Stroke is frequently accompanied by respiratory dysfunction, which limits ventilatory reserve and may hinder functional recovery. Respiratory muscle training (RMT) can improve selected ventilatory indices, but overall benefits remain modest. This pilot trial aimed to evaluate the clinical effects of calcium-regulating pulsed electromagnetic fields (Ca-R-PEMF) combined with RMT on poststroke respiratory function. This single-center, prospective, double-blind pilot trial was conducted at Yongsen Hospital of China Medical University, China, from July to December 2025. Thirty patients were randomly assigned to standard rehabilitation plus sham stimulation (control group), standard rehabilitation plus sham stimulation and RMT (RMT group), or standard rehabilitation plus Ca-R-PEMF stimulation and RMT (Ca-R-PEMF+RMT group; n=10 per group). The intervention lasted 4 weeks, RMT was administered 5 sessions per week (20 minutes/session), and Ca-R-PEMF stimulation was administered 2 sessions per week (15 minutes/session). Outcome measures were recorded at baseline and after 4 weeks of intervention. The primary outcome was the change rate in forced vital capacity. Secondary outcomes included forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, peak expiratory flow, inspiratory capacity, and vital capacity. A total of 27 participants completed the 4-week follow-up (n=9 per group), and baseline characteristics were comparable across groups. The change rate in forced vital capacity differed significantly among groups (P<0.01; η2=0.47). Ca-R-PEMF+RMT showed greater improvement than both control and RMT, whereas the difference between control and RMT was not significant. For secondary outcomes, overall between-group differences were significant for FEV1 (P<0.01; η2=0.39) and peak expiratory flow (P<0.01; η2=0.41). Ca-R-PEMF+RMT was superior to control for both outcomes, and RMT was superior to control for FEV1. No significant between-group differences were observed for the change rates in the FEV1/forced vital capacity, inspiratory capacity, or vital capacity. No adverse events related to the treatment were reported. In this pilot trial, Ca-R-PEMF combined with RMT was feasible and appeared safe in patients with stroke and respiratory dysfunction. Following 4 weeks of training, Ca-R-PEMF+RMT showed more favorable signals of improvement in selected pulmonary ventilatory indices than standard rehabilitation alone and RMT alone, suggesting its potential value as a combined rehabilitation strategy. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2300078947.

The concept of vascular neurology-specific education was launched nearly 50 years ago in response to a growing understanding of the pathophysiology of stroke. The vascular neurology field, and the training required to support its growth and evolution, has been heavily influenced by a simultaneously increasing breadth of knowledge in approaches to clinical management of stroke. There are increasing numbers of vascular neurology fellows each academic year, yet we continue to experience shortages in clinical coverage for patients with vascular neurological conditions. Here, we review the origins of vascular neurology training and current challenges in sustaining educational programs. We then propose action items to help shape the future of vascular neurology education.

Stroke is a leading cause of death and disability worldwide, and the recovery process is significantly influenced by a multitude of factors beyond immediate medical treatment. Social and environmental determinants of health-conditions in which people are born, grow, work, live, and age-play a crucial role in the functional outcomes of stroke survivors, and addressing these factors is essential to ensure equitable care and optimal recovery. Previous scientific statements have discussed the effects of social isolation on cardiovascular and brain health, as well as strategies to reduce racial and ethnic inequities in stroke preparedness, care, recovery, and risk factor control. In this statement, we review the effect of factors such as social and environmental determinants on stroke functional outcome primarily but also secondary stroke prevention when relevant. In addition, we provide actionable considerations for addressing them to improve stroke outcomes; strategies include the identification of upstream factors, use of impactful policies, and use of implementation science frameworks to translate evidence-based practices into real-world settings. Current gaps for future research include understanding the effect of cultural considerations on stroke recovery, recognizing the interaction of social and environmental determinants of health with each other and with biological factors in determining stroke outcomes, and finding effective ways to address these factors in different environments to achieve best outcomes for all stroke survivors.

Stroke causes neurological impairment through local plasticity mechanisms, such as synaptic sprouting, and large-scale network reorganization. Although poststroke Wallerian degeneration is well established, whether white matter (WM) tracts' remodel over time to support behavioral recovery remains controversial. We investigated whether longitudinal changes in WM microstructure and structural connectivity are coupled to poststroke behavior, and how structural connectivity reorganization relates to local disconnection microstructure. In this prospective cohort study (Washington University, St. Louis; 2016-2018), patients with first-time stroke underwent diffusion-weighted magnetic resonance imaging and behavioral assessments at 2 weeks and 3 months poststroke; healthy controls were assessed twice. Latent factorial analysis was applied to behavioral and microstructural data from diffusion tensor imaging and neurite orientation dispersion and density imaging. Primary measures were whole-brain structural connectivity gradient divergences computed from tractography, microstructural diffusion parameters extracted from both WM and cortical regions disconnected by the lesion, and behavioral factors. Linear mixed models (adjusted for sociodemographic values) assessed longitudinal changes, linear regression assessed brain-behavior associations, and machine learning algorithms assessed differences between healthy controls and stroke. Seventy-nine patients (age, 60±12 years; 43% female; diffusion-weighted magnetic resonance imaging: 48 at 2 weeks and 26 at 3 months) and 33 age-matched healthy controls were included. At 2 weeks, patients with stroke exhibited diffuse whole-brain alterations in WM organization. These widespread changes were closely linked to microstructural abnormalities in WM pathways disconnected by the lesion. Notably, WM degeneration progressed between 2 weeks and 3 months poststroke. Whole-brain structural connectivity alterations were associated with cognitive deficits acutely but not at 3 months, whereas microstructural parameters in disconnected tracts were primarily related to motor impairment. In patients with predominantly mild-severity stroke, we observed widespread and progressive alterations in WM microstructure that persists beyond the lesion and continues to evolve over time. Although acute structural disconnection relates to behavioral deficits, chronic WM degeneration appears largely uncoupled from functional recovery.

Sex differences in stroke cause, vessel anatomy, and thrombus composition are well established, yet whether these factors influence the efficacy of specific endovascular thrombectomy (EVT) techniques remains unknown. Here, we investigate sex-based differences in reperfusion outcomes across EVT techniques. Consecutive patients with anterior circulation large vessel occlusion including intracranial internal carotid artery and the M1 and M2 segments of the middle cerebral artery treated with EVT across 4 comprehensive stroke centers in the Greater Houston area (January 2021 to June 2024) were included from a prospectively maintained registry. EVT techniques were categorized as stent retriever, contact aspiration, or combined technique. The primary outcome was the first-pass effect (modified Thrombolysis in Cerebral Infarction 2c/3 after 1 pass). Secondary outcomes included achieving modified Thrombolysis in Cerebral Infarction 2c/3 within 2 passes, 90-day modified Rankin Scale score (0-2), intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality. Multivariable logistic regressions were used for binary outcomes adjusted for age, National Institutes of Health Stroke Scale score, atrial fibrillation, smoking, and prior thrombolysis. Linear regression was used for the number of thrombectomy passes. Among 724 patients that met inclusion criteria, 47% were female, the median age was 68 (interquartile range, 54-78) years, and the National Institutes of Health Stroke Scale score was 16 (interquartile range, 11-21). Presentation characteristics were balanced except for a greater rate of atrial fibrillation in females (23.0% versus 16.6%; P<0.05) and lower rates of intravenous thrombolysis in females (31% versus 40%; P<0.05). EVT techniques were comparable between sexes. The first-pass effect across the cohort was similar (female versus male, 37.9% versus 36.3%). In females, contact aspiration yielded higher odds of first-pass effect (adjusted odds ratio, 2.17 [1.07-4.35]) and modified Thrombolysis in Cerebral Infarction 2c/3 within 2 passes (adjusted odds ratio, 2.63 [1.32-5.26]) versus stent retriever, with fewer passes overall (β, 0.28; P<0.05). No difference in reperfusion outcomes was seen between EVT techniques in the male subgroup. Among patients receiving stent retriever as their first pass, female sex was associated with lower odds of achieving reperfusion within 2 passes (adjusted odds ratio, 0.43 [0.19-0.99]). This multicenter analysis provides the first evidence that EVT technique performance differs by sex. In females, contact aspiration achieved superior reperfusion with fewer passes compared with stent retrievers. These findings highlight the importance of sex-stratified EVT trials and support individualized, precision-based device selection in acute ischemic stroke.

Informed consent forms (ICFs) for clinical trials are often written above the recommended eighth-grade level. We aimed to compare the readability of original ICFs used for National Institutes of Health-funded stroke-related clinical trials with ICFs edited for readability using artificial intelligence. Publicly available ICFs associated with National Institutes of Health-funded stroke-related clinical trials were accessed through ClinicalTrials.gov (search period: inception to August 12, 2025). Using ChatGPT-4o, we created a customized Generative Pre-Trained Transformer (GPT) designed to lower the reading level to eighth grade or below while maintaining ICF content. We processed each ICF using this GPT to create edited ICFs. Standard readability metrics, including the Flesch-Kincaid grade level (primary outcome), were compared between original and edited ICFs using paired t tests or the McNemar test (cross-sectional design). We also assessed semantic similarity using the MPNet language model, which produced continuous scores from 0 (no similarity) to 1 (perfect similarity). ICFs were available for 46 stroke trials, including behavioral (n=21), device (n=15), drug (n=5), and other (n=5) intervention types. Mean reading levels were 11.52 for the original and 9.47 for the GPT-edited ICFs using the Flesch-Kincaid grade level (P<0.001). Only 1 (2%) of the original ICFs and 18 (39%) of the GPT-edited ICFs had a Flesch-Kincaid reading level at or below eighth grade (P<0.001). Both the Simple Measure of Gobbledygook and Gunning Fog Index favored the GPT-edited ICFs by 1 to 2 grade levels. The Flesch Reading Ease score favored the GPT-edited ICFs by about 8 points. The mean similarity score was 0.85 (SD=0.04). GPT-edited ICFs achieved a readability reduction of approximately 2 grade levels compared with the original ICFs while preserving high semantic similarity. Customized GPTs may be a useful tool to improve the readability of clinical trial ICFs.

Ischemic tolerance is an inducible state in which the brain becomes transiently resistant to injury. Across models, conditioning recruits 3 coordinated modules: (1) rapid synaptic downscaling that lowers excitability and delays ischemic depolarization, (2) metabolic reprogramming that matches demand with reduced mitochondrial reactive oxygen species, and (3) a delayed consolidation phase that stabilizes the phenotype. A delayed window integrates nicotinamide adenine dinucleotide (NAD)+/sirtuin pathways (PKCε [protein kinase C epsilon]→NAMPT [nicotinamide phosphoribosyltransferase]→NAD+, SIRT1 [sirtuin 1] control of glycolysis, and SIRT5 [sirtuin 5] desuccinylation), maintenance of the malate-aspartate shuttle, and proteostasis/innate-immune programs (HSP70 [heat shock protein 70]/HSP27 [heat shock protein 27]/HO-1 [heme oxygenase-1]; interferon-biased signaling). These mechanisms exhibit similarities with evolutionary adaptations while preserving the capacity for plasticity via homeostatic scaling. Both preconditioning and postconditioning mitigate ischemia-induced cognitive impairment by limiting pathology in the septal nuclei. Specifically, physical exercise restores septohippocampal oscillatory coherence, which is linked to cognitive improvement. Clinically, the best scenarios for treatment are predictable ischemia and well-phenotyped high-risk cohorts. Future priorities are further elucidation of mechanisms of conditioning mimetics, rational combinations (eg, exercise or remote conditioning layered with these mimetics), and preclinical designs incorporating aging and comorbidities to derisk translation.

Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21-1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97-1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10-0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83-1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04-0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15-0.73]). After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06398366.