Background:Meningoencephalitis can occur in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). Objective:To assess the clinical and radiologic features of MOG-IgG meningoencephalitis. Methods:Multicenter retrospective cases series of MOG-IgG meningoencephalitis and literature review of MOG-IgG-positive patients with the clinical syndrome of meningoencephalitis. Results:Ninety MOG-IgG-positive patients were identified from three academic medicine centers. 8/90 (8.9%) patients presented with a clinical syndrome of meningoencephalitis (age: 4-57 years; 5/8 male; 4/8 Caucasian; MOG-IgG titers 1:20-1:1000), which was the initial presentation in 7/8 patients. Symptoms included headaches (n = 8/8), encephalopathy (n = 7/8), seizures (n = 4/8), meningismus (n = 3/8), and aphasia (n = 3/8). Cerebrospinal fluid (CSF) pleocytosis was present in 7/8 patients (12-1745 cells/mm3) and frequently neutrophilic (>25%; n = 4/6). Magnetic resonance imaging (MRI) was notable for leptomeningeal enhancement with (n = 5/8) or without cortical edema (n = 1/8), focal dural enhancement (n = 1/8), and leptomeningeal loss of FLAIR suppression (n = 1/8). 7/8 patients sustained a relapsing disease course. Literature review identified 150 additional cases with MOG-IgG meningoencephalitis (initial attack in 86.7%) with median age of 20 (1-67) years, Asian (90.4%) and male (54.1%) predilection, and CSF pleocytosis in 87.9% of patients (82 [0-887] cells/cm3; ≥100 cells in 44.3%), which was frequently (51.7%) neutrophilic. Conclusions:MOG-IgG meningoencephalitis may represent the initial presentation of MOGAD with neutrophilic pleocytosis in CSF and meningo-cortical involvement on MRI.

Background Disease-modifying therapy (DMT) use in older adults with multiple sclerosis (MS) is debated due to age-related factors, effectiveness, and economic concerns of DMTs. Therefore, this study examined the factors influencing the discontinuation of DMTs in older adults with MS. Methods This retrospective cohort study included Medicare beneficiaries (≥66 years) with MS who are persistent DMT users. Discontinuation of DMT was defined as ≥12 consecutive months without DMT use, while continuation of DMT was defined as maintaining Proportion of Days Covered ≥80% for an additional 24 months. A multivariable logistic regression was used to identify the baseline factors associated with DMT discontinuation. Results Among 8,694 eligible aged Medicare beneficiaries with persistent DMT use, 1,025 (11.79%) discontinued DMTs. The discontinuation cohort had a mean age of 69.7 ± 3.9 years, with 79.5% females and 91.1% Whites. Older age, recent years, and clinical complexity, such as frailty and disability, were associated with lower odds of discontinuation. However, patients with dual eligibility and certain comorbidities were more likely to discontinue therapy. Conclusions Among older MS patients with persistent DMT use, about 12% discontinued, with significant sociodemographic and clinical characteristics influencing DMT discontinuation. Evaluation of the outcomes of DMT discontinuation is warranted to inform treatment decisions and enhance geriatric MS care.

BACKGROUND:There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. OBJECTIVE:To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. METHODS:DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. RESULTS:In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate (p = 0.043) and greater brain parenchymal fraction (p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment (p < 0.001) and relapse rate (p = 0.025). CONCLUSION:Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. CLINICAL TRIAL REGISTRATION:NCT03535298.

BACKGROUND:In 2015, Glatopa (generic name: Glatiramer Acetate) was the first US Food and Drug Administration-approved generic disease-modifying agent for multiple sclerosis (MS) patients based on structural and functional equivalence to Copaxone, the branded counterpart. However, there is limited comparative effectiveness and safety evidence of Glatopa and Copaxone. OBJECTIVES:This study compared the risk of MS relapse and serious infections in patients using Glatopa and Copaxone. METHODS:A retrospective cohort study that included MS patients aged 18-64 was conducted using the 2017-2019 Merative MarketScan® Commercial Claims data. The index was the first Glatopa or Copaxone prescription, with a 6-month washout period with no disease-modifying agents. The inverse probability of treatment weighting (IPTW) based on the Cox proportional hazards (CPH) regression models were conducted to compare the time to the first MS relapse and serious infection for Glatopa and Copaxone users during the 6-month follow-up period. RESULTS:Among 3193 MS patients who initiated GA, 20.9 % (n = 668) initiated Glatopa, while 79.1 % (n = 2525) received Copaxone. Bivariate analyses found no significant difference between Glatopa and Copaxone users with respect to relapse (11.9 % vs. 12.5 %; p = 0.9445) and serious infections (0.3 % vs. 0.4 %; p = 0.4292) during the folow-up period. The IPTW-based CPH model revealed no significant difference in the risk of MS relapse (adjusted hazard ratio [aHR] 0.93; 95 % confidence interval [CI], 0.81-1.08) and serious infection (aHR 0.74; 95 % CI, 0.33-1.64) between Glatopa and Copaxone users. CONCLUSIONS:This real-world study found that Glatopa was associated with comparable effectiveness (relapses) and safety (serious infections) to Copaxone.

BACKGROUND:With advances in disease-modifying therapies (DMTs), patients with multiple sclerosis (MS) are living longer. OBJECTIVE:This study examined MS prevalence and DMT use among older adults 65 years and above in the United States. METHODS:The study analyzed 2011-2021 Medicare fee-for-service claims data. RESULTS:The prevalence rate of MS in older adults increased by 15.49%, from 210.55 (per 100,000) in 2011 to 243.17 in 2021. Women comprised 75% of the aging MS population, and 90% were White. Over half were prescribed DMTs, mainly interferon-beta and glatiramer acetate. CONCLUSIONS:The study found an increasing prevalence of MS among older adults in the United States over the past decade, with over half using DMTs. Our findings highlight the need for increasing geriatric care for MS.

Objectives: To assess characteristics of increased intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: This is a multicenter retrospective review of 84 MOGAD cases at the University of Florida, Baylor College of Medicine, the University of California San Diego, and Providence Health and Services, Portland, Oregon, to identify cases with a documented increased opening pressure >25 cm H2O. A literature review was conducted to identify previously reported MOGAD cases with an opening pressure >25 cm H2O. Results: Of 28 MOGAD cases with available opening pressures, 6 (21.4%) patients (age: 5 to 36 y; 2/6 females) had documented increased ICP with an opening pressure of 26 to 46 cm H2O and optic nerve head edema on funduscopic examination. The increased ICP occurred in the setting of bilateral optic neuritis in all cases. In 5/6 patients, this was the initial presentation of the disorder. Anti-MOG titers were 1:40 (n = 1), 1:100 (n = 4), and 1:1000 (n = 1). In our literature review, we identified 13 additional MOGAD cases with ICP elevations in the setting of meningo-cortical presentations (n = 10), as well as bilateral optic neuritis (n = 3). Conclusions: Increased ICP may occur in MOGAD and may be more common in patients with optic neuritis or meningoencephalitis.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have a monophasic or relapsing disease course. To date, factors that may predict a relapsing disease course remain largely unknown and only limited data exist regarding the efficacy of different utilized immunotherapy regimens at preventing or reducing relapses. Objectives: To assess the characteristics, predictors, and immunotherapy of relapsing MOGAD. Methods: This multicenter retrospective analysis included all MOGAD cases at the University of Florida, Baylor College of Medicine and the University of California San Diego with minimum follow-up time of 6 months. Cox proportional hazards regression analyses, corrected for age and sex, were performed to evaluate hazard ratios (HR) of predictors of a relapsing disease course and to compare relapse hazards for utilized immunotherapies. Results: The majority of included participants (51/79 [64.6 %]) had a relapsing course, and of these individuals, 68.6 % (35/51) experienced their first relapse within the first year. However, 10/51 (19.6 %) participants experienced their first relapse >= 5 years (5-15 years) after the initial presentation. Predictors of a relapsing course were CSF pleocytosis (>150 cells/mm(3); HR 3.3 [1.18 - 9.24]; p = 0.023), a pediatric disease onset at age < 9 years (HR 2.69 [1.07-6.75]; p = 0.035), and an initial presentation with the clinical syndrome of meningoencephalitis (HR 3.42 [1.28 - 9.17]; p = 0.015),. In participants with a relapsing course, 13/24 (54.2 %) patients remained relapse-free on rituximab, 4/8 (50 %) on mycophenolate mofetil, and 11/14 (78.6 %) on scheduled immunoglobulins. Patients treated with immunoglobulins had significantly fewer relapses compared to patients treated with other immunotherapies (HR: 0.1 [0.2 - 0.63]; p = 0.014). Conclusions: In our cohort, the majority of MOGAD patients relapsed. The initial relapse occurred most frequently within the first year, but first relapses also took place over a decade after the initial presentation. Prepubertal onset, severe CSF pleocytosis, and the clinical syndrome of meningoencephalitis may be predictors of a relapsing course. Of the currently available off-label steroid-sparing treatments, scheduled immunoglobulins may be the most effective in relapse prevention.

We outline a case of a male with preexisting relapsing-remitting multiple sclerosis diagnosed with widespread metastatic melanoma to discuss the appropriate use of ICIs in persons with MS (pwMS) if necessary.

Background: Real-world effectiveness can vary across oral disease-modifying agents (DMAs) and their adherence trajectories in patients with multiple sclerosis (MS). However, previous studies have not considered longitudinal adherence patterns while evaluating oral DMAs. Objectives: This study aimed to evaluate the association of oral DMAs and their adherence trajectories with annualized relapse rate (ARR) in patients with MS. Methods: This retrospective observational cohort study based on the 2015-2019 MarketScan Commercial Claims and Encounters Database involved continuous enrolled adults (18-64 years) with >= 1 MS diagnosis (ICD-9/10CM:340/G35) and >= 1 oral DMA prescription. Patients were grouped into incident fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users based on the index DMA with a one-year washout period. Annual DMA adherence trajectories based on the monthly Proportion of Days Covered (PDC) one year after treatment initiation were identified using Group-Based Trajectory Modeling (GBTM). The validated claims-based ARR was evaluated during the one-year follow-up period using generalized boosted model-based inverse probability treatment weights with negative binomial regression model. Results: The study cohort consisted of 994 MS patients who initiated with FIN (23.0%), TER (22.3%), and DMF (54.7%) during the study period. GBTM grouped eligible patients into three adherence trajectories: complete adherers (59.2%), slow decliners (23.8%), and rapid decliners (17.0%). The proportion of complete adherers varied across the oral DMAs (FIN: 67.1%, TER: 55.4%, and DMF: 57.4%). The negative binomial regression modeling revealed that, while there was no difference in ARR across the three DMAs, rapid decliners (adjusted incidence rate ratio[aIRR]: 1.6, 95% CI: 1.1-2.4) had a higher rate of relapses compared to completely adherent patients. The type of oral DMAs did not moderate the relationship between ARR and the adherence trajectory groups. Conclusions: Adherence trajectories classified as rapid decliners were associated with a higher ARR than complete adherers after adjusting for their type of oral DMAs. Longitudinal medication adherence patterns are critical in reducing relapse rates in MS.

BACKGROUND:With multiple treatment options, choosing the initial disease-modifying agent (DMA) could be crucial to managing multiple sclerosis (MS). Common treatment strategies recommend starting patients with moderate-efficacy disease-modifying agents (meDMAs), while others advocate initiating high-efficacy disease-modifying agents (heDMAs). However, limited real-world evidence exists regarding the factors associated with utilizing differing treatment strategies in the MS. OBJECTIVE:This study evaluated the factors associated with the initiation of heDMAs in comparison to meDMAs among patients with MS. METHODS:A retrospective cohort study was conducted using the Merative MarketScan Commercial Claims Database. Adult (18-64 years) MS patients with ≥1 DMA prescription were identified from 2016 to 2019. Patients were classified as incident heDMA or meDMA users based on their earliest DMA prescription, with a 12-month washout period. All covariates were measured during the 12-month baseline before the index DMA date. A multivariable logistic regression model, guided by the Andersen Behavioral Model, was applied to examine the predisposing, enabling, and need factors associated with using heDMAs over meDMAs. RESULTS:There were 10,003 eligible MS patients, with the majority of users being female (74.92 %), middle-aged adults (35-54 years, 58.97 %), and enrolled in the Preferred Provider Organization (PPO, 53.10 %) healthcare plan. Overall, 2293 (22.92 %) MS patients initiated heDMAs. The multivariable logistic regression model revealed that male patients (adjusted odds ratio [aOR]: 1.46, 95 % Confidence Interval [CI]: 1.30-1.64) had higher odds of initiating heDMAs. Meanwhile, patients with bladder dysfunction medications (aOR: 1.39, 95% CI: 1.21-1.61), fatigue medications (aOR: 1.77, 95 %CI: 1.44-2.17), and impaired walking (aOR: 1.62, 95 %CI: 1.42-1.86) were more likely to initiate treatment with heDMAs. In contrast, patients with higher Elixhauser comorbidities scores, sensory symptoms (aOR: 0.47, 95 %CI: 0.42-0.53), visual symptoms (aOR: 0.63, 95 %CI: 0.54-0.73), and brainstem symptoms (aOR: 0.81, 95 %CI: 0.67-0.97) were less likely to be prescribed with heDMAs. CONCLUSION:The study found that approximately one in four MS patients initiated heDMAs. Both demographic and clinical factors influenced the selection of heDMA. More work is needed to understand the differential value of selecting heDMAs over meDMAs for personalizing DMA treatment.

OBJECTIVE:The optimal treatment strategy for the management of multiple sclerosis is widely discussed due to the increasing availability of high-efficacy disease-modifying agents (heDMAs). This study evaluated the comparative effectiveness of heDMA and moderate-efficacy disease-modifying agents (meDMAs) use in reducing annualized relapse rate (ARR) among multiple sclerosis patients. METHODS:A retrospective cohort study was conducted using the 2015-2019 United States Merative MarketScan Commercial Claims Data. Adult (18-64 years) patients with incident disease-modifying agents (DMA) use were included. Claim-based relapse algorithms were applied to measure relapse events. The inverse probability treatment weighting (IPTW) based negative binomial regression model with the offset of the follow-up period was used to compare the ARR. The moderation effect of sex on ARR was also examined. RESULTS:This study included 10,003 incident DMA users, with 22.9 % initiated heDMAs. The average ARR during follow-up among heDMA users was lower than meDMA users (0.25 vs. 0.28, p < 0.01). The IPTW-based regression found that sex moderated the relationship between the types of DMAs and ARR. Stratified analyses revealed that heDMAs were associated with a lower ARR in males (adjusted incidence rate ratio [aIRR] 0.74; 95 % confidence interval [CI] 0.59-0.94) compared with meDMAs. No significant differences were noted among females (aIRR 0.99; 95 % CI: 0.88-1.21). CONCLUSION:The study found that sex moderated the effect of heDMAs, with male multiple sclerosis patients using heDMAs associated with a 26 % decreased risk of relapse than those with meDMAs. However, there was no difference in comparative effectiveness for females.

In patients with multiple sclerosis (MS), infections represent a significant concern, particularly given the immunomodulatory effects of disease-modifying agents (DMAs). High-efficacy DMAs (heDMAs) play a pivotal role in delaying MS progression, yet their use also raises concerns regarding the risk of infection. This study aimed to compare the infection risk with the use of heDMA and moderate-efficacy disease-modifying agents (meDMAs) in MS patients. This retrospective cohort study involved adult (18-64 years) MS patients with incident DMA use based on the 2015-2019 MarketScan Commercial Claims and Encounters Database. Patients initiating heDMAs (natalizumab, alemtuzumab, and ocrelizumab) or meDMAs (interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and glatiramer acetate) were included. The outcomes of interest were comparative risk of overall infection, serious infection, and frequently reported types of infection. Adjusted hazard ratios (aHR) were estimated in inverse probability treatment weighting (IPTW) based on Cox proportional hazard models. Among 10,003 eligible incident DMA users, 22.92% of patients initiated heDMAs. The IPTW-CPH model revealed that patients with heDMAs were associated with a higher risk of serious infection (aHR: 1.24, 95% confidence interval (CI): 1.06-1.44) and urinary tract infection (UTI; aHR: 1.21, 95% CI: 1.14-1.30). Sensitivity analyses with different follow-up periods yielded consistent findings with the main analyses. In MS, heDMAs were associated with a greater risk of serious infection and UTI compared with meDMAs. These findings suggest the need to carefully monitor and manage the infection risk to optimize the use of heDMAs in MS.

STUDY OBJECTIVE:This study compared the adherence trajectories of fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users with multiple sclerosis (MS) as there is limited evidence regarding the comparative adherence patterns of different oral disease-modifying agents (DMAs).DESIGN:A retrospective cohort study DATA SOURCE: 2015-2019 IBM MarketScan Commercial Claims Database.PATIENTS:Adults (≥18 years) with MS (International Classification of Diseases [ICD]-9/10-Clinical Modification [CM]:340/G35) diagnosis and ≥1 DMA prescription.INTERVENTION:Incident FIN-, TER-, or DMF use based on the index DMA with 1 year of washout period.MEASUREMENTS:The DMA adherence trajectories based on the proportion of days covered (PDC) were examined using the Group-Based Trajectory Modeling (GBTM) one year after the treatment initiation. Generalized boosting models (GBM)-based inverse probability treatment weights (IPTW) were incorporated in multinomial logistic regression to assess the comparative adherence trajectories across oral DMAs with FIN group as a reference category.MEASUREMENTS AND MAIN RESULTS:The study cohort consisted of 1913 patients with MS who were initiated with FIN (24.2%, n = 462), TER (24.0%, n = 458), and DMF (51.9%, n = 993) during 2016-2018. The adherence rate (PDC ≥ 0.8) among FIN, TER, and DMF users was found to be 70.8% (n = 327), 59.6% (n = 273), and 61.0% (n = 606), respectively. The GBTM grouped patients into three adherence trajectories: Complete Adherers-59.1%, Slow Decliners-22.6%, and Rapid Discontinuers-18.3%. The multinomial logistic regression model involving GBM-based IPTW revealed that DMF (adjusted odds ratio [aOR]: 2.32, 95% confidence interval [CI]:1.57-3.42) and TER (aOR: 2.50, 95% CI: 1.62-3.88) users had higher odds to be rapid discontinuers relative to FIN users. In addition, TER users were more likely (aOR: 1.50, 95% CI: 1.06-2.13) to be slow decliners compared with FIN users.CONCLUSION:Teriflunomide and DMF were associated with poorer adherence trajectories than FIN. More research is needed to evaluate the clinical implications of these adherence trajectories of oral DMAs to optimize the management of MS.

La esclerosis múltiple (EM) es una enfermedad que afecta mujeres de ancestro europeo principalmente entre la tercera y cuarta década de la vida, y tiene una prevalencia aproximada de 60 a 100 habitantes/100.000 en los Estados Unidos y superior a 140/100.000 en países del norte de Europa. El diagnóstico es bastante infrecuente en niños; del total de pacientes con EM en el mundo se estima que solo el 2.7-5 por ciento son menores de 18 años, menos del 1 por ciento son menores de 10 años y las manifestaciones clínicas pueden ser diferentes en comparación con lo visto en poblaciones de mayor edad. Es importante tener siempre entre el diagnóstico diferencial la encefalomielitis aguda diseminada (EAD) con sus formas recurrente y multifásica, la neuromielitis óptica (NMO), las enfermedades mitocondriales y el síndrome clínico aislado (SCLA) entre otros. Los medicamentos utilizados para el tratamiento agudo o crónico en adultos de la enfermedad son los mismos utilizados en niños pero siempre teniendo en cuenta que los estudios no son tan amplios, además de la edad y el peso del paciente para determinar la mejor dosis del tratamiento. El presente documento tiene por objetivo formular recomendaciones en cuanto al diagnóstico, pronóstico y manejo más adecuado de la enfermedad en esta población.

Background: Patients with multiple sclerosis (MS) frequently switch their Disease-Modifying Agents (DMA) for effectiveness and safety concerns. This study aimed to develop and compare the random forest (RF) machine learning (ML) model with the logistic regression (LR) model for predicting DMA switching among MS patients. Methods: This retrospective longitudinal study used the TriNetX data from a federated electronic medical records (EMR) network. Between September 2010 and May 2017, adults (aged >= 18) MS patients with >= 1 DMA prescription were identified, and the earliest DMA date was assigned as the index date. Patients prescribed any DMAs different from their index DMAs were considered as treatment switch. . The RF and LR models were built with 72 baseline characteristics and trained with 70% of the randomly split data after up-sampling. Area Under the Curves (AUC), accuracy, recall, G-measure, and F-1 score were used to evaluate the model performance. Results: In this study, 7258 MS patients with >= 1 DMA were identified. Within two years, 16% of MS patients switched to a different DMA. The RF model obtained significantly better discrimination than the LR model (AUC = 0.65 vs. 0.63, p < 0.0001); however, the RF model had a similar predictive performance to the LR model with respect to F-and G-measures (RF: 72% and 73% vs. LR: 72% and 73%, respectively). The most influential features identified from the RF model were age, type of index medication, and year of index. Conclusions: Compared to the LR model, RF performed better in predicting DMA switch in MS patients based on AUC measures; however, judged by F-and G-measures, the RF model performed similarly to LR. Further research is needed to understand the role of ML techniques in predicting treatment outcomes for the decision-making process to achieve optimal treatment goals.

La neuritis óptica (NO) es la inflamación primaria del nervio óptico asociada con frecuencia a desmielinización, y en muchos casos puede ser el primer episodio de un paciente que va a desarrollar esclerosis múltiple (EM) con el tiempo. Es de naturaleza progresiva en pocas semanas, en su mayoría asociada a dolor retro-ocular, alteración de la sensibilidad al contraste y evidencia de defecto pupilar aferente. Casi siempre tiene buen pronóstico de recuperación. La resonancia magnética (RM) cerebral es esencial para identificar a los pacientes en riesgo de EM y los potenciales evocados nos pueden ayudar en pacientes en que está cuestionado el diagnóstico de EM. El LCR puede mostrar anormalidades leves con presencia de bandas oligoclonales aunque no se tiene claro el valor predictivo de este hallazgo en cuanto al desarrollo de EM especialmente si la RM es anormal. El tratamiento del evento agudo se hace con metilprednisolona IV seguido de prednisolona oral y el manejo crónico en pacientes con alto riesgo de desarrollar EM se realiza con interferones. Finalmente, siempre es importante tener en cuenta el diagnóstico de NMO, especialmente en pacientes con NO recurrentes y RM no sugestiva de EM. En estos casos el pronóstico y tratamiento de la enfermedad varía.