Introduction Collateral circulation is a critical determinant of outcomes in acute ischemic stroke (AIS). This bibliometric analysis evaluates research trends and future directions on this topic. Methods A systematic search was conducted in the Web of Science Core Collection to identify publications on AIS and collateral circulation between 1981 and 2025. Bibliometric analysis and visualization were performed using VOSviewer, CiteSpace, and the R package “bibliometric.” Results The analysis included 482 publications. China was the most productive countries, leading in publication volume (642). The University of California System emerged as top contributing institutions. Stroke was the most influential journals in terms of H-index (33), TP (53), and TC (3796). David S. Liebeskind and Gregory W. Albers were identified as leading authors. Keyword co-occurrence and cluster analysis revealed four main thematic areas: imaging and diagnostic assessment, treatment strategies, prognosis and outcome prediction, and pathophysiological mechanisms and hemodynamics. In addition, burst keyword analysis showed that terms like “large vessel occlusion”, “score”, “management”, and “endovascular thrombectomy” remained active through 2025. Conclusion Research on collateral circulation in AIS has evolved from exploring basic mechanisms to focusing on clinical applications. The current landscape integrates imaging-based collateral assessment with treatment decisions and prognosis to guide precise endovascular therapy. Future research will likely concentrate on collateral-guided precision treatment, imaging scores, and strategies for extending the therapeutic window. This study provides a comprehensive overview and valuable insights for researchers.

Convincing evidence suggests that FoxO signaling (FS) dysfunction is associated with cancer progression and tumorigenesis but its effect on the tumor microenvironment (TME) and immunotherapy response remains unclear. Here, we retrieved FS-related genes from the KEGG database, first analyzing their differential expression in 31 TCGA cancer types with matched Genotype-Tissue Expression (GTEx) normal tissue data. We then calculated FS scores via ssGSEA for 33 TCGA cancer types, systematically exploring their prognostic value and correlations with TME characteristics and immunotherapy response. High FS scores were consistently associated with an immunosuppressive TME and poorer OS across multiple tumor types. Analysis of the IMvigor210 immunotherapy cohort further revealed elevated FS scores correlated with anti-PD-1 treatment resistance. Focusing on gliomas, we identified FS-based molecular subtypes and constructed a PCA score that robustly predicted glioma prognosis and immune checkpoint inhibitor response. External validation was achieved in independent CGGA and GEO cohorts. Our findings indicate that FS is a key modulator of the immunosuppressive TME and support FS and PCA scores as potential prognostic and immunotherapeutic biomarkers for gliomas with their clinical utility pending experimental validation.

IMPORTANCE:Early post-stroke seizures (EPSS) are one of the early complications of large vessel occlusion (LVO) following endovascular treatment (EVT). However, the association between EPSS and functional outcomes remains poorly understood. Therefore, we aimed to investigate the incidence, risk factors, and clinical outcomes of EPSS in LVO patients after recanalization. MATERIALS AND METHODS:This study was an individual patient data level analysis of three randomized controlled trials conducted in China, including the RESCUE-BT, DEVT, and MARVEL trials. Acute ischemic stroke patients with LVO who underwent successful EVT within 24 h of symptom onset were enrolled. EPSS were defined as seizures occurring within 7 days of stroke onset, confirmed by clinical assessment with or without electroencephalography. The primary outcome was the poor outcome [90-day modified Rankin Scale (mRS) scores of 4-6]. Secondary outcomes included 90-day mortality, 90-day functional independence (mRS scores of 0-2), and early neurological function [defined as National Institutes of Health Stroke Scale (NIHSS) at 5-7 days or discharge]. RESULTS:Of the 2862 patients screened for eligibility, 2524 patients achieved recanalization and were included, with a median (IQR) age of 69 (58-76) years; 1452 (57.5%) were men. A total of 71 (2.8%) patients developed EPSS. After adjustment of confounders, independent predictors of EPSS included higher baseline NIHSS scores and worse recanalization grade [the expanded thrombolysis in cerebral infarction (eTICI) 2b; P < 0.05]. EPSS were significantly associated with the poor outcome [adjusted odds ratio: 2.85, 95% confidence interval (CI): 1.66-4.88, P < 0.01] and worse early neurological function (β coefficient: 7.48, 95% CI: 4.80-10.17, P < 0.01). Propensity score matching and sensitivity analyses also showed consistent results. Mediation analysis suggested that the harmful effect of an unfavorable recanalization grade on the poor outcome was partly explained by its association with an increased risk of EPSS, which accounted for 1.8% (95% CI: 0.3%-8.6%) of the total effect. CONCLUSION:EPSS is associated with the poor outcome in acute LVO patients who achieved successful recanalization. Complete recanalization might be associated with a lower risk of EPSS, potentially contributing to better functional outcomes. These findings provide clinically relevant insights for periprocedural management in acute LVO patients.

BACKGROUND:Cardiac complications rank among the leading contributors to poor outcomes in ischemic stroke patients along with the neurological impairment, while the risk stratification and prognostic significance of post-stroke acute heart failure (PSHF) remain poorly characterized. This study aimed to investigate the incidence, predictors, and impacts of PSHF in patients with large vessel occlusion stroke (LVO) undergoing endovascular treatment (EVT). Given that cardioembolic stroke inherently involves underlying cardiac pathology, a secondary aim was to test whether the effect of stroke severity on PSHF was modified by cardioembolic etiology and whether PSHF mediated the effect of stroke severity on functional outcome in these patients. METHODS AND FINDINGS:In a pooled analysis of individual patient data from four multicenter prospective studies conducted in China between January 2014 and June 2023, we included 3,415 patients with LVO who underwent EVT. The primary outcome was very poor functional outcome, defined as 90-day modified Rankin Scale (mRS) 5-6. Multivariable regression models, interaction testing, and mediation analysis were used, with adjustment for clinically relevant covariates including demographic characteristics, vascular risk factors, baseline stroke severity, imaging characteristics, and treatment-related factors. PSHF developed in 278 patients (8.14%), with its incidence reaching peak at 1 day after stroke onset. PSHF was significantly associated with a higher rate of very poor outcome (62.23% versus 31.08%, adjusted odds ratio (aOR) 3.09, 95% confidence interval (CI) [2.25, 4.24]). A significant interaction was observed between cardioembolism and the baseline National Institutes of Health Stroke Scale (NIHSS) score (p for interaction = 0.016). Moderate-to-severe stroke significantly increased the risk of PSHF in patients with cardioembolic stroke (aOR 1.91, 95% CI [1.28, 2.87]), but not in those with non-cardioembolic stroke (aOR 0.97, 95% CI [0.81, 1.82]). Mediation analysis showed that PSHF mediated 7.70% (95% CI [2.40, 12.40]) of the effect of moderate‑to‑severe stroke on very poor outcome among cardioembolic patients. The main methodological limitations were the pooled design using studies with different protocols and the potential for residual unmeasured confounding. CONCLUSIONS:PSHF was significantly associated with very poor outcome in LVO patients undergoing EVT. Moderate-to-severe cardioembolic LVO substantially elevated the risk of PSHF, with PSHF partially mediating the adverse prognostic impact of stroke severity. Early risk assessment and monitoring for PSHF may optimize management in this high-risk population.

Epilepsy, a common neurological disorder, is distinguished by abnormal neuronal activity. This study explored the mechanism of the long non-coding RNA (lncRNA) GABPB1-AS1/SLC12A5 pathway modulating neuronal ferroptosis during epileptic seizures. Loss- and gain-of-function approaches were conducted in a mouse model of kainic acid-induced seizures and glutamic acid (Glu)-treated HT22 neurons to explore the regulatory effect of lncRNA GABPB1-AS1/SLC12A5 on neuronal ferroptosis. Mouse seizures were assessed using the Racine scale. LncRNA GABPB1-AS1, SLC12A5, and ferroptosis-related markers were measured via RNA quantification, Western blot, and immunofluorescence. The direct or indirect interaction between lncRNA GABPB1-AS1 and SLC12A5 was validated using RIP, RNA pull-down, and Co-IP assays. CHX chase and ubiquitination assays assessed SLC12A5 stability and ubiquitination levels regulated by lncRNA GABPB1-AS1. LncRNA GABPB1-AS1 was upregulated in the hippocampal CA1 region of KA-induced mice. LncRNA GABPB1-AS1 knockdown suppressed neuronal ferroptosis-lowering Fe2+, MDA, and lipid peroxidation, while raising GSH, SLC7A11, and GPX4. Its knockdown also reduced seizure scores and frequency, prolonged seizure latency, and shortened seizure duration. An in vitro experiment verified the suppressive effect of lncRNA GABPB1-AS1 knockdown on neuronal ferroptosis. In addition to a direct binding relationship, this lncRNA further recruited the E3 ligase PRKN to enhance SLC12A5 ubiquitination and proteasomal degradation. SLC12A5 overexpression inhibited Glu-induced ferroptosis, and SLC12A5 knockdown partially reversed the effects exerted by lncRNA GABPB1-AS1. LncRNA GABPB1-AS1 recruits the E3 ligase PRKN to promote ubiquitination and proteasomal degradation of SLC12A5, thereby downregulating SLC12A5 expression and facilitating hippocampal neuronal ferroptosis that mediates epileptic seizures.

Aberrant dendritic changes in epilepsy, morphologically measured by the complexity and length of dendrite, as well as the density of dendritic spines, are dynamic and various considering disease course, developmental stages, and various neuronal type across different brain regions. Correspondingly, imbalanced excitatory and inhibitory synapses in epilepsy, quantitatively measured by the expression level and location of synaptic proteins, still vary considering etiology, disease course, and brain regions. And, various mechanisms involved in synaptic pruning add to the complexity of synaptic alterations in epilepsy. Still, sharing mechanisms underlying aberrant dendritic and synaptic plasticity in epilepsy exist, and cytoskeletal alterations can serve as a tool to decipher alterations of dendritic morphology and synaptic plasticity in epilepsy. Evidences supporting aberrant microtubule dynamics and post-translational modifications of tubulin in epilepsy emerge, combined with their involvement in dendritic morphology and synaptic plasticity. In conclusion, this review respectively summarizes the characteristics of dendritic pathology, synaptic alterations, microtubule dynamics, and tubulin's post-translational modifications in epilepsy, and discusses their interplay and correlation in epilepsy, providing insight into how cytoskeletal organization contributes to macroscopic changes in epilepsy.

IntroductionPost-stroke depression (PSD) adversely affects neurological functional recovery in patients. Transcutaneous auricular vagus nerve stimulation (ta-VNS) has demonstrated antidepressant potential. As the receptor ALK5 may regulate neuroplasticity by modulating the Smad2/3 and Gadd45β signaling pathways, we hypothesized that ta-VNS alleviates PSD by activating this pathway. This study aimed to evaluate the therapeutic effects of ta-VNS on a PSD rat model and to investigate the involvement of the ALK5/Smad2/3/Gadd45β signaling pathway in mediating these effects.MethodsA PSD rat model was established by combining middle cerebral artery occlusion (MCAO) with chronic unpredictable mild stress (CUMS). To investigate the underlying mechanisms, ALK5 expression was knocked down in the right prefrontal cortex (PFC) via AAV-shALK5 injection, followed by a 14-day ta-VNS treatment. Depression-like behaviors were evaluated using the sucrose preference, forced swimming, and open-field tests. Neuroprotection was assessed through hematoxylin–eosin, Nissl, and TUNEL staining. Neurotransmitter expression was measured by enzyme-linked immunosorbent assay (ELISA). Neurogenesis, along with axonal, dendritic, and synaptic plasticity, was assessed by immunostaining and Western blot analysis of DCX, Nestin, NF-200, GAP-43, MAP-2, and PSD95, SYN. Additionally, dendritic morphology was visualized by Golgi-Cox staining, and in addition, synaptic ultrastructure was characterized using transmission electron microscopy. Protein levels of the ALK5/Smad2/3/Gadd45β pathway were analyzed by Western blot.ResultsTa-VNS treatment restored the PSD-induced downregulation of ALK5. Furthermore, the beneficial effects of ta-VNS—including the amelioration of depressive-like behaviors, provision of neuroprotection, upregulation of serotonin (5-HT) and dopamine (DA) expression, promotion of neurogenesis, and enhancement of neuroplasticity—were all abolished upon ALK5 knockdown. Finally, ta-VNS was found to activate the Smad2/3/Gadd45β signaling pathway in an ALK5-dependent manner.ConclusionOur findings demonstrate that ta-VNS ameliorates depressive-like behaviors and enhances neuroplasticity in PSD by activating the ALK5/Smad2/3/Gadd45β signaling pathway in the PFC. These results elucidate a novel molecular mechanism underlying the therapeutic effects of ta-VNS, highlighting its potential as a treatment strategy for PSD.

Abstract Background Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number ChiCTR2300074147 ( www.chictr.org.cn ).

Compound acid chemical peeling is widely used to treat acne vulgaris (AV), but the biological mechanisms underlying its clinical effects remain incompletely understood. We hypothesized that compound acid chemical peeling would improve acne severity and would be associated with changes in the skin microbiome and a reduction in local inflammatory responses in patients with moderate AV. This study aimed to investigate the clinical, microbiological, and inflammatory effects of compound acid peeling in this population. We carried out a prospective, split‑face, randomized trial enrolling 30 patients with moderate AV. One hemiface received compound acid peeling twice weekly for 3 weeks (6 total sessions), followed by a 9‑week observation period. The contralateral hemiface received no treatment for the first 3 weeks and then underwent the same peeling protocol for 3 weeks, with a 6‑week follow‑up. Outcome measures included the Global Acne Grading System (GAGS), patient self‑assessment, standardized facial imaging, skin biopsy with immunohistochemistry, bacterial DNA extraction, PCR amplification, and 16S rRNA gene sequencing. Patients showed a statistically significant improvement in GAGS scores (P < 0.001). Facial imaging analysis revealed reductions in redness and porphyrin readings. Immunohistochemical staining for interleukin (IL)-1α, IL-6, IL-17, transforming growth factor-β (TGF-β), and toll-like receptor 2 (TLR2) was reduced. Skin microbiome alpha diversity decreased, with a notable decrease in the relative abundance of Staphylococcus (P < 0.05). Throughout the study, no adverse events were reported. Compound acid peeling was effective and well-tolerated during the observation period and was associated with changes in the skin microbiome and local inflammatory marker staining.

Diffuse glioma-related epilepsy (dGRE) frequently presents with epilepsy as the initial symptom and is closely associated with tumor progression or recurrence, imposing significant social and psychological burdens on patients. The pathogenesis of dGRE is highly complex, involving both peritumoral microenvironmental mechanisms and tumor-intrinsic factors. Diagnosis requires a comprehensive approach integrating neuroimaging, EEG, molecular biomarkers, and spatial correlation between the tumor and the epileptogenic zone. Management aims to control seizures and improve prognosis. Non-enzyme-inducing anti-seizure medications (ASMs), such as levetiracetam and lacosamide, are recommended as first-line therapy, while valproic acid serves mainly as a second-line agent. Surgical resection, particularly maximal safe and supratotal removal guided by electrophysiological monitoring, significantly improves seizure outcomes. Radiotherapy, chemotherapy, and targeted agents further contribute to seizure control. The updated 2025 Chinese clinical practice guidelines incorporate recent advances in ASM use, postoperative withdrawal strategies, and multidisciplinary treatment algorithms. These updates provide an evidence-based reference for standardized diagnosis and management of dGRE.

BACKGROUND:Whether cerebral microcirculation influences the likelihood of early neurological improvement (ENI) is poorly understood in patients with acute ischemic stroke (AIS). We assessed the microcirculation time using digital subtraction angiography (DSA) and analyzed its impact on ENI at discharge and long-term outcomes in AIS treated by endovascular treatment. METHODS:This was a retrospective cohort study of patients with AIS. All patients underwent standard cerebral DSA immediately after successful recanalization. We used the syngo iFlow software to assess the microvascular cerebral circulation time (mCCT) in the regions of interest on DSA. The primary outcome was ENI at discharge, defined as a decrease of ≥8 points or a National Institutes of Health Stroke Scale score of 0 or 1 when discharge. Logistic regression was conducted to analyze the impact of mCCT on prognosis. RESULTS:A total of 156 patients were included in the current study. The median age was 69 years, and 44.2% were male. Multivariate analysis showed that shorter mCCT was significantly associated with ENI at discharge (adjusted odds ratio[aOR] 4.79, 95% confidence interval [CI] 2.01-11.45, P<0.001) and functional independence at 90 days (aOR 3.64, 95% CI 1.53-8.67, P<0.001). The area under the receiver operating characteristic curve was significantly enhanced by including mCCT in the conventional model (0.830 vs 0.758, P=0.01, DeLong test). Finally, the mCCT model demonstrated good discrimination and calibration in this cohort, as well as the fivefold cross validation. CONCLUSION:DSA-based mCCT after successful recanalization is an independent predictor of ENI at discharge (aOR 4.79) and long-term functional outcomes (aOR 3.64).

RATIONALE AND OBJECTIVES: Successful recanalization fundamentally reshapes cerebral hemodynamics in acute ischemic stroke (AIS), making preprocedural hemodynamic biomarkers alone inadequate. We assessed postoperative venous outflow (PVO) based on digital subtraction angiography (DSA) and explored its prognostic role. MATERIALS AND METHODS: This retrospective cohort study included AIS patients who achieved recanalization. All patients underwent standard cerebral DSA immediately after successful recanalization. We assessed the microvascular cerebral circulation time (mCCT) and cortical vein opacification score (COVES) based on DSA. The primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Logistic regression and receiver operating characteristic (ROC) analysis were used. RESULTS: 156 patients were included (median age 69 years and 44.2% men). ROC curve analysis determined the optimal cut-off of 4 for COVES dichotomization. Multivariate analysis showed that the favorable PVO (COVES ≥ 4) was significantly associated with functional independence at 90 days (adjusted odds ratio 10.55, 95% confidence interval 3.86-28.88, p < 0.001). After incorporating PVO into the conventional model, the area under the receiver operating characteristic curve increased significantly (0.882 vs. 0.816, p = 0.008, DeLong test) and was not inferior to the mCCT model (0.882 vs. 0.860, p = 0.210). Finally, the PVO model demonstrated good discrimination and calibration, confirmed by fivefold cross-validation. CONCLUSION: The DSA-based PVO after successful recanalization is an effective and practical prognostic surrogate for functional outcomes in AIS, providing predictive value for 90-day functional outcomes comparable to the more complex mCCT.

Acute ischemic stroke (AIS) represents a major global contributor to mortality and chronic disability, with few effective therapeutic targets available. Identifying druggable genes associated with AIS is therefore critical for developing novel interventions. A comprehensive approach combining Mendelian randomization, multi-omics integration, and machine learning was employed to identify candidate druggable genes. Causal relationships were confirmed through genetic colocalization, and candidate genes were further validated in a retrospective clinical cohort comprising 60 patients who experienced AIS and 30 healthy controls. Functional and mechanistic investigations were performed using a male mouse middle cerebral artery occlusion/reperfusion (MCAO/R) model, oxygen–glucose deprivation/reperfusion (OGD/R) in HT22 cells, and 293 T cells. SLK emerged as a genetically causal AIS gene and a central component of the optimal predictive model. Plasma SLK levels were elevated in patients who experienced AIS, demonstrating strong diagnostic and prognostic value and serving as an independent predictor of unfavorable 3-month outcomes after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Knockdown of SLK conferred neuroprotection both in vivo and in vitro. SLK interacted with and phosphorylated the deubiquitinase USP8, increasing its activity and suppressing K48-linked polyubiquitination and degradation of HIF-1α. HIF-1α was stabilized following activation of the RhoA/ROCK signaling pathway, aggravating ischemic injury, whereas USP8 overexpression mitigated the neuroprotective effects of SLK knockdown. These findings identify SLK as a neuron-specific proischemic factor and a potential therapeutic target, elucidate the SLK–USP8–HIF-1α–RhoA/ROCK pathway as a key mechanistic pathway, and highlight plasma SLK as a promising diagnostic and prognostic biomarker with translational relevance.

Introduction and importance: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disorder with heterogeneous clinical presentations. Although headache is the most common symptom, atypical presentations without headache may lead to diagnostic challenges, particularly in elderly patients. Seizures are a recognized manifestation of CVST but are occasionally the sole initial presentation. Case presentation: We describe a 64-year-old man with recurrent seizures and transient right-sided weakness, without headache. Brain magnetic resonance imaging revealed left frontal encephalomalacia, which initially complicated the diagnostic evaluation. Markedly elevated D-dimer levels and bilateral calf vein thrombosis were identified, while subsequent multimodal imaging, including computed tomography venography, demonstrated superior sagittal sinus thrombosis with prominent collateral venous channels. The seizures were considered to be related to a combined mechanism, in which the pre-existing encephalomalacic lesion may have increased seizure susceptibility, and CVST may have acted as a precipitating factor. Anticoagulation therapy and appropriate antiseizure treatment led to seizure resolution and clinical improvement. Clinical discussion: This case highlights a diagnostic pitfall in which competing but plausible findings may delay recognition of CVST. In elderly patients with atypical presentations, reliance on a single explanatory finding may contribute to premature diagnostic closure. Persistent or unexplained neurological symptoms should prompt reconsideration and further vascular imaging. Conclusion: CVST should be considered in patients with unexplained seizures, even in the absence of a headache. Early recognition and timely anticoagulation are essential to improve outcomes.

Importance:Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion. Objective:To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. Design, Setting, and Participants:This investigator-initiated, randomized, open-label, blinded-end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024. Interventions:Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267). Main Outcomes and Measures:The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results:A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups. Conclusions and Relevance:Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days. Trial Registration:ChiCTR.org.cn Identifier: ChiCTR2200065617.

Importance Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion. Objective To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. Design, Setting, and Participants This investigator-initiated, randomized, open-label, blinded–end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024. Interventions Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267). Main Outcomes and Measures The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups. Conclusions and Relevance Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days. Trial Registration ChiCTR.org.cn Identifier: ChiCTR2200065617

Persistent postural-perceptual dizziness (PPPD) is a chronic functional dizziness often triggered by vestibular, psychological, or environmental factors. Current treatments, including pharmacological and cognitive therapies, show limitations. In recent years, transcranial magnetic stimulation (TMS) has been explored in other neuropsychiatric disorders but has not been studied extensively for PPPD. We aimed to evaluate the efficacy and safety of TMS of the left high-frequency dorsolateral prefrontal cortex (DLPFC) in improving dizziness and mood disorders in patients with PPPD in a single-blind, placebo-randomized controlled trial. This trial recruited patients from October 8, 2023, to June 30, 2024, with follow-up completed on September 30, 2024, of 80 patients screened from the second affiliated hospital of Chongqing Medical University in China. Totals of 4 patients were excluded and 66 patients were randomized. PPPD patients were randomized to receive either TMS (10 Hz, 20 min) or SHAM-TMS treatments to the left DLPFC over ten sessions within 2 weeks. Dizziness severity, anxiety, and depression quality were assessed at baseline, post-treatment, and 1 and 3 months. Adverse events were also monitored. Of 66 eligible patients [median (IQR) age, 54.5 (49.8–67.0) years; Of 42 women (63.6

Purpose:Although the predictive role of cerebral tissue impairment has been extensively investigated in acute ischemic stroke (AIS) patients undergoing endovascular treatment (EVT) in the late window, the impact of peripheral organs on clinical outcomes in these patients remains largely unknown. Therefore, we aimed to explore whether frailty, a reflection of the patient's physical status based on peripheral organ health at admission, could be associated with outcomes among AIS patients treated by EVT in the late window of 6-24 hours from stroke onset. Patients and Methods:This was a post-hoc analysis of our RESCUE-BT trial, with findings validated in an external cohort. The 5-factor modified frailty index (mFI-5), a scale of five factors that could reflect premorbid physical conditions, was applied to estimate frailty status. The primary outcome was functional independence, defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Results:There were 755 patients included in this study. After identifying the cut-off value of mFI-5 by the marginal effects approach, patients were divided into the frail group (mFI-5≥2) and the non-frail group (mFI-5<2). In multivariable analysis, frailty significantly reduced the likelihood of functional independence (aOR 0.37, 95% CI 0.21-0.65, P<0.001). Similar results were detected in the novel cohort constructed with propensity score matching (aOR 0.44, 95% CI 0.22-0.85, P=0.015) and in the external validation cohort (aOR 0.38, 95% CI 0.16-0.89, P=0.028). Moreover, frailty significantly improved the predictive performance of traditional predictors with an AUC of 0.77 (P=0.036 by DeLong's test). Conclusion:This study demonstrated that frailty according to the mFI-5 index was inversely associated with functional independence among AIS patients receiving EVT in the late window.

Importance:The impact of adjunctive intra-arterial tenecteplase administration following near-complete to complete reperfusion by endovascular thrombectomy (EVT) for acute ischemic stroke is unknown. Objective:To assess the efficacy and adverse events of adjunctive intra-arterial tenecteplase in patients with large vessel occlusion stroke who had achieved near-complete to complete reperfusion (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2c to 3) after EVT. Design, Setting, and Participants:Investigator-initiated, randomized, open-label, blinded outcome assessment trial implemented at 34 hospitals in China among 540 patients with stroke due to proximal intracranial large vessel occlusion within 24 hours of the time they were last known to be well, with an eTICI score of 2c to 3 after EVT, and without prior intravenous thrombolysis. Recruitment took place between October 26, 2022, and March 1, 2024, with final follow-up on June 3, 2024. Interventions:Eligible patients were randomly assigned to receive intra-arterial tenecteplase (n = 269) at 0.0625 mg/kg or no intra-arterial thrombolysis (control group; n = 271). Main Outcomes and Measures:The primary efficacy outcome was freedom from disability, defined as a score of 0 or 1 on the modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) at 90 days. The primary safety outcomes were death at 90 days and symptomatic intracranial hemorrhage within 48 hours. Results:A total of 539 participants (99.8%) completed the trial (median age, 69 years; 221 female [40.9%]). The proportion with a modified Rankin Scale score of 0 or 1 at 90 days was 49.1% (132/269) in the intra-arterial tenecteplase group and 44.1% (119/270) in the control group (adjusted risk ratio, 1.15 [95% CI, 0.97-1.36]; P = .11). Ninety-day mortality was 16.0% and 19.3% (adjusted hazard ratio, 0.75 [95% CI, 0.50-1.13]; P = .16), respectively. The proportions of symptomatic intracranial hemorrhage were 6.3% and 4.4% (adjusted risk ratio, 1.43 [95% CI, 0.68-2.99]; P = .35), respectively. Conclusions and Relevance:In patients with acute ischemic stroke due to large vessel occlusion presenting within 24 hours of time last known to be well and who had achieved near-complete to complete reperfusion after EVT, adjunctive intra-arterial tenecteplase did not significantly increase the likelihood of freedom from disability at 90 days. Trial Registration:ChiCTR.org.cn Identifier: ChiCTR2200064809.