Annals of Clinical and Translational Neurology最新文献

{"title":"Quantitative Shape Irregularity and Density Heterogeneity Predict Hematoma Expansion in Patients With Intracerebral Hemorrhage.","authors":"Zeqiang Ji, Yunyi Hao, Bin Gao, Xiaojing Zhang, Yani Zhang, Jiaokun Jia, Xue Xia, Yuhao Guo, Sijia Li, Jianwei Wu, Kaijiang Kang, Xingquan Zhao","doi":"10.1002/acn3.70141","DOIUrl":"https://doi.org/10.1002/acn3.70141","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the association between quantitative shape irregularity and density heterogeneity of hematomas and hematoma expansion (HE) for intracerebral hemorrhage (ICH) patients.</p><p><strong>Methods: </strong>This cohort study included patients arriving within 24 h of symptom onset between August 2021 and July 2022 as the derivation cohort and those between July 2023 and February 2024 as the external validation cohort. HE is defined as a hematoma increase of > 6 mL or > 33% from the baseline to the follow-up CT scan between 24 and 48 h. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the traditional image signs to fit the logistic regression as Model 1. Afterwards, the surface regularity index (SRI) and density coefficient of variation (DCV) of hematoma were added to form Model 2. Finally, we used the SRI and DCV to replace the selected traditional image signs as Model 3. The performance and clinical utilities were evaluated and compared in the external validation cohort.</p><p><strong>Result: </strong>The three models demonstrated good discrimination in both the derivation cohort and the validation cohort, with Model 2 and Model 3 showing significant improvements in area under the receiver operating characteristic curve (AUROC) and in clinical utility compared to Model 1 (Model 2 AUROC: 0.859 [95% CI: 0.802, 0.926] vs. Model 1 AUROC: 0.713 [95% CI: 0.625, 0.814], Delong test p < 0.001; Model 3 AUROC: 0.840 [95% CI: 0.776, 0.912] vs. Model 1 AUROC: 0.713 [95% CI: 0.625, 0.814], p = 0.006). The SRI and DCV can improve the prediction of HE based on traditional clinical indicators and imaging signs, also serving as possible alternatives to traditional imaging signs.</p><p><strong>Conclusions: </strong>The SRI and DCV can serve as effective substitutes for traditional imaging signs in predicting hematoma expansion.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial Fibrillary Acidic Protein Astrocytopathy Based on a Two-Center Chinese Cohort Study","authors":"Ti Wu,&nbsp;Hao Zhang,&nbsp;Chao Gao,&nbsp;Qiuhua Yu,&nbsp;Moli Fan,&nbsp;Lin-Jie Zhang,&nbsp;Haipeng Zhang,&nbsp;Hengri Cong,&nbsp;Yuzhen Wei,&nbsp;Chotima Böttcher,&nbsp;Alexej Verkhratsky,&nbsp;Friedemann Paul,&nbsp;Fu-Dong Shi,&nbsp;Tian Song","doi":"10.1002/acn3.70118","DOIUrl":"10.1002/acn3.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently defined nosological form belonging to the class of autoimmune inflammatory disorders affecting the central nervous system (CNS). Here, we report the clinical and MRI characteristics, treatment, and prognosis of a GFAP-A cohort from two centers in China.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed the data from 38 adult patients with positive GFAP antibodies and diagnosed as GFAP-A between June 2019 and September 2024. Clinical features, semiquantitative antibody test results, MRI features, treatment approaches, and prognosis were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 38 patients, 24 were male, and the median age at disease onset was 49.5 years. The clinical phenotype included encephalomyelitis (28.9%), myelitis (23.7%), encephalitis (18.4%), meningoencephalomyelitis (18.4%), meningitis/spinal meningitis (7.9%), and peripheral neuropathy (2.6%). In enhanced MRI images, 4 (10.5%) of the patients showed enhancement of the cerebral meninges, 2 (5.3%) had enhancement of the ependyma, and 5 (13.2%) had enhancement of the spinal cord pia mater. 77.1% of the patients responded to the glucocorticoid treatment, while 65.8% had a monophasic course. Spearman correlation analysis showed that CSF-specific oligoclonal bands were significantly correlated with 1-year relapse (CI = 0.527, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The clinical manifestations of GFAP-A are highly diverse, encompassing encephalitis, myelitis, and meningitis, including spinal meningitis. The enhancement of the spinal pia mater and ependyma on MRI was confirmed. Most patients exhibit a positive response to glucocorticoid therapy. The presence of CSF-specific oligoclonal bands could potentially serve as an indicator for predicting recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1813-1822"},"PeriodicalIF":3.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital Activity Markers in Chronic Inflammatory Demyelinating Polyneuropathy.","authors":"Lars Masanneck, Jan Voth, Noëmi Gmahl, Konstantin Jendretzky, Niklas Huntemann, Noah M Werner, Linea Schmidt, Menekse Oeztuerk, Paula Quint, Christina B Schroeter, Hans Peter Hartung, Thomas Skripuletz, Gerd Meyer zu Hörste, Tobias Ruck, Sven G Meuth, Marc Pawlitzki","doi":"10.1002/acn3.70137","DOIUrl":"10.1002/acn3.70137","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the utility of smartwatch and smartphone-based activity metrics for assessing disease severity and quality of life in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).</p><p><strong>Methods: </strong>In the electronic monitoring of disease activity in patients with CIDP (EMDA-CIDP) trial, we performed a prospective observational study from January 2023 to July 2024 at university hospitals in Düsseldorf and Münster, with an independent validation cohort in Hannover. Eligible participants were adults with CIDP on stable intravenous immunoglobulin (IVIG) therapy. Clinical evaluations included established disability scales (I-RODS and INCAT) and quality of life assessments. Activity metrics were captured via consumer-grade smartwatches, with adherence criteria applied to ensure data quality. A real-world smartphone-based cohort of 20 patients was used as a comparator.</p><p><strong>Results: </strong>Among 46 participants (median age 64 Years [IQR 57-69]; 24% female), smartwatch-derived maximum daily-step count emerged as a robust indicator of disease severity. In 43 patients meeting wearable adherence criteria, maximum daily steps showed strong correlations with clinical scores, positively with I-RODS (Spearman's ρ = 0.74) and inversely with INCAT (Spearman's ρ = -0.54). Additional smartwatch metrics correlated with quality of life domains, whereas smartphone-derived metrics of a validation cohort exhibited weaker correlations.</p><p><strong>Interpretation: </strong>These results indicate that smartwatches many patients already use can yield valuable, objective data for assessing disease status in CIDP. Integrating smartwatch-derived metrics into clinical assessments may enhance traditional evaluations and deepen understanding of disease progression and patient quality of life. These promising results warrant additional, larger-scale studies in the future.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Validated Model to Predict Severe Weight Loss in Amyotrophic Lateral Sclerosis","authors":"David G. Lester,&nbsp;Kevin Talbot,&nbsp;Martin R. Turner,&nbsp;Alexander G. Thompson,&nbsp;the Pooled Resource Open-Access ALS Clinical Trials Consortium","doi":"10.1002/acn3.70129","DOIUrl":"10.1002/acn3.70129","url":null,"abstract":"<p>Severe weight loss in amyotrophic lateral sclerosis (ALS) is common, multifactorial, and associated with shortened survival. Using longitudinal weight data from over 6000 patients with ALS across three cohorts, we built an accelerated failure time model to predict the risk of future severe (≥ 10%) weight loss using five single-timepoint clinical predictors: symptom duration, revised ALS Functional Rating Scale, site of onset, forced vital capacity, and age. Model performance and generalisability were evaluated using internal–external cross-validation and random-effects meta-analysis. The overall concordance statistic was 0.71 (95% CI 0.63–0.79), and the calibration slope and intercept were 0.91 (0.69–1.13) and 0.05 (−0.11–0.21). This study highlights clinical factors most associated with severe weight loss in ALS and provides the basis for a stratification tool.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1907-1912"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Modeling of Natural Killer Cell Cytotoxicity to Inform Personalized ALS Therapeutics.","authors":"Benjamin J Murdock, Jihyun Park, Dae-Gyu Jang, Bangyao Zhao, Samuel J Teener, Ian F Webber-Davis, Lili Zhao, Eva L Feldman, Stephen A Goutman","doi":"10.1002/acn3.70127","DOIUrl":"https://doi.org/10.1002/acn3.70127","url":null,"abstract":"<p><strong>Objective: </strong>Natural killer (NK) cells might contribute to motor neuron death in amyotrophic lateral sclerosis (ALS) through direct cytotoxicity, a process that could be inhibited with the FDA-approved JAK/STAT pathway inhibitor, tofacitinib. This study aimed to verify that tofacitinib can suppress NK cell cytotoxicity, investigate if immune cell profiles can predict responsiveness to tofacitinib, and assess the role of NK cell cytotoxicity in ALS progression.</p><p><strong>Methods: </strong>Primary NK cells were isolated from peripheral blood samples of ALS participants and healthy controls. NK cells were then co-cultured with target cancer cells, with or without tofacitinib, to assess their cytotoxic activity. Flow cytometry was used to generate immune profiles for each participant, based on 154 immune markers, to explore correlations with NK cell cytotoxicity and response to tofacitinib. The potential association between NK cell cytotoxicity and disease severity, as measured by the revised ALS Functional Rating Scale, was also assessed. All analyses were stratified by age and sex.</p><p><strong>Results: </strong>Tofacitinib effectively reduced the cytotoxicity of primary NK cells isolated from the blood of ALS participants (n = 80) and healthy controls (n = 71), with immune cell profiles correlating with the response to tofacitinib. However, NK cell cytotoxicity was lower in ALS participants compared to healthy controls and showed no association with ALS progression.</p><p><strong>Interpretation: </strong>These findings confirm that tofacitinib suppresses NK cell cytotoxicity, and that immune profiling may help identify treatment responder groups. However, further research is needed to fully understand the role and timing of NK cell activity in ALS pathogenesis.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of Composite Endpoints Defining Progression Independent of Relapse Activity in Multiple Sclerosis","authors":"Ludwig Kappos,&nbsp;Sean Yiu,&nbsp;Jason Reucassel,&nbsp;Jiwon Oh,&nbsp;Cristina Granziera,&nbsp;Joep Killestein,&nbsp;Robert A. Bermel,&nbsp;Claude Berge,&nbsp;Agne Kazlauskaite,&nbsp;Hans-Martin Schneble,&nbsp;Frank Dahlke,&nbsp;Bruce A. C. Cree","doi":"10.1002/acn3.70111","DOIUrl":"10.1002/acn3.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The characteristics and utility of composite progression independent of relapse activity (cPIRA; worsening on the Expanded Disability Status Scale [EDSS], or 9-Hole Peg Test, or Timed 25-Foot Walk Test) were evaluated as an endpoint in relapsing multiple sclerosis (RMS) trials using the ENSEMBLE (NCT03085810) and pooled OPERA I/II (NCT01247324/NCT01412333) studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated: (i) different definitions and the impact of rebaselining post-relapse on cPIRA, (ii) cPIRA and biomarkers (MRI activity and serum neurofilament light [sNfL] levels), (iii) sustainability of cPIRA events, and (iv) cPIRA impact on future outcomes, in patients treated with ocrelizumab (600 mg, OPERA I/II [<i>n</i> = 827] and ENSEMBLE [<i>n</i> = 1225]) or interferon β-1a (44 μg, OPERA I/II [<i>n</i> = 829]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Low disease activity (relapses/new MRI lesions) rendered rebaselining unnecessary for cPIRA status in &gt; 95% of ocrelizumab-treated participants, and variations of cPIRA definitions yielded similar event rates. In OPERA I/II and ENSEMBLE ocrelizumab arms, cPIRA events were independent of MRI activity (86.5% and 95.5%, respectively), and occurred when sNfL was low (risk of cPIRA, hazard ratio [HR]: 0.67; <i>p</i> = 0.11 and 0.57; <i>p</i> = 0.003); more cPIRA events were sustained until study end with interferon β-1a (80.3% OPERA I/II) vs. ocrelizumab (63.2% OPERA I/II, 56.6% ENSEMBLE). Across studies and treatments, cPIRA was associated with an increased risk of subsequent worsening on the EDSS (HR, 1.62–1.74; <i>p</i> = 0.121–0.037), Symbol Digit Modalities Test (HR, 1.16–2.62; <i>p</i> = 0.54–0.009), and Multiple Sclerosis Impact Scale-29 physical scale (HR, 1.76; <i>p</i> = 0.064).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>cPIRA is clinically relevant and demonstrates utility as a sensitive endpoint in MS clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifiers: OPERA I (NCT01247324; https://clinicaltrials.gov/study/NCT01247324); OPERA II (NCT01412333; https://clinicaltrials.gov/study/NCT01412333); ENSEMBLE (NCT03085810; https://clinicaltrials.gov/study/NCT03085810)</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1805-1812"},"PeriodicalIF":3.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remaining Burden of Spinal Muscular Atrophy Among Treated Patients: A Survey of Patients and Caregivers.","authors":"Julie A Parsons, Natalie Land, Melissa Culhane Maravic, Claire Cagle, Amal Jamaleddine, Hemal Shah, Thomas Brown, Christabella Cherubino, Mouhamed Gueye","doi":"10.1002/acn3.70132","DOIUrl":"https://doi.org/10.1002/acn3.70132","url":null,"abstract":"<p><strong>Objective: </strong>Spinal muscular atrophy (SMA) significantly impacts motor function. This study aimed to assess the persistent burden and unmet needs among currently treated patients with SMA and their caregivers.</p><p><strong>Methods: </strong>Two complementary web-based surveys were distributed in August 2024 among patients with SMA and their caregivers. Non-ambulant patients with SMA currently receiving risdiplam or nusinersen, and/or their primary, informal caregivers were eligible to participate. Survey modules captured clinical, humanistic, productivity, and caregiver-related burden of disease. The PROMIS Fatigue and EQ-5D-5L were used to assess fatigue and quality of life.</p><p><strong>Results: </strong>40 pediatric (mean age 8.3 years; represented by caregiver proxies) and 68 adult patients (mean age 37.5 years) were included, of which the majority were on SMN-targeted treatment for ≥ 2 years (82.5% and 94.1%, respectively), and nearly half were on treatment for ≥ 4 years. Despite continued treatment, muscle weakness was reported in 95% of pediatric and 100% of adult patients, with 63% of pediatric and 68% of adult patients reporting \"severe\" or \"very severe\" muscle weakness that substantially impacted motor function and performance of activities of daily living. Increased fatigue and muscle weakness were associated with worse overall health. Findings also demonstrated impacts of SMA on patient quality of life and well-being. Most participants reported mobility limitations and muscle weakness as being least improved by current treatment.</p><p><strong>Interpretation: </strong>Despite the use of current treatments, there remains a significant burden of SMA on patients and their caregivers. Muscle weakness and mobility limitations remain key areas of unmet need.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Intensive Versus Escalation Approach: Ten-Year Impact on Disability in Relapsing Multiple Sclerosis.","authors":"Pietro Iaffaldano, Giuseppe Lucisano, Tommaso Guerra, Francesca Caputo, Marta Simone, Massimiliano Copetti, Damiano Paolicelli, Emilio Portaccio, Francesco Patti, Paola Perini, Vincenzo Brescia Morra, Alessia Di Sapio, Matilde Inglese, Carlo Pozzilli, Giacomo Lus, Giuseppe Salemi, Erica Curti, Giovanna De Luca, Paola Valentino, Eleonora Cocco, Paola Cavalla, Carlo Avolio, Alessandra Lugaresi, Antonio Gallo, Pietro Annovazzi, Maria A Rocca, Clara Grazia Chisari, Massimo Filippi, Maria Pia Amato, Maria Trojano","doi":"10.1002/acn3.70131","DOIUrl":"https://doi.org/10.1002/acn3.70131","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the long-term impact of early intensive treatment (EIT) versus escalation (ESC) strategies using high-efficacy disease-modifying therapies (HE-DMTs) on disability progression in relapsing multiple sclerosis (RMS).</p><p><strong>Methods: </strong>This observational study included 4878 RMS patients from the Italian Multiple Sclerosis Register. Eligible participants initiated their first disease-modifying therapy (DMT) within 3 years of disease onset and had ≥ 5 years of follow-up with at least three Expanded Disability Status Scale (EDSS) evaluations. Patients were categorized into the EIT group if they started with HE-DMTs and into the ESC group if HE-DMTs were initiated after ≥ 1 year of moderate-efficacy therapy. Propensity score matching was performed to balance baseline characteristics. Outcomes included disability trajectories assessed using linear mixed models for repeated measures and risks of confirmed disability accrual (CDA), progression independent of relapse activity (PIRA), and relapse-associated worsening (RAW) evaluated using Cox proportional hazards models.</p><p><strong>Results: </strong>Post-matching analysis of 908 pairs revealed significantly slower disability progression in the EIT group compared to the ESC group. At 10 years, the delta-EDSS difference between groups was -0.63 (95% CI: -0.83 to -0.43; p < 0.0001). ESC was associated with higher risks of CDA (HR 1.36, 95% CI: 1.20-1.54; p < 0.0001), PIRA (HR 1.22, 95% CI: 1.05-1.40; p = 0.0074), and RAW (HR 1.55, 95% CI: 1.17-2.05; p = 0.0021).</p><p><strong>Interpretation: </strong>EIT significantly reduces long-term disability progression in RMS compared to ESC. These findings underscore the potential of EIT to optimize long-term outcomes in RMS patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Comparative Effectiveness and Tolerability of Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: A Network Meta-Analysis of Randomized Controlled Trials.","authors":"Faizan Shahzad, Taimoon Rasheed, Momina Riaz Siddiqui, Hamza Hamid, Marwah Bintay Khalid, Haroon Shabbir, Besher Shami, Abdullah, Syed Ijlal Ahmed","doi":"10.1002/acn3.70122","DOIUrl":"https://doi.org/10.1002/acn3.70122","url":null,"abstract":"<p><strong>Background: </strong>Sphingosine-1-phosphate receptor modulators (S1PRM) are used to treat relapsing multiple sclerosis (MS). Each drug has a different S1PR-subtype selectivity. They target the G-protein coupled S1P receptors and exert significant immunomodulatory effects, such as preventing the formation of new CNS lesions and the reactivation of pre-existing lesions.</p><p><strong>Objective: </strong>This study aims to explore the efficacy and safety of S1PRM in treating MS.</p><p><strong>Methods: </strong>A systematic literature search of PubMed, Embase, and Cochrane databases was conducted in August 2024. Randomized Controlled Trials that evaluated the efficacy of S1PRM in patients with MS were included. Changes in Annualized Relapse Rate and incidence of adverse effects were chosen as primary outcomes. Standardized mean differences (SMD) and odds ratio (OR) were calculated. Confidence interval was kept at 95%. Individual interventions were compared using the Surface Under Cumulative Ranking Curve (SUCRA). The risk of bias was assessed by the Cochrane risk-of-bias tool for randomized trials (RoB 2).</p><p><strong>Results: </strong>The search query resulted in a total of 1750 studies. After screening, 17 studies were included in the final analysis, with a population of 16,006. Fingolimod (1.25 mg) was significantly associated with a decreased ARR (SMD = -0.4422, 95% CI = [-0.5450 to -0.3394], p-value < 0.0001, SUCRA = 92.65%). Whereas, ozanimod (1 mg) was associated with the lowest number of new Gadolinium-enhanced lesions (SMD = -0.6516, 95% CI = [-0.8944 to -0.4087], p-value < 0.0001, SUCRA = 86.38%). Siponimod (1.25 mg) was associated with the least number of adverse events (OR = 0.4606, 95% CI = [0.1893 to 1.1205], p = 0.0874, SUCRA = 93.20%). Almost all of the studies had a low risk of bias.</p><p><strong>Conclusion: </strong>Fingolimod (1.25 mg) and ozanimod (1 mg) had the best efficacy, and siponimod (1.25 mg and 0.25 mg) had the best safety profile among the S1PRM. Further longitudinal studies should be conducted to assess the long-term effects of these drugs on patient-reported outcomes.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Efficacy Treatment in Neuromyelitis Optica Specturm Disorder Patients With Seropositive AQP4 Antibodies-A Real-World Study.","authors":"Xiang Li, Binbin Xue, Jia Li, Dewei Xie, Juyuan Pan, Lanbing Zhu, Qiaowen Tong, Jing Lin, Xu Zhang, Junhui Xia, Jie Lin","doi":"10.1002/acn3.70128","DOIUrl":"https://doi.org/10.1002/acn3.70128","url":null,"abstract":"<p><strong>Objective: </strong>To compare the effectiveness of high-efficacy treatments (HET) and low-efficacy treatments (LET) in NMOSD patients with anti-aquaporin-4 antibodies (AQP4-ab).</p><p><strong>Methods: </strong>In this multi-center study, we analyzed 183 AQP4-ab seropositive NMOSD patients who received immunosuppressive treatments (IST). Primary outcomes included annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS).</p><p><strong>Results: </strong>A total of 86 HET and 143 LET treatment episodes were included. Patients with HET had the lower relapse rate (41.9% vs. 59.4%, p = 0.015). At the final follow-up, the HET group had lower ARR (p = 0.003) and EDSS (p = 0.004) compared to LET. HET (p < 0.001, adjusted p < 0.001), early IST initiation after onset (p = 0.007, adjusted p = 0.008) and younger age of onset (p = 0.024, adjusted p = 0.028) were the protective factors for high EDSS, and HET (HR: 0.66, 95% CI: 0.44-0.99, p = 0.047) prolonged the remission after IST. Meantime, Anderson-Gill analysis indicated that HET is associated with a lower risk of relapse (p < 0.001). After PSM, patients receiving HET had significantly reduced ARR (p = 0.046) and EDSS scores (p =0.030) compared to those receiving LET.</p><p><strong>Interpretation: </strong>Our findings indicated the superior efficacy in reducing neurological disability and relapse risk of HET in AQP4-ab seropositive NMOSD patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}