Therapeutic Advances in Neurological Disorders最新文献

{"title":"Perfusion-guided thrombolysis beyond 4.5 hours for acute ischemic stroke: A time-stratified systematic review and meta-analysis.","authors":"Wen-Wen Tsai, Kuan-Hsien Lu, Kuan-Hung Lin, Jheng-Yan Wu, Chih-Cheng Lai, Kuo Chuan Hung, Yi-Ting Tsai, Meng-Tsang Hsieh","doi":"10.1177/17562864261474987","DOIUrl":"10.1177/17562864261474987","url":null,"abstract":"<p><strong>Introduction: </strong>In the contemporary endovascular thrombectomy (EVT) era, treatment decisions are often made without routine perfusion imaging. However, perfusion remains central to intravenous thrombolysis (IVT) beyond 4.5 hours. Evidence across extended and very late windows remains uncertain.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of perfusion-guided IVT beyond 4.5 hours after acute ischemic stroke and to assess the robustness of evidence across the 4.5-9 hour and 9-24 hour windows.</p><p><strong>Design: </strong>Time-stratified systematic review and meta-analysis of phase III randomized controlled trials.</p><p><strong>Data sources and methods: </strong>We systematically searched PubMed, Embase, and the Cochrane Library from inception to February 8, 2026. Phase III randomized controlled trials enrolling perfusion-selected AIS patients treated 4.5-24 hours from last known well were included; trials permitting stratification into 4.5-9 and 9-24 hours were prioritized. Outcomes included 90 days excellent outcome (mRS 0-1), favorable (mRS 0-2), good (mRS 0-3), mortality, and symptomatic intracerebral hemorrhage (sICH). Random-effects meta-analysis and trial sequential analysis (TSA) were performed.</p><p><strong>Results: </strong>Five randomized controlled trials (n=1,798) were included. IVT increased excellent outcome in both the 4.5-9 hour window (n=866; RR 1.30, 95% CI 1.08-1.56; I²=0%; absolute risk difference (ARD)=9.1%; NNT=11) and the 9-24 hour window (n=563; RR 1.41, 95% CI 1.10-1.79; I²=0%; ARD=11.1%; NNT=9). Across 4.5-24 hours, IVT improved favorable (RR 1.18, 95% CI 1.07-1.29; I²=0%) and good outcomes (RR 1.11, 95% CI 1.03-1.21; I²=0%), with no significant effect on mortality (RR 1.14, 95% CI 0.85-1.52; I²=0%). IVT increased sICH risk overall (RR 5.63, 95% CI 2.17-14.57; I²=0%; ARD=approximately 3.0%; NNH=33). TSA suggested that the cumulative evidence has not yet reached the required information size for firm conclusiveness.</p><p><strong>Conclusion: </strong>In the contemporary EVT era, perfusion-guided IVT may remain clinically relevant for selected patients treated beyond 4.5 hours, particularly those not eligible for thrombectomy or without immediate EVT access. Current phase III randomized evidence suggests improved functional outcomes but increased symptomatic intracerebral hemorrhage. However, TSA indicates that the evidence remains underpowered for definitive conclusions. Evidence for the 9-24 hour window is particularly limited and derived from China-based trials; therefore, these findings should be interpreted as hypothesis-supporting rather than conclusive.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261474987"},"PeriodicalIF":4.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680073","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":"The \"fidget spinner\" sign in cardioembolic bilateral medial medullary infarction: an imaging clue to proximal anterior spinal artery occlusion.","authors":"Can Çubuk","doi":"10.1177/17562864261470192","DOIUrl":"10.1177/17562864261470192","url":null,"abstract":"<p><p>Bilateral medial medullary infarction is a rare and clinically severe form of brainstem stroke. A patient presented with acute neurological deficits, and diffusion-weighted imaging revealed a distinctive pattern resembling a \"fidget spinner.\" CT angiography demonstrated marked asymmetry of the vertebral arteries, with hypoplasia of the right vertebral artery. A review of 97 previously reported cases confirmed the exceptional rarity of cardioembolic etiology in this condition. In this context, the present case represents an uncommon coexistence of a rare anatomical pattern and a rare vascular mechanism. These findings suggest that infarct morphology on diffusion-weighted imaging may reflect underlying vascular anatomy and the level of arterial involvement in bilateral medial medullary infarction.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261470192"},"PeriodicalIF":4.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680060","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":"Stratified screening-based cognitive measures reveals temporal patterns of recovery after the CSF tap test in idiopathic normal pressure hydrocephalus (iNPH): A single-centre retrospective study.","authors":"Wenqinyi Yang, Xudong Ma, Sitong Li, Jiaming Gao, Guanghui Zhu, Chunyan Liu, Zhijun Song, Kai Yu, Ning Nannan Zhang, Peng Zhao, Xiuyun Liu, Tao Zhu, Yan Xing, Huijie Yu","doi":"10.1177/17562864261474799","DOIUrl":"10.1177/17562864261474799","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic normal pressure hydrocephalus (iNPH) is a reversible disorder characterized by cognitive, gait, and urinary dysfunction. While the cerebrospinal fluid (CSF) tap test can predict surgical response, screening-based cognitive assessment protocols remain undefined, limiting prognostic accuracy.</p><p><strong>Objectives: </strong>To delineate temporal patterns of recovery for individual cognitive subdomains after the CSF tap test in patients with iNPH, and to establish high-sensitivity, time-stratified cognitive subdomains to improve preoperative prognostication and surgical decision-making.</p><p><strong>Design: </strong>Single-centre retrospective observational study with rigorous inclusion/exclusion criteria. All patients underwent a full series of multidimensional cognitive assessments before and at 24, 48, and 72 hours after the CSF tap test. Cognitive functions were stratified into six standardized subdomains using validated weighted composite scores. All enrolled patients underwent ventriculoperitoneal (VP) shunt surgery and completed 3-month postoperative cognitive follow-up. Longitudinal changes were analysed using repeated-measures ANOVA, linear mixed models, and receiver operating characteristic curve analysis.</p><p><strong>Methods: </strong>In this study, 53 patients with iNPH were included. Cognitive assessments were performed consistently across all time points using the Mini-Mental State Examination (MMSE), Animal Fluency Test (AFT), Trail Making Test (TMT and TMT-A), and Clock Drawing Test (CDT). Quantitative composite scores for each cognitive subdomain were computed and analysed longitudinally.</p><p><strong>Results: </strong>Stratified analyses showed that language ability at 24 hours (P < 0.01), orientation ability at 48 hours (P < 0.01), and recall combined with attention and calculation at 72 hours (recall: P < 0.001; attention and calculation: P < 0.01) were the most sensitive and predictive for assessing the effects of the CSF tap test across time points. All enrolled patients underwent VP shunt surgery after multi-index assessment. These improvements correlated with 3-month postoperative cognitive benefits.</p><p><strong>Conclusions: </strong>A time-stratified, subdomain-specific cognitive assessment protocol enhances tap test sensitivity, reduces misclassification, and supports personalized surgical decision-making for patients with iNPH.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261474799"},"PeriodicalIF":4.0,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670672","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":"Unexpected longevity in myasthenia gravis: a multi-state population-based comparison with multiple sclerosis and the U.S. population.","authors":"Bhupendra O Khatri, Scott Schutten, Sergey Tarima","doi":"10.1177/17562864261472638","DOIUrl":"10.1177/17562864261472638","url":null,"abstract":"<p><strong>Background: </strong>This study compares age at death in patients with myasthenia gravis (MG) and multiple sclerosis (MS) with the general U.S. population and examines age at death patterns during a period preceding modern high-efficacy therapies.</p><p><strong>Objective: </strong>To compare age at death among individuals with MG and MS with the general population and assess differences in age at death between MG and MS.</p><p><strong>Design: </strong>Retrospective population-based study using death certificate data from four U.S. states (Florida, Wisconsin, Texas, and New York) for 2000, 2005, 2010, and 2015.</p><p><strong>Methods: </strong>Individuals with MG or MS listed on death certificates were identified. Age at death was compared between MG and MS among four states and contemporaneously with U.S. population via Social Security life tables, adjusting for sex and geography. Because data were provided in different formats across states (individual-level, aggregated, and categorical), analyses were tailored to each dataset while addressing the same underlying question. During the study period, high-efficacy targeted therapies for both conditions were not yet available, allowing comparison of mortality patterns under standard-of-care treatment.</p><p><strong>Results: </strong>Age at death of MS patients was significantly lower than the general population (-12.4 years, <i>p</i> < 0.001). In contrast, MG patients showed a higher mean age at time of death compared with the general population (+4.8 years, <i>p</i> < 0.0001) and died significantly later than MS patients (+15.5 years, <i>p</i> < 0.001, adjusted for sex and year). These patterns were consistent across datasets. Despite a higher reported burden of age-related comorbidities in MG populations, MG patients demonstrated higher mean age at death than both MS patients and the general population.</p><p><strong>Conclusion: </strong>MG was associated with significantly older age at death compared with both MS and the general population under historical standard-of-care conditions. These findings suggest that survival patterns in MG differ from those in MS and raise questions about the factors driving this difference. Further studies are needed to clarify the roles of disease biology, comorbidity, age at diagnosis, and healthcare utilization in shaping long-term outcomes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261472638"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664615","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":"Comment on: Psoriasis under B-cell depleting therapies in multiple sclerosis: a retrospective multicenter analysis.","authors":"Meng Li, Zhining Mo","doi":"10.1177/17562864261468450","DOIUrl":"10.1177/17562864261468450","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261468450"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664604","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":"Medical cannabis improved self-reported spasticity rating in patients with chronic spinal cord injury: a placebo-controlled, double-blind, crossover pilot clinical trial.","authors":"Nattha Boonthanakorn, Sintip Pattanakuhar, Pratchayapon Kammuang-Lue, Siam Tongprasert, Apichana Kovindha","doi":"10.1177/17562864261468464","DOIUrl":"10.1177/17562864261468464","url":null,"abstract":"<p><strong>Background: </strong>Previous studies demonstrated that cannabinoids may reduce spasticity in patients with spinal cord injury (SCI); however, the effect of naturally extracted THC:CBD oil, the most commonly used naturally extracted cannabinoids, has yet to be elucidated.</p><p><strong>Objectives: </strong>To assess the effect of a 1:1 THC:CBD oil on reducing spasticity in chronic SCI patients.</p><p><strong>Design: </strong>A single-center, placebo-controlled, double-blind crossover clinical trial.</p><p><strong>Methods: </strong>Sixteen chronic SCI patients with intractable spasticity were randomly assigned to either the intervention (1:1 THC:CBD oil) or control (placebo) phase for 1 month, then crossed over. The primary outcome (combined Ashworth Scale [AS] of all involved muscle groups) and the secondary outcomes, including patient-rated visual analog scale (VAS) of spasticity, were assessed before and after both phases and analyzed using a multilevel mixed-effects model.</p><p><strong>Results: </strong>All participants completed the study. The average (SD) dose of THC:CBD oil was 11.6 (1.3) mg. No significant difference in the total AS score for all involved muscle groups was found between the pre- and post-treatment phases, or between the experimental and control phases (all <i>p</i> > 0.05). A significant reduction was observed in the patient rating VAS (effect size = -13.9 [95% CI: -25.5 to -2.3; <i>p</i> = 0.010).</p><p><strong>Conclusion: </strong>In people with chronic SCI who had intractable spasticity, there was no statistically significant effect of 1:1 THC:CBD oil on spasticity-related outcomes, except for patient rating VAS reduction. Further studies are needed to evaluate the efficacy of higher doses of THC (>12 mg/day) and to use patient-reported spasticity scores as the primary outcome measure.</p><p><strong>Trial registration: </strong>The study was registered with the Thai Clinical Trials Registry (TCTR identification number: TCTR20220329001).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261468464"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664538","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-specific effects of methylprednisolone on outcomes after endovascular treatment for acute ischemic stroke due to large vessel occlusion: A secondary analysis of the MARVEL trial.","authors":"Lijiao Zhang, Jie Pan, Lilan Wang, Chunye Chen, Mingrui Zhou, Sheng Zhou, Haoxuan Zhu, Xiaolei Shi, Shihai Yang, Mingyang Chen, Yihui Yang, Yuhan Fan, Binghan Wang, Guojian Liu, Linyu Li, Chawen Ding, Jiaxing Song, Lingyu Zhang, Gaoming Li","doi":"10.1177/17562864261473898","DOIUrl":"10.1177/17562864261473898","url":null,"abstract":"<p><strong>Background: </strong>Sex-based differences in treatment response to neuroprotective strategies during endovascular treatment (EVT) for acute ischemic stroke remain poorly understood.</p><p><strong>Objectives: </strong>This study aimed to evaluate sex-specific effects of methylprednisolone on outcomes after EVT for acute ischemic stroke due to large vessel occlusion.</p><p><strong>Design: </strong>Secondary analysis of the MARVEL (Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke) randomized controlled trial.</p><p><strong>Methods: </strong>We compared outcomes following methylprednisolone versus placebo, stratified by sex. We also compared outcomes between women and men receiving methylprednisolone. The primary outcome was defined as the 90-day modified Rankin Scale score (mRS) ordinal shift. Secondary outcomes included mRS score of 0-4, 0-3, 0-2, 0-1 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 hours.</p><p><strong>Results: </strong>This study included 1680 patients (49.9% methylprednisolone, 56.7% men). Stratified by sex, among men, the methylprednisolone group was more likely to have a primary outcome compared with placebo [adjusted OR (aOR) 1.26 (1.00-1.59), <i>P</i> = 0.047] and reduce mortality (<i>P</i> < 0.01) and sICH (<i>P</i> = 0.031); among women, the primary outcome was similar between two treatment arms (<i>P</i> = 0.66), with similar findings for the safety outcomes. Additionally, stratified by different treatment arms, no significant difference was found in the primary outcome between men and women treated with methylprednisolone (<i>P</i> = 0.31) and placebo (<i>P</i> = 0.68).</p><p><strong>Conclusions: </strong>In this exploratory analysis, methylprednisolone appeared to be associated with better clinical outcomes in men compared with placebo. Nevertheless, the interaction between treatment and sex was not statistically significant. Furthermore, among patients receiving methylprednisolone, clinical outcomes did not differ significantly between men and women.</p><p><strong>Registration: </strong>ChiCTR.org.cn Identifier: ChiCTR2100051729.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261473898"},"PeriodicalIF":4.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653992","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":"Cardiac photon-counting detector computed tomography in acute ischemic stroke: diagnostic accuracy for detection of left atrial appendage thrombus.","authors":"Annemarie Kirschfink, Mohamed Elhalal, Stefan Seidel, Stefanie Kammer, Dimah Hasan, Michael Frick, Nikolaus Marx, Jörg B Schulz, Martin Wiesmann, Ertunc Altiok, Hani Ridwan, Arno Reich, João Pinho","doi":"10.1177/17562864261466073","DOIUrl":"10.1177/17562864261466073","url":null,"abstract":"<p><strong>Background: </strong>In up to one-third of ischemic stroke patients, no cause can be identified. Left atrial appendage (LAA) is the primary anatomical origin of cardiac embolism, yet it is often inadequately assessed in stroke etiological workup.</p><p><strong>Objectives: </strong>The goal of this study was to analyze the diagnostic accuracy of cardiac photon-counting detector computed tomography (PCD-CT) integrated in the acute stroke imaging protocol for detection of LAA thrombus.</p><p><strong>Design: </strong>Retrospective diagnostic accuracy study.</p><p><strong>Methods: </strong>We selected consecutive patients with acute ischemic stroke or transient ischemic attack undergoing emergent cardiac PCD-CT and transesophageal echocardiography (TEE) between 2023 and 2025. Cardiac PCD-CT and TEE were assessed for the detection of LAA thrombus. Patients with and without LAA thrombus (defined by PCD-CT) were compared. Diagnostic performance metrics for cardiac PCD-CT for LAA thrombus detection were calculated using TEE as the gold standard.</p><p><strong>Results: </strong>We included 101 patients, 42 were female (42%), median age was 59 years, 87 patients had acute ischemic stroke (86%). Median time between cardiac PCD-CT and TEE was 2 days. LAA thrombus defined by PCD-CT was present in 12 patients (12%). Patients with LAA thrombus were older (74 vs 58 years, <i>p</i> < 0.001) and more frequently had atrial fibrillation (83.3% vs 23.6%, <i>p</i> < 0.001). Diagnostic accuracy of PCD-CT was 96% (95% confidence interval (95%CI) = 90%-99%), sensitivity was 90% (95%CI = 56-100), specificity was 97% (95%CI = 91%-99%), positive predictive value was 75% (95%CI = 49%-90%), and negative predictive value was 99% (95%CI = 93%-100%).</p><p><strong>Conclusion: </strong>Cardiac PCD-CT integrated as part of the acute stroke imaging protocol is a promising diagnostic tool that may reliably exclude the presence of LAA thrombus.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261466073"},"PeriodicalIF":4.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653964","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":"Cerebral small vessel disease impairs dynamic cerebral autoregulation and mediates outcomes after stroke thrombectomy.","authors":"Yue Qiao, Ran Liu, Lupei Cai, Min Zhao, Boyi Yuan, Siying Fan, Shengjun Wang, Jiameng Li, Longfei Wu, Yingqi Xing, Qingfeng Ma, Wenbo Zhao","doi":"10.1177/17562864261470197","DOIUrl":"10.1177/17562864261470197","url":null,"abstract":"<p><strong>Background: </strong>Cerebral small vessel disease (CSVD) is associated with poor outcomes after endovascular thrombectomy (EVT), but the underlying mechanism remains unclear. Impaired dynamic cerebral autoregulation (dCA), a fundamental function of cerebral microvasculature, has been proposed as a potential mediator but has not been systematically investigated.</p><p><strong>Objectives: </strong>To determine whether CSVD burden influences functional outcomes through alterations in dCA.</p><p><strong>Design: </strong>Observational-cohort-study.</p><p><strong>Methods: </strong>We included 107 patients with anterior circulation large-vessel occlusion and successful EVT (expanded Thrombolysis in Cerebral Infarction ⩾2b). CSVD burden was assessed using standardised neuroimaging markers and dichotomised as none-to-mild (score 0-1) versus moderate-to-severe (score 2-3). dCA was assessed at two time points: early phase (T1, around 24 h post-EVT) and early subacute phase (T2, around 4-5 days post-EVT). Mediation analysis was performed to assess whether dCA changes mediated the association between CSVD burden and functional independence (modified Rankin Scale (mRS) score 0-2) at 90 days.</p><p><strong>Results: </strong>Patients with moderate-to-severe CSVD (<i>n</i> = 38) demonstrated distinct dCA recovery patterns compared with those with none-to-mild CSVD (<i>n</i> = 69). While patients with none-to-mild CSVD exhibited improved very low frequency (VLF, 0.02-0.07 Hz) phase differences from T1 to T2 (+7.67° (-9.73, 35.53)), those with moderate-to-severe CSVD exhibited deterioration (-7.17° (-25.03, -0.74), <i>p</i> = 0.004), which remained significant after multivariable adjustment (β = -20.06, 95% confidence interval (CI): -37.78 to -0.90, <i>p</i> = 0.040). Functional independence was achieved in 73.9% of patients with none-to-mild CSVD versus 52.6% in those with moderate-to-severe CSVD (adjusted OR 0.25, 95% CI 0.09-0.74, <i>p</i> = 0.012). Mediation analysis revealed that VLF phase changes in the affected side mediated 24.48% of the association between CSVD burden and functional outcome (average causal mediation effect: -7%, <i>p</i> < 0.001; total effect: -29%, <i>p</i> = 0.020).</p><p><strong>Conclusion: </strong>Higher CSVD burden was associated with worse functional outcomes after EVT, partially explained by impaired dCA. Patients with moderate-to-severe CSVD exhibited deteriorating dCA, whereas those with none-to-mild CSVD showed progressive improvement. Larger powerful studies are warranted to validate these findings and elucidate underlying mechanisms.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06361017.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261470197"},"PeriodicalIF":4.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653932","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":"Impact of tobacco and alcohol consumption on disease progression and MRI in people with multiple sclerosis: results of the prospective cohort study NationMS.","authors":"Alex Maximilian Keller, Annika Möhl, Anke Salmen, Ralf Gold, Pia Renk, Luisa Klotz, Stefan Bittner, Vinzenz Fleischer, Friedemann Paul, Klemens Ruprecht, Katrin Giglhuber, Hayrettin Tumani, Gisela Antony, Uwe Zettl, Sven G Meuth, Antonios Bayas, Corinna Trebst, Brigitte Wildemann, Florian Then Bergh, Daniel Kotz, Christoph Heesen","doi":"10.1177/17562864261464304","DOIUrl":"10.1177/17562864261464304","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle factors, such as smoking cigarettes and alcohol consumption, can influence disease progression in Multiple Sclerosis (MS).</p><p><strong>Objective: </strong>This study aimed to investigate the associations of smoking cigarettes and alcohol consumption with clinical parameters in people with MS (pwMS).</p><p><strong>Design: </strong>This is a prospective cohort study, analysing data from the German NationMS cohort.</p><p><strong>Methods: </strong>We analysed data of 1374 patients recruited between 2010 and 2017. Main outcomes were Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW) and Paced Auditory Serial Addition Test (PASAT). Secondary outcomes were number of T2 and GD+ lesions. We conducted logistic and linear mixed model regression, adjusted for age, sex, educational level, MS subtype.</p><p><strong>Results: </strong>Smoking cigarettes was associated with increased odds of reaching pre-defined cut-off values for EDSS and T25FW, as well as with increased mean differences across follow-ups. Alcohol consumption was associated with decreased odds of reaching the cut-off for EDSS and T25FW. Findings for PASAT were less consistent. We found no significant associations for T2 and GD+ lesions.</p><p><strong>Conclusion: </strong>This study provides further evidence that smoking cigarettes accelerates MS progression and that pwMS should be advised to quit smoking. However, this negative impact could not be demonstrated for alcohol consumption. Reverse causation cannot be ruled out and further research in this area is warranted.</p><p><strong>Trial registration: </strong>Instead of registration in a primary trial registry, a comprehensive study protocol was published a priori and is available online: https://osf.io/3xscy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261464304"},"PeriodicalIF":4.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653995","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}