Multiple Sclerosis Journal - Experimental, Translational and Clinical最新文献

We present real-world data on patients switching from anti-CD20s to fumarates for various motivations in this retrospective observational study of 43 patients from three multiple sclerosis centers. Recurrent infections on anti-CD20s were the most common reason for switching to fumarates. Patients experienced limited disease activity on fumarates (83.7% were free from relapse and new MRI lesions), suggesting effectiveness was maintained. Of the 16.3% with disease activity on fumarates, 57.1% also had disease activity on anti-CD20s. Tolerability was the main reason for discontinuing fumarates. Future studies will provide additional insight into how to effectively and safely transition from anti-CD20s to fumarates.

Introduction: Multiple 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.

Methods: The 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.

Results: Sixty 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.

Conclusions: The 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.

Background: In relapsing-remitting multiple sclerosis (RRMS), smouldering inflammation at the rims of chronic active lesions is increasingly recognised as a key driver of disease progression. Paramagnetic rim lesions (PRLs), detected using susceptibility-weighted imaging, have emerged as a potential biomarker of this chronic inflammatory activity. However, their clinical relevance and relationship to lesion-specific features such as size and age remain poorly understood.

Objective: To investigate the association between PRL presence and clinical/radiological measures of disease progression, and to explore how PRLs relate to lesion size and age.

Methods: A retrospective study of 60 RRMS patients with over 5 years of magnetic resonance imaging data was conducted using susceptibility-weighted angiography. Lesions larger than 100 mm³ were analysed.

Results: PRLs were present in 48% of patients and represented 13% of lesions. PRLs were significantly larger and more structurally damaged, with volume correlating with EDSS change and brain atrophy. All lesions formed within 5 years of imaging were PRLs. This finding was validated in two independent international cohorts. Moreover, the proportion of rim-positive lesions decreased as lesion age increased.

Conclusion: PRLs are closely linked to lesion age and early development, supporting their role as a dynamic biomarker of lesion activity in multiple sclerosis.

Background: Patients with neuromyelitis optica spectrum disorders (NMOSD) often experience significant functional limitation, high rates of disability, and cognitive impairment (CI). The objective of this study was evaluating the factors associated with CI in patients diagnosed with NMOSD in Mexico. Methods: The study was cross-sectional in design. We included 65 NMOSD patients (34 NMOSD with CI and 31 NMOSD without CI). We utilized the Brief International Cognitive Assessment for Multiple Sclerosis to identify CI in NMOSD patients. Logistic regression was applied to identify the factors associated with CI. Results: Factors associated with CI in the crude analysis were education level (⩽6 years of schooling; odds ratio (OR) 4.37, 95% confidence interval (CI) 1.41-13.52, p = 0.010), disease duration (⩾60 months; OR 8.22, 95% CI 2.68-25.20, p < 0.001), time from onset to diagnosis (⩾12 months; OR 3.70, 95% CI 1.21-11.31, p = 0.022), brain lesion (on magnetic resonance imaging before azathioprine or rituximab; OR 3.46, 95% CI 1.20-10.00, p = 0.022), and relapses by NMOSD diagnosis (⩾4; OR 4.48, 95% CI 1.57-12.76, p = 0.005). Factors associated with CI in the adjusted analyses were education (⩽6 years; OR 5.92, 95% CI 1.57-22.23, p = 0.008), disease duration (⩾60 months; OR 5.73, 95% CI 1.69-19.40, p = 0.005), and relapses by NMOSD diagnosis (⩾4; OR 5.79, 95% CI 1.70-19.72, p = 0.005). Conclusion: One of the biggest factors associated with CI was relapse by NMOSD, specifically those with lower education levels and those with longer disease duration.

Background: Progression independent of relapse activity (PIRA) may occur in patients with relapsing multiple sclerosis (MS) and is a major contributor to disability accumulation.

Objectives: We evaluated whether a panel of cerebrospinal fluid (CSF) biomarkers (neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), total-Tau (T-Tau), ubiquitin C-terminal hydrolase 1 (UCHL-1), and the phospho-Tau (P-Tau)181/T-Tau ratio) at diagnosis could discriminate patients who will develop PIRA in early disease phases.

Methods: CSF levels of NfL, GFAP, T-Tau, and UCHL-1 were measured with SIMOA, of P-Tau181, and the ratio P-Tau181/T-Tau with chemiluminescent immunoassay in 80 newly diagnosed MS patients who were followed up for three years with six-month Expanded Disability Status Scale (EDSS) assessments and yearly MRI scans.

Results: Nineteen participants developing PIRA exhibited elevated GFAP and UCHL-1 levels, and reduced P-Tau181/T-Tau ratio. These biomarkers remained significant predictors of the outcome after adjusting for confounders, particularly older age at onset and higher baseline EDSS. Additionally, we identified moderate positive correlations between NfL-GFAP, NfL-UCHL-1, and GFAP-UCHL-1 levels, and moderate negative correlations between P-Tau181/T-Tau ratio and NfL, GFAP, and UCHL-1 levels.

Conclusions: The elevation of GFAP and UCHL-1 likely reflects the role of astrocytic activation, while the reduction of the P-Tau181/T-Tau ratio may indicate disrupted Tau metabolism in individuals at risk of PIRA. Our findings suggest that combining these innovative biomarkers with clinical risk factors could improve early prognostic accuracy.

Background: In relapsing-remitting multiple sclerosis (RRMS), the assessment of clinical disease activity can be challenging.

Objectives: To determine the diagnostic potential of serum neurofilament light (sNfL) and glial fibrillary acidic protein (sGFAP) to distinguish a relapse from other causes of deterioration.

Methods: In this multicenter, prospective study, RRMS patients with new neurological symptoms in the last 14 days were followed for 12 weeks. A diagnosis was established by the treating physician or, when in doubt, a panel of experienced neurologists. Blood samples were taken at baseline and week 12.

Results: A total of 65 patients were included. At baseline, patients with a clear relapse had a significantly higher median sNfL (14.6 pg/mL) than those with a clear other cause (9.5 pg/mL, p = 0.004). Although not significant after correction for multiple testing, median sGFAP was also higher in relapse patients (73.0 vs 64.6 pg/mL, p = 0.036). An sNfL value below 6.0 pg/mL had a high sensitivity (67% at baseline (CI 22.3-95.7%) and 100% at follow-up (CI 54.1-100%)) to rule out a relapse.

Conclusions: Analysis of sNfL level can be useful as an add-on investigation to determine whether disease activity is present in patients with RRMS presenting with new symptoms.

Background: SPRINT-MS was a placebo-controlled phase 2 trial of ibudilast in secondary and primary progressive multiple sclerosis. The trial included multimodal imaging to assess brain tissue integrity. This contribution focuses on improved analysis methods of diffusion tensor imaging to refine its application in clinical trials.

Objective: Reassess diffusion tensor imaging from the SPRINT-MS trial.

Methods: Postprocessing incorporated corrections for bulk motion, eddy current distortion, outlier replacement, and intra-volume movement. The ICBM-DTI-81 white matter parcellation map was coregistered into native space. Six unilateral and 21 bilateral regions of interest were identified. Median radial diffusivity was the primary outcome measure for this analysis. A linear mixed-effects model was used to assess the interaction between time and treatment for the outcome measure with Holm correction for multiple comparisons.

Results: Radial diffusivity in the cingulum and cerebellar peduncles showed a significant difference in rate of change between treatment and placebo groups (2.7-7.4 × 10^-3 mm²/s per 24-week time period, p < 0.04). Radial diffusivity was unchanged (declined) in the treatment (placebo) groups, consistent with preservation (deterioration) of tissue integrity.

Conclusion: Our results suggest that the diffusion tensor imaging of the cingulum and cerebellar peduncles may be useful target outcome metrics in neuroprotective trials in progressive multiple sclerosis.

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.

Background: Fingolimod was approved in 2010 for the treatment of relapsing-remitting multiple sclerosis, generally as second-line therapy. While its efficacy in reducing the relapse rate is well-recognized, the dermatologic complications of fingolimod remain unexplored. Herein, we aimed to report our experience with multiple sclerosis patients treated with fingolimod who underwent periodic dermatologic examinations.

Materials and methods: A prospective cohort of 323 patients with multiple sclerosis treated with fingolimod were assessed for dermatologic manifestations over 60 months. The neurologic and dermatologic examinations were done biannually to identify and categorize skin-related adverse events.

Results: Over a mean follow-up of 60 months, of the 323 patients, 32.19% (104 patients) developed skin abnormalities after a mean interval of 25.77 ± 24.36 months since fingolimod initiation. The majority of patients (91.34%) were female, with a mean age of 36.40 ± 7.45 years and a mean disease duration of 122 ± 58.56 months. The most common findings included melanocytic nevus (65.38%) and infectious lesions (11.53%). The severity of skin lesions varied, with most cases manageable with topical treatments. However, ten patients (9.61%) who developed refractory genital human papillomavirus (n = 2), melanocytic nevus (n = 3), dysplastic nevi (n = 3), fibrous papules (n = 1), and molluscum contagiosum (n = 1) had to discontinue their treatment.

Conclusion: Fingolimod treatment in patients with multiple sclerosis is associated with a range of dermatologic findings, predominantly mild to moderate in severity. This population warrants awareness of these potential adverse events and regular follow-up.