cerebrospinal fluid (CSF) oligoclonal bands and lower female-to-male ratio than typical onset multiple sclerosis (MS). Only about half fulfill the 2017 McDonald diagnostic criteria for MS at presentation. Therefore, our aim was to assess optic nerve involvement by optical coherence tomography (OCT) in patients with TD. Further, whether the presence of abnormalities on OCT would allow additional TD patients to be diagnosed with MS when the optic nerve is added as a fifth topography to the Barkhof criteria or 2017 McDonald criteria. METHODS:Observational retrospective chart review of patients seen at a tertiary referral center from 1/1/1990 to 2/21/2024 with TD. Inclusion criteria were: 1) brain MRI showing an active TD lesion; 2) medical records with at least one available clinical assessment by a neurologist; 3) available Cirrus OCT data to review. Exclusion criteria were: 1) patients with final diagnosis of vasculitis, abscess, CNS malignancies, or MOGAD; 2) presence of confounding ocular disease. RESULTS:OCT was available in 68 patients with TD. The tumefactive attack was the first demyelinating event in 45 (67 %) patients. At presentation, 29/68 (43 %) fulfilled 3 of 4 Barkhof criteria, and 34/68 (50 %) fulfilled the 2017 McDonald criteria for the diagnosis of MS. A clinical history of optic neuritis was present in 9/68 (13 %) patients and OCT was abnormal in 9/9 (100 %) of those patients. Regardless of clinical history, OCT was abnormal in 22/68 (32 %) patients. Therefore, OCT identified abnormalities suggestive of prior optic neuritis in 13/59 (22 %) TD patients without a clinical history of optic neuritis. If the optic nerve, as a firth topography, was assessed by OCT 39/68 (57 %) would fulfill McDonald criteria. CONCLUSIONS:OCT in patients presenting with TD lesions can frequently identify both clinical and subclinical optic neuritis. The addition of the optic nerve as a fifth topography assessed by OCT to fulfill dissemination in space criteria would allow additional TD patients to be diagnosed with MS.

BACKGROUND:Psychiatric comorbidities are increasingly recognised in demyelinating diseases, yet their frequency and timing in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not well defined. We aimed to characterise the spectrum and temporal pattern of psychiatric illness in MOGAD and compare to multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-IgG). METHODS:We conducted a cross-sectional study of patients with MOGAD (n=388), age-matched and sex-matched MS (n=257) and AQP4-IgG-positive NMOSD (n=58) evaluated at Mayo Clinic (1991-2025). Psychiatric diagnoses, timing relative to the first attack and patient-reported outcomes were extracted from electronic health records (EHRs). Complementary analyses were conducted using the NeuroBlu real-world EHR database. RESULTS:Among 388 patients with MOGAD, 54.8% had ≥1 psychiatric disorder, most commonly anxiety (47.7%), depression (36.6%) and attention-deficit/hyperactivity disorder (ADHD, 9%). After the first attack, 33.3% of patients with MOGAD developed a new psychiatric disorder, often within the first year. MOGAD showed a lower frequency of depression versus MS (36.6% vs 47.5%, p=0.02) but similar rates of anxiety and ADHD. Temporal patterns differed: psychiatric disorders often appeared years before onset in MS but clustered shortly after onset in MOGAD. NeuroBlu analyses supported high rates of psychiatric disorders across the three conditions. CONCLUSION:Psychiatric comorbidities are common in MOGAD, particularly depression and anxiety, typically emerging close after onset, whereas in MS they often preceded onset by years. These findings underscore the need for routine psychiatric screening in MOGAD and highlight unresolved questions regarding whether, and to what extent, MOG-IgG-mediated inflammatory demyelination contributes to psychiatric vulnerability.

ObjectivesMyelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-IgG) are a biomarker of MOG antibody-associated disease (MOGAD). However, false positives remain common. We aimed to develop a scoring tool to guide interpretation.MethodsObservational study of MOG-IgG-positive patients at Mayo Clinic (May 2022-December 2024). The primary outcome was fulfillment of 2023-MOGAD diagnostic criteria. Predictive variables were identified using logistic regression, and scoring systems were derived and evaluated using receiver operating characteristic analysis. Internal (n = 92) and external (Johns Hopkins, n = 117) validation was performed.ResultsOf 215 MOG-IgG positive patients, 144 were true positive per 2023-MOGAD diagnostic criteria (positive predictive value, 67.0%). The TRUE-MOGAD score included: Titers (MOG-IgG clear positive [+1 point]), Relapsing optic neuritis (>= 3 [+1 point]), Under 18 years at onset [+1 point], Encephalitis phenotype (ADEM or cerebral cortical encephalitis at onset [+2 points]), MRI or other supportive features from 2023-MOGAD-criteria [+2 points], Oligoclonal bands in CSF [-2 points], Gradually progressive or Abrupt onset [-2 points], and Disappearance >= 1 T2-lesion [+1 point]. The score showed an area under the curve (AUC) of 0.983 (95%CI 0.961-1.000). The score was validated internally (AUC = 0.976) and externally (AUC = 0.977).DiscussionThe TRUE-MOGAD score is a practical tool that accurately identifies MOGAD among positive MOG-IgG test results and may guide diagnostic and therapeutic decisions in clinical practice.Classification of EvidenceThis study provides Class II evidence that a TRUE-MOGAD score of 2 or more accurately predicts MOGAD in patients with MOG-IgG titers of 1:20 or higher using the assay described.

BACKGROUND:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) have both overlapping and distinct MRI lesion features, which vary with imaging timing. This study identified distinguishing MRI characteristics using paired MRIs at clinical attack and remission. METHODS:We retrospectively identified Mayo Clinic patients with MOGAD and MS that: (1) fulfilled respective diagnostic criteria; (2) had paired attack (≤30 days) and remission MRI scans (≥12 months) without interval attacks. MRIs were compared between groups for key features. RESULTS:We included 43 patients with MOGAD (median age 31 years (range, 3-67); 63% female) and 49 patients with MS (median age 39 years (range, 17-65); 65% female). Resolution of at least one T2-lesion differentiated MOGAD from MS (sensitivity, (95% CI 77% to 100%), specificity, (95% CI 86% to 99%); Youden's index (YI)=0.90). Resolution of at least two T2-lesions indicated MOGAD (sensitivity 62% (95% CI 41% to 79%); specificity, 100% (95% CI 94% to 100%); YI=0.62). MOGAD patients were more likely to have normal MRI scans at follow-up compared with MS (brain 14/44 (32%) vs 0/60 (0%), p<0.001; spine 21/27 (78%) vs 7/36 (19%), p<0.001). In addition, the presence of T1-hypointense, ovoid periventricular T2, and enhancing lesions were more common in MS versus MOGAD at attack and remission and in the spine, longitudinally extensive T2 lesions were more common in MOGAD attacks (8/27 (30%)). CONCLUSION:Paired MRI at attack and remission revealed distinctive characteristics of MOGAD and MS, with greater diagnostic value at remission driven by the discriminating power of T2-lesion resolution. In MOGAD patients with initial parenchymal involvement, a 1-year follow-up MRI may aid diagnosis and serve as a new baseline.

OBJECTIVES:Myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-IgG) are a biomarker of MOG antibody-associated disease (MOGAD). However, false positives remain common. We aimed to develop a scoring tool to guide interpretation. METHODS:Observational study of MOG-IgG-positive patients at Mayo Clinic (May 2022-December 2024). The primary outcome was fulfillment of 2023-MOGAD diagnostic criteria. Predictive variables were identified using logistic regression, and scoring systems were derived and evaluated using receiver operating characteristic analysis. Internal (n = 92) and external (Johns Hopkins, n = 117) validation was performed. RESULTS:Of 215 MOG-IgG positive patients, 144 were true positive per 2023-MOGAD diagnostic criteria (positive predictive value, 67.0%). The TRUE-MOGAD score included: Titers (MOG-IgG clear positive [+1 point]), Relapsing optic neuritis (≥3 [+1 point]), Under 18 years at onset [+1 point], Encephalitis phenotype (ADEM or cerebral cortical encephalitis at onset [+2 points]), MRI or other supportive features from 2023-MOGAD-criteria [+2 points], Oligoclonal bands in CSF [-2 points], Gradually progressive or Abrupt onset [-2 points], and Disappearance ≥1 T2-lesion [+1 point]. The score showed an area under the curve (AUC) of 0.983 (95%CI 0.961-1.000). The score was validated internally (AUC = 0.976) and externally (AUC = 0.977). DISCUSSION:The TRUE-MOGAD score is a practical tool that accurately identifies MOGAD among positive MOG-IgG test results and may guide diagnostic and therapeutic decisions in clinical practice. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that a TRUE-MOGAD score of 2 or more accurately predicts MOGAD in patients with MOG-IgG titers of 1:20 or higher using the assay described.

Background: Increased chronological age correlates with reduced relapse rates and increased disability in multiple sclerosis (MS). Biological age may better capture ageing's impact on MS and might accelerate due to MS itself. Establishing accelerated biological ageing in adults is complicated by normal ageing and comorbidities. Telomere length, a well-recognised biological ageing marker, is shortened in adults with MS and associated with disability. Demonstrating accelerated biological ageing in paediatric-onset MS (POMS) would strengthen the hypothesis that MS drives premature biological ageing. This study aimed to determine if telomere length differs in POMS compared to age-similar healthy controls. Methods: We performed a cross-sectional case-control study of whole blood samples and clinical data from The US Network of Pediatric MS Centers. Real-time quantitative PCR measured telomere length, expressed as a telomere to somatic DNA ratio (T/S ratio). T/S ratio was compared between cases and age-similar healthy controls using multivariate regression analysis adjusting for chronological age, sex, race, ethnicity, tobacco exposure, socioeconomic status and body mass index. Results: We analysed 300 POMS cases and 200 controls. The unadjusted mean T/S ratios were 1.66 (SD 0.32) for cases and 1.71 (SD 0.29) for controls (mean difference -0.05, 95% CI -0.10 to 0.01, p=0.08). After adjusting for key covariables with face validity, POMS participants had a mean 0.086 shorter T/S ratio than controls (95% CI 0.015 to 0.157, p=0.018). Conclusions: POMS participants demonstrated shorter telomeres than age-similar controls in a multivariable model adjusting for sociodemographic variables, suggesting that MS may contribute to accelerated biological ageing.

Background:Large-scale studies examining the demographic, serological, and seasonal characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) remain limited, despite their potential to provide crucial information for resource allocation, clinical trial design, and recruitment. Objective:To investigate demographic, serological, and seasonal variations in MOGAD and AQP4+NMOSD using a large neuroimmunology laboratory registry validated by clinical cohorts. Methods:We conducted a retrospective, laboratory-based study using data from the Mayo Clinic Neuroimmunology Laboratory registry and clinical cohorts between July 2014 and April 2024. The first available serum sample from each patient tested for MOG-IgG and AQP4-IgG was included. Analyses focused on age and sex distributions, antibody titers, and seasonal patterns of seropositivity, as well as the month and season of disease onset and attacks among the clinical cohorts of MOGAD and AQP4+NMOSD. Results:We included 89,495 sera tested for MOG-IgG and 198,401 for AQP4-IgG, supplemented by validated clinical cohorts of 528 patients with MOGAD and 534 with AQP4+NMOSD. MOG-IgG was detected in 6,313 samples (7.1%), with 1,566 (24.8%) exhibiting high titers (≥1:1,000). AQP4-IgG was positive in 5,057 samples (2.5%). Individuals with MOG-IgG positivity were younger than those with AQP4-IgG positivity (mean age, 34.1 years [SD=20.0] vs 47.7 years [SD=17.9]; p<0.0001). The frequency of MOG-IgG positivity was highest among patients younger than 12 years (1,052 [17.9%]) and declined with older age, while AQP4-IgG positivity increased with older age. AQP4-IgG revealed a strong female predilection (female-to-male ratio 6.2:1), varying by age, whereas MOG-IgG showed a modest female predominance (female-to-male ratio 1.5:1), consistent across all ages. MOG-IgG-titers peaked in younger children and older adults, while AQP4-IgG titers remained stable across ages. Both diseases showed a winter peak in seropositivity, disease onset, and relapses. Conclusions:This large-scale registry analysis provides comprehensive demographic and serological characterization of MOGAD and AQP4+NMOSD. The modest winter peak suggests that seasonal infectious triggers may play an important role in disease pathogenesis. Limitations include incomplete clinical information within the laboratory registry and a referral-based testing population. These findings have important implications for healthcare planning and optimization of clinical trial design and recruitment.

BACKGROUND:Epstein-Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. OBJECTIVES:POMS participants and controls were recruited from 16 pediatric MS clinics between 1 November 2011 and 1 July 2017. Clinical and demographic information, including history of adenotonsillectomy, EBV serostatus, and HLA-DRB1*15:01:01 status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. RESULTS:The case-control analysis included 359 POMS participants and 560 pediatric controls. Individuals with a history of adenotonsillectomy had a 63% increased odds of MS (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.01-2.64, p = 0.046). Among the 239 POMS participants with available follow-up data, adenotonsillectomy was associated with a twofold increase in annualized relapse rate (adjusted incidence rate ratio (IRR) = 2.00, 95% CI = 1.15-3.48, p = 0.013). CONCLUSIONS:Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.

BACKGROUND:Diet may influence MS activity, but most studies use a single dietary measure. The stability of diet over time in pediatric-onset MS (POMS) is unclear. OBJECTIVES:To evaluate the reproducibility and short-term temporal stability of dietary intake in youth with POMS using repeated food frequency questionnaires (FFQ). METHODS:This longitudinal study included participants with a baseline FFQ (the Block Kids Food Screener, 2014). Intraclass correlation coefficients (ICCs) were estimated using random-intercept mixed-effects models to quantify the relative contributions of between-person and within-person variability. Temporal trends in intake were assessed by modeling time since baseline as a fixed effect, using log-transformed dietary variables to estimate percent change over time. RESULTS:Of 419 FFQs from 195 participants, 140 (71.8%) completed ≥2 FFQs over a median of 6.5 months (range 2.8-18). ICCs ranged from 0.41 to 0.78 across dietary measures, with the highest reproducibility observed for vegetables and fiber (ICCs 0.78 and 0.72). Log-transformed models showed small declines in several nutrients over time, corresponding to <10% change over a six-month period. CONCLUSIONS:Dietary intake demonstrated moderate to good reproducibility over the 6 to 18 month follow-up period. Vegetable and fiber intake had the strongest reliability. These findings suggest that reported dietary intake assessed by a single or infrequent FFQ may remain reasonably stable over a 6- to 18-month period in longitudinal POMS studies. However, the moderate-to-good reproducibility observed indicates that within-person variability persists and may attenuate diet-disease associations when only a single dietary assessment is available.

To describe individuals with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) manifesting with isolated meningitis/meningoencephalitis.

To report myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) epidemiology in two American regions using 2023 diagnostic criteria. We compared age- and sex-adjusted incidence and prevalence of MOGAD per 2023 diagnostic criteria in Olmsted County (Minnesota [USA]) and Martinique (Caribbean [FR]) (01/01/2003–12/31/2018, prevalence day) using Poisson regression. Archived sera in 68–85

BACKGROUND:Acute disseminated encephalomyelitis (ADEM) is a demyelinating syndrome observed in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) but there are limited data on application of this definition to its cerebral attacks or in adults with this disease. METHODS:We analyzed patients from the Mayo Clinic MOGAD cohort (n = 263) with cerebral attacks. We assessed whether children (<18 years-old) and adults (⩾18 years-old) fulfilled the 2013 ADEM definition. RESULTS:We identified 89 patients (children, 34; adults, 55) and 55/89 (62%) were of female sex. Acute magnetic resonance imaging (MRI) abnormalities included: poorly demarcated T2 lesions (white matter, 85 (96%); deep gray matter, 41 (46%); T1-hypointense lesions (42 (47%)). Forty-two patients did not fulfill the ADEM definition due to: monofocal syndrome, 9; or no encephalopathy, 33. The remaining 47 patients (53%: children, 27/34 (79%); adults, 20/55 (36%)) fulfilled the ADEM definition, and 14 had preceding attacks, and 34 had subsequent attacks relative to ADEM episode. The features in children and adults with ADEM were broadly comparable. CONCLUSION:Applying the ADEM definition to MOGAD cerebral attacks highlighted that an update of the 2013 ADEM definition would be beneficial and could explicitly state its application to both adults and children and allow it to be applied to attacks at any time during the disease course.

BACKGROUND AND OBJECTIVES:Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD. METHODS:This international multicenter retrospective cohort study included patients from 18 tertiary care centers in 6 countries. Inclusion criteria included fulfillment of the 2023 International MOGAD panel criteria, receipt of at least 3 sessions of PLEX, and follow-up of ≥3 months after PLEX. Patients with coexisting neuroinflammatory disorders were excluded. We assessed the frequency of complete recovery (CR), clinically significant improvement (CSI), visual acuity (VA), and Expanded Disability Status Scale (EDSS). Logistic regression analyses were performed to identify predictors of CR and CSI. RESULTS:Of 234 patients, 135 (58%) were female. The median (interquartile range [IQR]) age at attack was 34 (IQR 22-49) years, and 42 (17%) were children. In 165 of 243 (68%), the attack treated with PLEX was the first attack. Attack phenotypes included 161 optic neuritis (235 eyes), 77 myelitis, 24 acute disseminated encephalomyelitis, 15 brainstem/cerebellar, 3 cerebral-cortical encephalitis attack, and 1 cerebral polyfocal deficit-36 with >1 core phenotypes. A total of 239 (99%) attacks were also treated with corticosteroids and 32 (13%) with IV immunoglobulins. VA in optic neuritis improved from 20/400 (20/70-hand motion) to 20/20 (20/20-20/30), p < 0.001, and EDSS decreased from a median of 4.0 (3.0-6.5) to 1.0 (0.0-2.5), p < 0.001. Of 229 attacks without subsequent attacks within 3 months, 100 (44%) achieved CR and 213 (93%) CSI. The probability of CR was decreased with advanced age (adjusted odd ratio [95% CI] 0.97 [0.96-0.99] per year), higher EDSS worsening from baseline (0.66 [0.54-0.81] per 0.5 increment) and delayed PLEX (0.98 [0.96-0.99] per day). Advanced age (0.97 [0.96-0.99] per year) and delayed PLEX (0.95 [0.94-0.96] per day) decreased the probability of CSI. DISCUSSION:We observed favorable outcomes after PLEX in MOGAD attacks. However, advanced age and delayed initiation of PLEX were associated with a reduced probability of improvement. The absence of a control group limits our ability to differentiate PLEX effects from spontaneous recovery, prior corticosteroid response, or long-term immunotherapy. Future prospective studies are needed to assess the impact of PLEX on improvement. CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that PLEX is associated with favorable clinical outcomes in patients with MOGAD.