Multiple Sclerosis Journal最新文献

Background: While treatment with ocrelizumab has proven effective in preventing relapse-associated worsening (RAW) in relapsing multiple sclerosis (RMS), a significant number of patients experience progression independent of relapse activity (PIRA).

Objectives: To investigate the association between B-cell depletion status and the risk of disability accumulation in RMS patients receiving ocrelizumab treatment.

Methods: In this monocentric cohort study of 148 RMS patients (2017-2023), we categorized participants into three groups: no evidence of disease activity (NEDA), evidence of disease activity (EDA), and PIRA. B-cell counts were measured every 6-12 months, with suboptimal depletion defined as ⩾10 CD19+ B-cells/µL. Logistic regression and Cox proportional hazards models analyzed the relationship between B-cell depletion and disability progression.

Results: Of 148 patients, 70 (47%) achieved NEDA, 51 (34%) showed EDA, and 25 (17%) developed PIRA. NEDA patients demonstrated significantly lower B-cell counts compared to EDA (p < 0.01) and PIRA (p < 0.001) groups. Insufficient B-cell depletion was the strongest PIRA predictor (OR 3.73, 95% CI: 2.50-5.43, p < 0.001) and increased EDSS progression risk (HR 0.50, 95% CI: 0.26-0.97, p = 0.039).

Conclusions: PIRA occurs in the context of suboptimal B-cell depletion in RMS patients, highlighting the need for close monitoring and potential adjustment of infusion intervals.

Background: Monitoring of cognition in multiple sclerosis (MS) is critical. Traditional cognitive testing is resource intensive and insensitive to subtle changes. Digital tests could address this need; however, their long-term usability remains unexplored.

Objectives: To determine the long-term acceptability and feasibility of digital cognitive measures in MS.

Methods: Participants with relapsing or secondary progressive MS were prospectively enrolled. MSReactor, a web-based test evaluating processing speed, attention and working memory, was performed 6-monthly for up to 36 months. Patient acceptability, anxiety, depression and quality of life were collected concurrently. Correlations between test acceptability, psychosocial measures, physical disability and cognition were analysed using Spearman's correlation.

Results: This study included participants with complete data at 12 (n = 601), 24 (n = 280) and 36 (n = 317) months. Attrition after 12 months was low (3.5%). Acceptability of MSReactor was high, although interest and enjoyment decreased slightly. Minor correlations were observed between reduced acceptability and increased anxiety, depression and disability and lower quality of life.

Conclusion: Long-term cognitive monitoring was highly acceptable. We identified characteristics, such as increased anxiety, that were associated with reduced acceptability. Patients with these characteristics may benefit from support to maintain monitoring. These findings underscore the potential for integrating such tools into MS care.

The past 25 years have brought extraordinary advances in our understanding of MS pathogenesis and the subsequent development of effective therapies. Collaborative genetics efforts have uncovered the association of 236 common DNA variants with disease susceptibility and the first association with disease severity, paving the way to more effective therapies, particularly for progressive forms of the disease. In parallel, and in addition to established environmental disease triggers or modifiers, new collaborative work has revealed new associations with components of the gut microbiome. This research opened a new and exciting prospect for exploring the gut-brain axis, with the potential to also provide new pharmacologic targets and diet-based therapies. Finally, with the availability of massive amounts of information and unprecedented computer power, a new wave of artificial intelligence (AI)-based research is sprawling. These investigations will result in statistically powerful predictive models to identify individuals at risk even years before the disease is clinically apparent. Furthermore, using approaches like semantic representation and causal inference, some of these approaches will be explainable in biomedical terms, thus making them trusted and facilitating their implementation in the clinical setting. The common thread that characterizes all of these advances is multi-disciplinary collaboration among scientists in the form of formal consortia, working groups, or ad hoc partnerships. This may be the "secret sauce" of modern science and the best strategy to stop, restore, and end MS.

Background: Multiple sclerosis (MS) slowly expanding lesions (SELs) are defined on magnetic resonance imaging (MRI) as contiguous regions of pre-existing focal non-contrast-enhancing T2 lesions with constant and concentric local expansion on conventional T1-weighted and T2-weighted images. SELs are associated with an increased risk of disability progression.

Methods: Myelin-related changes detected using myelin water fraction (MWF) and magnetisation transfer ratio (MTR) in SELs and T2 lesions were measured over 192 weeks in participants with relapsing MS.

Results: In participants with SELs (SEL+), SELs (MWF: 0.12 ± 0.03, MTR: 33.1 ± 3.6 pu) showed reduced myelin measures at baseline compared to T2 lesions (MWF: 0.13 ± 0.02, MTR: 35.1 ± 2.4 pu). In participants without SELs (SEL-), T2 lesions had higher myelin measures (MWF: 0.15 ± 0.02, MTR: 36.2 ± 2.0 pu) compared to T2 lesions in SEL+. Over 4 years, only SELs showed decreases in MWF (-11.4%). The percentage of abnormal voxels within normal-appearing white matter was higher in SEL+ and increased over time (SEL+ MWF Week 0: 0.56%, Week 192: 0.98%; SEL- MWF Week 0: 0.13%, Week 192: 0.25%).

Conclusion: Our results indicate progressive focal and global demyelination in SEL+ participants and that the presence of SELs might be a biomarker for participants with ongoing diffuse or smouldering inflammation within the whole brain.

Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that, when untreated, can lead to significant disability in young adults. Despite the increase in the number of disease-modifying therapies (DMTs), many people living with MS in low-resource settings do not have access to treatment.

Objective: The primary aim was to develop recommendations on the minimum essential DMTs for MS that should be available in low-resource settings.

Methods: The Multiple Sclerosis International Federation established an independent, international panel including healthcare professionals and people with MS. This panel, in collaboration with the Cochrane MS Group and McMaster GRADE Centre, reviewed evidence for use of MS DMTs following standardized GRADE protocols including consideration of balance of benefits and harms; certainty of evidence; resources required and cost-effectiveness and values, equity, feasibility and availability in low-resource settings.

Results: For active and/or worsening forms of relapsing MS, the panel recommends use of ocrelizumab, cladribine, fingolimod, dimethyl fumarate, interferon beta and glatiramer acetate. For active and/or worsening forms of progressive MS, the panel recommends use of rituximab, ocrelizumab, glatiramer acetate, fingolimod and interferon beta.

Conclusions: Recommendations for the minimum essential DMTs for MS in low-resource settings were developed based on robust consideration of evidence and relevant context.

Background: Pain is a common symptom of multiple sclerosis (MS). The reliability of outcome measures for pain and the accuracy of screening tools are essential for treatment purposes.

Objectives: This study investigated the test-retest reliability of Neuropathic Pain Scale (NPS), Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory-Short Form (BPI-SF), Nordic Musculoskeletal Questionnaire (NMQ), Douleur Neuropathique 4 (DN4), and painDETECT, and the accuracy of DN4 and painDETECT.

Methods: 110 persons with MS were included (mean age: 45.35 ± 12.73; Expanded Disability Status Scale (EDSS): 3 (Interquartile range, IQR: 2.6)). The reliability (internal consistency, test-retest, measurement error) and accuracy (area under the curve (AUC), specificity, sensitivity, positive predictive value, and negative predictive value) were analyzed.

Results: All included pain assessment tools showed good test-retest reliability (Intraclass correlation coefficient, ICC, (95% confidence interval, CI): 0.85 (0.79-0.89)-0.89 (0.84-0.92)) and good-to-excellent internal consistency (Cronbach's α: 0.73-0.93). The test-retest reliability of NMQ was moderate to substantial (Cohen's κ = 0.54-0.87). The overall accuracy of DN4 compared to the neurologist's diagnosis was acceptable (AUC = 0.762), while that of painDETECT was poor (AUC = 0.682) and demonstrated inadequate predictive ability.

Conclusion: All pain outcome measures were reliable in patients with MS (pwMS). DN4 can be used to screen neuropathic pain in MS.Clinical trial registry name:Reliability and Validity of Outcome Measures for Pain in MS https://register.

Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S000CRMD&selectaction=Edit&uid=U0006NAA&ts=2&cx=-jzvd6m Registration number: NCT05742152.

Background: It is essential to exclude alternative diagnoses to diagnose multiple sclerosis (MS). However, detailed descriptions of alternative diagnoses in patients with suspected MS presenting with clinically isolated syndrome (CIS) are limited.

Objectives: To describe alternative diagnoses in patients presenting with CIS suggestive of MS.

Methods: We conducted a descriptive analysis of patients from the Barcelona CIS cohort including subjects under 50 years of age with a CIS suggestive of MS but later diagnosed with conditions other than MS. We collected clinical, biological, and radiological data, and described the alternative etiologies identified.

Results: Among 1468 patients in the Barcelona CIS cohort, 100 (6.8%) were diagnosed with an alternative condition. The most common neurological syndrome was optic neuritis (43.0%). Four patients (4.0%) had inflammatory-demyelinating lesions in at least two typical MS topographies on baseline magnetic resonance imaging (MRI), and 2 (2.0%) met the 2017 McDonald MS criteria. The most common etiologies were immune-mediated diseases (42.0%), especially MOGAD, followed by functional neurological disorders (15.0%) and vascular disease (10.0%).

Conclusion: The range of alternative diagnoses encountered during the MS diagnostic process highlights the need to rule out better explanations than MS. However, current MS diagnostic criteria effectively identify patients without MS in this context.

Background: Sacral neuromodulation (SNM) is commonly used in the treatment of overactive bladder, but few studies have evaluated its efficacy in patients with multiple sclerosis (MS).

Objectives: To assess the efficacy of SNM in the treatment of neurogenic overactive bladder (nOAB) in patients with MS.

Methods: All MS patients that underwent a two-stage SNM to treat nOAB between 2013 and 2023 in four university hospitals were considered eligible. The primary outcome was clinical efficacy, defined as the implantation of an implantable pulse generator (IPG). Secondary outcome included the Patient Global Impression of Improvement (PGI-I), the 3-day bladder diary parameters and the maintenance of efficacy within 5 years.

Results: A total of 38 patients were included. The IPG was implanted in 33 patients (87%). The median daily (9.0 to 7.0; p < 0.001) and nocturnal (2.5 to 1.0; p < 0.01) number of micturition/clean self-intermittent catheterization (CISC), the presence of urinary urgency (97% vs 58%; p < 0.01) and urinary incontinence (84% vs 25%, p < 0.001) significantly decreased at the end of the test phase. Efficacy was maintained at 5 years in 46% of cases.

Conclusions: In MS patients with nOAB, SNM exhibits clinical efficacy comparable to that observed in the non-neurological population.