Multiple Sclerosis Journal最新文献

Climate change poses significant challenges for people with multiple sclerosis (PwMS), exacerbating symptoms such as heat sensitivity. Increasing levels of air pollution contribute to neuroinflammation and has been associated with symptom flares, and mobility impairments complicate resource access for PwMS during climate-related weather emergencies. This paper explores the broad implications of climate change on multiple sclerosis (MS) and offers strategies for clinicians to address these emerging challenges, as understanding the broad impacts of climate change on MS is crucial to provide effective care in a changing world.

Background: The Neurostatus-Expanded Disability Status Scale (EDSS) is the most frequently used measure of disability in multiple sclerosis (MS) trials. However, EDSS scores ⩾4.5 are mainly based on ambulation and may fail to capture relevant disability patterns in other functional domains.

Objective: The objective was to determine how assessments categorized with the same EDSS score may reflect distinct disability patterns.

Methods: We analysed 13,103 assessments from 1636 people with secondary progressive MS, from the EXPAND trial. The data set is composed of Functional System scores (FSS) and their corresponding subscores, Ambulation scores and EDSS scores. We performed a descriptive analysis to define the relevant Functional Systems (FS). The subscores were then binarized based on the Neurostatus definition and grouped by respective EDSS scores. Finally, we applied two consecutive machine learning algorithms, to cluster the data. New subscore patterns were then created by aggregating clusters based on their dominant features.

Results: The clustering algorithm yielded numerous clusters, grouping assessments with similar patterns. In patients with EDSS ⩾4.0, our approach allowed differentiation into four subscore patterns within the same EDSS score.

Conclusion: Applying Artificial Intelligence (AI) to large data sets of high-quality clinical assessments allows for distinguishing among different subscore patterns within identical EDSS scores.

Background: Treatment with cladribine tablets (CladT) in relapsing-remitting multiple sclerosis (RRMS) reduced global grey matter (GM) atrophy, but the effects on regional GM are unknown.

Objectives: This study aimed to investigate the effect of CladT compared with placebo on magnetic resonance imaging (MRI)-derived patterns of GM atrophy.

Methods: We used MRI and clinical data from the CLARITY study, including 393 people with RRMS (CladT (3.5 mg/kg), n = 200 or placebo, n = 193) at baseline, 24, 48 and 96 weeks after treatment initiation. SynthSeg-derived volume changes and GM atrophy patterns derived from source-based morphometry were analysed for group differences over time and associations with disability using mixed-effect models.

Results: Deep GM (β = -0.03, p < 0.01), thalamus (β = -0.04, p < 0.01) and the brainstem-thalamus pattern (β = -0.03, p < 0.05) showed higher reduction in the placebo compared with treated group. These regions showed no effect during a predefined pseudo-atrophy period, where global volume loss was worse in the treatment group. Between W24 and W96, Expanded Disability Status Scale (EDSS) scores were associated with lower deep GM volume (β = -0.16, p = 0.001), thalamic volume (β = -0.16, p < 0.001), and the brainstem-thalamus pattern (β = -0.12, p < 0.05).

Conclusion: CladT are associated with clinically relevant and slower neurodegeneration in RRMS. Strongest effects were seen in deep GM, thalamus, and brainstem, underlining the importance of regional MRI measures for assessing treatment effects.

Background: Multiple sclerosis (MS) often causes impairment in working memory (WM), information processing speed (IPS), and verbal memory (VM). These deficits are linked to disrupted neural oscillatory activity. Transcranial alternating current stimulation (tACS), which modulates cortical oscillations, may hold promise for treating cognitive impairment in MS.

Objectives: To evaluate online and offline effects of gamma (γ)-tACS on WM, IPS, and VM while assessing changes in brain rhythms using electroencephalography (EEG).

Methods: Thirty-six MS patients with single-domain impairment in WM (12), IPS (13), or VM (11) underwent γ-tACS and sham-tACS over the left dorsolateral prefrontal cortex (DLPFC) (WM, IPS) or precuneus (VM). Cognitive performance was assessed pre-tACS (T0), during (T1), and post-tACS (T2) using the Digit Span Backward (DSBW) for WM, Symbol Digit Modalities Test (SDMT) for IPS, and Rey Auditory Verbal Learning Test (RAVLT) for VM. EEG was recorded at T0 and T2 to analyze local power spectral density and local-to-global connectivity.

Results: DSBW, SDMT, and RAVLT scores transiently improved during γ-tACS and not during sham. IPS-impaired patients showed a reduction in spectral power across all frequency bands, at the stimulation site, post-DLPFC γ-tACS.

Conclusion: γ-tACS briefly improves WM, IPS, and VM in MS patients, warranting further trials of this non-invasive intervention.

Background: Cryptogenic organizing pneumonia (COP) is an interstitial lung disease, with causes including anti-CD20 antibodies. Ocrelizumab is a humanized monoclonal antibody against CD20 approved for use in relapsing-remitting or primary progressive multiple sclerosis (MS), with no conclusive data regarding pulmonary toxicity.

Cases: We describe two cases of COP associated with ocrelizumab use in multiple sclerosis patients.

Conclusions: We suggest considering COP whenever respiratory symptoms arise in MS patients receiving ocrelizumab therapy. COP diagnosis requires clinical and radiological exclusion of alternative diagnoses such as opportunistic infections, autoimmunity, drugs, and neoplasms. Appropriate steroid therapy has an excellent clinical response rate.

Background: Measuring brain volume changes over time is an objective and dependable surrogate marker for the pathological processes that damage the brain in relapsing-remitting multiple sclerosis (RRMS). These measures are particularly valuable for monitoring the long-term impact of immunomodulatory treatments such as cladribine.

Objectives: To evaluate the long-term impact of oral cladribine treatment on brain volume loss in patients with RRMS.

Methods: This real-world study processed magnetic resonance imaging (MRI) scans using FreeSurfer's recon-all-clinical pipeline leveraging SynthSeg for brain segmentation. Piecewise linear regression was used to analyze brain atrophy changes over 4.5 years before and after cladribine treatment and estimate the time breakpoint of atrophy rate change.

Results: A total of 448 MRI exams from 102 RRMS patients were analyzed. Before the initiation of cladribine treatment, brain atrophy rates were significantly steep with an α1 slope between -1.27 and -0.62 for the Thalamus, DGM, Subcortical GM, Cerebral WM, and BP. Over 2 years after treatment, breakpoints marked a shift in atrophy rates, with post-breakpoint slopes (α2) becoming non-significant, reflecting stabilization of brain atrophy.

Conclusions: Cladribine treatment in highly active RRMS patients protects the brain from atrophy, with stabilization occurring over 2 years after initiation. The extended observation period highlights its sustained benefits compared with shorter clinical trials.

Eculizumab proved a strong anti-inflammatory effect in neuromyelitis optica spectrum disorders (NMOSD), rare autoimmune diseases affecting the central nervous system in which aquaporin 4-immunoglobulin G (AQP4-IgG) is the main pathogenic antibody. Pregnancy in NMOSD patients is considered at high-risk for neurological and gynecological outcomes, requiring a careful consideration about treatment maintenance. In this case report, we describe a successful pregnancy, resulting in the birth of a healthy child, in a young woman with AQP4-IgG-seropositive NMOSD who was maintained on eculizumab during all pregnancy.

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.