BackgroundThe Patient-Determined Disease Steps (PDDS) and Neuro-QoL Lower Extremity Function—Short Form (Neuro-QoL LEF-SF) are patient-reported outcome measures used to monitor mobility symptoms in multiple sclerosis (MS).ObjectiveTo develop and validate a crosswalk between the PDDS and Neuro-QoL LEF-SF.MethodsUsing equipercentile equating, we created a crosswalk from a training sample of 619 MS patients (mean PDDS = 2.4 ± 2.3; mean Neuro-QoL LEF-SF = 33.0 ± 8.3). Validation was performed in a separate sample of 147 MS patients (mean PDDS = 0.6 ± 1.2; mean Neuro-QoL LEF-SF = 38.9 ± 2.8). Agreement between original and converted scores was evaluated using paired t-tests and concordance correlation coefficients.ResultsPDDS and Neuro-QoL LEF-SF scores were strongly correlated in both training (r = −0.89) and validity (r = −0.76) samples. No significant differences in change scores were observed. Concordance coefficients of original and converted scores supported good to very good agreement.ConclusionWe developed a crosswalk for the conversion of scores between the PDDS and the Neuro-QoL LEF-SF for patients with MS. Evidence for the preliminary validity of this crosswalk was demonstrated with both the initial training sample and a separate validity sample. This crosswalk facilitates score comparisons and data harmonization across studies and clinical registries using either measure.

In multiple sclerosis (MS), delays in initiation of disease-modifying therapy (DMT) are associated with worse clinical outcomes. This single-center retrospective chart review study included treatment-naive and previously treated people with MS (PwMS) initiated on DMT between 01 September 2021 and 01 September 2023. A generalized linear model was utilized to evaluate associations between start-up times (initial treatment decision to completion of first dose) and distance to the clinic, utilization of the center's infusion center and specialty pharmacy, insurance and educational status, route of administration, race/ethnicity, and household income. A total of 116 PwMS were included (median age 41 [15-74] years; 87.9% female). Increased geographic distance from the MS center correlated with longer start-up times (>100 km: 76.5 [0-393] days vs. ≤100 km: 53.5 [2-524] days); p = 0.04). People with MS with private insurers had longer start-up times (66 [0-524] vs. 50.5 [0-201] days; p = 0.016). The utilization of outside infusion centers and specialty pharmacies delayed initiation (82.5 [0-524] vs. 39.5 [0-372] days; p = 0.024). This small retrospective study demonstrates an association between longer start-up times and greater geographic distance, private insurance status, and use of outside infusion centers and specialty pharmacies.

To evaluate the feasibility and potential efficacy of percutaneous spinal stimulation (epidural stimulation, ES) combined with task-specific training to reduce spasticity and improve gait and balance in individuals with progressive multiple sclerosis (MS). Two men with progressive MS (EDSS 6.5) underwent ES lead implantation targeting the lower spinal cord, followed by one month of rehabilitation involving 12 ES-assisted training sessions. Assessments included instrumented gait analysis, Modified Ashworth Scale (MAS), pendulum test, and static balance testing performed at baseline, and at end of the study with ES-Off and ES-On conditions. Participant 1, with spastic hemiparetic gait, demonstrated improved lower extremity joint kinematics and muscle activation during gait, reduced knee extensor spasticity, and enhanced functional movement patterns with ES-On. Participant 2, with significant paraparesis and minimal spasticity, showed limited gait changes but experienced marked improvements in static balance, particularly under eyes-closed conditions. No adverse events were reported. This pilot study demonstrates the feasibility and tolerability of ES paired with task-specific training in progressive MS. Participant-specific responses were observed, including improvements in gait kinematics, neuromuscular activation, spasticity, or balance; however, spatiotemporal gait parameters did not improve. These preliminary findings highlight response heterogeneity and the need for individualized ES parameter tuning. Trial registry name and URL: https://clinicaltrials.gov/study/NCT06019611.

BackgroundEarly life stress (ELS) has been implicated in the risk of developing autoimmune disorders including multiple sclerosis (MS), but less is known about its relationship to the clinical course of MS.ObjectiveInvestigate the relationship between ELS and MS patient-reported outcomes (PRO)MethodsIn a single-center, cross-sectional study, persons with MS completed a composite of surveys assessing ELS and PRO including the adverse childhood experiences (ACE) survey, the Childhood Trauma Questionnaire, MS Performance Scales, MS Impact Scale (MSIS-29) and MS Quality of Life (MSQOL-54). Multiple linear regression models were used to assess the associations between ELS and outcomes while adjusting for potential confounding variables.ResultsA total of 133 persons with MS completed the study. ELS was significantly associated with worse outcomes on the MSQOL-54. Persons with MS with ACE score ≥ 4 were 25.6 points lower (95% CI −15.7 to −35.6) on the Mental Health Composite and 24.6 points lower (95% CI −14.4 to −34.8) on the Physical Health Composite scores of the MSQOL-54. ELS was also associated with worse outcomes on the MS Performance Scale and the MSIS-29.ConclusionIn persons with MS, a history of ELS is associated with significantly worse MS symptom burden and quality of life.

IntroductionMultiple sclerosis (MS) is a central nervous system disorder and is frequently associated with fatigue. The Fatigue Scale for Motor and Cognitive Functions (FSMC) is an instrument to assess both motor and cognitive dimensions of fatigue in MS.MethodsThe study included 60 MS patients who completed the Persian version of the Modified Fatigue Impact Scale (MFIS) and a translated version of FSMC questionnaire. The FSMC was translated using standardized forward–backward translation, expert review, and patient feedback to ensure linguistic and conceptual validity. To evaluate test–retest reliability, participants completed the translated version of FSMC again after two weeks. Content validity was examined by a panel of eight experts.ResultsSixty individuals with a mean age of 36.36 ± 9.7 years and an Expanded Disability Status Scale score of 3.00 ± 2.0 were enrolled in this study. Fifty-one (85%) of the participants were female. The Persian FSMC demonstrated strong content validity (Content Validity Index: 0.875–1.00; content validity ratio: 0.75–1.00). Internal consistency was excellent (Cronbach's alpha = 0.964). Test–retest reliability was strong for average scores (intraclass correlation coefficient (intraclass correlation coefficient (ICC) = 0.979), though fair to good for single measures (ICC = 0.540). Convergent validity was supported by strong correlations with MFIS scores (FSMC-total: r = 0.88; motor: r = 0.87; cognitive: r = 0.85; all p < .001). No floor/ceiling effects were observed.ConclusionsThe Persian version of the FSMC is a valid and reliable instrument for assessing fatigue in Iranian patients with MS. With strong psychometric properties, it is well-suited for clinical and research use in Persian-speaking populations.

The deep cervical lymph nodes (dCLNs) are sites of immune presentation and B-cell maturation from the brain, and potentially involved in mechanisms of neuroinflammation. We hypothesized a reduction in dCLN volume following B-cell depletion therapy. In a retrospective cohort, we segmented bilateral dCLN from T2-FLAIR MRI at “prebaseline,” “baseline,” and “post-B-cell depletion” timepoints. Using a multivariable mixed-effect regression model, we find no changes in dCLN volumes between prebaseline and baseline timepoints (p > 0.05), but a significant decrease of 158 mm3 following ocrelizumab infusion (t = −3.3, p = 0.005). Baseline use of a disease-modifying therapy was also significantly associated with a smaller dCLN volume and attenuated the effects of B-cell depletion. These results are congruent with therapeutic mechanisms, although other alternative explanations for reductions in dCLN volumes cannot be ruled out based on this data. Deep CLN represent potential imaging biomarkers of pharmacological or clinical utility and warrant further investigation.

Epilepsy is two to three times more common in patients with multiple sclerosis (pwMS) compared to the general population. Patients with MS and epilepsy without other identifiable causes (MS + E) show greater cortical damage than those without epilepsy (MS-E). However, it's unclear whether MS + E patients exhibit distinct cognitive and neuropsychological features requiring specific management. In a cohort of pwMS from three MS centers, MS + E patients were identified and data on MS clinical features, epilepsy history, and treatments were collected. A matched group of MS-E patients was included. Assessments included cognitive and neuropsychiatric tests. Cognitive impairment (CI) was defined as scoring ≥1.5 standard deviations below normative values in ≥1 cognitive domain. CI was more prevalent in MS + E (n = 33) patients than in MS-E (n = 33). MS + E patients had lower processing speed (p < 0.01) and visuospatial memory (p = 0.03). MS + E was independently associated with CI (odds ratio 3.6, 95% confidence interval 1.21-12). Somatization, phobia, anxiety, and depression were the most affected neuropsychological domains in MS + E, with global psychological distress negatively correlating with processing speed (rho -0.36, p = 0.048). MS + E is associated with higher CI, particularly in processing speed and visuospatial memory, alongside psychological distress, highlighting the need for targeted multidisciplinary care to improve outcomes and quality of life.

Persistence to B cell depleting therapies (BCDT) like ocrelizumab and rituximab may be higher compared with other disease-modifying therapies (DMT) in multiple sclerosis (MS). Clinical trials directly comparing these treatments are lacking. To compare the risk of treatment discontinuation, relapse, and confirmed disability worsening in patients starting BCDT vs other DMT within real-world settings. In a longitudinal cohort study, patients with relapsing MS starting BCDT (ocrelizumab/rituximab, n = 269) after enrolment into the Swiss MS Cohort (SMSC) were evaluated for treatment discontinuation, occurrence of relapses, and disability worsening in comparison with platform (n = 57) and oral (n = 454) DMT, or natalizumab (n = 73) using Cox regression with double robust adjustment for baseline covariates. Patients starting BCDT were less likely to discontinue treatment than all other DMT combined (HR = 0.26, 95% CI = 0.18-0.36, p < .01), oral DMT (HR = 0.28, 95% CI = 0.20-0.39, p < .01) and natalizumab (HR = 0.35, 95% CI = 0.21-0.58, p < .01). BCDT were associated with lower risk of relapses as compared to oral DMT HR = 0.59, 95% CI = 0.39-0.88, p < .01), but not to natalizumab (HR = 0.90, 95% CI = 0.45-1.82, p = .778). Disability worsening was not significantly different between treatment groups. We provide real-world evidence for patients being more persistent to BCDT than to other treatments, and better clinical outcomes may partly explain this.

To recover normal functions, remyelination in multiple sclerosis is crucial. Although endogenous remyelination occurs, it is often insufficient, and finding molecules promoting repair of demyelinated lesions is needed. To compare the remyelination potential of evobrutinib, an inhibitor of Bruton's tyrosine kinase and clemastine, an antagonist of M1 muscarinic acetylcholine receptor. Remyelination was investigated in lysolecithin demyelinated organotypic mouse cerebellar slices and a transgenic Xenopus model of inducible-demyelination. Evobrutinib (100 nM) and clemastine (200 nM) potentiated remyelination of mouse cerebellar slices by a factor of 2.9 and 1.76, respectively. In conditionally demyelinated Xenopus, evobrutinib and clemastine increased remyelination by a factor of 1.61 and 1.92, respectively. Evobrutinib targets Bruton's tyrosine kinase expressed by microglia, and we showed that the increase in number of myeloid cells following demyelination is due to an extravasation from nearby vessels of macrophages migrating toward the optic nerve. In contrast, clemastine is expected to antagonize muscarinic receptor 1 expressing cells of the oligodendroglial lineage. We investigated a possible synergistic effect on remyelination by adding simultaneously both molecules. In both experimental models tested no significative improvement on remyelination of co-treatment with evobrutinib plus clemastine was observed. While evobrutinib increased 1.59 fold the number of microglia/macrophages, in the presence of clemastine the number of innate immune cells was decreased by 0.39 fold, therefore counteracting the beneficial effect of microglia/macrophages on remyelination.

This scoping review aimed to identify existing information and gaps in knowledge regarding the diversity characteristics of the multiple sclerosis (MS) population in Canada. We searched MEDLINE, EMBASE, Cumulated Index in Nursing and Allied Health Literature (CINAHL), SCOPUS and ProQuest's global dataset of theses and dissertations from 2010 to January 12, 2024. Data sources were case reports/series, cohort studies, case-control studies, analytical cross-sectional studies, randomized clinical trials, qualitative, mixed methods, participatory studies and systematic reviews conducted in Canada, published in English or French, that included participants with clinically isolated syndrome or MS. Sample characteristics were extracted applying Cochrane's PROGRESS-Plus framework. We included 259 studies, most often studying disease-modifying therapy (24.3%) and access to care (20.9%). Among primary data collection studies 40% used one recruitment strategy, usually MS Clinics and MS Canada. Age (92.7%) and sex (86.9%) were reported most often, ≤10% of studies reported race or ethnicity; religion, sexual orientation and language were not reported. We lack an understanding of characteristics of people living with MS in Canada relevant to health equity. Existing research has been insufficiently inclusive. Better reporting of diversity characteristics is needed, along with specific efforts to recruit and retain more diverse samples.