Multiple Sclerosis And Related Disorders[JOURNAL]
Sun
200 papers
Diagnostic delay in patients with myelin oligodendrocyte antibody-associated disease presenting with elevated intracranial pressure.
Lakusta-Wong TM, Wysong KE, Solomon AJ
Mult Scler Relat Disord · 2026 Jun · PMID 42364567 · Publisher ↗
BACKGROUND: Elevated intracranial pressure (ICP) is a recently recognized complication of myelin oligodendrocyte antibody associated disease (MOGAD). OBJECTIVE: We describe 5 patients with MOGAD presenting with elevated...
BACKGROUND: Elevated intracranial pressure (ICP) is a recently recognized complication of myelin oligodendrocyte antibody associated disease (MOGAD). OBJECTIVE: We describe 5 patients with MOGAD presenting with elevated ICP. METHODS: Serum MOG antibody testing completed at the University of Vermont Medical Center between January 1, 2017 to May 1, 2025 was reviewed. Patients with MOGAD were included. Elevated ICP was defined as opening pressure > 25 cm HO, or opening pressure >20 cm HO with an initial diagnosis of idiopathic intracranial hypertension (IIH). RESULTS: Of 9 patients with MOGAD who had opening pressures measured, 5 patients (56%) had elevated ICP. Corticosteroid treatment was delayed due to higher clinical suspicion for alternate diagnoses, with idiopathic intracranial hypertension being the most common misdiagnosis. One patient underwent brain biopsy given concern for malignancy. CONCLUSION: Red flags including rapidly progressive vision loss, lack of improvement on acetazolamide, CSF pleocytosis, and enhancement on neuroimaging may help differentiate MOGAD from IIH. Increased recognition of elevated ICP as a complication of MOGAD is needed to prevent potential morbidity associated with unnecessary diagnostic evaluation and treatment delay.
Economic and social burden of multiple sclerosis in Morocco: a tertiary care center study.
El Otmani H, Simma K, El Omari H … +6 more , Sikkal A, Khattab H, Haddouali K, Bellakhdar S, El Moutawakil B, Rafai MA
Mult Scler Relat Disord · 2026 Jun · PMID 42364566 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS) imposes substantial clinical, economic, and social consequences, particularly in young adults during their most productive years. While the societal cost of MS has been extensively stu...
BACKGROUND: Multiple sclerosis (MS) imposes substantial clinical, economic, and social consequences, particularly in young adults during their most productive years. While the societal cost of MS has been extensively studied in high-income countries, data from low- and middle-income countries remain scarce. We aimed to provide the first comprehensive societal cost-of-illness analysis of MS in Morocco. METHODS: We conducted a single-center, cross-sectional study including 100 adults with MS followed at a tertiary university hospital in Casablanca. Costs were assessed from a societal perspective and annualized at the individual level, including direct medical, direct non medical, and indirect costs (human capital approach). Disability was measured using the Expanded Disability Status Scale (EDSS). Health-related quality of life was evaluated using the EQ-5D-5L Moroccan value set to derive utility scores. RESULTS: The mean age was 37.9 years, and 71.0% were women. Median EDSS was 2.0 (IQR: 1.0-6.0; range: 0-10). The mean annual total cost per patient was 92,646 MAD (≈9,358 USD). Direct medical costs averaged 58,884 MAD (5,948 USD), predominantly driven by disease-modifying therapies (47,759 MAD). Direct non medical costs were modest (984 MAD). Indirect costs averaged 32,777 MAD (3,311 USD), largely reflecting productivity losses and informal caregiving. Cost distribution shifted with disability severity: direct medical costs predominated at lower EDSS levels, whereas indirect costs became the principal contributor with increasing disability. The mean EQ-5D-5L utility score was 0.688. CONCLUSIONS: MS in Morocco generates a substantial societal burden that extends far beyond medical expenditures. While early stage disease is mainly associated with pharmacological costs, advancing disability shifts the burden toward productivity loss and informal care. These findings underscore the necessity of context-specific pharmacoeconomic frameworks and policies that integrate clinical severity, social vulnerability, and healthcare system constraints in low and middle-income settings.
Metabolic dysfunction in multiple sclerosis: Elevated lactate and impaired post-exercise creatine response in the anterior cingulate cortex.
Brownbill G, Dekerle J, Cercignani M … +2 more , Ronen I, Stone J
Mult Scler Relat Disord · 2026 Jun · PMID 42364565 · Publisher ↗
BACKGROUND: Multiple Sclerosis (MS) is characterised by altered brain metabolism and increased chronic perceived fatigue. However, the relationship between brain metabolites, fatigue, and physical task effects in MS rema...
BACKGROUND: Multiple Sclerosis (MS) is characterised by altered brain metabolism and increased chronic perceived fatigue. However, the relationship between brain metabolites, fatigue, and physical task effects in MS remains unclear. This study investigated brain metabolite concentrations (glutamate + glutamine (Glx), lactate, and total creatine (tCr)) in the anterior cingulate cortex (ACC), a region involved in interoceptive processing and fatigue perception, before and after a physical task. METHODS: Twenty-two people with MS (pwMS) and 22 matched controls underwent Magnetic Resonance Spectroscopy before and after fatiguing isometric wrist extension tasks. Perceptual measures of state fatigue and effort were recorded. Linear mixed models analysed group differences and task-induced metabolite changes. RESULTS: PwMS showed higher ACC lactate concentrations than controls at rest and post-exercise (F = 7.08, p = 0.011, 95% CI[0.033, 0.228]). No significant Glx differences were observed. A significant group × exercise interaction for tCr occurred (F = 4.63, p = 0.037, 95% CI[0.027, 0.581]), with tCr decreasing post-exercise in controls (t = 3.09, p = 0.02) but remaining stable in pwMS. Metabolite concentrations did not correlate with baseline fatigue measures in either group. Changes in lactate correlated moderately with perceived effort in pwMS only (r = 0.51, p = 0.04). CONCLUSIONS: This study provides novel evidence of metabolic differences in pwMS, characterised by elevated lactate and stable post-exercise tCr, suggesting altered energy metabolism potentially linked to mitochondrial dysfunction. While these metabolic alterations did not directly correlate with perceived fatigue, they may contribute to the complex pathophysiology of MS-related fatigue.
Is serum neurofilament light chain accurate enough to guide multiple sclerosis care? Diagnostic performance and optimal cutoff in a systematic review and meta-analysis.
Santana JLS, Themoteo RM, Allioni GA … +8 more , Marzano LAS, Bernal HM, Veiga ML, Sales ABL, Apóstolos-Pereira SL, Adoni T, Callegaro D, Silva GD
Mult Scler Relat Disord · 2026 Jun · PMID 42364564 · Publisher ↗
BACKGROUND: Serum neurofilament light chain (sNfL) has emerged as a minimally invasive biomarker reflecting neuroaxonal injury in multiple sclerosis (MS), with potential utility for detecting inflammatory disease activit...
BACKGROUND: Serum neurofilament light chain (sNfL) has emerged as a minimally invasive biomarker reflecting neuroaxonal injury in multiple sclerosis (MS), with potential utility for detecting inflammatory disease activity. However, uncertainty persists regarding its diagnostic accuracy, reproducibility, and optimal clinical cutoff. This systematic review and meta-analysis evaluated the diagnostic performance of sNfL for MS disease activity, assessed the impact of methodological bias, and estimated an optimal cutoff for predicting clinical relapses. METHODS: The review protocol was registered on PROSPERO (CRD420251027150). We conducted a PRISMA-compliant systematic review and meta-analysis of studies assessing sNfL in adults with MS. PubMed/MEDLINE, Embase, and Scopus were searched from inception to May 2026. Eligible studies evaluated sNfL measured by single-molecule array (Simoa™) and reported disease activity outcomes, including clinical relapse, MRI activity, or no evidence of disease activity (NEDA-3). Diagnostic accuracy was assessed through reconstruction of 2 × 2 contingency tables, hierarchical summary receiver operating characteristic (sROC) analyses, subgroup analyses, and multi-cutoff meta-analysis modeling. RESULTS: Twenty-eight studies comprising 11,213 patients were included. Considerable heterogeneity was identified across studies regarding disease-activity definitions, analytical methods, and cutoff strategies. Fourteen studies (50%) were judged to have high risk of bias, mainly due to post hoc threshold selection. Across analyses, diagnostic performance remained modest, with pooled AUC values ranging from 0.61 to 0.71, consistently below the prespecified threshold of 0.80 considered indicative of good clinical accuracy. Similar results were observed across subgroup analyses according to outcome definition and threshold strategy. Multi-cutoff modeling identified an optimal cutoff of 10 pg/mL for predicting clinical relapse, but discriminative performance remained limited, with sensitivity of 0.69, specificity of 0.65, and AUC of 0.72. CONCLUSION: The current literature on sNfL in MS is affected by substantial methodological heterogeneity and risk of bias. Nevertheless, even after subgroup and multi-cutoff analyses, sNfL did not achieve sufficient diagnostic accuracy for routine clinical use as a standalone biomarker of inflammatory disease activity.
Fingolimod for pediatric multiple sclerosis: The Ped-MS group systematic review and meta-analysis.
Kaveyee H, Etemadifar M, Abhari AP … +7 more , Ramezani A, Ebne-Ali-Heydari Y, Miralaei P, Norouzi M, Eshraghi R, Salari M, Deputy S
Mult Scler Relat Disord · 2026 Jun · PMID 42361660 · Publisher ↗
BACKGROUND: Selecting the optimum disease-modifying therapy (DMT) for pediatric multiple sclerosis (Ped-MS) poses a significant challenge and requires special attention. If untreated or treated inappropriately, PED-MS ca...
BACKGROUND: Selecting the optimum disease-modifying therapy (DMT) for pediatric multiple sclerosis (Ped-MS) poses a significant challenge and requires special attention. If untreated or treated inappropriately, PED-MS can lead to cognitive impairment affecting the patient's whole life and causing irreversible sequelae. OBJECTIVE: To comprehensively review the efficacy and safety of fingolimod, the only FDA-approved DMT in Ped-MS. METHODS: Our PRISMA-based review included a systematic search of PubMed, Embase, Web of Science, and Scopus. The primary endpoint for meta-analysis was the mean difference (MD) in annualized relapse rate (ARR) after fingolimod compared to before treatment. Secondary outcomes were the MD of Expanded Disability Status Scale (EDSS) and the proportion of Ped-MS patients persisting on fingolimod. RESULTS: A total of 2997 articles were identified from databases, and after screening and selection, 15 studies encompassing 585 patients were included in our systematic review. Fingolimod was associated with a significant ARR change of -1.17 relapses per patient-year (95% CI -1.76 to -0.59) from baseline. Fingolimod was not able to significantly decrease EDSS (p = 0.24) and showed a - 0.27 change from baseline (95% CI -0.86 to 0.32). After almost 24 months of fingolimod therapy, 79.8% of Ped-MS patients were still on fingolimod and did not switch their DMT. Overall adverse events ranged from 10.8% to 88%, with leukopenia/lymphopenia, headache, cough, and infections being the most reported. CONCLUSION: Fingolimod, with a convenient oral route of administration, showed a significant effect on ARR and stabilized EDSS. Most patients remained on this DMT after 24 months, which shows relatively favorable efficacy and acceptable safety.
The effects of smoking and vaping on multiple sclerosis onset and disease progression: An umbrella review.
Keller AM, Wills O, Karahalios A … +1 more , Marck CH
Mult Scler Relat Disord · 2026 Jun · PMID 42349068 · Publisher ↗
BACKGROUND: Tobacco smoking has been implicated in multiple sclerosis (MS) onset and progression. However, findings are dispersed across reviews with differing quality and scope. OBJECTIVES: This umbrella review synthesi...
BACKGROUND: Tobacco smoking has been implicated in multiple sclerosis (MS) onset and progression. However, findings are dispersed across reviews with differing quality and scope. OBJECTIVES: This umbrella review synthesised systematic reviews to provide a comprehensive overview of evidence, knowledge gaps, and inform future research about the effects of exposure to combustible tobacco and the use of e-cigarettes/heated tobacco products on MS onset and progression. METHOD: We searched CINAHL, Embase, MEDLINE, Web of Science, Cochrane and Epistemonikos for reviews published between 2014 and March 2025. Two independent reviewers assessed eligibility, extracted data, and evaluated risk of bias using the Risk Of Bias In Systematic Reviews (ROBIS) tool. This study was prospectively registered (Prospero: CRD420251033269). RESULTS: Eleven systematic reviews, encompassing 97 unique studies, were included. Nine systematic reviews assessed MS onset and six assessed progression. Active cigarette and waterpipe smoking were consistently associated with an increased risk of MS onset, with some evidence of a dose-response relationship. Findings for passive cigarette smoking were mixed. No association was found between prenatal smoking and MS risk. Smoking was associated with a higher risk of disability progression and progression to secondary progressive MS, particularly with higher pack-years, though findings varied. Evidence on the effects of waterpipe and prenatal smoking on MS progression, and the impact of e-cigarettes/vapes on any MS outcomes was lacking. Reviews commonly reported high heterogeneity, and all were at high risk of bias. CONCLUSION: Observational evidence consistently links smoking with MS onset and progression. However, methodological issues and potential biases in primary data highlight the need for future high-quality research to address limitations and investigate evidence gaps.
Predicting clinical progression in patients with relapsing remitting multiple sclerosis retrospectively using a myelin content proxy.
van den Boogaard LJM, Monachino S, Drenthen GS … +8 more , Knippenberg SAM, Kreiter D, Zinger S, Fernandes CD, Breeuwer M, Jolani S, Jansen JFA, Gerlach OHH
Mult Scler Relat Disord · 2026 Jun · PMID 42341567 · Publisher ↗
BACKGROUND: Progression independent of relapse- and magnetic resonance imaging (MRI)-activity (PIRMA) in relapsing-remitting multiple sclerosis (RRMS) may result from subtle myelin pathology in normal-appearing white mat...
BACKGROUND: Progression independent of relapse- and magnetic resonance imaging (MRI)-activity (PIRMA) in relapsing-remitting multiple sclerosis (RRMS) may result from subtle myelin pathology in normal-appearing white matter (NAWM) and perilesions. OBJECTIVE: To evaluate whether short-term myelin changes, estimated with the MRI-based T1w/FLAIR ratio, are associatied with long-term clinical progression in patients with RRMS receiving natalizumab. METHODS: For 29 patients with RRMS, short-term, six-month myelin changes were calculated for three areas, i.e. white matter hyperintensities (WMH), a perilesional area of 2 mm, and NAWM. Expanded disability status scale (EDSS) scores at baseline and after at least three years were used to define long-term clinical progression. RESULTS: Logistic regression models demonstrated significant associations between long-term progression using short-term changes in myelin proxy in NAWM (β = -77.962; p = .039), but not in perilesional tissue (β = -3.999; p = .717) and WMH (β = -4.324; p = .752). ROC-curve of the logistic regression model of NAWM showed a good discriminative value (area under the curve (AUC) = 0.892, 95% CI [.755-1.000]) for clinical progression. CONCLUSION: By assessing short-term myelin changes outside lesions, using readily available clinical MRI scans, long-term clinical progression in patients with RRMS may be predicted.
EEG functional connectivity as a neurophysiological biomarker of cognitive function in relapsing remitting multiple sclerosis patients.
Elkholy MM, Hosny H, Hussein M … +1 more , Bayoumi HM
Mult Scler Relat Disord · 2026 Jun · PMID 42330727 · Publisher ↗
OBJECTIVE: Multiple Sclerosis (MS) is a common neuroinflammatory disorder in young adults. Disrupted neural connectivity due to demyelination and axonal degeneration contributes to cognitive impairment. The aim is to exa...
OBJECTIVE: Multiple Sclerosis (MS) is a common neuroinflammatory disorder in young adults. Disrupted neural connectivity due to demyelination and axonal degeneration contributes to cognitive impairment. The aim is to examine EEG functional connectivity (coherence and phase lag) in relapsing-remitting MS (RRMS) and explore its correlation with cognitive function. METHODS: Thirty-five RRMS patients and 35 age- and sex-matched healthy controls (HC) were included. Neurological (Expanded Disability Status Scale), MRI, and cognitive (Paced Auditory Serial Addition Test) assessment were conducted, in addition to neurophysiological evaluation using quantitative EEG (coherence and phase lag) and P300 response. RESULTS: RRMS patients showed lower PASAT scores (30.2 ± 10 RRMS, 36.8 ± 9.6 HC (P = 0.024)) and significant disruption in resting-state EEG functional connectivity; lower coherence of alpha at inter-temporal (P = 0.001), inter-parietal (P = 0.005), and inter-temporal beta (P = 0.001). Phase lag of beta band was higher in patients at the left frontal-temporal (P = 0.002), left frontal-parietal (P = 0.007) and inter-temporal (P = 0.01) levels. This disruption correlated with disease severity markers. Phase lag alterations were linked to cognitive performance. (PASAT correlated with: left frontal-temporal beta phase lag (r = -0.626, P ≤ 0.001) and global theta phase lag (r = -0.398, P = 0.02) CONCLUSION: EEG functional connectivity measures provide valuable insights into cognitive impairment in RRMS. These findings are preliminary and require independent validation in future studies. SIGNIFICANCE: Understanding the cognitive-connectivity inter-relation may help to tailor treatment and rehabilitation plans.
Pregnancy outcomes in patients with multiple sclerosis with or without exposure to disease-modifying treatment: A retrospective cohort study on Iranian population.
Paybast S, Asl Fallah E, Sahraian MA … +1 more , Azimi AR
Mult Scler Relat Disord · 2026 Jun · PMID 42322960 · Publisher ↗
INTRODUCTION: Multiple sclerosis (MS) is often diagnosed in women of childbearing age. While MS does not negatively influence most pregnancy outcomes, there is a lack of data on Iranian patients. The present study aimed...
INTRODUCTION: Multiple sclerosis (MS) is often diagnosed in women of childbearing age. While MS does not negatively influence most pregnancy outcomes, there is a lack of data on Iranian patients. The present study aimed to reveal our experience with pregnancy outcomes in MS women. MATERIAL AND METHODS: This retrospective cohort was conducted between January 2016 and February 2023 at the MS Clinic of Sina and Imam Hossein Hospital. One hundred seventy-eight patients with a history of pregnancy were enrolled. Patients' demographics, MS characteristics, and pregnancy-related outcomes were collected from their reports. Eventually, statistical analysis was carried out by using SPSS 26.0. RESULTS: 178 patients with a mean age of 32.24 ± 5.02 years, a mean disease duration of 6.17 ± 4.26 years, and a median Expanded Disability Status Scale (EDSS) of 1.00 ± 1.38 were enrolled. 94.4% of patients were classified as relapse-remitting MS (RRMS), mainly treated with low to moderate efficacy disease-modifying treatment (DMT). We identified an incidence rate of 3.4% for spontaneous abortion and 1.7% for stillbirth, which was not affected by the fetus's exposure to DMTs (P = 0.99). The results revealed a significant increase in the relapse rate within the first six months after childbirth (12.4%vs 2.2%) (P = 0.009), followed by a subsequent decline (3.4%) over the next six months (P = 0.06), leading to a comparable rate in a year before pregnancy (P = 0.44). The clinical relapse a year before pregnancy was the only risk factor to develop early postpartum relapse (p = 0.02). Moreover, patients treated with high-efficacy DMTs were less likely to develop early postpartum relapse (P = 0.02). CONCLUSION: Our preliminary results suggest that DMT exposure before or during pregnancy does not adversely increase the rate of congenital anomalies or spontaneous abortions. Most patients were stable during and in a year after pregnancy. Moreover, the pre-pregnancy use of high-efficacy DMTs might decrease the risk of postpartum relapse.
ST8SIA4 and the repair-inflammation axis of lesion remodeling in RRMS.
Sökmen O
Mult Scler Relat Disord · 2026 Jun · PMID 42322959 · Publisher ↗
Abstract loading — click title to view on PubMed.
Exploratory analysis of pupillography-based machine learning for assessing autonomic dysfunction in multiple sclerosis.
Parmak Yener N, Fırat Y, Seferoğlu M … +2 more , Kargın AM, Kılıçaslan Y
Mult Scler Relat Disord · 2026 Jun · PMID 42322958 · Publisher ↗
BACKGROUND: The pupillary light reflex (PLR) is mediated by autonomic pathways, offering a potential noninvasive biomarker for Multiple sclerosis (MS). Pupillography enables objective quantification of PLR dynamics. Howe...
BACKGROUND: The pupillary light reflex (PLR) is mediated by autonomic pathways, offering a potential noninvasive biomarker for Multiple sclerosis (MS). Pupillography enables objective quantification of PLR dynamics. However, its diagnostic utility in MS remains underexplored. This study aimed to investigate the feasibility of an ML-based analytical framework applied to pupillographic features rather than automated diagnosis. METHODS: A total of 692 pupillographic images were obtained from 25 patients diagnosed with relapsing-remitting MS (RRMS) without optic neuritis (ON) and 38 age- and sex-matched healthy controls. For model development, data from 9 MS patients and 26 controls were used for training, and 16 MS patients and 12 controls for testing. Twenty-two quantitative features related to pupil size, shape, reflex dynamics, and symmetry were extracted. A random forest classifier was trained and evaluated using accuracy, sensitivity, specificity, and AUC-ROC. An independent validation set of 384 images from 18 MS patients and 14 controls was used to assess generalizability. RESULTS: The model achieved 85.7% accuracy, 93.8% sensitivity, and an AUC-ROC of 0.945 on the test set, correctly identifying 15 of 16 MS cases. On the independent dataset, performance was lower (75.0% accuracy, 88.9% sensitivity, 57.1% specificity; AUC-ROC: 0.627). Features reflecting quadrant-based PLR variations contributed most to classification. CONCLUSIONS: Pupillography-based ML models showed high sensitivity in distinguishing RRMS patients from healthy controls, may have potential as noninvasive adjunctive approaches. Although specificity decreased in the independent dataset, sensitivity remained relatively high. However, given the exploratory design and lack of disease controls, the findings should be interpreted with caution and require further validation.
Effects of high-dose vitamin D supplementation in patients with multiple sclerosis: A systematic review of efficacy and safety.
Ghamdi KA, Alqarni M, Alamri Z … +4 more , Wahhas MA, Alkhaldi M, Alsanni A, Alhawaj AF
Mult Scler Relat Disord · 2026 Jun · PMID 42320168 · Publisher ↗
BACKGROUND: Multiple sclerosis (MS), a chronic autoimmune disease, is the leading cause of non-traumatic neurological disability in young adults. Vitamin D plays a vital immunomodulatory role, and deficiency has been lin...
BACKGROUND: Multiple sclerosis (MS), a chronic autoimmune disease, is the leading cause of non-traumatic neurological disability in young adults. Vitamin D plays a vital immunomodulatory role, and deficiency has been linked to increased MS risk and activity. High-dose vitamin D supplementation has been proposed as a therapeutic approach. However, safety concerns and inconsistent evidence on efficacy highlights the need for systematic evaluation. OBJECTIVES: To evaluate the efficacy and safety of high-dose vitamin D supplementation in patients with MS, with emphasis on immune markers, disability progression, magnetic resonance imaging (MRI) findings, and reported adverse-events. METHODS: This systematic review follows the PRISMA 2020 guidelines. The protocol was registered on PROSPERO (CRD420251128444). Relevant studies were systematically retrieved and searched in public databases. Randomized controlled trials were included that evaluates high-dose vitamin D supplementation (≥10,000 IU/day) in adults with multiple sclerosis, reporting efficacy and/or safety. Data extraction was performed independently by two reviewers. Risk of bias was assessed using RoB-2 for randomized trials. Outcomes of interest are safety, MRI findings, clinical measures, and immunological biomarkers. RESULTS: Eleven randomized controlled trials were included. High-dose vitamin D increased serum 25‑hydroxy vitamin D levels and was surprisingly safe, with rare and transient disturbances in calcium serum levels. MRI and clinical outcomes showed variable effects. Several trials demonstrated immunomodulatory effects, particularly reductions in interleukin-17-related pro-inflammatory activity. CONCLUSION: High-dose vitamin D is safe under appropriate monitoring. While clinical and radiological benefits remain inconsistent, evidence of immune modulation suggests a promising adjunctive role requiring further investigation in larger, long-term trials.
Relating perivascular imaging measures to longitudinal lesion evolution and chronic inflammation in multiple sclerosis.
Tranquille A, Bergsland N, Reeves JA … +6 more , Bartnik A, Weinstock-Guttman B, Eckert SP, Hojnacki D, Dwyer MG, Zivadinov R
Mult Scler Relat Disord · 2026 Jun · PMID 42320167 · Publisher ↗
BACKGROUND: Perivascular space (PVS) alterations may be associated with acute and chronic inflammatory activity in people with multiple sclerosis (pwMS). PURPOSE: Investigate whether diffusion tensor image analysis along...
BACKGROUND: Perivascular space (PVS) alterations may be associated with acute and chronic inflammatory activity in people with multiple sclerosis (pwMS). PURPOSE: Investigate whether diffusion tensor image analysis along the PVS (DTI-ALPS) or PVS number/volume are associated with lesion evolution in pwMS over 5-years. METHODS: 182 patients (142 relapsing-remitting MS [pwRRMS] and 40 progressive MS [pwPMS]) underwent clinical and MRI examinations at baseline and 5-year follow-up. All pwMS were assessed for contrast enhancing lesions (CELs), T2 lesions, T1 lesions and cortical lesions (CLs). A subset of 86 pwMS were analyzed for presence of paramagnetic rim lesions (PRL). Associations between DTI-ALPS, PVS number/volume and lesion types were evaluated using regression and ANCOVA models, adjusting for age, sex, disease duration and normal-appearing white matter mean diffusivity, with false discovery rate correction for multiple comparisons, resulting in q values. RESULTS: In pwRRMS, baseline DTI-ALPS was associated with baseline CEL number (q < 0.001), T1 lesion number (q = 0.013), T2 lesion volume (q = 0.037) and T1 lesion volume (q < 0.002). It was associated with accumulation of new/enlarging CL (q = 0.013) and T1 lesions (q = 0.007), absolute change in T1 lesion volume (q = 0.025) and trended with newly appearing PRLs (q = 0.066). Absolute 5-year change in PVS volume was related to PRL presence at baseline (q = 0.018). CONCLUSION: PVS alterations are associated with lesion evolution in pwRRMS.
Down-sloping high-frequency audiometric findings in ENT-MS-12 auditory screen-positive patients with relapsing-remitting multiple sclerosis: A pilot case series.
Di Stadio A, Francavilla B, Ralli M … +6 more , Koohi N, Kaski D, Turchetta R, Indovina I, Dipietro L, Altieri M
Mult Scler Relat Disord · 2026 Jun · PMID 42314530 · Publisher ↗
BACKGROUND: Audio-vestibular symptoms, including hearing loss and tinnitus, are increasingly reported in people with multiple sclerosis (pwMS), yet their clinical significance and underlying mechanisms remain unclear. Bo...
BACKGROUND: Audio-vestibular symptoms, including hearing loss and tinnitus, are increasingly reported in people with multiple sclerosis (pwMS), yet their clinical significance and underlying mechanisms remain unclear. Both central demyelination and peripheral involvement along the brain-cochlea axis have been proposed as potential contributors.This study aims to explore and describe pure-tone audiometry (PTA) findings in pwMS who screened positive for auditory complaints on the ENT-MS-12 questionnaire, and to summarize associated clinical and magnetic resonance imaging (MRI) features during follow-up. METHODS: In this prospective pilot study, 40 pwMS with relapsing-remitting MS were screened using the ENT-MS-12 questionnaire. Patients reporting auditory complaints and meeting predefined exclusion criteria were invited to undergo pure-tone audiometry (125-8000 Hz). Clinical data and MRI findings obtained within three months of audiometric testing were reviewed and compared with imaging from the previous year. RESULTS: Twenty-seven patients (67.5%) reported auditory symptoms. Eleven met the inclusion criteria and five consented to audiometric testing. All five patients showed a down-sloping audiometric configuration with elevated high-frequency thresholds, particularly at 6000-8000 Hz. Mean high-frequency thresholds were higher than age-matched reference values reported in the literature. During follow-up, four of five patients experienced clinical relapses; one of these also showed disease progression, auditory brainstem response abnormalities, and a temporal lobe lesion on MRI. CONCLUSIONS: In this pilot study, pwMS who reported hearing concerns and underwent audiometry presented subtle high-frequency auditory threshold elevations with a down-sloping audiometric pattern. These preliminary, descriptive findings suggest that incorporating auditory assessment may provide complementary clinical information in pwMS. Larger, controlled studies with electrophysiological testing and advanced neuroimaging are warranted to clarify the relevance and mechanisms of auditory involvement in multiple sclerosis, including potential central and peripheral contributions.
Tear CHI3L1 in multiple sclerosis: a non-invasive biomarker linked to disease progression.
Castillo-Villalba J, Gasque-Rubio R, Forés-Toribio L … +11 more , Tortosa-Carreres J, García-Lluch G, Ferrer-Pardo C, Carratalá-Boscá S, Alcalá C, Gorriz D, Quintanilla-Bordás C, Poyatos-García J, Casanova B, Cubas-Núñez L, Pérez-Miralles F
Mult Scler Relat Disord · 2026 Jun · PMID 42302565 · Publisher ↗
OBJECTIVE: To evaluate tear CHI3L1 (tCHI3L1) as a minimally invasive biomarker in multiple sclerosis (MS), compare it with serum and cerebrospinal fluid (CSF) CHI3L1, and assess associations with clinical phenotype and d...
OBJECTIVE: To evaluate tear CHI3L1 (tCHI3L1) as a minimally invasive biomarker in multiple sclerosis (MS), compare it with serum and cerebrospinal fluid (CSF) CHI3L1, and assess associations with clinical phenotype and disease measures. METHODS: This cross-sectional study included 111 MS patients (71 relapsing-remitting MS [RRMS] and 40 progressive MS [PMS]) and 23 healthy controls (HC). tCHI3L1 was quantified by optimized ELISA and normalized to tear volume (tCHI3L1 ratio). Paired tear-serum samples were available for 99 patients to measure sCHI3L1, sGFAP, and sNFL. Associations with age, Expanded Disability Status Scale (EDSS), and disease duration, were analyzed. An independent cohort of 34 patients with paired tear-serum-CSF samples was used to assess biomarker relationships across biological fluids. Receiver operating characteristic analyses evaluated discrimination between PMS and RRMS. RESULTS: PMS patients showed higher tCHI3L1 ratios than RRMS patients (p = 0.033) and HC (p = 0.024). Tear and serum CHI3L1 levels were not correlated. In patients with matched tear-serum-CSF samples, the tCHI3L1 ratio showed a trend toward correlation with CSF CHI3L1 (r = 0.3; p = 0.08), becoming significant in patients without inflammatory activity (r = 0.45; p = 0.038). Serum biomarkers correlated with age, disease duration, and EDSS. sNFL, followed by sGFAP, showed the best discrimination between PMS and RRMS, whereas serum and tear CHI3L1 showed the lowest discriminatory power. CONCLUSION: tCHI3L1 is elevated in PMS and may provide complementary information on compartment-specific disease biology. Its minimally invasive nature supports further evaluation as an accessible biomarker in MS.
Real world drug utilization patterns in the first years following a relapsing-remitting multiple sclerosis diagnosis.
Molenaar PCG, Weir DL, Arnoldus EPJ … +19 more , Beenakker EAC, van den Bos RPM, van Eijk JJJ, Feenstra C, van Geel BM, Heersema DJ, Hoitsma E, Horvath KM, Killestein J, Kragt JJ, van Munster CEP, Snoeijen AHWJM, Wokke BHA, Goettsch WG, Strijbis EMM, de Beukelaar JWK, Kalkers NF, de Jong BA, Dutch-MSR consortium
Mult Scler Relat Disord · 2026 May · PMID 42296726 · Publisher ↗
BACKGROUND: Real-world drug utilization studies provide valuable insights into the treatment of relapsing-remitting multiple sclerosis (RRMS). As treatment dynamics in the Dutch context are limited, we studied drug utili...
BACKGROUND: Real-world drug utilization studies provide valuable insights into the treatment of relapsing-remitting multiple sclerosis (RRMS). As treatment dynamics in the Dutch context are limited, we studied drug utilization patterns in the first two years following a RRMS diagnosis in the Netherlands. METHODS: People diagnosed with RRMS between 2016 and 2022 were included from the Dutch Multiple Sclerosis Registry, a registry-based observational study. Disease modifying therapies (DMTs) were categorized as low-, moderate- or high-efficacy. Initiation, discontinuation, reasons for discontinuation, and switches in the first two years post-diagnosis were evaluated. We calculated proportions with 95% confidence intervals (CI). RESULTS: We included 806 PwMS. 2-year discontinuation was highest for low- (51%, CI: 45-57) and moderate-efficacy (37%, CI: 32-42) DMTs, mainly due to adverse events or insufficient efficacy. Of those switching from these therapies, 26% (CI: 21-33) switched to low-efficacy and 37% (CI: 30-44) to moderate-efficacy therapies, of which 32% (CI: 34-41) discontinued their second DMT. Anti-CD20 therapies were discontinued in 5% (CI: 2-15) of initiations. High-efficacy DMT use rose from 12% (CI: 10-15) at initiation to 29% (CI: 26-33) at year two. CONCLUSION: Our results indicate high risks of discontinuation of low- and moderate-efficacy DMTs, in contrast to low risk of discontinuation of anti-CD20 therapies. These findings may give further direction to research on finding the optimal treatment strategy and may inform health care providers in the Netherlands.
The effect of exercise interventions on physiological fitness, physical and cognitive function, common symptoms, and disease impact for people with severe Multiple Sclerosis: A systematic review.
Brooks W, Preston J, Barclay A … +3 more , Wilson G, Ainslie D, Coulter E
Mult Scler Relat Disord · 2026 Jun · PMID 42287858 · Publisher ↗
INTRODUCTION: Exercise may slow Multiple Sclerosis (MS) progression and is considered safe for all people with MS. A review of exercise for those with severe MS was published in 2017, with guidelines for physical activit...
INTRODUCTION: Exercise may slow Multiple Sclerosis (MS) progression and is considered safe for all people with MS. A review of exercise for those with severe MS was published in 2017, with guidelines for physical activity and exercise updated in 2020. The evidence base has subsequently increased, warranting further review. OBJECTIVE: To investigate the effectiveness of exercise interventions on physiological fitness, physical and cognitive function, common symptoms, and disease impact in people with severe MS. METHODS: A search was conducted across five electronic databases. Randomised control trials applying an exercise intervention to participants diagnosed with MS, EDSS 6.5-8.0, with outcome measures of physiological fitness, physical function, cognitive function, spasticity, fatigue, or disease impact were included. RESULTS: In total 29 studies published in 31 articles were included, with 1181 participants. Only six studies included participants exclusively with an EDSS ≥6.5. Studies predominantly reported outcome measures of physiological fitness (n = 16), physical function (n = 25), and MS symptoms and disease impact (n = 25), with the majority finding an improvement in at least one outcome measure. Comparatively few studies reported outcome measures of upper limb function (n = 4) and cognitive performance (n = 3). CONCLUSIONS: Exercise appears to improve physiological fitness, physical function, and disease impact, but not disability status. These improvements largely occurred in studies which included participants at an EDSS <6.5. Improvements were limited in studies which exclusively recruited participants at an EDSS ≥6.5. Further research is required to establish the specific effects for those severely affected by MS, especially those who are non-ambulatory.
Anti-JCV antibody seroprevalence and testing practices in multiple sclerosis patients considered for natalizumab therapy: a retrospective study from King Saud Medical City, Riyadh, Saudi Arabia.
Althobaiti AH, Elrashidy MA, Alabdulhadi AS … +2 more , Almuqarrab AJ, Alharbi HS
Mult Scler Relat Disord · 2026 Jun · PMID 42287857 · Publisher ↗
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a feared complication of natalizumab therapy, and anti-John Cunningham virus (JCV) antibody serology is central to risk stratification. Data on JCV seroprev...
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a feared complication of natalizumab therapy, and anti-John Cunningham virus (JCV) antibody serology is central to risk stratification. Data on JCV seroprevalence and testing practices in Saudi Arabia remain limited. OBJECTIVES: To determine the prevalence of anti-JCV seropositivity in a cohort of patients with multiple sclerosis (pwMS), assess the proportion tested prior to natalizumab initiation, and evaluate laboratory turnaround time. METHODS: A cross-sectional observational study at King Saud Medical City, Riyadh, Saudi Arabia, including all pwMS diagnosed according to the 2017 revised McDonald criteria who underwent at least one anti-JCV antibody test between January 2019 and December 2024. Follow-up data were truncated on February 18, 2025. Testing was performed using the STRATIFY JCV assay (Biogen/Unilabs). RESULTS: Ninety-one patients were included; 68 (74.7%) were female, with median age of 28.8 years (IQR 24.4-34.8). Anti-JCV seropositivity was identified in 36 patients (39.6%); of these, 4 (11.1%) had an index value ≤0.9, 8 (22.2%) had a value >0.9-1.5, and the majority exceeded 1.5 (24 patients, 66.7%). Eighty-three patients (91.2%) received natalizumab; of these, only 4 (4.8%) were tested prior to initiation, and none had their result available before the first infusion. Among seropositive patients, 32 (88.9%) initiated natalizumab, with a median treatment duration of 12.1 months (IQR 3.9-24.4). The median laboratory turnaround time was 20 days (IQR 13-27). CONCLUSION: JCV seropositivity was identified in approximately 39.6% of MS patients considered for natalizumab therapy at our center, consistent with regional estimates. Pre-treatment JCV testing was largely absent, and turnaround time was prolonged.
Initial treatment choice for multiple sclerosis and prognosis at year 3 are associated with few poor prognosis factors.
Bonnan M, Wu KY, Wahab A … +4 more , Zedet M, Grimaldos A, Lafont C, Creange A
Mult Scler Relat Disord · 2026 Jun · PMID 42287856 · Publisher ↗
INTRODUCTION: Predicting the clinical outcomes of patients with multiple sclerosis (MS) is important at onset, depending on multiple prognostic factors. The early choice of high efficacy treatment is only driven by some...
INTRODUCTION: Predicting the clinical outcomes of patients with multiple sclerosis (MS) is important at onset, depending on multiple prognostic factors. The early choice of high efficacy treatment is only driven by some of these factors, mainly the frequency of attacks. We examined the combined effect of all the predictive elements associated with poor outcomes at year 3, in relation with the choice of first-line disease-modifying therapies or high-efficacy DMT (fl-DMT or he-DMT). OBJECTIVE: To analyze the influence of poor prognosis risk factors on clinical outcomes. METHODS: Clinical data, imaging data, cerebrospinal fluid (CSF) data, and therapies were retrospectively analyzed in large monocentric series of patients with relapsing-remitting MS. The primary and secondary outcomes were the risk of reaching ≥+1 point EDSS or ≥1 relapse at year 3, respectively. RESULTS: he-DMT was first initiated in 25.1% of patients (44/175). The primary outcome (impairment) was observed in 41.7% of the patients and associated with younger age, EDSS≥3, and multiple clinical involvement at the first attack. Multivariate modelling confirmed the strong influence of age, baseline impairment, and he-DMT. The secondary outcome (relapse) occurred in 55.4% of patients and was associated with younger age, CSF white cell count, and absence of early he-DMT. CONCLUSIONS: Delayed high-efficacy therapy was a major negative factor, followed by younger age, EDSS≥3 at onset, and abnormal CSF white cells. Some factors might be active very early in MS history and could be mitigated by early he-DMT initiation.
Immunotherapy decision coaching for people with multiple sclerosis - Implementation of an interprofessional decision support programme into clinical practice.
Wiechel NC, Schneider A, Peper J … +5 more , Grentzenberg K, Lau S, Krause N, Rahn AC, Heesen C
Mult Scler Relat Disord · 2026 Jun · PMID 42276023 · Publisher ↗
BACKGROUND: Aiming at actively involving patients in the complex immunotherapy decision-making process in multiple sclerosis (MS), we developed DECIMS (Decision Coaching in people with Multiple Sclerosis). This interprof...
BACKGROUND: Aiming at actively involving patients in the complex immunotherapy decision-making process in multiple sclerosis (MS), we developed DECIMS (Decision Coaching in people with Multiple Sclerosis). This interprofessional decision-support programme consists of nurse-led coaching sessions, an online accessible information tool (DECIMS-Wiki), and a physician's consultation. OBJECTIVE: To assess the implementation of nurse-led decision coaching in clinical care and to evaluate associated outcomes, including effectiveness, feasibility, and sustainability, alongside a revised DECIMS-Wiki. METHODS: 1-2 coaching sessions led by a nurse (up to 90 min) followed by a physician consultation integrated into the clinical routine care of a university based MS day hospital. Questionnaires were completed by people with MS (PwMS) and health care professionals. The key outcome was acceptance. DECIMS-Wiki was evaluated through an online survey and telephone interviews focusing on the DECIMS-Wiki, which were analysed using qualitative content analysis. RESULTS: Among 105 participating PwMS, 45% rated the nurse-led coaching as the most helpful component during the decision-making process. Many PwMS (58%) favoured autonomous roles. Patients' decisions matched the physician's perceptions in 77% of consultations. 49% of PwMS chose to start immunotherapy and 30% decided to watch and wait. Data from 53 participants evaluating the DECIMS-Wiki indicated convenient handling, but difficulties in navigation. >80% of participants reported a better understanding of and denied feeling upset by the uncertainties communicated through the material. This was confirmed in interviews (n = 8). CONCLUSION: DECIMS was successfully implemented in routine outpatient care. Nurse-led decision coaching was feasible, effective, and potentially sustainable, enabling task-sharing between nurses and physicians in shared decision-making. The revised DECIMS-Wiki was well received and facilitated implementation as a complementary tool.
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