Multiple Sclerosis And Related Disorders[JOURNAL]
Sun
200 papers
Validation of a new diagnostic ELISA to detect anti-JCV antibodies in serum of patients with multiple sclerosis considering or receiving treatment with natalizumab.
Adler F, Andersen M, Bartl T … +5 more , Derlacz R, Frese MA, Keller T, Schelcher C, Wiegand R
Mult Scler Relat Disord · 2026 Jun · PMID 42134893 · Publisher ↗
BACKGROUND: Anti-John Cunningham virus (JCV) antibody testing is integral to progressive multifocal leukoencephalopathy (PML) risk stratification in patients with multiple sclerosis (MS), considering or receiving nataliz...
BACKGROUND: Anti-John Cunningham virus (JCV) antibody testing is integral to progressive multifocal leukoencephalopathy (PML) risk stratification in patients with multiple sclerosis (MS), considering or receiving natalizumab. We report on analytical and clinical validation of the two-step ImmunoWELL JCV enzyme-linked immunosorbent assay (ELISA) for anti-JCV antibody testing in this patient population. METHOD: Assay cut-off points were established using MS patient sera (N = 329), with a combined test strategy incorporating a screening test with a percentage inhibition test for those screening in an 'equivocal zone'. Clinical performance was evaluated in sera from 888 patients with MS (blinded) against STRATIFY® JCV DxSelect™ (the 'reference test'), with primary endpoints of sensitivity and specificity. RESULTS: Variability (imprecision) was low (total coefficient of variation 6.5-11.3%); samples were stable, and no relevant hook effect was observed. Cross-reactivity was also analyzed. The optimized cut-off strategy achieved 96.4% sensitivity and 80.9% specificity. In the clinical validation study, sensitivity was 97.2%, specificity 74.1%, positive predictive value 83.5%, and negative predictive value 95.3%. Polymerase chain reaction-based false-negative estimates were similar between the ImmunoWELL JCV test (1.6%) and the reference test (3.3%). Reported serostatus change (17.3% vs 15.8%, respectively) and seroconversion (6.7% vs 10.1%, respectively) were comparable between assays. CONCLUSIONS: The ImmunoWELL JCV test is a reliable two-step ELISA with high sensitivity and clinically relevant specificity versus the reference test, supporting its use to inform PML risk management in patients with MS considering, or receiving, natalizumab.
External validation and improvement of an algorithm that identifies multiple sclerosis relapses in the French national healthcare claims database.
Carcaillon-Bentata L, Abouelfath A, Lignot-Maleyran S … +35 more , Lassalle R, Jové J, Blin P, Berger E, Bourre B, Camdessanche JP, Casez O, Ciron J, David T, De Seze J, Defer G, Doghri I, Santos AD, Hankiewicz K, Heinzlef O, Labauge P, Page EL, Lebrun-Frenay C, Leclancher A, Louapre C, Manchon E, Mathey G, Montcuquet A, Papeix C, Pelletier J, Pottier C, Ruet A, Sarov-Riviere M, Vukusic S, Magy L, Moulin M, Brochet B, Casey R, Leray E, OFSEP Investigators
Mult Scler Relat Disord · 2026 Jul · PMID 42134166 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) is a frequent neurological condition affecting young adults with acute disabling neurological episodes (relapses). MS relapses are not recorded in claims databases despite their import...
BACKGROUND: Multiple sclerosis (MS) is a frequent neurological condition affecting young adults with acute disabling neurological episodes (relapses). MS relapses are not recorded in claims databases despite their importance for (pharmaco)epidemiological studies. This study aimed to validate and improve an algorithm identifying relapses in relapsing-remitting MS initiating disease-modifying therapy (DMT) within the French nationwide claims database (SNDS). METHODS: Clinical data from the French MS registry (OFSEP) linked to the SNDS were used. The cohort included MS patients with a first DMT claim between July 2015 and December 2017, naive to any MS treatment, followed until December 2018 (n=1,640). The initial relapse algorithm combined high-dose corticosteroid prescriptions and hospitalization duration. Incidence of the first relapse identified in the SNDS was compared with OFSEP confirmed relapses that have been treated by corticosteroid or hospitalized (gold standard). Performances were estimated using Sensitivity, Specificity, PPV, NPV. Algorithm were reevaluated after revision of its criteria based on experts' review of false positive and negative cases' claims, and finally after adding non-naive MS patients (n=9,966). RESULTS: The performances of the initial algorithm were Specificity 85.2%, Sensitivity 74.0%, NPV 89.8%, PPV 65.3%. After revision of corticosteroid dosages and hospitalization durations thresholds, performance slightly improved: 85.0%, 75.4%, 90.2%, 65.3%, respectively. When considering naive and non-naive MS patients, Sensitivity and NPV stayed similar (75.1% and 91.6%) while Specificity and PPV decreased (81.8% and 55.4%). CONCLUSION: The final algorithm of treated/hospitalized relapses can be applied accurately in naïve MS patients initiating a DMT, in the SNDS and likely in other claims databases after adapting to each country's reimbursement and care practices.
Updated systematic literature review and network meta-analysis of cladribine tablets versus currently approved disease-modifying treatments for active relapsing-remitting multiple sclerosis.
Harty GT, Jones M, Maheshwari V … +1 more , Saipriya J
Mult Scler Relat Disord · 2026 Jul · PMID 42134165 · Publisher ↗
BACKGROUND: To update previous work assessing the relative efficacy and safety of cladribine tablets compared to currently approved disease-modifying treatments (DMTs) in patients with active relapsing-remitting multiple...
BACKGROUND: To update previous work assessing the relative efficacy and safety of cladribine tablets compared to currently approved disease-modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), using systematic literature review (SLR) and network meta-analysis (NMA). METHODS: Systematic literature searches were conducted in MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017, and then further updated from January 2017 to September 2022. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), proportion relapse-free (RF), and safety. RESULTS: Of 21,181 unique articles retrieved and screened, 66 studies met the inclusion criteria and had their data extracted, including 17 new studies since the previous review; of these, 57 studies assessing 20 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo; cladribine tablets were similar or significantly better than other DMT regimens. For 6-month CDP, improvements with cladribine tablets were significantly greater than those of placebo, with no comparator DMT demonstrating significantly better results. For both efficacy endpoints, cladribine tablets ranked sixth among DMTs, behind ofatumumab, ublituximab, alemtuzumab, natalizumab, and ocrelizumab. The overall adverse event risk for cladribine tablets was statistically comparable to all other oral DMTs and both interferon beta-1a regimens. CONCLUSIONS: In this updated SLR and NMA, cladribine tablets remain a comparatively effective and safe alternative to other currently approved DMTs in populations of patients with active RRMS.
Toxocara seropositivity in sensory-predominant cervical myelitis from an endemic region: A six-case series and systematic review.
Alkhuder H, Iskandar S, Toufaili H … +5 more , Maalouf N, Zeineddine M, Shatila A, Tourbah A, Dassouki ME
Mult Scler Relat Disord · 2026 Jul · PMID 42127637 · Publisher ↗
BACKGROUND: Toxocara species are globally prevalent zoonotic helminths. Spinal neurotoxocariasis is uncommon but clinically relevant because it may mimic inflammatory demyelinating myelitis. OBJECTIVE: To describe a six-...
BACKGROUND: Toxocara species are globally prevalent zoonotic helminths. Spinal neurotoxocariasis is uncommon but clinically relevant because it may mimic inflammatory demyelinating myelitis. OBJECTIVE: To describe a six-patient institutional series of sensory-predominant cervical myelitis with Toxocara seropositivity from an endemic region and to contextualize these cases within the published literature. METHODS: We retrospectively reviewed six institutional cases of sensory-predominant non-compressive cervical myelitis associated with positive Toxocara serology and performed a structured literature review of reports published from January 1980 to March 2025. Institutional cases were classified by diagnostic confidence according to microbiologic support and exclusion of alternative diagnoses. No case was labelled definitive without histopathologic proof or paired CSF/serum confirmation; serum Western blot-supported cases were classified as higher-support/probable, whereas serum ELISA-only cases were classified as possible. RESULTS: Thirty-two published cases met inclusion criteria. Thoracic and cervical lesions predominated, eosinophilia was inconsistent, and most reported patients improved after albendazole-based therapy. Clearly sensory-only myelitis was rarely documented in the published literature; most reports described mixed sensory, motor, and/or autonomic syndromes or lacked sufficient symptom detail for confident classification. In contrast, the institutional series showed a sensory-predominant cervical pattern: five patients had sensory-only myelitis and one had sensory-predominant myelitis with mild urinary urgency and gait imbalance. Two cases had stronger supportive serologic evidence based on serum Western blot positivity, whereas four cases had serum ELISA positivity only and were classified as possible Toxocara-associated myelitis. Clinical improvement was described as an outcome and was not used as diagnostic confirmation because all patients received corticosteroids with albendazole. CONCLUSION: Toxocara-associated myelitis should be considered in non-compressive cervical or thoracic cord lesions in endemic settings, but diagnostic certainty varies across cases and positive serum ELISA alone should not be interpreted as definitive evidence of CNS infection. The institutional series supports a sensory-predominant cervical pattern while underscoring the need for paired serum/CSF testing, standardized imaging, and follow-up MRI when feasible.
The effects of hybrid assistive limb (HAL) application on locomotor function and balance parameters in individuals with multiple sclerosis.
Açar G, Baser M, Özkeskin M … +5 more , Özden F, Seyhan S, Kavak MF, Sarı Z, Aktürk A
Mult Scler Relat Disord · 2026 Jul · PMID 42119269 · Publisher ↗
BACKGROUND: Multiple Sclerosis (MS) often causes walking and balance impairments, limiting daily independence. Hybrid Assistive Limb (HAL), a wearable robotic exoskeleton, may assist in improving these functions. OBJECTI...
BACKGROUND: Multiple Sclerosis (MS) often causes walking and balance impairments, limiting daily independence. Hybrid Assistive Limb (HAL), a wearable robotic exoskeleton, may assist in improving these functions. OBJECTIVE: To investigate the effect of HAL-assisted rehabilitation on locomotor function, balance performance, and functional mobility in individuals with MS. METHODS: Thirteen individuals with MS were included in this single-group pre-post quasi-experimental study. This study did not include a control group. Participants underwent gait rehabilitation using a lower-limb HAL device for 1 h per day, 5 days a week, for 2 months. Locomotor function and balance were assessed using the 10-Meter Walk Test (10MWT), the Timed Up and Go (TUG) test, and the 6-Minute Walk Test (6MWT). Spatiotemporal parameters of the gait were analyzed using the Tecnobody Walker View system. Static balance was evaluated using the Tecnobody d-Wall system. RESULTS: Thirteen adults with MS (mean age 46.2 ± 7.5 years) completed the 2-month HAL-assisted rehabilitation program. Significant improvements were observed in locomotor function and functional mobility: TUG time decreased from 18.85 ± 12.20 s to 14.04 ± 11.04 s (p < 0.001), 10MWT time decreased from 25.64 ± 21.54 s to 21.05 ± 21.08 s (p = 0.001), and 6MWT distance increased from 174.62 ± 58.68 m to 261.54 ± 95.03 m (p = 0.001). EDSS scores showed a decrease from 4.62 ± 1.33 to 2.62 ± 1.85 (p = 0.002). Static balance improved under both eyes-open and eyes-closed conditions, and step length increased significantly bilaterally. Cadence and hip/lumbar ROM showed no significant changes, while left knee ROM improved significantly (p = 0.008). These findings should be interpreted as preliminary, given the absence of a control group. CONCLUSIONS: HAL-assisted rehabilitation may be a feasible and promising approach for improving walking performance, balance, and functional mobility in individuals with MS. However, these preliminary findings from a single-group pre-post design without a control group should be interpreted with caution, and further randomized controlled trials are needed to confirm these results.
Reliability and validity of the modified O'Sullivan functional balance test in patients with multiple sclerosis.
Uzun M, Polat H, Horata ET … +1 more , Erel S
Mult Scler Relat Disord · 2026 Jul · PMID 42119268 · Publisher ↗
OBJECTIVE: This cross-sectional, observational study aimed to evaluate the validity and reliability of the modified O'Sullivan Functional Balance Test (mOFB) in patients with multiple sclerosis (pwMS). METHODS: Fifty pwM...
OBJECTIVE: This cross-sectional, observational study aimed to evaluate the validity and reliability of the modified O'Sullivan Functional Balance Test (mOFB) in patients with multiple sclerosis (pwMS). METHODS: Fifty pwMS (22 males, 28 females), aged 18 to 65 years, were included in the study. Intraclass correlation coefficients (ICC) were used to assess the reliability of the mOFB, and the minimal detectable change (MDC) values were calculated based on ICCs obtained from repeated measurements across two sessions. The convergent validity of the mOFB was examined by analyzing its correlations with the Trunk Impairment Scale (TIS), L test, Mini-BESTest, and Berg Balance Scale (BBS). RESULTS: The median EDSS score of the participants was 2.50 (1.50-4.00). Test-retest reliability of the mOFB test for Rater A was moderate for the sitting subscale (ICC = 0.699), good for the standing subscale (ICC = 0.829), and good for the total score (ICC = 0.892). For Rater B, test-retest reliability was moderate for the sitting subscale (ICC = 0.731), good for the standing subscale (ICC = 0.758), and excellent for the total score (ICC = 0.905). Inter-rater reliability was moderate for the sitting subscale (ICC = 0.690), good for the standing subscale (ICC = 0.785), and good for the total score (ICC = 0.895). For the mOFB total score, SEM, SEM%, MDC, and MDC% values were 0.813, 7.65, 2.253, and 21.21, respectively. The mOFB sitting subscale showed moderate correlations with TIS subscale scores (ρ = 0.548 to 0.674) and strong correlations with the TIS total score, L Test, Mini-BESTest, and BBS (ρ = 0.749 to 0.854). The mOFB standing subscale demonstrated moderate correlations with TIS subscale scores (ρ = 0.541 to 0.600) and strong correlations with the other balance measures (ρ = 0.708 to 0.851). The total mOFB score showed a very strong correlation with the Mini-BESTest (ρ = 0.912), moderate correlations with TIS subscale scores (ρ = 0.585 to 0.661), and strong correlations with the remaining balance assessments (ρ = 0.735 to 0.897). CONCLUSION: mOFB is a reliable and valid tool for assessing balance in pwMS.
Patient reported outcomes in NMOSD reflect a high disease burden and do not correlate with the EDSS.
Saeedzadeh E, Vyas MV, Sharma S … +12 more , Vas N, Carruthers R, Chertcoff A, Casserly C, Freedman MS, Lee L, Marrie RA, McCombe JA, Morrow SA, Parks NE, Smyth P, Rotstein DL
Mult Scler Relat Disord · 2026 Jul · PMID 42116255 · Publisher ↗
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 n...
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.
Longitudinal changes in serum protein levels are associated with disability progression in multiple sclerosis.
Andreu LS, Martín JCV, Muñoz AH … +4 more , Pascual PA, Santelesforo MF, Montero YEB, Velasco A
Mult Scler Relat Disord · 2026 Jul · PMID 42116254 · Publisher ↗
BACKGROUND: Early identification of patients with multiple sclerosis (MS) at risk of transitioning from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) remains a major cli...
BACKGROUND: Early identification of patients with multiple sclerosis (MS) at risk of transitioning from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) remains a major clinical challenge. Although magnetic resonance imaging (MRI) is widely used to monitor disease activity, imaging markers alone may not adequately predict progression. The identification of accessible biochemical markers associated with disability progression could improve long-term monitoring. METHODS: This retrospective observational study evaluated clinical, radiological, and biochemical parameters in 45 MS patients followed at a single tertiary center. Twenty-three patients remained in the RRMS phase, while 22 developed SPMS. Cerebrospinal fluid (CSF) biomarkers obtained at diagnosis and serum biomarkers measured at two time points separated by two years were analyzed. Group comparisons used non-parametric tests, and associations with disability were assessed using Spearman correlation. RESULTS: Serum albumin and total protein levels measured two years before progression were significantly lower in patients who later developed SPMS compared with those who remained RRMS. Creatinine and ferritin did not differ between groups. In RRMS patients, ferritin levels decreased significantly over time, whereas albumin and total protein remained stable. CSF IgG index values tended to be higher in patients who later developed SPMS, without reaching statistical significance. MRI activity was not associated with progression. Total serum protein levels were inversely correlated with EDSS scores. CONCLUSIONS: Lower serum protein levels may precede clinical transition to SPMS and reflect processes related to disability progression. Despite not being independent predictors, their accessibility supports their potential role in longitudinal monitoring strategies.
The timed up and go obstacle test in people with multiple sclerosis: a reliability and validity study.
Keskin AO, Gülşen Ç, Özcan Gülşen E … +1 more , Söke F
Mult Scler Relat Disord · 2026 Jul · PMID 42107472 · Publisher ↗
OBJECTIVE: The aim of the study was to investigate test-retest reliability, the concurrent validity and the known-groups validity, and the cut-off times of the Timed Up and Go Obstacle Test (TUGO) in people with multiple...
OBJECTIVE: The aim of the study was to investigate test-retest reliability, the concurrent validity and the known-groups validity, and the cut-off times of the Timed Up and Go Obstacle Test (TUGO) in people with multiple sclerosis (PwMS). METHOD: 30 PwMS and 30 controls were included. Intraclass correlation coefficients (ICC) and the minimal detectable change (MDC) were determined for reliability. Correlations between the TUGO times and the Expanded Disability Status Scale, the Timed Up and Go Test, the Timed 25-Foot Walk Test, Dynamic Gait Index, and the Falls Efficacy Scale-International were used to assess validity. TUGO times were compared between PwMS and controls, and between fallers and non-fallers with MS. RESULTS: The TUGO completion times for 0 cm, 5 cm, and 17 cm obstacles demonstrated excellent test-retest reliability (ICC = 0.980, 0.972, and 0.967 respectively). The MDC values of TUGO were calculated as 2.80 s for 0 cm, 3.38 s for 5 cm, and 4.28 s for 17 cm obstacles. The TUGO completion times demonstrated moderate to strong correlations with other measurements (correlation coefficients ranging from -0.891 to 0.907; p < 0.001 for all). All TUGO completion times of PwMS were higher than controls (p < 0.001 for all) and all TUGO completion times of fallers with MS were also higher than non-fallers with MS (p = 0.017, p = 0.007, and p = 0.005 respectively). CONCLUSION: TUGO is a reliable, valid, low-cost and easy-to-administer clinical assessment tool in evaluating the obstacle negotiation ability of PwMS.
Incidence of multiple sclerosis in Switzerland - results from the Swiss multiple sclerosis registry.
Iaquinto S, Müller J, Salmen A … +14 more , Kuhle J, Roth P, Stanikić M, Kamm CP, Calabrese P, Baum C, Kesselring J, Zecca C, Rapold I, Yaldizli Ö, Ammann S, Puhan MA, von Wyl V, Swiss Multiple Sclerosis Registry
Mult Scler Relat Disord · 2026 Jul · PMID 42107471 · Publisher ↗
BACKGROUND: While data on multiple sclerosis (MS) prevalence are widely available, incidence data, crucial for understanding disease onset dynamics, are less frequently reported. This study aims to estimate MS incidence...
BACKGROUND: While data on multiple sclerosis (MS) prevalence are widely available, incidence data, crucial for understanding disease onset dynamics, are less frequently reported. This study aims to estimate MS incidence in Switzerland from 2017 to 2021 and characterize persons newly diagnosed with MS. METHODS: The Swiss MS Registry is an ongoing longitudinal study in Switzerland. It has established an innovative methodology to assess MS epidemiology by integrating SMSR data with administrative data on reimbursement approvals for disease-modifying therapies and by use of a modified benchmark-multiplier method. We calculated overall, sex- and age-specific MS incidence (2017-2021) and described the demographic and clinical characteristics of newly diagnosed individuals. RESULTS: The estimated annual MS incidence in Switzerland was 663 [95% simulation interval 617-711] cases, corresponding to an annual MS incidence of 7.7 [7.1-8.3] per 100,000 inhabitants. This equates to approximately two new MS diagnoses per day. Incidence remained stable throughout the study period. Peak incidence occurred in the 30 to 35-year age group for women and 35 to 40-year age group for men. Most individuals were diagnosed with relapsing-remitting MS (94.0%). Following diagnosis, 56.9% received oral therapy, 27.7% infusion therapy, and 15.4% injectable therapy. CONCLUSION: Our study found stable MS incidence over five years, consistently higher in women than men. Most diagnoses occurred between ages 20-40, though new diagnoses among middle-aged individuals appear to be increasingly common.
Differential safety profiles of disease-modifying therapies in MS: Age- and sex-based analysis from a real-world cohort.
Ercan MC, Cakan E, Gumus Y … +3 more , Ozen NPA, Tuncer A, Karabudak R
Mult Scler Relat Disord · 2026 Jul · PMID 42107470 · Publisher ↗
BACKGROUND/OBJECTIVES: Age and sex may modulate adverse events (AE) under disease-modifying therapies (DMTs) in Multiple Sclerosis (MS), yet comparative real-world data across agents remain limited. We assessed age- and...
BACKGROUND/OBJECTIVES: Age and sex may modulate adverse events (AE) under disease-modifying therapies (DMTs) in Multiple Sclerosis (MS), yet comparative real-world data across agents remain limited. We assessed age- and sex-specific adverse event (AE) patterns within individual disease-modifying therapy (DMT) cohorts (dimethyl fumarate, fingolimod, natalizumab, and ocrelizumab) in a real-world setting. METHODS: Demographics, EDSS, laboratory parameters (CBC, LFTs, immunoglobulins), infections (PCR/culture), and first-dose ECG/HR were extracted for single-centre retrospective cohort (2010-2021). The primary outcome was AE incidence. Predictors of AEs were analysed using Cox proportional hazards regression, while predictors of COVID-19 infection were assessed using Poisson regression. RESULTS: Among 1137 evaluations (DMF 228; fingolimod 539; natalizumab 70; ocrelizumab 300) in 658 patients, lymphopenia was the most frequent AE. In the fingolimod cohort, female sex and younger age at treatment onset were associated with grade 3-4 lymphopenia (adjusted HR 0.33, 95% CI 0.23-0.48 and HR 0.97, 95% CI 0.96-0.99; BH-adjusted P = 0.005 for both), and male sex with LFT abnormalities (adjusted HR 3.10, 95% CI 1.51-6.32; BH-adjusted P = 0.007). First-dose bradycardia occurred in 13.7%, with comparable heart rate reductions across age groups and sexes. Nominal associations in DMF (older age with lymphopenia) and ocrelizumab (male sex with bacterial infection and neutropenia) did not survive BH correction. Older age was associated with lower COVID-19 incidence in the fingolimod and ocrelizumab cohorts (BH-adjusted P = 0.036 and P < 0.001). CONCLUSION: In this real-world cohort, fingolimod showed robust sex- and age-specific AE patterns, whereas nominal associations in DMF and ocrelizumab cohorts are interpreted as hypothesis-generating pending validation. These findings support further investigation of therapy-specific, demographically informed monitoring strategies in MS.
The national neuromyelitis optica spectrum disorders registry system of Iran (NMORI): Aspects and methodological dimensions.
Ayoubi S, Sahraian MA, Heidari H … +2 more , Moghadasi AN, Eskandarieh S
Mult Scler Relat Disord · 2026 Jul · PMID 42105477 · Publisher ↗
BACKGROUND: The Neuromyelitis optica spectrum disorder (NMOSD) needs a reliable standardized information registry system to support policy-makers strategy to improve quality of care. Consequently, systematic monitoring o...
BACKGROUND: The Neuromyelitis optica spectrum disorder (NMOSD) needs a reliable standardized information registry system to support policy-makers strategy to improve quality of care. Consequently, systematic monitoring of NMOSD patients is warranted. OBJECTIVES: To describe aspect and strategy method of national NMOSD registry system in Iran (NMORI). METHODS: The NMORI is a population-based registry that systemically recognizes and collects wholly NMOSD subjects' data. The system focuses on collecting inclusive and important data on the epidemiological and clinical indicators of NMOSD, this includes a set of variables: baseline characteristics, diagnosis and disease progress, treatments, laboratory findings, pregnancy & medical history, risk factors and lab data. Data are gathered from all available sources, including public and private hospitals, clinics, and neurologists' offices. RESULT: The NMORI designed in 2024 and currently includes 10 provinces across Iran. The goals of NMORI are to monitor and supervise how to treat and follow-up patients and ultimately improve the quality of care and life of subjects, reasonable allocation of treatment resources and providing scientists with novel ideas to carry out research projects. Consequently, NMORI has adopted frequent national and international collaborations aimed at addressing important health and clinical issues. A robust supervisory framework governs the scientific and systematic registry system, which operates under the oversight of four committees CONCLUSION: The NMORI system provides valuable insights into NMOSD diagnosis, care and treatment by offering comprehensive data on disease incidence, risk factors and progression. This system has capacity to increase the effectiveness of care protocols and management.
Painful tonic spasms in neuromyelitis optica spectrum disorders: Prevalence, clinical phenotype, symptomatic management, and patient-reported burden in a Chinese cohort.
Luo W, Du Y, Wei Z … +4 more , Huang S, Tang J, Tang Y, Wu Y
Mult Scler Relat Disord · 2026 Jul · PMID 42105476 · Publisher ↗
BACKGROUND: Tonic spasms in neuromyelitis optica spectrum disorder (NMOSD) range from painless tonic posturing to painful tonic spasms (PTS). However, the real-world management, tolerability, and patient-reported burden...
BACKGROUND: Tonic spasms in neuromyelitis optica spectrum disorder (NMOSD) range from painless tonic posturing to painful tonic spasms (PTS). However, the real-world management, tolerability, and patient-reported burden of PTS remain insufficiently described. METHODS: We screened consecutive patients with NMOSD at a tertiary center in China between January 2020 and July 2025. PTS were identified through medical record review and a structured questionnaire. We described their clinical features, timing in relation to myelitis, magnetic resonance imaging findings, symptomatic treatments, patient-reported response, tolerability, and daily-life burden. RESULTS: PTS were identified in 77 of 229 patients (33.6%). They were more frequent in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMOSD than in AQP4-IgG-negative NMOSD (72/183, 39.3% vs 5/46, 10.9%; p < 0.001). Forty-six of 77 patients (59.7%) reported PTS onset after the first myelitis attack. Marked or partial improvement with symptomatic treatment was reported by 64 of 77 patients (83.1%). Combination pharmacotherapy was common (59/77, 76.6%), and 9 of 77 patients (11.7%) discontinued at least one symptomatic medication because of adverse effects. PTS also imposed a substantial burden, with effects on mood, sleep, and work productivity each reported by approximately one-quarter of patients. CONCLUSIONS: PTS are common after myelitis in NMOSD. Most patients report improvement with symptomatic therapy, but polypharmacy and treatment intolerance are frequent, and the daily-life burden is substantial. Routine screening after spinal cord attacks and pragmatic comparative studies that address both effectiveness and tolerability are needed.
Real-world outcomes of cladribine in people ≥55 years of age with multiple sclerosis.
Smoot K, Stuchiner T, Gervasi-Follmar T … +1 more , Chen C
Mult Scler Relat Disord · 2026 Jul · PMID 42096862 · Publisher ↗
BACKGROUND: Treatment strategies for older adults with relapsing multiple sclerosis (RMS) require reassessment, particularly for those seeking to simplify or discontinue disease‑modifying therapy (DMT). Cladribine may re...
BACKGROUND: Treatment strategies for older adults with relapsing multiple sclerosis (RMS) require reassessment, particularly for those seeking to simplify or discontinue disease‑modifying therapy (DMT). Cladribine may represent a transition option. We aimed to describe clinical outcomes and treatment‑related adverse events in individuals ≥55 years with RMS who initiated cladribine within a western US health system. METHODS: We conducted a retrospective chart review of patients ≥18 years with RMS who received at least one course of cladribine between March 2019, and April 2024. RESULTS: Of 267 patients reviewed, 107 were ≥55 years old (72.9% female; median age 63.0 [58.4-67.2]). During a median follow‑up of 16.0 (7.0-28.0) months, the annualized relapse rate on cladribine was 0.00. Median Expanded Disability Status Scale (EDSS) at year 2 was 3.3 (2.5-6.5; n = 44). Three patients transitioned to another DMT, with a median time to new DMT of 35.0 (19.0-35.0) months. CONCLUSIONS: In this older cohort, most patients were stable after switching to cladribine. While cladribine was generally well-tolerated, larger prospective studies are needed to better define its effectiveness in older adults with RMS.
Mining online peer support communities to understand treatment side effects in Multiple Sclerosis.
Ayine B
Mult Scler Relat Disord · 2026 Jul · PMID 42096861 · Publisher ↗
Online peer-support forums provide valuable insights into how people living with Multiple Sclerosis (MS) experience and interpret treatment-related side effects. While clinical literature documents the physiological prof...
Online peer-support forums provide valuable insights into how people living with Multiple Sclerosis (MS) experience and interpret treatment-related side effects. While clinical literature documents the physiological profiles of these effects, less is known about their emotional framing in patient-generated discourse. This study analysed discussions from the r/MultipleSclerosis subreddit to examine patterns of engagement, sentiment, and emotional expression across four treatment categories: Disease-Modifying Therapies (DMTs), Treatments for MS Attacks, Symptom-Management Medicines, and "Other treatments". Sentiment analysis was conducted using VADER, and emotional profiling was performed using the NRC Emotion Lexicon, followed by statistical comparisons across categories. DMT-related side effects accounted for 74% of discussions. Although engagement levels did not significantly differ across treatment types, negative sentiment predominated. Emotional analyses revealed significantly higher levels of anger and disgust in DMT-related posts, while fear was prevalent across all categories. These findings highlight the emotional burden associated with long-term MS therapies and demonstrate the potential of online patient discourse as a complementary source of insight into treatment experiences and patient-centred care. Implications for practice and future directions are discussed.
Assessment of serum FAM19A5 level in patients with Neuromyelitis Optica spectrum disorder.
El-Tellawy HN, Abd-Elhameed MA, Elzohne RA … +4 more , Rageh TA, Danial SK, Mahmoud DM, Shalaby NM
Mult Scler Relat Disord · 2026 Jul · PMID 42090976 · Publisher ↗
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is currently classified as a principal astrocytopathy accompanied by secondary demyelination . The neuroinflammatory protein FAM19A5 is released by reactive astr...
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is currently classified as a principal astrocytopathy accompanied by secondary demyelination . The neuroinflammatory protein FAM19A5 is released by reactive astrocytes following CNS injury. However, data on its role in NMOSD are limited. AIM: This study aimed to evaluate serum levels of FAM19A5 in patients with NMOSD compared to healthy controls . METHODS: A cross-sectional comparative study was conducted on 50 NMOSD patients and 40 healthy controls at the Neurology Department, Assiut University Hospitals, Egypt,over a two-year period. Serum aquaporin-4 IgG (AQP4-IgG) antibodies were assessed using a cell-based immunofluorescence assay. Serum FAM19A5 levels were measured using the Human TAFA-5 ELISA kit. Clinical and radiological data from studied sample were collected and analyzed. RESULTS: Serum FAM19A5 levels were significantly elevated in NMOSD patients compared to healthy controls (median 673.95 ng/L vs. 355.25 ng/L, p < 0.001). ROC curve analysis demonstrated that FAM19A5 had good diagnostic performance in distinguishing NMOSD patients from healthy controls, with an area under the curve (AUC) of 0.836, a sensitivity of 64.0%, and a specificity of 97.5% at a cutoff value >600 ng/L. CONCLUSION: Serum FAM19A5 levels are significantly elevated in patients with NMOSD compared to healthy individuals, suggesting its potential utility as a diagnostic biomarker of NMOSD.
The evolution of criteria for assessing disease activity and progression in multiple sclerosis (or the "saga of acronyms").
Mekies C
Mult Scler Relat Disord · 2026 Jul · PMID 42085923 · Publisher ↗
Therapeutic advances in multiple sclerosis have led to the evolution of criteria used to assess disease activity and progression. The concept of NEDA aims for the complete absence of clinical and radiological activity bu...
Therapeutic advances in multiple sclerosis have led to the evolution of criteria used to assess disease activity and progression. The concept of NEDA aims for the complete absence of clinical and radiological activity but is very strict and difficult to sustain. MEDA was proposed as a more realistic goal, allowing minimal disease activity. Disability progression can no longer be assessed using the EDSS alone, leading to the development of composite measures such as NEP and NEPAD. Studies have shown that most disability worsening occurs independently of relapses, giving rise to the key concept of PIRA, and then PIRMA. This silent progression begins early and is driven by neurodegenerative and chronic inflammatory mechanisms. New concepts (SAW) further characterize this slow progression. An integrated framework separating inflammatory activity (NEIDA) from smouldering progression (NESDA) is now proposed to better guide therapeutic strategies.
Targeted lipidomics approach reveals the role of ceramide signalling in the pathophysiology of Neuromyelitis optica spectrum disorders.
John M, Maria E, Mohan V … +6 more , Krishna U S, George L, Harisuthan T, Varghese P, Lalu A, Varghese PR
Mult Scler Relat Disord · 2026 Jul · PMID 42085922 · Publisher ↗
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a group of chronic autoimmune disorder affecting the central nervous system, involving optic nerves and spinal cord, leading to recurrent episodes of optic ne...
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a group of chronic autoimmune disorder affecting the central nervous system, involving optic nerves and spinal cord, leading to recurrent episodes of optic neuritis and transverse myelitis. The objective of the present study is to identify differentially expressed ceramide species that contributes to neuro inflammation associated with pathophysiology of NMOSD. METHODOLOGY: The study used a labelled mass spectrometric approach to identify differentially expressed ceramide species (DECS) in AQP-4 IgG NMOSD and MOG IgG NMOSD variants of NMOSD. RESULT: It was observed that lactosyl and glucosyl ceramide species of C16 and C18 types were upregulated in both variants of NMOSD along with sphingomyelin and their derivatives. The LIPEA analysis showed the upregulation of apoptotic, inflammatory and oxidative stress pathways in both AQP-4 IgG NMOSD and MOG IgG NMOSD variants. CONCLUSION: The study for the first time employed a labelled approach to identify DECS in NMOSD variants and their involvement in mediation of neuroinflammation in dictating its underlying pathophysiology. This study provides insight into mechanistic involvement of ceramide species and their signalling for better diagnosis and therapeutic interventions.
Frequency of MRI abnormalities in adult-onset MOG-IgG-associated disease at disease presentation: A cohort of Latin American patients.
Pestchanker C, Ciampi E, Castro Suarez S … +14 more , Caparo Zamalloa C, Daccach Marques V, Messias K, Gortari JI, Tkachuk V, Silva B, Mainella C, Reyes S, Toro J, Rodriguez J, Correa-Diaz E, Rojas JI, Tseriotis VS, Carnero Contentti E
Mult Scler Relat Disord · 2026 Jun · PMID 42070455 · Publisher ↗
INTRODUCTION: The 2023 diagnostic criteria for myelin oligodendrocyte glycoprotein-associated disease (MOGAD) compiled magnetic resonance imaging (MRI) features associated with core clinical demyelinating events. We aime...
INTRODUCTION: The 2023 diagnostic criteria for myelin oligodendrocyte glycoprotein-associated disease (MOGAD) compiled magnetic resonance imaging (MRI) features associated with core clinical demyelinating events. We aimed to characterize the frequency and distribution of typical MRI abnormalities in adult-onset MOGAD at disease onset in a Latin American (LATAM) cohort. METHODS: We retrospectively reviewed medical records and MRI studies of 144 LATAM MOGAD patients that met the 2023 MOGAD criteria at their first documented attack (Chile, n = 40; Peru, n = 36; Argentina, n = 31; Brazil, n = 26; Colombia, n = 8; Ecuador, n = 3). Demographic and clinical characteristics, including relapse type, and MRI scans features performed within 30 days of the initial manifestation were evaluated. RESULTS: Out of 144 MOGAD patients, 129 (89.6%) had MRI scans performed within 30 days of their first attack. In ON, perineural enhancement was the most common MRI finding (52 patients, 40.3%), followed by longitudinal compromise (48 patients, 37.2%); in spinal cord MRI, longitudinal lesions were most frequent (38 patients, 29.5%), followed by the H-sign (33 patients, 25.6%). Brain MRIs most frequently showed multiple ill-defined T2-hyperintense white matter lesions (27 patients, 21%), followed by ill-defined brainstem lesions (13 patients, 10.1%). Notably, 23 patients (17.8%) showed none of the typical features described in the 2023 diagnostic criteria. CONCLUSION: This study highlights the variability of MRI findings in adult MOGAD patients at disease onset, in a LATAM cohort. Most patients (82.2%) exhibited MRI features consistent with the 2023 diagnostic criteria, reinforcing their applicability in clinical practice, whereas 17.8% did not, underscoring the need for a comprehensive diagnostic approach.
The gut microbiome in pediatric-onset acquired demyelinating syndromes by myelin oligodendrocyte glycoprotein antibody status.
Tsai W, Zhu F, Bar-Or A … +11 more , Bernstein CN, Bonner C, Graham M, Marrie RA, Mirza AI, O'Mahony J, Yeh EA, Banwell B, Waubant E, Tremlett H, Canadian Pediatric Demyelinating Disease Network
Mult Scler Relat Disord · 2026 Jun · PMID 42068931 · Publisher ↗
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 micro...
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.
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