Therapeutic Advances in Neurological Disorders最新文献

{"title":"Environmental risk factors of neuromyelitis optica spectrum disorder: a systematic review.","authors":"Mahsa Mohammadi Lapevandani, Elham Bazmi, Shima Jahani, Nasrin Asgari, Mohammad Ali Sahraian","doi":"10.1177/17562864251363293","DOIUrl":"https://doi.org/10.1177/17562864251363293","url":null,"abstract":"<p><strong>Background: </strong>Neuromyelitis optica spectrum disorder (NMOSD) may be triggered by environmental risk factors.</p><p><strong>Objectives: </strong>We aimed to explore and integrate the recent research advances in this field. Here we describe relevant studies and summarize current knowledge on non-genetic factors that influence the onset of the disease.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Methods: </strong>We performed a systematic review up to May 21, 2024, following preferred reporting items for systematic reviews and meta-analyses guidelines. Two independent reviewers evaluated the quality of the included studies using the Joanna Briggs Institute checklist for risk of bias assessment.</p><p><strong>Data sources: </strong>MEDLINE, EMBASE, Scopus, and Web of Science databases.</p><p><strong>Results: </strong>A total of 15,869 articles were evaluated. Of those 50 studies met the eligibility criteria. A total of 21,410 NMOSD patients were included in the studies; 17,080 patients were females. Totally, 14 risk factors, including vitamin D deficiency, vaccination, virus infections, lifestyle, and dietary factors, were assessed. A total of 37% of the included articles were conducted in East Asia, mainly focusing on the effects of infection and vitamin D deficiency. These studies suggested vitamin D deficiency as a possible NMOSD risk factor. A total of 25% of the studies included Caucasian populations from Western countries. They showed that smoking decreased the odds of NMOSD, in contrast to observations from Eastern studies. Few cases reported NMOSD onset after COVID-19 vaccination. Antibodies against Epstein-Barr virus, <i>Mycobacterium paratuberculosis</i>, and <i>Helicobacter pylori</i> were observed to be more frequently positive in the serum of NMOSD patients. Lower protein and fat and higher carbohydrate intakes were correlated with NMOSD development.</p><p><strong>Conclusion: </strong>Vitamin D deficiency, cigarette smoking, <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> infection, and diet were reported as environmental risk factors for NMOSD. The difference in the onset of NMOSD between Asian and Caucasian populations could be affected by smoking and vitamin D deficiency. Knowledge of modifiable risk factors for NMOSD may be beneficial in preventing and improving disease outcomes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251363293"},"PeriodicalIF":4.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281167","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":"Optimal 24-h NIHSS threshold of ⩽9 predicts 90-day outcomes after posterior circulation thrombectomy: ANGEL-ACT Registry Insights.","authors":"Yiming Deng, Ligang Song, Hanlin Chen, Yue Yin, Anxin Wang, Xiaoli Zhang, Yijun Zhang, Baixue Jia, Xiaochuan Huo, Gang Luo, Ning Ma, Dapeng Mo, Xuan Sun, Feng Gao, Zhongrong Miao","doi":"10.1177/17562864251376818","DOIUrl":"10.1177/17562864251376818","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In patients with posterior circulation stroke, the association between National Institutes of Health Stroke Scale (NIHSS) scores after thrombectomy and 90-day functional outcomes remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;We aimed to explore which factors among the 24-h NIHSS score, ΔNIHSS (baseline NIHSS minus 24-h NIHSS), and NIHSS score change rate (ΔNIHSS/baseline NIHSS × 100%) are associated with favorable functional outcomes at 90 days postoperatively in patients with posterior circulation stroke.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;We performed a post hoc analysis of a prospective observational study utilizing key techniques of endovascular treatment and emergency workflow improvements from the acute ischemic stroke registry. The study included a cohort of 353 patients who underwent thrombectomy due to posterior circulation stroke. For all patients, we collected baseline characteristics, lesion locations, NIHSS scores, ΔNIHSS (baseline NIHSS minus 24-h NIHSS), NIHSS score change rate (ΔNIHSS/baseline NIHSS × 100), and 90-day postoperative modified Rankin Scale (mRS) score.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A 90-day postoperative mRS score of 0-2 was defined as a favorable functional outcome, while a score of 3-6 was defined as an unfavorable functional outcome. The 24-h NIHSS score and ΔNIHSS score were converted into binary variables based on the Youden index to determine the optimal thresholds that best predict favorable functional outcomes at 90 days postoperatively. Adjusted logistic regression analysis was used to assess the predictive efficacy of the 24-h NIHSS score, ΔNIHSS (baseline NIHSS minus 24-h NIHSS), and NIHSS score change rate (ΔNIHSS/baseline NIHSS × 100) for the 90-day mRS. Subsequently, patients were categorized into cardioembolic embolism (CE) and large artery atherosclerosis (LAA) subgroups according to the Trial of Org 10172 in Acute Stroke Treatment classification, and the predictive efficacy of the optimal thresholds was examined within these subgroups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multivariate logistic regression analysis revealed that the 24-h NIHSS score was an independent predictor of 90-day functional outcomes (odds ratio (OR): 10.61, 95% confidence interval: 6.44-17.46, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). The Youden index identified a 24-h NIHSS score of ⩽9 as the threshold for predicting an mRS score of 0-2, demonstrating good sensitivity (78.5%) and specificity (76.3%). The receiver operating characteristic curve indicated that the predictive model had good discriminative ability (area under the ROC curve = 0.8223). In subgroup analysis, a 24-h NIHSS score of ⩽9 also showed superior predictive efficacy in both the CE (sensitivity 67.8%, specificity 73.5%) and LAA (sensitivity 81.1%, specificity 74.4%) groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The 24-h postoperative NIHSS score is a reliable predictor of 90-day functional outcomes in patients with posterior circulation stroke undergoing e","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251376818"},"PeriodicalIF":4.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259228","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":"Drip and ship in patients with acute ischemic stroke: a narrative review.","authors":"Lina Palaiodimou, Nikolaos M Papageorgiou, Eleni Bakola, Aikaterini Theodorou, Michele Romoli, Amrou Sarraj, Robert Mikulik, Nitin Goyal, Diana Aguiar de Sousa, Theodoros Karapanayiotides, Ioanna Koutroulou, Pierre Seners, Mira Katan, Simona Sacco, Guillaume Turc, Georgios Tsivgoulis","doi":"10.1177/17562864251378833","DOIUrl":"10.1177/17562864251378833","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) is a leading cause of long-term disability and mortality worldwide, necessitating the rapid implementation of time-sensitive reperfusion therapies to improve outcomes. The \"drip and ship\" (DS) model, in which intravenous thrombolysis (IVT) is initiated at a primary stroke center (PSC) followed by transfer for endovascular thrombectomy (EVT) at a comprehensive stroke center, is widely adopted, particularly in regions with limited immediate EVT access. This narrative review synthesizes evidence from randomized-controlled clinical trials, large-scale observational registries, meta-analyses, and expert-consensus statements to comprehensively analyze the DS model in AIS management, compare it with the mothership (MS) paradigm, and evaluate current evidence regarding workflow optimization, pharmacologic strategies, and system-level innovations. Evidence comparing DS and MS models highlights the complexity of balancing early IVT with minimizing delays to EVT, with regional factors influencing the optimal approach. Reducing door-in-door-out times is critical within DS pathways, as prolonged interhospital transfer is associated with worse outcomes, emphasizing the need for streamlined protocols, prehospital notification, and telemedicine integration. Bridging therapy with IVT, particularly using tenecteplase, is associated with improved rates of early recanalization, supporting its continued use within DS workflows. Emerging adjunctive therapies offer potential for enhancing arterial recanalization and microcirculatory reperfusion without delaying transfer. The \"drive-the-doctor\" paradigm, involving the transfer of neurointerventionalists to PSCs, may further reduce onset-to-reperfusion times in geographically challenging settings. Mobile stroke units, equipped with CT imaging and telemedicine capabilities, represent an additional strategy to initiate IVT in the field while expediting triage decisions for EVT. Collectively, these advancements support the continued refinement of the DS model, emphasizing the need for structured system-level improvements to optimize timely reperfusion and functional recovery in AIS patients. Continued research is necessary to further define optimal strategies within the DS framework to ensure equitable and effective stroke care across diverse healthcare environments.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251378833"},"PeriodicalIF":4.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252832","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":"Migraine with brainstem aura with abnormal EEG discharges easily misdiagnosed as epilepsy: a case series study.","authors":"Xianyun Liu, Jing Ran, Yu Tong, Wenqi Yang, Xi Peng","doi":"10.1177/17562864251378208","DOIUrl":"10.1177/17562864251378208","url":null,"abstract":"<p><p>Migraine with brainstem aura (MBA) constitutes a rare subtype of migraine, characterized by aura symptoms including vertigo, dysarthria, diplopia, tinnitus, ataxia, and impaired consciousness. Patients with MBA have been reported to exhibit abnormal electroencephalograms (EEGs) featuring diffuse slow-wave activity and bilateral slowing of the posterior head activity. Notably, there have been no documented reports of abnormal discharges specifically localized in the anterior head. The presence of abnormal EEG discharges in MBA patients who experience loss of consciousness may lead to potential misdiagnosis, especially as epilepsy, in the early stages. This study describes three patients who were ultimately diagnosed with MBA, offering a retrospective analysis of their clinical features, electroencephalographic manifestations, and diagnostic procedures. In the three cases described, all patients were female, aged 16-21, and had been admitted to the hospital due to recurrent loss of consciousness. They exhibited a consistent EEG pattern, characterized by paroxysmal moderate-to-high amplitude theta activity in the anterior head, interspersed with spikes and sharp waves. Laboratory tests and imaging studies yielded unremarkable results. They all received a diagnosis of epilepsy and were treated with antiseizure medication, which proved ineffective. After evaluation by an epilepsy specialist, they received a final diagnosis of MBA. Following flunarizine administration, all three patients demonstrated improvement, with no subsequent occurrences of loss of consciousness during the follow-up period. This study describes the pattern of abnormal discharges that may be observed in the interictal EEGs of these MBA patients, which is characterized by a predominantly anterior head pattern. Recognizing this specific condition constitutes a crucial element in the differential diagnosis of epilepsy, with the aim of preventing misdiagnosis. Concurrently, we investigate their pathophysiological origins.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251378208"},"PeriodicalIF":4.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252814","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":"A multimodal approach to distinguish multiple sclerosis phenotypes at diagnosis using biomarker profiles.","authors":"Aurora Zanghì, Paola Sofia Di Filippo, Annamaria Greco, Claudia Rutigliano, Ermete Giancipoli, Cristiana Iaculli, Carlo Avolio, Emanuele D'Amico","doi":"10.1177/17562864251369747","DOIUrl":"10.1177/17562864251369747","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a complex and heterogeneous disease characterized by variable clinical outcomes.</p><p><strong>Objective: </strong>We aimed to develop a predictive model combining principal component analysis (PCA) and clustering techniques to identify biomarker sets associated with MS and characterize distinct phenotypes.</p><p><strong>Design: </strong>A monocentric, cross-sectional study on treatment naïve patients at the time of MS diagnosis.</p><p><strong>Methods: </strong>Clinical, laboratory, and neuroimaging data were collected, including retinal layer measurements via optical coherence tomography and neurofilament light (NFL) chains levels.</p><p><strong>Results: </strong>The cohort included 71 MS patients with mean age 35.7 years (SD = 9.8). PCA yielded five components with eigenvalues >1.0, explaining 68.1% of total variance. Component 1 showed strong negative coefficients for retinal thickness (ganglion cell-inner plexiform layer: -0.82, peripapillary retinal nerve fiber layer (RNFL): -0.79, macular RNFL: -0.75) and moderate positive coefficient for serum NFL (0.45). Component 2 featured high positive coefficients for NFL in cerebrospinal fluid (0.88) and serum (0.56). <i>K</i>-means clustering identified two distinct groups: one (<i>n</i> = 33) with thicker retinal layers, better cognitive performance, and unexpectedly higher serum NFL levels compared to the other group (<i>n</i> = 38).</p><p><strong>Conclusion: </strong>These findings suggest that MS may present with distinct phenotypic profiles even at diagnosis. Future longitudinal studies are needed to validate these early biomarkers and refine personalized treatment approaches.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251369747"},"PeriodicalIF":4.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239753","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":"Increased middle cerebral artery velocity predicts malignant media infarction after endovascular stroke thrombectomy.","authors":"Enayatullah Baki, Victoria Kehl, Marlene Topka, Felix Hess, Sebastian Lambrecht, Bernhard Hemmer, Silke Wunderlich, Johanna Haertl","doi":"10.1177/17562864251374935","DOIUrl":"10.1177/17562864251374935","url":null,"abstract":"<p><strong>Background: </strong>Increased peak systolic velocity (PSV) in transcranial Doppler or Duplex sonography (TCD) of the middle cerebral artery (MCA) after endovascular thrombectomy (EVT) for large vessel occlusion in acute ischemic anterior circulation stroke has been associated with poor functional outcome and increased risk of symptomatic intracranial hemorrhage (ICH).<b>Objective:</b> We evaluated whether increased MCA-PSV is associated with the development of malignant media infarction after EVT.</p><p><strong>Methods: </strong>We retrospectively identified all patients who underwent EVT for acute anterior circulation ischemic stroke at our stroke center from January 2021 to July 2024. Increased MCA-PSV on TCD was defined as >30% mean PSV in the treated MCA compared with the contralateral MCA. The development of malignant media infarction was evaluated according to predefined clinical and neuroimaging criteria. Multivariable regression models were used to identify associations between MCA-PSV and the development of malignant media infarction.</p><p><strong>Results: </strong>Out of a total cohort of 377 patients, 49 (13.0%) developed malignant media infarction. In multivariable analysis, MCA-PSV increase was significantly associated with malignant media infarction (odds ratio (OR), 53.3 (95% confidence interval (CI): 18.74, 151.54); <i>p</i> < 0.001). Furthermore, the development of malignant media infarction was also associated with secondary ICH (OR, 6.4 (95% CI: 2.16, 19.03); <i>p</i> < 0.001) and higher baseline National Institutes of Health Stroke Scale (OR, 1.25 (95% CI: 1.14, 138); <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Increased MCA-PSV can act as a predictive marker for the development of malignant media infarction. TCD may serve as a valuable bedside tool in individual risk assessment in early postinterventional surveillance.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251374935"},"PeriodicalIF":4.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233381","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":"Improving quality of life in rare diseases using disease-specific, multidisciplinary online interventions on the example of rare X-linked adrenoleukodystrophy: a randomized-controlled trial.","authors":"Lisa Schäfer, Astrid Unterlauft, Brit Froebrich-Andreß, Carolin Wollny, Marie Rößler, Ronja Fischer, Carla Bähr, Julia Lier, Daniel T Wasmus, Christa-Caroline Bergner, Wolfgang Köhler","doi":"10.1177/17562864251376109","DOIUrl":"10.1177/17562864251376109","url":null,"abstract":"<p><strong>Background: </strong>People with rare diseases (RDs) often require intensive multidisciplinary care in disease-specific centers of excellence (CoE). However, access is limited for most patients living remotely. X-linked adrenoleukodystrophy (X-ALD) is a genetic RD leading to demyelination of the central and peripheral nervous system.</p><p><strong>Objectives: </strong>This randomized-controlled trial tested the feasibility, acceptance, and effectiveness of a multidisciplinary online intervention provided by a CoE on the quality of life (QoL) and well-being of symptomatic women with X-ALD.</p><p><strong>Design: </strong>Single-center, randomized-controlled clinical trial involving 68 German-speaking women with symptomatic X-ALD.</p><p><strong>Methods: </strong>Participants were randomized into an experimental group (EG, <i>n</i> = 34) receiving 12-month online intervention SMART-ALD and a waiting-list control group (WL-CG, <i>n</i> = 34) receiving 6-month SMART-ALD after a 6-month waiting period. Within SMART-ALD, participants were offered regular web-based neurological, social, psychological, and nutritional counseling and fitness training provided by the Leukodystrophy Outpatient Clinic at Leipzig, Germany. Group, time, and interaction effects on primary (self-reported QoL) and secondary (physical and mental health) outcomes after 6-month SMART-ALD were tested by repeated measures ANOVAs.</p><p><strong>Results: </strong>One WL-CG participant dropped out after the waiting period and was excluded from the final analysis. Significant QoL improvements in the EG versus WL-CG were found on self-reported mental health (mean difference (MD): 5.4, 95% confidence interval (CI) (2.8, 13.6), <i>p</i> = 0.020, η² = 0.08) and vitality (MD: 8.8, 95% CI (0.1, 17.4), <i>p</i> = 0.002, η² = 0.14). Further significant interaction effects emerged for improved knowledge about nutrition (MD: 0.4, 95% CI (-0.7, 1.4), <i>p</i> = 0.002, η² = 0.15), socio-medical benefits (MD: 1.8, 95% CI (0.5, 3.0), <i>p</i> = 0.033, η² = 0.07), and intense physical activity (MD: 2.2, 95% CI (-3.9, 8.4), <i>p</i> = 0.024, η² = 0.10).</p><p><strong>Conclusion: </strong>The study shows that easily accessible, multidisciplinary online interventions provided by the CoE have the potential to improve the QoL in people with RDs by providing regular access to specialized care.</p><p><strong>Trial registration: </strong>This study was registered on ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT04687007).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251376109"},"PeriodicalIF":4.1,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201515","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":"Sex differences in relapse-independent and relapse-associated disability progression in relapsing-remitting multiple sclerosis: a real-world inverse-probability weighted study.","authors":"Matteo Foschi, Damiano Marastoni, Ivan Panzera, Luca Mancinelli, Cristiana Ganino, Gianmarco Abbadessa, Lucio D'Anna, Francesca Gabriele, Simona Sacco, Elisabetta Signoriello, Alessandra Lugaresi, Elena Tsantes, Maria Grazia Piscaglia, Andrea Surcinelli","doi":"10.1177/17562864251376807","DOIUrl":"10.1177/17562864251376807","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in multiple sclerosis (MS) progression are poorly characterized, especially for disability worsening independent of relapses.</p><p><strong>Objectives: </strong>To assess sex-specific risks of progression independent of relapse activity (PIRA), relapse and magnetic resonance imaging (MRI) activity (PIRMA), and relapse-associated worsening (RAW) in a real-world MS cohort, quantify each event's contribution to disability accumulation, and explore variation across clinical subgroups.</p><p><strong>Design: </strong>Inverse probability-weighted analysis of adults with relapsing-remitting MS ambispectively enrolled in a local registry who had their first recorded neurological evaluation within 12 months of MS onset.</p><p><strong>Methods: </strong>We used weighted conditional proportional hazard models for recurrent events, adjusted for visit/MRI frequency, to compare risks between sexes. We also tested the homogeneity of sex effects across prespecified subgroups: age at MS onset, symptom location at onset, presence of ⩾10 T2-hyperintense brain lesions, ⩾1 spinal T2 lesion, ⩾1 Gadolinium-enhancing brain lesion at baseline, initial MS treatment type, and percentage of follow-up time on disease-modifying therapy (DMT).</p><p><strong>Results: </strong>We included 492 people with MS (median age 44.0 years, interquartile range (IQR) 35.0-53.6; 68.9% women), followed for a median of 5.1 years (IQR 3.1-7.2). In the weighted cohort, women had higher hazards of PIRA (hazard ratio (HR) 2.44, 95% confidence interval (CI) 1.56-3.70; <i>p</i> < 0.001) and PIRMA (HR 2.13, 95% CI 1.25-3.70; <i>p</i> < 0.001), mainly postmenopausal (56.6% and 52.4%). RAW risk was similar (HR 1.07, 95% CI 0.54-2.11; <i>p</i> = 0.843), despite higher relapse rates in women (0.13 ± 0.18 vs 0.06 ± 0.16; <i>p</i> < 0.001). Men had greater Expanded Disability Status Scale worsening per PIRA (+0.29 ± 0.71 vs +0.16 ± 0.53; <i>p</i> = 0.023) and PIRMA (+0.25 ± 0.71 vs +0.09 ± 0.38; <i>p</i> = 0.001). Age ⩾50 at onset increased PIRA/PIRMA risk without sex interaction. Significant sex interaction was seen for onset symptom location (<i>p</i> < 0.001 for both outcomes) and initial DMT (<i>p</i> = 0.013 for PIRA; <i>p</i> = 0.022 for PIRMA).</p><p><strong>Conclusion: </strong>Women, especially postmenopausal, had higher PIRA/PIRMA risk, but disability worsening per event was greater in men, associations varied by onset phenotype and initial DMT strategy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251376807"},"PeriodicalIF":4.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150954","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":"Aggressive treatment of early acute focal inflammatory activity to extend the window for BTK inhibition in multiple sclerosis.","authors":"Joost Smolders, Ide Smets, Beatrijs Wokke","doi":"10.1177/17562864251359002","DOIUrl":"10.1177/17562864251359002","url":null,"abstract":"<p><p>The development of novel therapy classes such as Bruton's tyrosine kinase (BTK) inhibitors, which target disability progression independent of relapses and largely independent of new lesion formation, requires a reappraisal of strategies in the treatment of multiple sclerosis (MS). We argue that this novel class of treatment further emphasizes the need for early and aggressive treatment with classical disease-modifying compounds for the prevention of both relapses and new MRI lesion formation and their associated disability accrual. This will extend the window to recognize early progressive disability accumulation independent of acute focal inflammatory activity, and for people with MS to benefit from novel therapies such as BTK inhibition, which target damaging pathophysiological processes independent of peripherally driven focal inflammation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251359002"},"PeriodicalIF":4.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125789","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":"Approaches for treating cardiovascular symptoms in Parkinson's disease.","authors":"Wolfgang H Jost, Jiri Koschel","doi":"10.1177/17562864251375181","DOIUrl":"10.1177/17562864251375181","url":null,"abstract":"<p><p>Cardiovascular symptoms are common in Parkinson's disease (PD), either as non-motor symptoms (NMS) of PD or as coexisting cardiovascular diseases (CVD), since both PD and CVD primarily affect the elderly population. Autonomic dysfunction in PD often involves blood pressure issues, including orthostatic hypotension, postprandial hypotension, and supine hypertension (SH). The combination of these NMS is particularly challenging to diagnose and treat. Other atherosclerotic vascular diseases, such as stroke or myocardial infarction, appear to be more common in PD patients. Prophylactic measures, such as statins or managing hypertension/SH, are essential for PD patients with an elevated risk of CVD, although PD patients usually undergo polypharmacy due to the short half-life of levodopa and the requirement of multiple drugs for CVD. This review presents studies in the literature on the current state-of-the-art therapy for CVD in PD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251375181"},"PeriodicalIF":4.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087461","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}