Multiple Sclerosis And Related Disorders[JOURNAL]
Sun
200 papers
Neuromyelitis optica spectrum disorder: a 5-year experience in a tertiary hospital in Northern Vietnam.
Nguyen QH, Tran HT, Nguyen DM … +3 more , Tran HH, Le AD, Nguyen NH
Mult Scler Relat Disord · 2026 Jun · PMID 42401157 · Publisher ↗
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, severe autoimmune disease of the central nervous system more prevalent in African and Asian ancestries. The data within the Vietnamese community remai...
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, severe autoimmune disease of the central nervous system more prevalent in African and Asian ancestries. The data within the Vietnamese community remain limited. OBJECTIVES: To evaluate the clinical, laboratory, and radiological profiles of a Vietnamese NMOSD cohort, identifying patterns of diagnostic delays, misdiagnosis, and immunotherapy adherence. METHODS: This retrospective study re-evaluated patients admitted to a tertiary hospital from January 2019 to August 2024 meeting the 2015 diagnostic criteria. Data were collected from records, phone interviews, or follow-ups. RESULTS: We identified 40 patients with 106 disease attacks (73 documented). The female-to-male ratio was 39:1; mean onset age was 44.83 ± 14.07 years. Transverse myelitis was most common initially (57.5%) and overall (63.6%). Aquaporin-4 antibody was positive in 91.9%. Longitudinally extensive transverse myelitis appeared in 83.7% of abnormal spinal MRIs; brain MRI abnormalities in 74%. Only 20% of patients received an accurate etiological diagnosis at onset, with a mean diagnostic delay 24.15 ± 41.1 months. Relapses occurred within the first year in 60% of patients, and within five years in 83.3%. Preventive treatment was prescribed to 85%; long-term adherence was 60% with rituximab showing the highest adherence (15 patients). CONCLUSION: NMOSD in Vietnamese patients features a marked female predominance, prominent spinal cord involvement, high relapse rates, and low accurate etiological diagnosis rates at onset. Long-term treatment non-compliance, limited antibody test availability, and low physician awareness likely remain major clinical challenges.
Cell-type-specific Mendelian randomization analysis of brain single-nucleus eQTLs and neuromyelitis optica spectrum disorder risk.
Ye H, Huang S, Shi L … +1 more , Chai L
Mult Scler Relat Disord · 2026 Jun · PMID 42401156 · Publisher ↗
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system autoimmune disease characterized by aquaporin-4 antibody-mediated astrocyte injury. Although genetic risk variants in the major...
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system autoimmune disease characterized by aquaporin-4 antibody-mediated astrocyte injury. Although genetic risk variants in the major histocompatibility complex (MHC) region have been consistently implicated in NMOSD susceptibility, the cellular context in which these genetic risk factors operate in the brain remains uncharacterized. We aimed to identify cell-type-specific genetic associations between brain gene expression and NMOSD risk through a systematic Mendelian randomization screen. METHODS: Cis-eQTL summary statistics from control-only single-nucleus RNA sequencing data of 183 individuals across eight major brain cell types were used as exposures, and the largest European-ancestry NMOSD GWAS (215 cases, 1244 controls) as the outcome. Two-sample Mendelian randomization was performed using the Wald ratio method with Bonferroni correction (P < 2.87 × 10⁻⁵). Steiger directionality testing was performed. Colocalization analysis (coloc.abf) was performed for the Bonferroni-significant loci. Exploratory subtype-stratified analyses were conducted for Bonferroni-significant exposures using NMOSD-IgG+ (132 cases) and NMOSD-IgG- (83 cases) GWAS data. RESULTS: Of 1465 cell-type-gene exposures screened, three reached Bonferroni significance, all in the MHC region: HLA-DRB1 in excitatory neurons (OR = 2.50, 95% CI 1.84-3.41), HLA-B in oligodendrocytes (OR = 0.23, 95% CI 0.12-0.44), and HLA-B in inhibitory neurons (OR = 0.32, 95% CI 0.20-0.51). Steiger testing supported the assumed direction of effect for all three. All three associations were substantially stronger in NMOSD -IgG+ and attenuated or absent in NMOSD -IgG-. Colocalization supported a shared causal signal for HLA-DRB1 in excitatory neurons (PP.H4 = 0.90) but not for either HLA-B association (PP.H4 <0.5), consistent with the latter tagging the shared risk haplotype. CONCLUSIONS: Cell-type-specific Mendelian randomization identified three MHC-region genetic associations with NMOSD that exhibited clear AQP4-IgG+ subtype specificity, providing a cell-type-resolved perspective on the genetic architecture of seropositive NMOSD. Because of the extensive linkage disequilibrium across the MHC, these signals most plausibly tag the shared HLA-DRB1×03:01/HLA-B*08:01 risk haplotype rather than reflecting independent cell-type-specific causal effects, and should be regarded as hypothesis-generating.
Detection of Aquaporin-4 antibody in cerebrospinal fluid in neuromyelitis optica spectrum disorder.
Linnet T, Maas MB, Mateen FJ … +1 more , Shah S
Mult Scler Relat Disord · 2026 Jun · PMID 42401155 · Publisher ↗
Neuromyelitis optica spectrum disorder is an astrocytopathy associated with aquaporin-4 immunoglobulin G (AQP4-IgG). Although live cell-based serum assays have improved antibody detection, the diagnostic value of cerebro...
Neuromyelitis optica spectrum disorder is an astrocytopathy associated with aquaporin-4 immunoglobulin G (AQP4-IgG). Although live cell-based serum assays have improved antibody detection, the diagnostic value of cerebrospinal fluid (CSF) AQP4-IgG testing remains uncertain. To assess its incremental utility, we retrospectively identified patients who underwent paired serum and CSF AQP4-IgG testing using live cell-based assays. Among 606 paired serum-CSF samples, 7 were serum-positive. Of these, 5 of 7 were also CSF-positive. The two remaining serum-positive patients were CSF-negative. No CSF-restricted cases were identified. Despite a low number of serum-positive cases, our findings add to an existing body of evidence supporting limiting routine CSF AQP4-IgG testing.
Adjunctive gypenosides for acute optic neuritis: A prematurely terminated randomized, double-blind, placebo-controlled pilot trial in a cohort with frequent AQP4-IgG positivity.
Lu Y, Zhao M, Luo W … +1 more , Du Y
Mult Scler Relat Disord · 2026 Jun · PMID 42398278 · Publisher ↗
BACKGROUND: Gypenosides are neuroprotective in experimental optic neuritis, but human data are lacking. METHODS: In this single-center, double-blind, placebo-controlled randomized pilot trial, adults with first-episode o...
BACKGROUND: Gypenosides are neuroprotective in experimental optic neuritis, but human data are lacking. METHODS: In this single-center, double-blind, placebo-controlled randomized pilot trial, adults with first-episode optic neuritis in the study eye within 28 days received standard corticosteroids and were assigned to gypenosides (180 mg/day for 10 days) or placebo. Planned enrollment was 28, but the trial stopped after 10 randomizations. The primary outcome was peripapillary retinal nerve fiber layer (pRNFL) thickness at 6 months. The registered secondary structural outcome was total macular volume; macular ganglion cell-inner plexiform layer (mGCIPL) thickness was exploratory. Mixed-effects models adjusted for aquaporin 4 immunoglobulin G (AQP4-IgG) serostatus. RESULTS: Ten participants were randomized (gypenosides n = 6; placebo n = 4), nine contributed post-baseline data, and six were AQP4-IgG positive. At 6 months, adjusted between-group differences were +16.2 μm for pRNFL thickness (95% CI -16.3 to 48.6; P = 0.274) and +0.034 mm³ for total macular volume (95% CI -0.166 to 0.234; P = 0.696). Exploratory mGCIPL change showed a nominal difference (+18.0 μm, 95% CI 7.8 to 28.3; nominal P = 0.004), without consistent functional benefit. CONCLUSIONS: This prematurely terminated pilot trial was severely underpowered and did not meet the pRNFL primary endpoint. The exploratory mGCIPL finding should not be interpreted as evidence of efficacy. The study provides feasibility and endpoint information that may inform the design of future antibody-stratified trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02976766).
Genetic and molecular architecture of multiple sclerosis in gulf cooperation council populations: A scoping review and regional precision-neurology perspective.
Alsharoqi IA, Alsharoqi AIS, Bohlega SA
Mult Scler Relat Disord · 2026 Jun · PMID 42398277 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) is increasingly recognized across Gulf Cooperation Council (GCC) countries, where rising disease burden intersects with distinctive ancestry, family structure, consanguinity patterns,...
BACKGROUND: Multiple sclerosis (MS) is increasingly recognized across Gulf Cooperation Council (GCC) countries, where rising disease burden intersects with distinctive ancestry, family structure, consanguinity patterns, vitamin D deficiency, rapid environmental transition, and an unevenly developed genetic literature. Most global MS genetic models have been derived from European-ancestry datasets and may not fully capture susceptibility patterns, allele frequencies, familial structure, or gene-environment interactions in Arabian Gulf populations. A regionally focused synthesis is therefore needed, while recognizing that the available GCC evidence remains too limited, heterogeneous, and insufficiently replicated for conventional pooled meta-analysis. OBJECTIVE: To map and critically synthesize available HLA, non-HLA, vitamin D pathway, transcriptomic, biomarker, familial, registry-related, and emerging mitochondrial evidence relevant to MS genetic and molecular susceptibility in GCC populations, and to define research priorities that could support future precision-neurology approaches. METHODS: A PRISMA-ScR-informed scoping review and narrative evidence synthesis was conducted. PubMed, Embase, Scopus, Web of Science, Cochrane Library, and selected regional sources were searched for publications from January 2000 to February 2026, with an update before resubmission in June 2026. Eligible sources included GCC-based MS studies reporting HLA, non-HLA SNP, transcriptomic, serum biomarker, vitamin D pathway, familial, registry, or molecular evidence relevant to MS susceptibility or disease biology. Study-level effect estimates were extracted when available. No pooled meta-analysis was performed because repeated variant-level data across independent GCC cohorts were unavailable for most loci. RESULTS: Fourteen studies were included in the scoping synthesis; four provided directly extractable study-level effect estimates. The available evidence suggests, but does not prove, that MS susceptibility in GCC populations may be heterogeneous and not fully explained by Western-derived HLA-DRB1×15:01-centered models. Bahrain contributes HLA and transcriptomic/biomarker evidence, including inflammatory molecular signals involving IL-1RA, OASL, TNF-AIP6, CLC, DOCK4, and TMEM66 that require prospective validation. Saudi Arabia contributes familial and registry-based observations, with exploratory mitochondrial studies representing an additional future-oriented non-HLA research layer. Kuwait provides the most extractable non-HLA replication and vitamin D pathway data, including immune, metabolic, vitamin D receptor, and vitamin d-binding protein signals. Qatar, the United Arab Emirates, and Oman remain underrepresented in accessible primary MS genetic literature. Across all layers, the evidence is biologically informative but constrained by small cohorts, single-country designs, incomplete extractability, limited replication, and heterogeneous methods. Importantly, transcriptomic, biomarker, familial, registry, and mitochondrial findings were interpreted separately from inherited DNA-level association studies to avoid overstating clinical readiness or combining biologically related but methodologically distinct evidence types. CONCLUSIONS: GCC MS genetics should be interpreted as an emerging, fragmented, and hypothesis-generating field rather than a mature meta-analytic evidence base. Its value lies in clarifying evidence layers, identifying reproducibility gaps, and defining the infrastructure needed for future regional validation. Harmonized GCC registries, high-resolution HLA typing, non-HLA genotyping, vitamin D phenotyping, family-structured recruitment, biomarker validation, biobanking, mitochondrial substudies, ancestry documentation, transparent allele/genotype reporting, and registry-linked longitudinal outcomes could support future precision-neurology research without implying current readiness for routine genetic risk prediction or treatment selection, or individualized therapeutic stratification in routine clinical practice across the Arabian Gulf at present.
Rising burden and future projections of multiple sclerosis in East Asia: Findings from the global burden of disease study 2021.
Liu W, Liu P, Wang Q … +1 more , Li X
Mult Scler Relat Disord · 2026 Jun · PMID 42398276 · Publisher ↗
Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by immune-mediated inflammation and demyelination. Although East Asia was historically regarded as a low-prevalence region, recent eviden...
Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by immune-mediated inflammation and demyelination. Although East Asia was historically regarded as a low-prevalence region, recent evidence suggests a rising MS burden, yet region-wide analyses of long-term trends and future projections remain limited. Using data from the Global Burden of Disease (GBD) 2021 study, we assessed MS burden in China, Japan, South Korea, North Korea, and Mongolia from 1990 to 2021. Age-standardized prevalence (ASPR), incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) were analyzed, with temporal trends quantified using estimated annual percentage change (EAPC) and future burdens projected to 2041 through autoregressive integrated moving average (ARIMA) models. Between 1990 and 2021, ASPR in East Asia steadily increased, while ASDR declined. Mongolia consistently carried the highest burden, whereas China experienced the fastest growth, with ASPR projected to rise by more than 80% by 2041. Japan and South Korea showed relatively stable patterns, while North Korea exhibited moderate increases. Across all countries, females consistently bore higher burdens than men, and MS indicators were positively correlated with the Sociodemographic Index (SDI). Overall, the burden of MS in East Asia is increasing, with China projected to experience the steepest rise by 2041 and Mongolia continuing to carry a disproportionately high load. This study integrates long-term trends, cross-country comparisons, and gender-specific analyses to evaluate the burden of MS in East Asia, providing relevant evidence for formulating region-specific and gender-sensitive policies, enhancing preparedness, and strengthening health systems in East Asia to respond to the increasing burden of multiple sclerosis.
Impact of pain subtypes on disability and quality of life in multiple sclerosis: Neuropathic pain demonstrates the strongest association.
Alizada S, Tuba Özdoğar A, Kara I … +3 more , Zengin ES, Kahraman T, Ozakbas S
Mult Scler Relat Disord · 2026 Jun · PMID 42398275 · Publisher ↗
BACKGROUND: Pain is a common and disabling symptom in multiple sclerosis (MS) and may arise from different mechanisms. Among pain subtypes, neuropathic pain (NP) and musculoskeletal pain (MSP) are the most frequent, yet...
BACKGROUND: Pain is a common and disabling symptom in multiple sclerosis (MS) and may arise from different mechanisms. Among pain subtypes, neuropathic pain (NP) and musculoskeletal pain (MSP) are the most frequent, yet their differential clinical and functional associations remain insufficiently characterized. OBJECTIVE: To compare the prevalence, anatomical distribution, and clinical characteristics of pain subtypes in people with MS (pwMS) and to examine differences in disability and health-related quality of life (HRQoL) across these subgroups. METHODS: This cross-sectional study included 1503 pwMS followed at the Multiple Sclerosis Center of Izmir University of Economics Medical Point Hospital. PainDETECT and the Nordic Musculoskeletal Questionnaire were used to classify participants into three groups: no pain, MSP, and NP. Disability was measured using the Expanded Disability Status Scale (EDSS), and HRQoL was assessed with the EQ-5D-3 L and EQ-VAS. RESULTS: Pain was reported by 68.2% of participants, with 17.7% classified as NP and 50.5% as MSP. Participants with NP had higher disability (median EDSS = 2.0) than those with MSP or no pain (p < 0.001). HRQoL scores were significantly lower in the NP group across all EQ-5D domains and EQ-VAS (p < 0.001), while MSP was associated with moderately reduced HRQoL. CONCLUSION: NP was linked to greater disability and poorer HRQoL compared with MSP or the absence of pain. These findings underline the importance of routine screening for pain subtypes in MS and support early, targeted interventions to reduce their functional and psychosocial burden.
Bridging to low-dose corticosteroids after satralizumab discontinuation in unplanned pregnancy: Two cases of AQP4-positive NMOSD.
Li S, Yao H, Li T … +9 more , Huang L, Lai W, He S, Zhang S, Lin P, Lin G, Zhang W, Shen Y, Long Y
Mult Scler Relat Disord · 2026 Jun · PMID 42391798 · Publisher ↗
BACKGROUND: Satralizumab is effective for relapse prevention in AQP4-positive neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. While several cases have reported co...
BACKGROUND: Satralizumab is effective for relapse prevention in AQP4-positive neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. While several cases have reported continued satralizumab use in planned pregnancies, the management of unplanned pregnancy in patients already on satralizumab remains undefined. CASES: We report two AQP4-positive NMOSD patients (aged 32 and 21 years) who conceived unexpectedly during satralizumab maintenance therapy (8 and 7 months of treatment, respectively). Upon pregnancy confirmation, satralizumab was discontinued. Both patients received low-dose corticosteroid monotherapy throughout gestation as bridging maintenance: one with methylprednisolone 4 mg/day, the other with prednisolone 10 mg/day. No NMOSD relapses occurred during pregnancy. Both delivered healthy full-term neonates without congenital anomalies. Satralizumab was resumed immediately postpartum, with no relapses during follow-up. CONCLUSION: Among two AQP4-IgG-positive NMOSD patients with sustained pre-conception remission who experienced unplanned pregnancy during satralizumab maintenance, switching to low-dose corticosteroid monotherapy after drug cessation coincided with relapse-free gestation. The strategy avoids fetal exposure to satralizumab with unconfirmed gestational safety, yet the benign clinical course cannot be solely attributed to steroid bridging. Persistent residual satralizumab activity, inherent long-term disease quiescence, and pregnancy-mediated immune shifts all likely contributed to the stable disease state. These paired clinical observations only generate preliminary hypotheses and cannot support broad clinical recommendations for pregnant NMOSD patients.
Does laughter yoga really improve fatigue, sleep quality and psychological wellbeing in people living with MS?
Laslett LL, Breslin M, Jemere T … +1 more , van der Mei I
Mult Scler Relat Disord · 2026 Jun · PMID 42391797 · Publisher ↗
Abstract loading — click title to view on PubMed.
The many faces of the multiple sclerosis population in Canada.
Marrie RA, Gottheil C, Fakolade A … +5 more , Maxwell CJ, Rotstein DL, Tremlett H, Yeh EA, Finlayson M
Mult Scler Relat Disord · 2026 Jun · PMID 42391796 · Publisher ↗
BACKGROUND: We lack an understanding of the diversity characteristics of people with multiple sclerosis (MS) in Canada; most studies report only age and sex. We conducted a national survey to better understand the divers...
BACKGROUND: We lack an understanding of the diversity characteristics of people with multiple sclerosis (MS) in Canada; most studies report only age and sex. We conducted a national survey to better understand the diversity characteristics of people living with MS in Canada METHODS: From June 2025 to February 2026, we administered an anonymous online survey regarding diversity characteristics to people with MS in Canada who were aged 18 years and older. We measured diversity characteristics based on the PROGRESS-Plus framework. We summarized participant characteristics using descriptive statistics and UpSet plots. RESULTS: Over eight months, 857 eligible people completed the survey. Most participants primarily identified as White (93.0%), followed by Indigenous (including First Nations, Metis and Inuk/Inuit, 4.9%), and Black (2.1%). Ten percent of participants (n = 86) were born outside Canada. The most common languages spoken at home were English (94.7%) and French (7.4%). Most participants were female at birth (83.5%) and 101 (11.9%) identified as 2SLGBTQI+. Half (51.2%) of the cohort had a household income exceeding $100,000, and 47.4% had at least one university degree. CONCLUSION: Like Canada's population, the MS community is diverse, underscoring the need for future research and clinical care to be more inclusive.
Patterns of psychological resilience and social avoidance among the patients of Neuromyelitis Optica Spectrum Disease: a latent profile analysis.
Wang AN, Wang LX, Yang Q … +2 more , Liu ZY, Zhang XP
Mult Scler Relat Disord · 2026 Jun · PMID 42385520 · Publisher ↗
BACKGROUND: Neuromyelitis Optica Spectrum Disease (NMOSD) is a highly disabling autoimmune disease. Many patients engage in social withdrawal due to disease-related concerns and physical limitations, leading to widesprea...
BACKGROUND: Neuromyelitis Optica Spectrum Disease (NMOSD) is a highly disabling autoimmune disease. Many patients engage in social withdrawal due to disease-related concerns and physical limitations, leading to widespread social avoidance behaviors that further exacerbate psychological distress. Psychological resilience, as a critical individual capacity for coping with adversity, may play a significant role in regulating this process. This study aims to identify the coexistence patterns of psychological resilience and social avoidance in NMOSD patients and explore the specific predictors of these subgroups. METHODS: A cross-sectional study was conducted to recruit 216 NMOSD patients via WeChat groups from October 10 to 30, 2023. Data were collected using questionnaires, including sociodemographic characteristics, disease-related variables, and scales for psychological resilience, social support, social avoidance, anxiety, and depression. Latent profile analysis (LPA) was employed to explore potential profile patterns of psychological resilience and social avoidance in NMOSD patients, followed by multivariate logistic regression analysis to identify factors influencing these profiles. RESULTS: The results of LPA indicate that the three types are the most suitable, and their characteristics were HR-LSA Group (High Resilience, Low Social Avoidance) (25.9%), MR-MSA Group (Moderate Resilience, Moderate Social Avoidance) (47.7%) and LR-HSA Group (Low Resilience, High Social Avoidance) (26.4%). Different patterns were related to depression score, social support and relapse frequency. CONCLUSION: These findings enhance clinicians' understanding of the coexistence of psychological resilience and social avoidance, and provide valuable references for implementing appropriate management and support interventions for different patterns.
Discontinuation of disease-modifying therapies in patients with multiple sclerosis: A retrospective case-control study.
Cabañas Engenios G, Mena García N, Garay Albízuri P … +13 more , Llanes Ferrer A, Sánchez Asensio A, Romero Ferro J, Gil Martinez L, Campos Jiménez M, Pastor González R, Rodríguez Jorge F, Sainz De La Maza S, Monreal Laguillo E, Villar LM, Masjuan Vallejo J, Costa-Frossard L, Chico García JL
Mult Scler Relat Disord · 2026 Jun · PMID 42385519 · Publisher ↗
INTRODUCTION: The long-term benefit-risk balance of disease-modifying therapies (DMTs) in multiple sclerosis (MS) becomes increasingly relevant with ageing and prolonged disease stability. Discontinuation of DMTs has bee...
INTRODUCTION: The long-term benefit-risk balance of disease-modifying therapies (DMTs) in multiple sclerosis (MS) becomes increasingly relevant with ageing and prolonged disease stability. Discontinuation of DMTs has been proposed for selected patients, but its impact on disability progression remains uncertain. OBJECTIVE: To evaluate the effect of DMTs on confirmed disability progression (CDP) in patients with previously stable MS. METHODS: We conducted a single-center retrospective case-control study including patients with relapsing-onset MS followed between 2010 and 2025. Eligible patients had been clinically and radiologically stable for at least three years while receiving a moderate-efficacy DMT (injectables, teriflunomide or fumarates). Patients who discontinued were compared with those who continued treatment. The primary outcome was CDP at two years. Inverse probability of treatment weighting (IPTW) was applied to address imbalances in baseline data. RESULTS: 118 patients were included (56 discontinuers and 62 continuers, median age 58.19 vs 51.63 respectively, p < 0.001, without differences in sex distribution or baseline EDSS). DMT discontinuation was associated with higher risk of CDP at two years (aOR=5.10; p = 0.031). No significant differences were observed in relapse rates, MRI activity, NEDA-3 status, or sNfL levels. The risk of PIRA was higher in the discontinuation group at two years (aOR = 5.96; p = 0.036). Among patients who discontinued, higher baseline EDSS was associated with subsequent CDP. CONCLUSIONS: Discontinuation of moderate-efficacy DMTs in stable MS patients may increase the risk of disability progression despite no clear increase in inflammatory activity.
Real-world analytical and clinical evaluation of the Siemens Atellica® immunoassay for plasma neurofilament light chain in multiple sclerosis.
Nicolella V, Polito C, Criscuolo V … +11 more , Sirica R, Fiorenza M, Novarella F, Sorvillo D, Carotenuto A, Petracca M, Lanzillo R, Castaldo G, Brescia Morra V, Moccia M, Terracciano D
Mult Scler Relat Disord · 2026 Jun · PMID 42378934 · Publisher ↗
BACKGROUND: Plasma neurofilament light chain (pNfL) is an established biomarker of neuroaxonal injury in multiple sclerosis (MS), but analytical variability across platforms may limit clinical comparability. OBJECTIVE: W...
BACKGROUND: Plasma neurofilament light chain (pNfL) is an established biomarker of neuroaxonal injury in multiple sclerosis (MS), but analytical variability across platforms may limit clinical comparability. OBJECTIVE: We compared pNfL values obtained using Lumipulse® and Atellica® assays, and evaluated the clinical correlates (associations with disability status, disease activity, MRI outcomes, and treatments) of Atellica® pNfL in a real-world MS cohort. METHODS: Baseline plasma samples from people with MS were analysed using both immunoassays. Agreement was assessed using Passing-Bablok regression, Lin's concordance correlation coefficient, and Bland-Altman analysis. Associations between Atellica® pNfL and demographic and clinical variables were evaluated using multivariable regression. RESULTS: We included 394 people with MS (mean age 41.0 ± 13.0 years; 61.5% female; median EDSS 2.5). Lumipulse® and Atellica® pNfL values showed strong association, with Passing-Bablok regression indicating proportional bias (slope 0.78; 95% CI 0.70-0.86; intercept 3.24; 95% CI 2.46-3.90) and moderate concordance (ρc = 0.49). Higher Atellica® pNfL levels were independently associated with older age and greater disability, but not with short-term clinical or radiological activity. CONCLUSIONS: Atellica® and Lumipulse® showed strong association but only moderate concordance in pNfL measurements. These findings indicate that the two platforms cannot be considered interchangeable. Atellica® pNfL reflects disability status and represents a clinically meaningful biomarker when interpreted within assay-specific frameworks in real-world MS care.
Comparative immunopathology and clinical features of MOGAD and AQP4-IgG NMOSD in children: A scoping review.
Vampertzi O, Vavilis T, Zelilidou A … +1 more , Vargiami E
Mult Scler Relat Disord · 2026 Jun · PMID 42378933 · Publisher ↗
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct immune-mediated demyelinating central nervous system disorder, frequently presenting as optic neuritis in children and adolescents. Co...
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct immune-mediated demyelinating central nervous system disorder, frequently presenting as optic neuritis in children and adolescents. Conversely, aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) is an astrocytopathy characterized by more severe relapses and greater residual visual impairment. This scoping review, conducted according to PRISMA-ScR and JBI methodology, mapped evidence from 23 studies identified across PubMed and Scopus over the last decade. The objective was to examine the epidemiology, clinical presentation, imaging, serological findings, therapeutic strategies, and visual outcomes of these conditions in pediatric populations. Results indicate that pediatric MOGAD-associated optic neuritis often presents with optic disc swelling and bilateral anterior optic nerve involvement with perineural enhancement on MRI, typically resulting in reversible visual loss. The 2023 MOGAD diagnostic criteria show high performance in children. In contrast, AQP4-associated optic neuromyelitis more commonly involves the posterior optic nerve and chiasm, leading to poorer visual outcomes. Regarding treatment, maintenance intravenous immunoglobulin (IVIG) reduces relapse risk in selected MOGAD cases, while B-cell-depleting regimens are primarily used for relapse prevention in AQP4-positive NMOSD. In conclusion, pediatric optic neuritis in MOGAD and AQP4-associated optic neuromyelitis are distinct phenotypes with differing pathobiology and therapeutic requirements. Early serological confirmation and individualized immunotherapy are crucial for preventing relapses and preserving functional vision in pediatric patients.
Self-perception of speech impairment in MS: Associations with dysarthria severity and speech measures.
Peres MLMK, Schuh N, Brzoskowski Dos Santos V … +1 more , Olchik MR
Mult Scler Relat Disord · 2026 Jun · PMID 42372430 · Publisher ↗
OBJECTIVE: To investigate the relationship between patient-reported speech difficulties, clinician-rated dysarthria severity, and acoustic speech measures in persons with multiple sclerosis (MS). METHODS: This cross-sect...
OBJECTIVE: To investigate the relationship between patient-reported speech difficulties, clinician-rated dysarthria severity, and acoustic speech measures in persons with multiple sclerosis (MS). METHODS: This cross-sectional study included individuals with a diagnosis of MS, excluding those who had a relapse within the last three months. The sociodemographic variables (age, sex, and education level) and clinical variables (disease duration, age at symptom onset, and Expanded Disability Status Scale score) were collected. Participants completed a self-perception questionnaire. Speech assessment consisted of auditory-perceptual evaluation and acoustic speech analysis, based on recordings of the following speech tasks: sustained vowel /a/; sentences with different intonation patterns; diadochokinesis; spontaneous speech; and repeated production of the diphthong /iu/. RESULTS: Forty-seven participants were included, 34 (72.3%) were female, with a mean age of 47.7 (±11.83) years, a mean education level of 10.7 (±2.92) years, and a mean disease duration of 13.66 (±6.49) years. Self-perceived speech impairment (LwD total score) was significantly associated with dysarthria severity (p = 0.0277) and with articulator acoustic measures, including phonation time, number of syllables, and phonation rate. The regression model indicated that phonation time was a significant predictor of self-perceived speech difficulty (p = 0.016), explaining 20.6% of the variance. CONCLUSION: Speech self-perception in individuals with MS was associated with both auditory-perceptual and objective acoustic parameters. Phonation time emerged as a sensitive acoustic marker, associated with perceived speech impairment, supporting the inclusion of brief articulatory tasks in screening protocols and reinforcing the clinical relevance of patient-reported speech outcomes within an integrative assessment framework.
Taking progressive biology seriously in the time of B-cells and BTK.
Camara-Lemarroy CR
Mult Scler Relat Disord · 2026 Jun · PMID 42372429 · Publisher ↗
The successful landscape of relapsing remitting multiple sclerosis (RRMS) treatments has revolutionized our conceptualization of the disease. This led to a shifting interest towards finding ways of stopping neurodegenera...
The successful landscape of relapsing remitting multiple sclerosis (RRMS) treatments has revolutionized our conceptualization of the disease. This led to a shifting interest towards finding ways of stopping neurodegeneration in progressive MS. The past decade brought us lots of new definitions, such as compartmentalized inflammation, progression free of relapsing activity and the proposal of MS as a disease continuum. It also brought novel therapeutic candidates, the Bruton´s Tyrosine Kinase inhibitors. Unfortunately, the results (reported and announced) of clinical trials in progressive MS have been underwhelming. A recurring theme that may explain the current state of the field is the handling of classical inflammatory "relapsing biology" in progressive MS populations. Although co-pathology of these processes along with neurodegeneration is expected, the time is ripe to take progressive biology seriously.
Microstructural changes in juxtacortical white matter regions and their relationship with PASAT score in multiple sclerosis: A proof of concept using machine learning.
Montalba C, Franco P, Caulier-Cisterna R … +4 more , Cruz JP, Cárcamo C, Andia ME, Ciampi E
Mult Scler Relat Disord · 2026 Jun · PMID 42365747 · Publisher ↗
BACKGROUND: Cognitive impairment is a common early feature of multiple sclerosis (MS). This decline may be linked to microstructural damage in juxtacortical U-fibers, which are highly vulnerable to early demyelination an...
BACKGROUND: Cognitive impairment is a common early feature of multiple sclerosis (MS). This decline may be linked to microstructural damage in juxtacortical U-fibers, which are highly vulnerable to early demyelination and essential for connectivity between adjacent cortical gyri. While these changes are undetectable in conventional MRI protocols, we employed a diffusion MRI and Machine Learning (ML) approach to identify subtle alterations in these short-range fibers. OBJECTIVE: We designed a proof of concept study to investigate the structural integrity of juxtacortical U-fibers and its correlation with cognitive impairment in MS patients by using ML as a robust analytical framework for understanding brain-behavior relationships. METHODS: Thirty-five cognitively preserved healthy controls and fifty-eight MS patients, including cognitively preserved and cognitively impaired individuals, were included. The dataset comprised fractional anisotropy (FA) maps extracted from 100 U-fiber regions. Working memory was assessed using the Paced Auditory Serial Addition Test (PASAT), expressed as Z-scores adjusted for age and education. Sequential forward selection (SFS) and fifteen regression models were trained to account for PASAT Z-scores. Model performance was evaluated using 5-fold nested cross-validation with mean squared error (MSE), mean absolute error (MAE), and coefficient of determination (R²). RESULTS: Tree-based ensemble models showed superior performance in estimating the relationship between FA measures and working memory (CatBoost: MSE = 0.256 ± 0.068; MAE = 0.421 ± 0.068; R² = 0.488 ± 0.128). SFS identified sixteen FA features, with left superior temporal and right inferior parietal regions emerging as the most informative features. CONCLUSION: ML analysis reveals that Diffusion MRI-derived short-range association U-fiber FA features can estimate working memory performance with clinically meaningful accuracy in MS, supporting their potential to detect early juxtacortical dysconnectivity, serving as a biomarker for early cognitive monitoring.
The value of neutrophil to high-density lipoprotein ratio in anti-NMDAR encephalitis.
Wang S, Li L, Hou H … +6 more , Yong L, Tang Y, Wang G, Guo Z, Zhu L, Wu J
Mult Scler Relat Disord · 2026 Jun · PMID 42364570 · Publisher ↗
PURPOSE: This study aimed to investigate the association of the neutrophil to high-density lipoprotein ratio (NHR) with disease severity and short-term prognosis at discharge in anti-N-methyl-D-aspartic acid receptor (NM...
PURPOSE: This study aimed to investigate the association of the neutrophil to high-density lipoprotein ratio (NHR) with disease severity and short-term prognosis at discharge in anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis patients. PATIENTS AND METHODS: A retrospective study enrolled 186 patients with anti-NMDAR encephalitis, who were stratified by mRS and CASE to identify independent influencing factors for disease severity and short-term prognosis at discharge. Multivariate regression models including these independent influencing factors were established to assess disease severity and predict short-term prognosis at discharge. Receiver operating characteristic curves, bootstrap, concordance index, calibration curves, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the generalization ability of these models. The train set, test set, and validation set were used to verify the generalization ability of these models. Spearman's correlation analysis was applied to investigate the correlation between CASE and mRS. RESULTS: Anti-NMDAR encephalitis patients were assessed by mRS and CASE, and were grouped separately. Both results indicated that NHR was a predictor of disease severity and short-term prognosis. The regression models established based on NHR and other independent influencing factors exhibited good discrimination, accuracy, and generalization ability in disease severity assessment and short-term prognosis prediction. Statistical analysis demonstrated that CASE was positively correlated with mRS. CONCLUSION: NHR had potential clinical value in the assessment of disease severity at admission and prediction of short-term prognosis at discharge in anti-NMDAR encephalitis patients. CASE, a dedicated scale for autoimmune encephalitis, was positively correlated with mRS.
Predictors of early response to cladribine in mexican patients with multiple sclerosis: A real world multicenter retrospective cohort study.
Moreno-Bernardino CJ, Treviño-Frenk I, Ortiz-Maldonado JF … +8 more , Sánchez-Rosales NA, Skromne-Eisenberg E, Cortés-Enriquez F, Sauri-Suarez S, Del León-Murillo A, Bazan-Rodríguez AL, Torres-Mora C, Gómez-Figueroa E
Mult Scler Relat Disord · 2026 Jun · PMID 42364569 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. In Mexico, its impact is considerable, driven by functional impairments and cognitive decline. Cladribine, an oral immune...
BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young adults. In Mexico, its impact is considerable, driven by functional impairments and cognitive decline. Cladribine, an oral immune reconstitution therapy, has demonstrated efficacy in relapsing MS. However, predictors of therapeutic response in real-world Latin American populations remain unclear. OBJECTIVE: To identify baseline clinical and radiological predictors of early non-response to cladribine in Mexican patients with MS, using NEDA-3 status at one year as the primary outcome. METHODS: We conducted a multicenter, observational, retrospective study from 2019 to 2024 involving 155 patients with relapsing-remitting MS (RRMS) treated with cladribine across 8 clinical centers in Mexico. Inclusion criteria included age ≥18 years, MS diagnosis based on McDonald criteria, ≥12 months of follow-up, and at least one cladribine dose. Data included demographics, prior treatments, MRI findings, EDSS, relapses, and adverse events The primary outcome was NEDA-3 status at one year. Univariable and multivariable logistic regression models were used to identify baseline predictors of response to cladribine. RESULTS: Among the 155 RRMS patients the mean age was 36.9 ± 18.5 years, the mean disease duration was 7.6 (± 6.6) years, the median number of prior relapses was 3 (IQR 2-4), and the median baseline EDSS was 2.0 (IQR 1.0-3.0). Fifty-two patients (40.0%) were treatment-naïve. Based on NEDA-3, 95 (61.3%) patients achieved responder status at year 1. In the multivariable analysis, baseline cognitive decline was the only independent predictor of non-response to cladribine at one year (aOR 4.86 [95% CI 1.40-19.6]; p = 0.017). Adverse events were reported in 79 patients (51.0%), most commonly grade 1-2 lymphopenia; no serious adverse events required treatment withdrawal. CONCLUSION: In this real-world Mexican cohort, cladribine demonstrated a favorable efficacy and safety profile. Baseline cognitive decline was the only independent predictor of non-response to cladribine in the multivariate analysis. These findings may support early treatment decision-making and patient stratification in Latin American populations with MS.
Real-world impact of national policy on high-efficacy therapy use in multiple sclerosis: A Brazilian big data analysis.
Marques AC, Siqueira MM, Pereira GR … +6 more , Paiva LEB, Lin V, Correa LH, Souza DGB, Junior EA, Dutra LA
Mult Scler Relat Disord · 2026 Jun · PMID 42364568 · Publisher ↗
BACKGROUND: In 2021, Brazil updated its Clinical Protocol and Therapeutic Guidelines (PCDT) for multiple sclerosis (MS), expanding first-line eligibility for natalizumab (NTZ) in patients with highly active disease and i...
BACKGROUND: In 2021, Brazil updated its Clinical Protocol and Therapeutic Guidelines (PCDT) for multiple sclerosis (MS), expanding first-line eligibility for natalizumab (NTZ) in patients with highly active disease and incorporating alemtuzumab (ALE). Evidence on temporal changes in disease-modifying therapy (DMT) dispensation within the Brazilian public health system (SUS) after this update is lacking. METHODS: Using big data, we analyzed 1711,342 DMT dispensation authorizations for MS from the national outpatient registry (SIA/SUS) between 2019 and 2023. DMTs were categorized as: high-efficacy (NTZ, ALE), intermediate/moderate-efficacy (FNG), and platform therapies (IFN, GA, DMF, TERI). Quasi-Poisson space-time regression models compared pre-PCDT (2019-2021) and post-PCDT (2022-2023) periods at national and regional levels, while state-level variation was assessed relative to the national mean. Treatment switches were evaluated across periods and regions. RESULTS: From 2019 to 2023, the number of MS patients treated through the SUS increased by 25.9%. Nationwide, dispensation of NTZ (+44.5%, p < 0.001), DMF (+53.1%, p < 0.001), TERI (+32.5%, p < 0.001), and FNG (+15.8%, p < 0.001) increased, while IFN (-40.3%, p < 0.001) and GA (-27.6%, p < 0.001) decreased. NTZ increased across all regions, with the largest growth in the North (+82.0%, p = 0.042), whereas IFN reduced only in the North (-41.9%, p = 0.049). State-level analyses showed heterogeneous NTZ uptake, with higher rates in parts of the Northeast (Ceará, Paraíba, Sergipe), Center-West (Federal District, Goiás), North (Pará), and Southeast (São Paulo), and lower rates across all Southern states. Most treatment switches occurred within the same efficacy class, with no differences between pre- and post-PCDT periods or across regions. ALE dispensation was limited to the late post-PCDT period. CONCLUSIONS: In this nationwide observational analysis, DMT dispensation patterns in Brazil were characterized by higher NTZ and increased dispensation of FNG, DMF, and TERI in the post-PCDT period. However, persistent regional disparities and conservative switching patterns may suggest barriers to equitable access to HE DMTs. These findings highlight the role of national guidelines in shaping real-world therapeutic practices and the value of administrative data for monitoring treatment patterns and healthcare organization in MS.
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