Multiple Sclerosis And Related Disorders[JOURNAL]
Sun
200 papers
EBV viral load and miR-BART10-3p expression in multiple sclerosis: A case-control study.
Rahimi SB, Hashemi SMA, Poursadeghfard M … +4 more , Tamaddon G, Jamalidoust M, Daryabor G, Sarvari J
Mult Scler Relat Disord · 2026 Jun · PMID 42066693 · Publisher ↗
BACKGROUND: The Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), but the underlying molecular mechanisms are not fully understood. This case-control study from Southern Iran investigated the associati...
BACKGROUND: The Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), but the underlying molecular mechanisms are not fully understood. This case-control study from Southern Iran investigated the association of EBV viral load and EBV-encoded miR-BART10-3p expression with MS. METHODS: The study included 110 participants: 40 newly diagnosed MS patients (ND-MS), 20 patients treated with interferon-β (MS-IFN), 20 patients receiving B-cell-depleting monoclonal antibody therapy (MS-mAb), and 30 age- and sex-matched healthy controls (HC). Peripheral blood samples were collected, and the isolated buffy coat fractions and sera were stored at -70 °C until analysis. Total DNA and RNA were extracted from the buffy coat using TRIzol reagent. EBV genomic load per cell and EBV-encoded microRNA BART10-3p expression were quantified by q-PCR and q-RT-PCR, respectively. EBV viral capsid antigen (VCA) IgG serostatus was determined by ELISA. RESULTS: The mean age of the participants was 37.7 ± 8.5 years (range: 22-61). The cohort consisted of 26 (32.5%) males in the patient group (n = 80) and 10 (33.3%) in the HC group (n = 30). EBV viral load was significantly elevated in the ND-MS (2.1-fold increase; p < 0.001) and MS-IFN (1.7-fold increase; p = 0.03) groups compared to HCs. In contrast, the MS-mAb group showed a lower, non-significant viral load (0.2-fold; p = 0.17). Similarly, miR-BART10-3p expression was significantly higher in ND-MS (mean = 4.06; 2.74-fold increase; p < 0.001) and MS-IFN (mean = 2.91; 1.97-fold increase; p < 0.001) groups, but it was markedly lower in the MS-mAb group (mean = 0.43; 0.29-fold; p < 0.001). No significant differences in EBV-VCA IgG seropositivity were observed among the groups (p = 0.55). Furthermore, EBV viral load, miR-BART10-3p expression, and EBV-VCA IgG seropositivity showed no significant association with the age or sex of the participants (p > 0.05). CONCLUSION: These findings suggest a potential role for EBV viral load and miR-BART10-3p expression in the pathogenesis of MS. These molecular markers may serve as complementary indicators for monitoring EBV activity and disease progression. Further studies are needed to validate these results and explore their clinical utility.
Contribution of thalamus-cortex network and cortical habituation mechanisms in multiple sclerosis.
Pitzalis B, Ciavatta L, Leodori G … +7 more , Ziccardi L, Parisi V, Conte A, Capone F, Di Lazzaro V, Pauri F, Coppola G
Mult Scler Relat Disord · 2026 Jun · PMID 42066692 · Publisher ↗
OBJECTIVE: Fatigue is one of the most prevalent and debilitating symptoms in individuals with multiple sclerosis (MS). We recorded somatosensory high-frequency oscillatory (HFO) thalamocortical activity in a group of MS...
OBJECTIVE: Fatigue is one of the most prevalent and debilitating symptoms in individuals with multiple sclerosis (MS). We recorded somatosensory high-frequency oscillatory (HFO) thalamocortical activity in a group of MS patients without history of optic neuritis (ON). Furthermore, we examined if, like what was previously observed in response to visual stimuli, patients exhibit diminished amplitude habituation, and whether this may further exacerbate fatigue in individuals with MS. METHODS: Twenty patients diagnosed with relapsing-remitting MS were prospectively enrolled. The MS cohorts were compared with a cohort of 20 healthy volunteers (HV). Fatigue Severity Scale (FSS) was employed to evaluate the trait levels of reported fatigue. We assessed the N20 somatosensory evoked potentials (SSEPs) parameters and N20-P25 amplitude habituation, and, following the application of a band-pass filter (450-750 Hz), we evaluated electrophysiological parameters of pre- and post-synaptic HFOs. RESULTS: The latency and amplitude of the N20 SSEP and its habituation do not exhibit significant differences between MS patients and HVs. MS patients exhibited delayed latency of negative oscillatory maximum and reduced maximum peak-to-peak amplitude of the pre-synaptic HFOs (all p < 0.01). In patients, post-synaptic HFOs showed a significant delayed latency and a trend towards a reduction in the maximal peak-to-peak amplitude. The pre-synaptic HFO latency of the negative oscillatory maximum, reflecting thalamocortical activity, shows a correlation with the FSS in MS patients (r = 0.522, p = 0.018). No significant ophthalmological anomalies were identified. CONCLUSIONS: Our data revealed a significant reduction and slowing of somatosensory thalamocortical network activity in MS patients without history of ON. Furthermore, our findings showed that fatigue levels may be affected by slowed thalamocortical activity, but not by habituation of cortical responses. SIGNIFICANCE: Our findings suggest a potential role of the thalamo-cortical network on the genesis of MS-related fatigue.
Diagnostic yield of the 2022 optic neuritis criteria and an antibody-stratified adjunct in an antibody-predominant Chinese clinical sample.
Liang Y, Yang J, Luo W … +7 more , Wei S, Wang K, Song R, Fu R, Zhao Y, Bai Y, Du Y
Mult Scler Relat Disord · 2026 Jul · PMID 42066614 · Publisher ↗
BACKGROUND: The real-world performance of the 2022 international consensus criteria for optic neuritis (ICON) in antibody-predominant Chinese practice is uncertain. We evaluated diagnostic yield and an antibody-stratifie...
BACKGROUND: The real-world performance of the 2022 international consensus criteria for optic neuritis (ICON) in antibody-predominant Chinese practice is uncertain. We evaluated diagnostic yield and an antibody-stratified adjunct for settings with high antibody prevalence and timely antibody testing. METHODS: We retrospectively studied 151 consecutive patients admitted with acute optic neuritis between 2020 and 2023. All cases were reclassified using strict 2022 ICON. We then evaluated an assumed-dyschromatopsia scenario in which dyschromatopsia was assumed unless normal color vision was explicitly documented. On top of that scenario, we applied an antibody-stratified adjunct using aquaporin-4 immunoglobulin G (AQP4-IgG) seropositivity or clear-positive myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG; fixed cell-based assay titer ≥1:100) plus objective optic nerve evidence. RESULTS: Strict 2022 ICON classified 30/151 (20%) cases as Definite ON, 113/151 (75%) as Possible ON, and 8/151 (5%) as Not ON. Under the assumed-dyschromatopsia scenario, Definite ON increased to 112/151 (74%). With the antibody-stratified adjunct, Definite ON further increased to 124/151 (82%), while Not ON remained 8/151 (5%). Definite ON reached 82/82 (100%) in AQP4-IgG-positive cases, 20/21 (95%) in MOG-IgG-positive cases, 18/37 (49%) in double-seronegative cases, and 4/11 (36%) in cases with incomplete AQP4-IgG/MOG-IgG testing. CONCLUSIONS: In this antibody-predominant clinical sample, strict 2022 ICON yielded a low Definite ON classification rate, driven largely by incomplete bedside documentation, especially color vision assessment. Assuming complete dyschromatopsia documentation improved yield, and the antibody-stratified adjunct provided further gains without increasing the Not ON category.
Intrathecal IgM species as potential prognostic biomarkers in relapsing-remitting multiple sclerosis.
Hvaring C, Alawad N, Salvesen Ø … +3 more , Hovdal H, White LR, Boullerne AI
Mult Scler Relat Disord · 2026 Jul · PMID 42061166 · Publisher ↗
BACKGROUND: Although biomarkers exist for the diagnosis of MS, there is no consensus regarding a prognostic marker, though several forms of intrathecal IgM expression have been suggested, including CSF-restricted bands o...
BACKGROUND: Although biomarkers exist for the diagnosis of MS, there is no consensus regarding a prognostic marker, though several forms of intrathecal IgM expression have been suggested, including CSF-restricted bands of oligoclonal IgM (OCMB), and IgM to protein nitrosylation. MATERIALS AND METHODS: The study used a cohort of patients with a diagnosis of relapsing-remitting MS (RRMS), n = 37, studied for up to 17 years. Three biological parameters for IgM were investigated for their prognostic potential. A cohort of patients with diffuse symptoms but no demonstrable neurological disease served as controls (n = 57). RESULTS: Patients with RRMS had signs of inflammation, frequently including an increase in total CSF IgM, the presence of OCMB, as well as an increase in CSF anti-S-nitrosylated protein IgM (α-SNOcys). There was a strong correlation between these IgM species. Patients without both OCMB and α-SNOcys had more benign development of disease, compared to patients with both IgM species at baseline. These latter patients had more aggressive disease development. Whereas the presence of only OCMB indicated worse long-term prognosis, the additional presence of α-SNOcys indicated earlier progression. CONCLUSIONS: This retrospective pilot study suggests that α-SNOcys as well as OCMB are both useful for the prognosis of RRMS, respectively in the shorter and longer term, and might therefore assist the physician in clinical decisions.
Beyond serology: clinical and prognostic determinants in patients with dual AQP4-IgG and MOG-IgG seropositivity.
Dogan IG, Sen S, Tezer DC … +9 more , Aslan SK, Gumus H, Cinar BP, Bilge N, Ethemoglu O, Kizilay F, Boz C, Terzi M, Demir S
Mult Scler Relat Disord · 2026 Jul · PMID 42061165 · Publisher ↗
BACKGROUND: Dual seropositivity for AQP4-IgG and MOG-IgG represents a rare and diagnostically challenging immunological phenotype within CNS inflammatory demyelinating disorders, and its clinical implications and prognos...
BACKGROUND: Dual seropositivity for AQP4-IgG and MOG-IgG represents a rare and diagnostically challenging immunological phenotype within CNS inflammatory demyelinating disorders, and its clinical implications and prognostic significance remain poorly defined; therefore, this study was undertaken to address these gaps in knowledge. METHODS: We conducted a retrospective multicenter case series using a targeted case-ascertainment approach across neuroimmunology centers in Türkiye. The inclusion criteria were as follows: (1) confirmed dual seropositivity for AQP4-IgG and MOG-IgG through validated cell-based assays, specifically indirect immunofluorescence assay or flow cytometry-based live cell assay; (2) a clinical phenotype consistent with central nervous system inflammatory demyelination; and (3) a minimum follow-up duration of six months. Clinical, radiological, cerebrospinal fluid, therapeutic, and outcome data were systematically collected and analyzed. RESULTS: Eleven patients (7 female; median age: 40 years) were included. Initial presentations included optic neuritis (n = 7) and myelitis (n = 4). Longitudinally extensive transverse myelitis was observed in 4 patients (36.4%), while 3 had short-segment lesions. Long-segment optic nerve hyperintensity was seen in 5 of 7 optic neuritis cases. Two patients relapsed and two died due to systemic comorbid conditions. At last follow-up, patients with comorbidities had significantly higher EDSS scores than those without comorbidities (median: 4.0 vs. 1.0; p = 0.008). CONCLUSION: Although dual AQP4-IgG and MOG-IgG seropositivity is rare, it is clinically significant. Prognosis is more strongly influenced by systemic comorbidities and overall clinical burden than by serostatus alone. Clinical management should therefore be guided by the overall disease phenotype and coexisting systemic conditions rather than antibody status in isolation.
A systematic review of the clinical utility of retinal optical coherence tomography in childhood acquired demyelinating syndromes.
Buijze MSJ, de Mol CL, Loudon SE … +1 more , Neuteboom RF
Mult Scler Relat Disord · 2026 Jul · PMID 42048775 · Publisher ↗
INTRODUCTION: Retinal optical coherence tomography (OCT) is rapidly emerging in the field of inflammatory demyelinating disease of the central nervous system (CNS), but its role in the pediatric population remains unclea...
INTRODUCTION: Retinal optical coherence tomography (OCT) is rapidly emerging in the field of inflammatory demyelinating disease of the central nervous system (CNS), but its role in the pediatric population remains unclear. This review aims to provide a comprehensive overview of the clinical utility of OCT in childhood acquired demyelinating syndromes (cADS). METHODS: A systematic literature search was conducted in Embase, Medline, Cochrane Library, Web of Science, and Google Scholar to identify studies reporting OCT findings in cADS. Meta-analyses were performed to compare retinal thickness in multiple sclerosis (MS) eyes with and without prior optic neuritis (ON) to healthy controls. Remaining data were synthesized using an explorative, theme-based approach, focusing on retinal atrophy patterns across cADS subgroups and the utility of OCT as a diagnostic, prognostic, or monitoring tool. RESULTS: Consistent evidence was found for retinal thinning in pediatric acquired demyelinating syndromes, particularly in eyes affected by ON, across multiple OCT metrics. Distinct atrophy patterns were observed in diagnostic subgroups. Retinal thinning was also present in MS eyes without a history of ON, suggesting subclinical optic nerve lesions or CNS neuroaxonal loss transmitted to the retina via trans-synaptic degeneration. While OCT may have prognostic value for visual outcomes, evidence is lacking for broader prognostic utility or for monitoring disease progression or treatment response. CONCLUSIONS: OCT is a valuable diagnostic modality in cADS, particularly for detecting optic nerve lesions. Further research is needed to explore its potential as a biomarker for CNS neurodegeneration and establish its role for prognostication and disease monitoring in cADS.
Prescriptions and healthcare use in multiple sclerosis patients within general practices in the Netherlands.
Lemmens CMC, Vanhommerig JW, Knottnerus BJ … +3 more , Mostert JP, Killestein J, de Jong BA
Mult Scler Relat Disord · 2026 Jun · PMID 42030886 · Publisher ↗
BACKGROUND: General practitioners (GPs) have an essential role in Dutch healthcare for people with multiple sclerosis (PwMS), addressing diverse disease symptoms and coordinating supportive care. METHODS: This cross-sect...
BACKGROUND: General practitioners (GPs) have an essential role in Dutch healthcare for people with multiple sclerosis (PwMS), addressing diverse disease symptoms and coordinating supportive care. METHODS: This cross-sectional population-based study cohort was sourced from the 2019 Nivel Primary Care Database in the Netherlands. Non-disease-modifying therapy (DMT) prescriptions and GP healthcare use among PwMS were compared with an age- and sex matched control population, using negative binomial regression adjusting for socio-economic status (SES) and comorbidity burden. Factors associated with polypharmacy (concurrent use of ≥5 medications) and healthcare use in the GP setting in PwMS were evaluated with regression models. RESULTS: Non-DMT prescriptions were prescribed to PwMS (N = 3,013) approximately 1.5 times more frequently than in controls (N = 15,103). Polypharmacy was observed in 28.3% of MS patients (adjusted odds ratio 1.80 compared to controls). Medication classes predominantly contributing to polypharmacy were systemic antibiotics, vitamin supplements, medication for acid related disorders, antihypertensive drugs, and laxatives. PwMS received more GP consultations compared to controls (adjusted incidence rate ratio (aIRR) 1.56 (95% CI 1.49 - 1.63) and were twice as likely to seek care for infectious episodes (aIRR 2.30; 95% CI 2.20 - 2.41). Older age, female sex, higher comorbidity burden, and lower SES were associated with increased polypharmacy and GP healthcare use. Polypharmacy was linked to increased all-cause mortality (aHR 1.69; 95% CI 1.20 - 2.37), albeit similar to controls. CONCLUSION AND DISCUSSION: Polypharmacy of non-DMT prescriptions is prevalent in PwMS and often accompanied by frequent GP visits, highlighting the need for targeted medication review and coordinated primary care.
Comorbidity of uveitis and multiple sclerosis.
Mäkelä HM, Kuusisto H, Leinonen S
Mult Scler Relat Disord · 2026 Jun · PMID 42030885 · Publisher ↗
BACKGROUND: The comorbidity of uveitis and multiple sclerosis (MS) is recognized but reported prevalence rates vary. We aimed to investigate the prevalence and characteristics of uveitis in people with multiple sclerosis...
BACKGROUND: The comorbidity of uveitis and multiple sclerosis (MS) is recognized but reported prevalence rates vary. We aimed to investigate the prevalence and characteristics of uveitis in people with multiple sclerosis (pwMS) in Finland by conducting a prospective screening study. METHODS: pwMS 18-60 years of age were identified from the Finnish MS registry in Tampere University Hospital, Finland. Identified pwMS who were capable of independently attend an ocular examination were invited for a comprehensive uveitis screening examination. RESULTS: In total 22 of 344 (6 %) of pwMS had uveitis, of whom eight were newly diagnosed at screening examination with no ocular symptoms. The median age at diagnosis of uveitis was 38 years (range, 19 - 58). Uveitis was bilateral in 16 of 22 (73 %). Sixteen pwMS presented with intermediate uveitis and six had symptomatic anterior uveitis. Ocular complications were seen in 9 of 22 (41 %) of pwMS and uveitis. None of the pwMS with uveitis had been treated with tumor necrosis factor alpha inhibitors, known to increase the risk for MS. CONCLUSION: Uveitis was newly diagnosed in 2 % of our cohort, whereas the overall comorbidity of uveitis in pwMS was 6 %. We recommend comprehensive eye examination performed by a uveitis specialist for pwMS with visual symptoms suggestive of uveitis.
Patient experiences with systematically-administered patient-reported outcome measures in multiple sclerosis.
Desbiens V, Wong G, Liu S … +4 more , Chu NY, Watson KE, Smyth P, Tsuyuki RT
Mult Scler Relat Disord · 2026 Jun · PMID 42025274 · Publisher ↗
INTRODUCTION: There have been limited studies on the views of persons with MS (PwMS) around the systematic use of Patient Reported Outcome Measures (PROMs). The objective of this study was to explore the perspectives of...
INTRODUCTION: There have been limited studies on the views of persons with MS (PwMS) around the systematic use of Patient Reported Outcome Measures (PROMs). The objective of this study was to explore the perspectives of PwMS on the integration of PROMs into clinical practice as part of a randomized trial. METHODS: We conducted a qualitative substudy of our previous randomized controlled trial (RCT)(Clinicaltrials.gov NCT0497954), which was conducted from November 2021 to April 2024 and evaluated the effect of the systematic use of PROMs on depression and anxiety in PwMS. In this sub-study that ran from May 6, 2025 to August 31, 2025, we used purposive sampling of the participants from our RCT and conducted virtual semi-structured interviews. Thematic analysis of the interview transcripts was performed by two researchers independently using an inductive approach to create codes, categories, and abstract themes. RESULTS: 33 PwMS participated in semi-structured interviews that ranged from 10 to 40 minutes. Three main themes emerged to describe the perspectives of PwMS on the use of PROMs within their treatment: (i) Patient empowerment; (ii) Reassurance that their provider had reviewed their results; (iii) Individualized PROMs. Additionally, PwMS described challenges to incorporating PROMs, the perceived impact of PROMs on their care, and facilitating factors of PROMs. DISCUSSION: PROMs within this clinical setting were accepted by patients and created opportunities for patient empowerment. Some improvements to the use of PROMs were suggested, such as the addition of open-ended questions, making sure the physicians are ready to review the PROMs, and individualizing the PROMs to better serve the patient's needs.
TSPO-PET-measurable neuroinflammation associates with brain atrophy in multiple sclerosis.
Yenikekaluva A, Sjöros T, Matilainen M … +6 more , Snellman A, Rinne J, Alfaifi BQ, Hinz R, Saraste M, Airas L
Mult Scler Relat Disord · 2026 Jun · PMID 42025273 · Publisher ↗
BACKGROUND: In neurodegenerative conditions, neuroaxonal damage and tissue destruction lead to central nervous system atrophy. In multiple sclerosis (MS), widespread glial activation can contribute to disease progression...
BACKGROUND: In neurodegenerative conditions, neuroaxonal damage and tissue destruction lead to central nervous system atrophy. In multiple sclerosis (MS), widespread glial activation can contribute to disease progression and nervous tissue destruction. We aimed to assess the cross-sectional association between brain atrophy and diffuse glial activation. METHODS: One-hundred-and-twenty-eight participants with MS (92 relapsing-remitting and 36 progressive MS) and 73 healthy controls (HC) underwent brain MRI and positron emission tomography (PET) using 18-kDa translocator protein (TSPO)-binding radioligand [C]-PK11195. Associations between [C]-PK11195 distribution volume ratios (DVR) and brain parenchymal fractions were examined using correlation and multivariable linear regression analyses. RESULTS: In MS, higher normal-appearing white matter (NAWM) DVR correlated with smaller whole brain (ρ=-0.38, p < 0.001), NAWM (ρ=-0.43, p < 0.001), and thalamus (ρ=-0.42, p < 0.001) volumes. These correlations remained significant after adjustment for age, body mass index, sex, disease modifying treatment status, T2 lesion volume, and MRI field strength. Among HC, higher NAWM DVR values correlated with larger ventricular volume (ρ=0.26, p < 0.05), which remained significant after adjustment for potential confounders. CONCLUSIONS: Increased TSPO-PET measurable glial activation represents an adverse pathological factor in both MS and HC brains and is likely to contribute to the development of brain atrophy.
Antinuclear antibody and delayed immunotherapy predict disease evolution in isolated optic neuritis-onset NMOSD: A long-term cohort study.
Sun L, Chen C, Wu Y … +3 more , Dai F, Wang J, Guo Y
Mult Scler Relat Disord · 2026 Jun · PMID 42019203 · Publisher ↗
BACKGROUND: The disease course of neuromyelitis optica spectrum disorder (NMOSD) presenting with isolated optic neuritis (ON) is heterogeneous. Predictive factors for progression to other core phenotypes or bilateral ON...
BACKGROUND: The disease course of neuromyelitis optica spectrum disorder (NMOSD) presenting with isolated optic neuritis (ON) is heterogeneous. Predictive factors for progression to other core phenotypes or bilateral ON (BON) remain poorly defined. OBJECTIVE: To delineate disease evolution patterns and identify risk factors for phenotypic conversion and BON in a long-term cohort of ON-onset NMOSD, with a specific focus on the impact of antinuclear antibody (ANA) and the timing of immunosuppressive therapy (IMT). METHODS: This single-center retrospective cohort study enrolled 231 AQP4-IgG-seropositive NMOSD patients with isolated ON onset (2010-2022). All had ≥3 years of follow-up (median 7 years). Disease evolution was categorized as: sustained isolated ON, conversion to other core phenotypes (e.g., myelitis), or progression from unilateral to BON. Multivariable Cox regression and logistic models were used to assess predictors, including ANA status and IMT initiation timing (Early: ≤3 months; Delayed: >3 months after first attack). RESULTS: During follow-up, 35.1% (81/231) experienced phenotypic conversion, and 68.4% (130/190 of unilateral-onset cases) progressed to BON. Multivariable analyses identified ANA seropositivity (HR = 1.65, 95% CI 1.10-2.49, p=0.016) and delayed IMT initiation (HR = 2.76, 95% CI 1.12-6.77, p=0.027) as independent predictors of phenotypic conversion. For BON conversion, delayed IMT was the strongest independent risk factor (HR 3.23, 95% CI 1.49-7.00, p=0.003). Notably, among patients not receiving maintenance IMT (71/231), a subgroup (42/71, 59.2%) maintained minimal disability (EDSS ≤3), often in the setting of comorbidities contraindicating treatment; although this proportion declined substantially with very long-term follow-up. CONCLUSION: In AQP4-IgG-positive NMOSD presenting with isolated ON, ANA seropositivity and delayed IMT are independent predictors of disease evolution toward more severe phenotypes, whereas longer follow-up duration itself confers a modest protective effect. These findings highlight a critical early therapeutic window for IMT and support risk-stratified, individualized management in this clinically diverse population.
Sleep disturbances and their clinical and psychiatric correlates in pediatric-onset multiple sclerosis.
Konuskan B, Ozbudak P, Celik YS … +18 more , Aliyev SA, Direk MC, Caglar E, Kurt ANC, Altas H, Gunbey C, Aykol D, Yilmaz S, Simsek E, Kanmaz S, Dundar NO, Didinmez E, Yucel G, Ozcelik A, Gozen H, Oncel I, Solmaz I, Bayram AK
Mult Scler Relat Disord · 2026 Jun · PMID 42013712 · Publisher ↗
BACKGROUND: Sleep disturbance is increasingly recognized as a contributor to disease burden in adult-onset multiple sclerosis (MS), and emerging pediatric studies suggest that sleep-related problems may also be prevalent...
BACKGROUND: Sleep disturbance is increasingly recognized as a contributor to disease burden in adult-onset multiple sclerosis (MS), and emerging pediatric studies suggest that sleep-related problems may also be prevalent early in pediatric-onset MS (POMS). However, the multidimensional nature of sleep disturbance and its clinical correlates in POMS remain insufficiently characterized. This study aimed to evaluate multidimensional sleep disturbances in children and adolescents with POMS and to examine their associations with emotional symptoms, fatigue, quality of life (QoL), and MRI features. METHODS: In this multicenter cross-sectional study, children and adolescents with POMS were compared with age- and sex-matched healthy controls. Sleep disturbance and daytime sleepiness were assessed using standardized questionnaires covering multiple sleep domains. Emotional symptoms, fatigue, and quality of life were evaluated using validated scales. Clinical characteristics and MRI data, including lesion distribution, were obtained from medical records. Associations were examined using correlation and hierarchical regression analyses. RESULTS: Compared with healthy controls, patients with POMS demonstrated significantly higher global sleep disturbance and daytime sleepiness across several domains, including sleep initiation and maintenance difficulties, sleep-breathing symptoms, and altered sleep-wake transitions (all p < 0.05). Greater sleep disturbance was associated with higher depressive symptoms, increased fatigue, and lower QoL. In regression analyses, depressive symptoms emerged as the strongest independent correlate of sleep disturbance, while brainstem lesion involvement remained independently associated, together explaining approximately 30% of the variance in the POMS group, whereas this association was not observed in healthy controls. CONCLUSIONS: Sleep disturbance represents an early, multidimensional, and clinically meaningful non-motor component of disease burden in POMS. Our findings support a biologically plausible framework in which sleep disturbance is associated with emotional distress and neurobiological factors contributing to reduced quality of life. Sleep may represent a potentially modifiable target for early screening and intervention in pediatric MS.
Effectiveness and safety of ocrelizumab in relapsing-onset multiple sclerosis: A nationwide real-world study from Slovakia.
Vitková M, Szilasiová J, Fedičová M … +14 more , Kahancová E, Filippi P, Koleňáková K, Kiačiková M, Dziaková J, Bilá A, Laurincová S, Koleda P, Kováčová S, Hančinová V, Bullová A, Kantorová E, Karlík M, Slezáková D
Mult Scler Relat Disord · 2026 Jun · PMID 42013711 · Publisher ↗
BACKGROUND: Ocrelizumab (OCR) is a high-efficacy anti-CD20 monoclonal antibody approved for multiple sclerosis (MS) treatment. This nationwide real-world study evaluated the effectiveness and safety of OCR in patients wi...
BACKGROUND: Ocrelizumab (OCR) is a high-efficacy anti-CD20 monoclonal antibody approved for multiple sclerosis (MS) treatment. This nationwide real-world study evaluated the effectiveness and safety of OCR in patients with relapsing-onset MS (ROMS) in Slovakia. METHODS: This multicenter retrospective study included 499 patients with ROMS treated between January 2019 and January 2024. Outcomes included annualized relapse rate (ARR), confirmed disability progression (6mCDP), MRI activity, NEDA-3, and safety parameters. RESULTS: During a mean follow-up of 2.4 years, ARR decreased from 1.1 to 0.04; 6mCDP occurred in 7.1% of patients, and NEDA-3 was achieved in 75.5%. OCR was well tolerated with infusion-related reactions (12.2%) and infections (<6%) as the most common adverse events. CONCLUSIONS: OCR demonstrated high effectiveness and a favorable safety profile in routine clinical practice, supporting early initiation of high-efficacy therapy in relapsing-onset MS.
Depression severity and discordance between fatigue patient-reported outcomes in people with multiple sclerosis.
Queisi MM, Tomatsu S, Jacobs Z … +19 more , Dada M, Wuppalapati SN, Posada F, Weller J, Wilken J, Hancock L, Penner I, Golan D, Morrow S, Bogaardt H, Barerra M, Feinstein A, Zarif M, Bumstead B, Buhse M, Covey TJ, Cipriani V, Attarian H, Gudesblatt M
Mult Scler Relat Disord · 2026 Jun · PMID 42001607 · Publisher ↗
OBJECTIVE: Fatigue and depression are common and disabling symptoms in people with Multiple Sclerosis (PwMS). This study aimed to examine the relationship between discordant fatigue measures and depression severity in Pw...
OBJECTIVE: Fatigue and depression are common and disabling symptoms in people with Multiple Sclerosis (PwMS). This study aimed to examine the relationship between discordant fatigue measures and depression severity in PwMS. METHODS: A retrospective analysis was conducted on 712 PwMS evaluated over 14 years at a comprehensive MS center. All participants completed the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI) as part of routine clinical care. Fatigue score concordance was defined as both FSS and MFIS being above or below the threshold; discordance was defined as one above and one below. Statistical analyses compared demographic, clinical, and depression-related variables between groups. RESULTS: Of the 712 patients (75.3% female; mean EDSS 2.8), 78.9% demonstrated concordant fatigue scores, while 21.1% showed discordance-most commonly with elevated MFIS and low FSS. The discordant group had significantly higher mean BDI scores (23.0 vs. 9.8; P < 0.0001) and elevated suicidality scores, despite similar clinical characteristics. CONCLUSIONS: PwMS with discordant fatigue profiles, particularly those with higher MFIS than FSS scores, exhibit significantly greater depressive symptoms. Discordance between fatigue measures may serve as a clinical marker for underlying depression, supporting the need for comprehensive psychosocial evaluation in this subgroup.
Implementation of the first adolescence-to-adulthood transition programme for Multiple Sclerosis in Latin America.
Silva BA, Kenny JI, Jerez J … +2 more , Míguez J, González A
Mult Scler Relat Disord · 2026 Jun · PMID 42000451 · Publisher ↗
INTRODUCTION: Structured transition programmes have shown benefits in chronic paediatric conditions, but no transition models for multiple sclerosis (MS) have been documented in Latin America. OBJECTIVE: To evaluate the...
INTRODUCTION: Structured transition programmes have shown benefits in chronic paediatric conditions, but no transition models for multiple sclerosis (MS) have been documented in Latin America. OBJECTIVE: To evaluate the implementation of an adolescence-to-adulthood transition programme for patients with paediatric-onset MS (POMS) in Argentina. METHODS: A prospective study was conducted involving patients aged 18 to 24 years with MS onset before the age of 18, currently followed at the MS centre. The European Quality of Life - 5 Dimensions (EQ-5D), the MS International Quality of Life Questionnaire (MusiQoL), and the Transition Readiness Assessment Questionnaire 5 (TRAQ-5) were administered. RESULTS: Thirty-three patients were included, 36.4% (n = 12) enrolled in the hospital transition programme. Significant differences were observed in TRAQ-5 and MusiQoL scores between those who had and had not participated in the transition programme (p < 0.0001 and p = 0.0002), with a positive correlation between both scales (p < 0.0001). TRAQ-5 scores increased significantly at the end of the transition period (p = 0.0005). In multiple linear regression, participation in the transition programme was significantly associated with higher MusiQoL scores (adjusted R² = 0.331). CONCLUSION: Transition programmes improve quality of life, autonomy, and self-management in young adults with MS.
Collaborative Latin American Imaging Network In Neuroimmunology Research (BRAIMS): Rationale, Structure, Challenges, and Future Directions.
Carnero Contentti E, Alonso R, Boldrini V … +17 more , Cárcamo C, Casas M, Ciampi E, Damanesco A, Dos Santos Silva J, Rimkus CM, Marrodan M, Navas C, Patrucco L, Pitombeira M, Ramari C, Sato HK, Soler B, Treviño Frenk I, Wagner M, Ontaneda D, Becker J
Mult Scler Relat Disord · 2026 Jun · PMID 42000450 · Publisher ↗
Magnetic resonance imaging (MRI) plays a central role in the diagnosis, differential diagnosis, and monitoring of neuroimmunological disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (N...
Magnetic resonance imaging (MRI) plays a central role in the diagnosis, differential diagnosis, and monitoring of neuroimmunological disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, in Latin America (LATAM), variability in healthcare systems, imaging infrastructure, technical protocols, and subspecialized expertise limits the implementation of standardized MRI-based approaches and contributes to heterogeneity in diagnostic pathways and clinical decision-making. In this context, the Collaborative Latin American Imaging Network in Neuroimmunology Research (BRAIMS) was established as a regional initiative to strengthen MRI research and clinical practice in neuroimmunological diseases. BRAIMS emerged from a collaborative effort among neuroimmunologists, neuroradiologists, and researchers across multiple LATAM countries, with the aim of promoting methodological alignment, facilitating multicenter research, and generating region-specific real-world evidence. The network is structured to integrate core and collaborating centers under a coordinated governance model, enabling the development of shared research agendas and collaborative projects. Initial priorities include mapping MRI availability and practices across the region, standardizing acquisition protocols and reporting frameworks, identifying imaging-related sources of diagnostic variability, and developing consensus-based recommendations adapted to resource-variable settings. Despite sustained growth in neuroimmunology expertise in LATAM, important challenges persist, including unequal access to MRI technology, limited availability of advanced imaging techniques, variability in interpretation, and diagnostic complexity in populations with diverse clinical and epidemiological characteristics. By fostering regional collaboration and strengthening integration with international initiatives, BRAIMS aims to generate context-specific evidence, improve diagnostic accuracy, and enhance research capacity. This initiative represents a shift toward the production of regionally driven data, with the potential to contribute meaningfully to global neuroimmunology research and reduce disparities in access to high-quality neuroimaging.
Analytical and cross-sectional clinical validity of a smartphone-based U-Turn Test in multiple sclerosis.
Płonka M, Klimas R, Stanev D … +12 more , Angelini L, Napiórkowski N, González Chan G, Bunn L, Glazier PS, Hosking R, Freeman J, Hobart J, Zanon M, Marsden J, Craveiro L, Rinderknecht MD
Mult Scler Relat Disord · 2026 Jun · PMID 41996844 · Publisher ↗
BACKGROUND: Gait and balance impairment can profoundly impact people with multiple sclerosis (PwMS). OBJECTIVES: To evaluate the analytical and clinical validity of the U-Turn Test (UTT), a smartphone-based assessment of...
BACKGROUND: Gait and balance impairment can profoundly impact people with multiple sclerosis (PwMS). OBJECTIVES: To evaluate the analytical and clinical validity of the U-Turn Test (UTT), a smartphone-based assessment of dynamic balance in PwMS. METHODS: The GaitLab study (ISRCTN15993728) enrolled adult PwMS (EDSS 0.0 - 6.5). PwMS performed the UTT in a gait laboratory (supervised) using six smartphones at different wear locations and daily during a two-week remote period (unsupervised) using one smartphone (belt front). Median turn speed was computed per UTT. In the supervised setting, turn detection accuracy of smartphones was compared to motion capture (mocap) via F1 scores. Agreement between smartphone- and mocap-derived turn speed was assessed by Bland-Altman and ICC(3,1). In the unsupervised setting, test-retest reliability (ICC[2,1]) and correlations with Timed 25-Foot Walk (T25FW), EDSS, Ambulation score, 12-item Multiple Sclerosis Walking Scale (MSWS-12), and Activities-specific Balance Confidence scale (ABC) were evaluated. RESULTS: Ninety-six PwMS were included. Turn speed was comparable across supervised (1.44 rad/s) and unsupervised settings (1.47 rad/s). In the supervised setting, turn detection was highly accurate (F1 > 95% across wear locations). Turn speed agreement with mocap was high (ICC[3,1]: 0.87 - 0.92), with minimal bias (-0.04 to 0.11 rad/s). Unsupervised test-retest reliability (ICC[2,1]) was > 0.90 when aggregating ≥ 2 tests. Turn speed correlated with T25FW (rho = -0.79), EDSS (rho = -0.75), Ambulation score (rho = -0.73), MSWS-12 (rho = -0.65), and ABC (rho = -0.61). CONCLUSION: The UTT accurately and reproducibly measures turn speed across wear locations and settings, providing complementary dynamic balance insights to clinical measures and showing potential for use in multiple sclerosis trials.
Alliance for research in hispanic multiple sclerosis registry as a facilitator to clinical research participation.
Orlando C, Narasimhan S, Martinez A … +9 more , Mata F, Reasbeck S, Manrique CP, Cardenas-Iniguez C, Vicente I, Chinea A, McCauley JL, Islam T, Amezcua L
Mult Scler Relat Disord · 2026 Jun · PMID 41996843 · Publisher ↗
BACKGROUND: Patient registries can facilitate recruitment of underrepresented groups to research studies. The Alliance for Research in Hispanic MS (ARHMS) registry was established to advance knowledge of multiple scleros...
BACKGROUND: Patient registries can facilitate recruitment of underrepresented groups to research studies. The Alliance for Research in Hispanic MS (ARHMS) registry was established to advance knowledge of multiple sclerosis (MS) in people of Hispanic background. OBJECTIVE: To evaluate the ARHMS registry as a recruitment platform and identify barriers to research participation. METHODS: ARHMS enrollees were randomly sampled and contacted for recruitment to an access to care study (AcT-MS). Demographic (site, age, sex, language, place of birth) and clinical (disease duration) data were collected from the ARHMS database. Number and outcomes of contact attempts and reasons given for declining to participate were recorded. Contacted and not contacted groups were compared. Multivariable logistic regression assessed factors associated with participation in AcT-MS. RESULTS: We attempted to contact 809 enrollees. Most were female (73.6%) with mean±SD age 48.4 ± 13.5 years and disease duration 16.5 ± 9.8 years. We successfully contacted 516 (63.8%) after a median of 2 (range 1-4) attempts. Primarily Spanish-speaking enrollees were less likely to be contacted than primary English-speakers (55.1% vs. 72.0%, p < 0.001). 500 of 516 (96.9%) contacted enrollees participated in AcT-MS, with time constraints reported by 9 of 16 who declined. In multivariable analysis, Spanish primary language [0.46 (0.28-0.75); p = 0.002] and greater years since ARHMS enrollment [0.82(0.76-0.89); p < 0.001] were associated with lower odds of participation. CONCLUSIONS: These results suggest that recent engagement in the ARHMS registry facilitates ongoing research participation. Further research should focus on building retention strategies and culturally-tailored approaches to sustain engagement in Hispanic populations.
Increased PET C-PBR28 binding in multiple sclerosis normal-appearing white matter correlates with MRI measures of myelin loss.
Vavasour IM, Vafai N, Beauchemin P … +6 more , Shahinfard E, Laule C, Traboulsee A, Sossi V, Kolind SH, Carruthers RL
Mult Scler Relat Disord · 2026 Jun · PMID 41990479 · Publisher ↗
INTRODUCTION: The Positron Emission Tomography (PET) tracer C-PBR28 binds to the Translocator Protein (TSPO), a marker of activated microglia. Advanced Magnetic Resonance (MR) techniques are sensitive to different tissue...
INTRODUCTION: The Positron Emission Tomography (PET) tracer C-PBR28 binds to the Translocator Protein (TSPO), a marker of activated microglia. Advanced Magnetic Resonance (MR) techniques are sensitive to different tissue properties such as myelin (myelin water fraction, MWF; magnetisation transfer ratio, MTR; radial diffusivity, RD; choline, tCho), axons (axial diffusivity, AD; n-acetylaspartate, tNAA) and gliosis (myo-inositol, mI). OBJECTIVE: To compare C-PBR28 binding across MS subtypes and investigate the correlation between C-PBR28 binding and advanced MR measures in normal-appearing white matter (NAWM) and lesions. METHODS: Twelve people living with MS (7 relapsing-remitting MS (RRMS) and 5 progressive MS (PMS)) and 6 healthy controls (HC) were scanned with PET and MRI. A 70-minute C-PBR28 PET session was used to determine the non-displaceable binding potential (BP). Advanced 3T MR included myelin water imaging, diffusion tensor imaging and spectroscopy. Mean measurements were extracted from lesion and NAWM masks. RESULTS: Within NAWM, C-PBR28 binding was different between groups (BP HC=0.70, RRMS=0.72, PMS=0.79; p = 0.03) and lesions exhibited lower BP (NAWM=0.75, lesion=0.63; p = 0.0002). Lesions also had lower MWF (NAWM=0.13, lesion=0.08) and MTR (NAWM=41.5, lesion=33.5), and higher AD (NAWM=1.05, lesion=1.41) and RD (NAWM=0.50, lesion=0.83) than NAWM (all p < 0.0001). In NAWM, correlations were found between PBR-BP and MWF (R=-0.71, p = 0.001) and MTR (R=-0.68, p = 0.003). CONCLUSIONS: Increased inflammation and gliosis indicated by elevated C-PBR28 binding in NAWM are associated with demyelination (decreased MWF and MTR), especially in PMS. The ability to measure and monitor diffuse inflammation could help evaluate therapies designed to target whole brain immune activity and more specifically microglia.
Eccentric exercise training in multiple sclerosis management -a scoping review.
Vandenbroeck B, Slomian J, Cassol H … +3 more , Kaux JF, Schleich F, Hody S
Mult Scler Relat Disord · 2026 Jun · PMID 41990478 · Publisher ↗
The movement that occurs when a muscle exerts tension while lengthening is called eccentric muscle action. This type of contraction has been the focus of numerous studies in recent years, enhancing our understanding of t...
The movement that occurs when a muscle exerts tension while lengthening is called eccentric muscle action. This type of contraction has been the focus of numerous studies in recent years, enhancing our understanding of the mechanisms that underpin its production and its effects in rehabilitation when compared with traditional concentric training. The capacity to generate high forces with minimal metabolic expenditure, coupled with the neurological attributes associated with its production, underscores its validity as a training modality. However, few studies have focused on its use in neurological rehabilitation, particularly in the context of multiple sclerosis. This scoping review summarizes 10 experimental studies that have evaluated the effects of eccentric training in the rehabilitation of multiple sclerosis. Taken together, the findings suggest that this training modality is effective in terms of strength gains and functional improvements, but also on reducing fatigue and fatigability, and leading to adaptations of neurological activity. Nevertheless, the number of studies is limited, and there remains a paucity of consensus regarding the relative effectiveness of eccentric training in comparison with concentric training. Further experimental studies involving large cohorts and standardized protocols will provide a better understanding of the benefits and mechanisms underlying eccentric training in multiple sclerosis.
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