Multiple Sclerosis Journal最新文献

Background: Predicting treatment response and disease progression in multiple sclerosis (MS) is challenging. Treatment Response Scoring Systems (TRSS) are potentially useful, but their utility in patients receiving high-efficacy therapies and very high-efficacy therapies (HET/vHET) remains unclear.

Objective: This study aimed to evaluate the performance of TRSS in patients treated with HET/vHET.

Methods: We retrospectively studied MS patients treated with HET/vHET in an MS specialized centre. TRSS, including the Rio Score, modified Rio Score and MAGNIMS score, were applied to assess response to treatment. We evaluated the predictive value of the TRSS on disease activity and disability progression.

Results: TRSS effectively predicted disease activity and progression of disability in patients treated with HET/vHET. Patients with high TRSS scores at 12 months post-HET/vHET initiation had a significantly increased risk of relapses, new lesions on magnetic resonance imaging (MRI) scans and progression of disability at 4 years.

Discussion: Our findings highlight the importance of personalized treatment strategies in MS. TRSS are valuable tools for monitoring treatment response, guiding clinical decision-making and optimizing patient care.

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: Existing metrics of patient-reported cognitive difficulties in multiple sclerosis (MS) are lengthy, lack psychometric rigor, and/or fail to query prevalent expressive language deficits.

Objective: Develop a brief psychometrically robust metric of patient-reported cognitive deficits that includes language items; the Multiple Sclerosis Cognitive Scale (MSCS).

Method: Exploratory factor analysis (EFA) was conducted on 20 Perceived Deficits Questionnaire (PDQ) items plus five newly developed language questions in a large MS sample and matched respondents without neurologic disease. Independent confirmatory principal components analysis (PCA) assessed EFA factor structure. Reliability of the new scale and subscales, and relationships with objective cognitive impairment and cognitive change, were assessed.

Results: EFA in patients (n = 502) and controls (n = 350), item analyses, and confirmatory PCA in an independent sample (n = 361 patients; 150 controls) supported construction of an eight-item scale with four two-item subscales: Executive/Speed, Working Memory, Expressive Language, and Episodic Memory. Internal consistency and test-retest reliability were excellent for the total MSCS (α = 0.93, ICC = 0.95) and good for each subscale (α's:0.83-0.87; ICCs: 0.86-0.92). MSCS showed medium-size links to cross-sectional objective cognitive impairment (η² = .06) and cognitive change over time (η² = .07); the traditional PDQ did not (η²s = 0.01 and 0.02).

Conclusion: The brief MSCS is a psychometrically robust, reliable, and valid metric of patient-reported cognitive deficits in MS that holds promise for improving assessment of MS cognitive dysfunction.

Background: Previous studies have shown that people with multiple sclerosis (MS) had frequent healthcare visits up to 10 years before being diagnosed but with no information from magnetic resonance imaging (MRI) scans of the connection with the radiologically isolated syndrome (RIS).

Objective: To analyze healthcare use 3 years before the RIS diagnosis.

Methods: We examined healthcare usage before the first scan in RIS cases from 2010 to 2019. RIS subjects were identified from the French National MS observatory and compared to the general population (matched 10:1) and MS patients (matched 4:1).

Results: Among 482 RIS individuals, 223 (46.3%) were not linked to the healthcare resources database. The remaining RIS individuals (53.7%) had higher healthcare usage before their RIS diagnosis for issues related to neurology visits, headaches (odds ratio (OR): 3.34, confidence interval (CI): [2.00-5.57], p < 0.0001), and the use of anti-migraine drugs (OR: 2.61, CI: [1.37-4.99], p = 0.004) compared to MS.

Conclusion: Only about half of RIS patients had MS-selected healthcare resources, which allowed for data linkage. Those who did seek care before their RIS diagnosis were most commonly known for other neurological comorbidities. These findings do not support the idea of a systemic prodrome before RIS diagnosis.

Background: The understanding of disease pathophysiology is pivotal for tailored treatments. The spatial distribution of brain damage relies on the regional antigen expression and the local balance of susceptibility and protective elements.

Objective: As proof-of-concept, we investigated the spatial association between brain damage and gene expression in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD).

Methods: In this multicenter cross-sectional study, 90 AQP4 + NMOSD patients and 94 age-matched healthy controls underwent a brain magnetic resonance imaging (MRI). We used T2-hyperintense lesion probability maps and white/gray matter atrophy as proxies of inflammation and neurodegeneration. The association with the expression of 266 candidate genes was obtained with the Multimodal Environment for Neuroimaging and Genomic Analysis platform. A functional-enrichment analysis investigated overrepresented biological processes.

Results: In AQP4 + NMOSD, T2-hyperintense lesions were mainly periventricular; atrophy mostly involved the visual pathway. The expression of AQP4 and complement (C4a and C5) was associated with both inflammation and neurodegeneration. Complement activation and regulation/uptake of the insulin-like growth factor were the most relevant enriched pathways. Nonspecific pathways related to DNA synthesis and repair were associated with brain atrophy.

Conclusions: Quantitative MRI and gene expression atlas identified the key elements of AQP4 + NMOSD pathophysiology. This analysis could help in understanding the pathophysiology of antibody-mediated autoimmune disorders.

Live-attenuated vaccines provide robust immunity against diseases like tuberculosis, measles, mumps, rubella, polio, yellow fever, dengue, typhoid fever, and varicella, with just one or a few doses. However, concerns arise regarding potential pathogen reversion to virulence, which is particularly risky for immunocompromised individuals, contraindicating their administration in multiple sclerosis (MS) patients under modified disease treatments due to the possibility of triggering infections, or stimulating the immune system, precipitating new exacerbations. On the contrary, these vaccines offer enduring immunity that is crucial for protecting MS patients from endemic infectious diseases, leading to severe complications if contracted. These concerns underscore the complex balance between vaccination benefits and the risks of exacerbating MS in patients residing in regions with endemic diseases. This review explores the challenges and considerations associated with their use in MS patients, aiming to maximize benefits while minimizing risks.

Background: Memory decline is common in multiple sclerosis (MS), although pathophysiological mechanisms are not fully understood.

Objective: The objective was to investigate the relationship of changes in structural and functional neuroimaging markers to memory decline over 3-year follow-up.

Methods: Participants with MS underwent cognitive evaluation and structural, diffusion, and functional 3T magnetic resonance imaging (MRI) scans at baseline and 3-year follow-up. Changes in neuroimaging metrics from baseline to follow-up were compared between memory stable and memory decline groups. Our hypothesis that structural and functional connectivity changes mediate the association of atrophy to memory decline was tested.

Results: A total of 249 MS patients completed baseline visit; 169 (67.8%) returned at 3-year follow-up. Based on ⩾10% decline, memory decline was observed in 44.4% (n = 75). Those with memory decline showed marginally greater whole-brain volume loss over time compared with those with stable memory performance (p = 0.08). In those with memory decline, changes in white matter tract integrity were related to regional cortical thinning (p < 0.01). Exploratory mediation analysis revealed structural and functional connectivity to mediate the relationship of atrophy to verbal and visual memory decline.

Conclusion: Further work is needed to characterize complex interrelationships of atrophy and structural/functional connectivity changes to memory decline in MS.

Background: In the DISCOMS (DISCOntinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)) randomized clinical trial, we could not demonstrate that discontinuing MS DMTs in older, stable adults was not inferior to continuing DMTs. Relapses were rare in both groups, and most new disease activity was one to two new brain magnetic resonance imaging (MRI) lesions unassociated with clinical changes.

Objective/aims: Describe results of the DISCOMS extension study.

Methods: Among 10/19 of the original sites, we enrolled patients who completed DISCOMS; did not reach the primary endpoint during the original trial; and retained original randomized assignment. Participants completed one study visit and brain MRI at least 30 months after original enrollment in DISCOMS. Primary endpoint was time from entry into the primary study to relapse or new brain MRI activity.

Results: Mean (SD) total follow-up was 40 (11.7) months. There were no relapses, and new brain MRI lesions (1/30 continuer, 2/44 discontinuers) were uncommon during the extension. Time from primary trial entry to disease event was significantly shorter for subjects in the discontinue group (p = 0.043 from log-rank test).

Conclusions: From entry into DISCOMS extension study, time to new MS activity remained shorter in discontinuers, but relapses were absent and new brain MRI lesions were rare.