BACKGROUND:Genetic predisposition is increasingly recognized as an important contributor to cerebral venous thrombosis (CVT), yet findings from individual studies remain inconsistent. We conducted an updated meta-analysis to quantify associations between specific genetic variants and adult CVT. METHODS:We systematically searched PubMed, EMBASE, and Web of Science up to January 2025 for case-control studies comparing the prevalence of genetic variants in adults with CVT versus healthy controls. Pooled odds ratios (ORs) with 95% CIs were calculated using random-effects models in this meta-analysis. RESULTS:Sixty-one studies comprising 4106 patients with CVT and 12 323 controls were analyzed. Significant associations were identified for germline variants, including factor V Leiden (238/2753 [8.6%] versus 387/8747 [4.4%]; OR, 2.59 [95% CI, 2.06-3.26]; P<0.00001), prothrombin G20210A (290/2483 [11.7%] versus 235/8197 [2.9%]; OR, 6.05 [95% CI, 4.59-7.98]; P<0.00001), and inherited deficiencies of protein C (24/624 [3.8%] versus 7/2027 [0.3%]; OR, 10.30 [95% CI, 4.19-25.30]; P<0.00001), protein S (9/567 [1.6%] versus 1/1125 [0.1%]; OR, 6.86 [95% CI, 2.12-22.24]; P=0.001), and antithrombin (11/440 [2.5%] versus 3/989 [0.3%]; OR, 5.73 [95% CI, 1.98-16.55]; P=0.001). The somatic JAK-2 (Janus kinase-2) V617F mutation was likewise associated with increased risk (27/569 [4.7%] versus 13/1777 [0.7%]; OR, 9.17 [95% CI, 3.61-23.27]; P<0.00001). By contrast, MTHFR (methylenetetrahydrofolate reductase) C677T and PAI-1 (plasminogen activator inhibitor-1) 4G/5G polymorphisms showed no significant associations. Overall effect sizes were comparable to those reported in pediatric CVT but exceeded those in adult arterial ischemic stroke. CONCLUSIONS:These findings support a genetic basis for adult CVT. Risk associations are broadly similar to pediatric CVT yet stronger than those reported for adult arterial ischemic stroke, highlighting distinct patterns of genetic susceptibility in venous stroke and the potential value of selective genetic testing for risk stratification and management.

Abstract Background and aims Advanced age is associated with worse outcomes in acute ischemic stroke and may influence treatment decisions for endovascular therapy (EVT) in vertebrobasilar artery occlusion (VBAO). However, the interaction between age and EVT benefit in posterior circulation stroke remains unclear. Methods We pooled individual patient data from BASICS, BEST, ATTENTION, and BAOCHE trials. Patients were stratified by age (≤60, 61-70, 71-80, >80 years). Primary outcome was favorable functional outcome (mRS 0-3) at 90 days. Multiple imputation using chained equations (MICE, 20 imputations) addressed missing data. Multivariable logistic regression assessed age-outcome association. Age and treatment interaction was tested. Results Among 988 patients (median age 67 years; 30.6% female), 556 (56.3%) received EVT. Age distribution: ≤60y (n=310), 61-70y (n=314), 71-80y (n=286), >80y (n=78). Favorable outcome rates decreased with age: ≤60y 47.1%, 61-70y 39.8%, 71-80y 31.8%, >80y 21.8% (P<0.001). Age >80 years was independently associated with lower favorable outcome (aOR 0.40, 95% CI 0.22-0.75; P=0.004) and higher mortality (aOR 2.28, 95% CI 1.35-3.86; P=0.002). EVT benefit was preserved across all ages (aOR 2.47, 95% CI 1.83-3.34). No significant age and treatment interaction was observed (P=0.81). Conclusions While advanced age is independently associated with worse outcomes in VBAO, the relative benefit of EVT is preserved across all age groups. Age alone should not preclude consideration for EVT in this patient subgroup. Conflict of interest None

Abstract Background and aims Although the Stroke Preclinical Assessment Network (SPAN) reported neutral effects of tocilizumab in rodent stroke models, this does not fully exclude the translational potential of IL-6R inhibition, as tocilizumab is a humanized antibody that does not bind the murine IL-6 receptor. We aim to use a species-matched anti-mouse IL-6R antibody (15A7) to evaluate the efficacy, optimal dose, and underlying mechanisms of IL-6R blockade in ischemic stroke. Methods Transient middle cerebral artery occlusion was induced in mice, followed by intravenous administration of 15A7 (25, 50, or 75 mg/kg) 30 min after ischemia. Infarct volume and neurological deficits were evaluated to determine the lowest effective dose. BBB disruption was assessed by Evans blue extravasation, brain water content, tight-junction protein expression (ZO-1, occludin, claudin-5), and MMP-9 levels. Neutrophil infiltration and NETs formation were examined by immunofluorescence and western blotting. Clinically, serum citH3, MPO-DNA, and occludin were measured using serum samples from 108 stroke patients receiving tocilizumab or placebo. Results 15A7 at 50 and 75 mg/kg comparably reduced infarct volume and improved neurological outcomes; therefore, 50 mg/kg was selected for subsequent experiments. At this dose, 15A7 reduced BBB leakage and cerebral edema, restored tight-junction proteins, decreased MMP-9 expression, and suppressed neutrophil infiltration and NETs formation. Clinically, tocilizumab-treated patients exhibited lower serum citH3, MPO-DNA, and occludin levels. NETs markers correlated with occludin and largely mediated the treatment effect. Conclusions IL-6R blockade could reduce infarct volume and improve neurological function, by preserving BBB integrity and reducing NETs. Conflict of interest

Abstract Background and aims The cerebroprotective effects of hypothermia via selective intra-arterial cooling infusion (SI-AC) as an adjunct to endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) are uncertain. Methods We conducted a multicenter, randomized, controlled, and sigle blinded clinical trial conducted at 12 hospitals in China. Patients with anterior circulation LVO-AIS presenting within 24 hours of symptom onset were randomized 1:1 to receive SI-AC plus EVT (SI-AC group) or EVT (control group). The primary outcome was mRS score distribution at 90 days. Results A total of 258 patients were randomized (130 to the SI-AC group and 128 to the control group) . There was no significant difference between the groups in the distribution of mRS scores at 90 days (unadjusted common odds ratio, 1.15; 95% CI, 0.75 to 1.77). Secondary outcomes showed no significant differences in mRS (0-2), mRS (0-1), or early neurologic improvement. For safety outcomes, SI-AC was associated with a significantly lower incidence of intracranial hemorrhage at 24 hours compared to the control group (unadjusted risk ratio, 0.64; 95% CI, 0.43 to 0.95). There was no significant difference in symptomatic intracranial hemorrhage rates (unadjusted risk ratio, 0.82; 95% CI, 0.26 to 2.62) or 90-day mortality (unadjusted risk ratio, 0.93; 95% CI, 0.49 to 1.75). Conclusions SI-AC did not improve functional recovery at 90 days compared to EVT alone, but it reduced the incidence of intracranial hemorrhage. Further research is needed to better understand its role in improving clinical outcomes in AIS patients undergoing EVT. Trial registration: ClinicalTrials.gov (NCT06485427). Conflict of interest Figure 1 - belongs to Conclusions

The safety and efficacy of albumin combined with endovascular therapy for participants with acute ischemic stroke is unknown. This randomized, double blinded, multicenter study was conducted in China and completed in 2025. Eligible participants were randomly assigned in a 1:1 ratio to albumin group (0.5 g/kg; maximum dose 150 mL; intravenously infusion once daily for 4 days) or placebo group (equivalent volume of placebo). The primary endpoint was the change in infarct volume from baseline to day 5. A total of 134 patients were randomized (66 in albumin group and 68 in placebo group) and 134 patients were included in the final analysis. Albumin reduced infarct volume growth from baseline to day 5 compared with placebo (median growth 7.5 mL vs 16.5 mL, adjusted median difference -8.63, 95%CI (-13.85 to -5.07); P = 0.003). The safety outcomes did not differ between the two groups. This work suggests that albumin plus endovascular therapy could significantly reduce infarct volume growth compared with the placebo group, without raising safety concerns. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov registration: NCT06538844.).

Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent thrombus propagation, venous hypertension with blood–brain barrier disruption, and secondary parenchymal brain injury. Comprehensive clinical assessment, including diagnosis and differential diagnosis, disease severity scores, imaging-based metrics, and prognostic scoring systems, enables accurate evaluation and risk stratification. Emerging therapeutic strategies, including direct oral anticoagulants, corticosteroids for selected patients, natural-origin agents, immunomodulatory therapy, endovascular treatment, optic nerve sheath fenestration, and neuromodulation, provide novel and alternative options for the management of CVT. This review provides a comprehensive overview of CVT pathophysiology, clinical assessment tools, and novel therapeutic strategies to guide clinical decision-making and inform future research.

Hemorrhagic transformation (HT) remains a life-threatening complication after acute ischemic stroke (AIS), yet no active predictive tool is available for early risk assessment. Herein, we develop an integrated triplex electrochemical aptasensing platform for the parallel and simultaneous quantification of three HT-associated biomarkers-matrix metalloproteinase-9 (MMP-9), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1). The system enables parallel detection by inserting three independent screen-printed carbon electrodes (SPCEs) into a multi-channel electrochemical workstation, each functionalized with a distinct aptamer, allowing simultaneous quantification of MMP-9, FN, and PAI-1 within 30 min. Each SPCE is modified with a conductive polypyrrole/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate/polyvinyl alcohol hydrogel and gold nanoparticles, followed by immobilization of specific thiolated aptamers via Au-S bonds. Upon target binding, aptamer conformational changes induce a concentration-dependent decrease in differential pulse voltammetry current. The sensor achieves ultralow detection limits of 4.04 fg/mL, 0.30 fg/mL, and 2.79 fg/mL for MMP-9, FN, and PAI-1, respectively, with a total assay time of 30 min. Clinical validation using plasma from 12 AIS patients demonstrates excellent agreement with enzyme-linked immunosorbent assay (mean bias <10%) and high reproducibility (RSD <5%). This work presents the first electrochemical aptasensor for FN and PAI-1 detection and provides a clinically validated, point-of-care-compatible platform for personalized HT risk prediction in thrombolytic therapy.

BACKGROUND:Tenecteplase improves reperfusion and functional outcomes compared with alteplase in patients with large vessel occlusion. We assessed whether this superiority varies with thrombolysis-to-puncture time (TTP). METHODS:This retrospective analysis of a prospective multicenter cohort included patients with large vessel occlusion who received bridging therapy with either tenecteplase or alteplase between January 2022 and September 2025. Patients were stratified by TTP (<60 versus ≥60 minutes). We subsequently assessed the association of TTP with efficacy and safety outcomes between the alteplase and tenecteplase groups using multivariable logistic regression adjusted for age, baseline National Institutes of Health Stroke Scale score, and time from stroke onset to arterial puncture. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. RESULTS:Of 1106 patients who received bridging therapy, 1003 were included in the primary analysis (tenecteplase, 488; alteplase, 515). The median age was 68 (interquartile range, 58-75) years in both groups, with men comprising 64.3% and 66.0%, respectively. Tenecteplase was associated with superior 3-month functional independence compared with alteplase (53.6% versus 48.1%; adjusted odds ratio, 1.37 [95% CI, 1.03-1.82]). This benefit was concentrated in patients with a TTP <60 minutes, where tenecteplase yielded higher rates of both early recanalization (19.0% versus 9.1%; adjusted odds ratio, 2.36 [95% CI, 1.32-4.23]; Pinteraction=0.047) and functional independence (61.0% versus 49.0%; adjusted odds ratio, 1.77 [95% CI, 1.13-2.77]; Pinteraction=0.111). No between-agent differences were significant with TTP ≥60 minutes. Safety outcomes were comparable, but each 30-minute TTP increase independently elevated hemorrhagic risks for both agents. CONCLUSIONS:The recanalization superiority of tenecteplase over alteplase is time-dependent, evident only within a TTP <60 minutes. Although the translation of this advantage into functional outcome was not statistically modified by time, optimizing workflow to achieve this rapid window maximizes the potential benefit of tenecteplase, which should be prioritized in capable settings.

Background: Therapeutic hypothermia has demonstrated robust neuroprotective effects in experimental models of ischemic stroke. However, clinical translation has been hindered by delays in cooling initiation. To address this limitation, we investigated whether initiating selective mild hypothermia during the ischemic phase could improve outcomes and examined the underlying mechanisms. Astrocyte-to-neuron mitochondrial transfer has recently emerged as a critical endogenous neuroprotective process following cerebral ischemia and may be enhanced by early hypothermia. Methods: Selective brain cooling was initiated 30 minutes after stroke onset to mimic early mild hypothermia and maintained for 2 hours in adult mice, subjected to transient middle cerebral artery occlusion (MCAO). Astrocytic mitochondria were fluorescently labeled to track intercellular transfer. Single-cell RNA sequencing was performed on ischemic brain tissue. Cyclic AMP (cAMP) signaling was modulated using pharmacological agonists and antagonists. Results: Early mild hypothermia significantly reduced infarct volume and improved neurological outcomes when induced during cerebra ischemia. It enhanced astrocyte-to-neuron mitochondrial transfer in the peri-infarct cortex. Single-cell analysis revealed upregulation of cAMP-related pathways in astrocytes following early mild hypothermia. Activating cAMP signaling mimicked the protective effects of hypothermia, while its inhibition partially attenuated mitochondrial transfer and functional recovery because of early mild hypothermia after stroke. Conclusions: Early mild hypothermia promotes neuroprotection by enhancing astrocytic mitochondrial transfer through a cAMP-dependent mechanism. Targeting this glia-mediated pathway may improve therapeutic strategies for ischemic stroke.

Introduction and Hypothesis: Successful large-vessel recanalization only leads to functional independence in approximately half of patients. Futile recanalization or microcirculatory failure (no-reflow) is considered a key contributor, yet its mechanisms are unclear. Moreover, there is no optimal animal model to mimic its major features currently. Piezo1 is a mechanosensitive ion channel that responds to mechanical forces. Previous studies found that the endothelial Piezo1 channel mediated mechano-feedback control of brain blood flow. We therefore hypothesize that Piezo1 activation might be closely associated with the no-reflow phenomenon. Targeting Piezo1 activation may provide a novel and feasible animal model of no-reflow. Methods: Piezo1 distribution was analyzed using single-cell RNA sequencing datasets, and its expression changes after AIS were examined from the existing database, the endothelial oxygen-glucose deprivation (OGD) model, and the mouse middle cerebral artery occlusion/ reperfusion (MCAO/R) model. Yoda1, a Piezo1-specific agonist, was administrated to the lateral ventricle. Perfusion situation was measured by two-photon microscopy and laser speckle contrast imaging (LSCI). To validate the model across species, arterial spin labeling (ASL) magnetic resonance imaging (MRI), infarct volume measurement and neurological scoring were applied in both rats and mice. Results: Piezo1 was enriched in cerebrovascular endothelial cells and its expression increased within 24 hours after infarction. In normal mice, intracerebroventricular injection of Yoda1 led to capillary occlusion and reduced flow velocity. Furthermore, intracerebroventricular administration of Yoda1 resulted in major pathological features of no-reflow in the mouse MCAO model, including a markedly reduced perfusion after the reperfusion in LSCI, a significantly reduced cerebral blood flow in ASL MRI, a higher infarct size, and a deteriorated neurological function. However, these features were not observed in brain endothelial-specific Piezo1 knock-out mice after stroke onset when Yoda1 was used. In addition, Yoda1 also led to no-reflow features in a rat MCAO model. Conclusion: Piezo1 activation may contribute to no-reflow after AIS recanalization. Intracerebroventricular Yoda1 establishes a reproducible no-reflow model in both mouse and rat. This model may provide a platform for mechanistic studies and therapeutic exploration targeting no-reflow.

Background Venous sinus stenting (VSS) effectively resolves mechanical outflow obstruction in idiopathic intracranial hypertension (IIH), yet recurrence remains a non-negligible risk. Metabolic drivers, particularly obesity, may undermine long-term success. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide offer potent weight loss and potential cerebrospinal fluid modulation, but their role in post-stenting management is unestablished. We investigated whether baseline body mass index (BMI) predicts IH recurrence following VSS and whether adjunctive semaglutide reduces recurrence risk in a non-randomized exploratory cohort. Methods We conducted a two-phase cohort study. Phase 1 retrospectively analyzed 50 IIH patients with transverse sinus stenosis (TSS) undergoing VSS (2018–2023) to identify recurrence predictors. Phase 2 prospectively assigned 34 IIH patients (2024–2025) to semaglutide (n = 17) or standard care (n = 17). The primary outcome was intracranial hypertension (IH) recurrence (lumbar puncture opening pressure ≥ 250 mmH₂O) at 16 weeks. Secondary outcomes included pressure metrics, weight change, symptom scores, and optic measures. Results In Phase 1, higher baseline body mass index (BMI) (OR 1.206, 95% CI 1.008–1.444, P = 0.041) independently predicted intracranial hypertension (IH) recurrence after VSS. In Phase 2, semaglutide significantly reduced IH recurrence compared to controls (5.9% vs 35.3%, P = 0.034). Semaglutide also lowered follow-up opening pressure (205.29 vs 249.71 mmH₂O, P = 0.007), reduced BMI (median ΔBMI − 4.00 vs 0.00 kg/m², P < 0.001), a lower rate of persistent papilledema (17.6% vs 52.9%; P = 0.031), and alleviated tinnitus (median ΔTFI − 15.40 vs 0.00, P = 0.040). Adverse events were mild-to-moderate gastrointestinal symptoms. Conclusion In this cohort, higher baseline BMI was identified as a risk factor for IH recurrence after VSS in IIH. Adjunctive semaglutide therapy was associated with a lower recurrence rate ang greater weight loss, supporting its integration into post-stenting metabolic management. Given the exploratory design and small sample size, all findings are hypothesis-generating and require confirmation in larger randomized trials. Trial registration: NCT06361823. Registered on March 2, 2024, by Xuanwu Hospital, Capital Medical University.

AIM: The purpose of this study is to investigate the safety and effectiveness of remote ischemic conditioning (RIC) as a therapeutic intervention for cerebral ischemia in patients with Takayasu arteritis (TA). METHODS: TARIC-1 is a randomized, double-blind, parallel-group pilot trial conducted at Xuanwu Hospital, Capital Medical University. Participants with TA and reduced cerebral blood perfusion are randomly allocated to either the RIC or sham-RIC groups. Both the groups receive conventional medical care, with the RIC group receiving twice-daily sessions of 200 mmHg inflation pressure and the sham-RIC group receiving 60 mmHg inflation pressure, for 24 consecutive weeks. OUTCOMES: The primary outcome is the change in mean cerebral blood flow across the entire brain and regions of interest following the 24-week RIC treatment. Secondary outcomes include clinical assessments using the Indian Takayasu Clinical Activity Score 2010, Vasculitis Damage Index, and Birmingham Vasculitis Activity Score at 24 weeks postintervention. Changes in arterial transit time and the incidence of major adverse cerebrovascular events are additional secondary outcomes. Safety outcomes include mortality and any adverse events, including skin changes and pain ratings, within the 24-week period. SAMPLE SIZE ESTIMATES: This pilot study plans to enroll 22 patients per group, totaling 44 participants. CONCLUSIONS: In individuals with TA, RIC may be a well-tolerated treatment that enhances cerebral perfusion and lowers the risk of ischemic cerebrovascular episodes. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT06178419).

BACKGROUND:Intermittent hypoxia (IH) preconditioning enhances brain resilience, thereby protecting against subsequent ischemic injury, yet its precise mechanisms remain elusive. We tested the novel hypothesis that peripheral paracrine mechanisms mediate IH-induced neuroprotection. METHODS:A total of 492 C57BL/6J mice were used: 434 young males (2-3 months), 29 young females (2-3 months), and 29 aged males (18 months). A 2-week IH regimen (13% O2, 5-minute intervals, 10 cycles/d) was applied to generate IH-derived plasma (IHP). To test the hypothesis, IHP or normoxic plasma (100 μL/injection) was intravenously administered every 3 days (6 doses total) before distal middle cerebral artery occlusion. For therapeutic evaluation, plasma was administered daily for 3 days after distal middle cerebral artery occlusion or 60-minute transient middle cerebral artery occlusion, followed by additional doses every 3 days for 6 doses in long-term transient middle cerebral artery occlusion studies. Infarct volume and neurological deficits were primary outcomes. Candidate circulating mediators were identified via proteomics and validated by antibody-mediated depletion and recombinant protein supplementation. Blood-brain barrier integrity was further examined. RESULTS:Systemic IHP administration protected against acute brain injury after distal middle cerebral artery occlusion, reducing infarct volume and improving sensorimotor performance. Poststroke administration of IHP conferred acute and sustained neuroprotection in transient middle cerebral artery occlusion, but not distal middle cerebral artery occlusion, improving sensorimotor and cognitive recovery and reducing brain atrophy up to 4 weeks after stroke. Proteomic profiling identified 120 IH-upregulated plasma proteins, notably PF4 (platelet factor 4), a cytokine with potent neuroprotective properties. PF4 immunodepletion abolished IHP-induced neuroprotection, whereas recombinant PF4 replicated these benefits across sex and age. Furthermore, PF4 treatment protected against blood-brain barrier disruption after transient middle cerebral artery occlusion, attenuating IgG extravasation and loss of endothelial expression of zonula occludens-1. CONCLUSIONS:These findings identify PF4 as a key paracrine mediator of IH-induced neuroprotection and support the therapeutic potential of both IHP and PF4-based interventions for ischemic stroke.

"Stroke 1-2-0" is a Chinese numeric mnemonic linking face drooping, arm weakness, and speech difficulty to calling emergency services (1-2-0). We propose an enhanced repeated version-"Stroke 1-2-0, Stroke 1-2-0"-that adds visual impairment and imbalance to better detect posterior-circulation strokes, while repetition may boost recall and stresses zero delay in seeking help.

Abstract: The relationship between intracranial hypertension (IH) and cerebral venous outflow insufficiency (CVOI), including cerebral venous sinus stenosis (CVSS) and internal jugular vein stenosis (IJVS), remains controversial. Although elevated intracranial pressure (ICP) is often regarded as a hallmark of CVOI, recent evidence indicates that a subset of patients with radiologically confirmed CVSS or IJVS exhibit normal or only mildly elevated ICP (< 250 mmH 2 O). This challenges the notion that ICP elevation is essential for diagnosis and raises concern about misdiagnosis when relying solely on ICP thresholds. This review summarizes the clinical features, imaging findings, and hemodynamic characteristics of CVOI and examines the bidirectional relationship between CVOI and ICP. Possible mechanisms for normal ICP include preserved lymphatic cerebrospinal fluid drainage, collateral venous pathways, and anatomical variation. Moreover, persistent ICP elevation may itself cause secondary venous collapse, creating a feedback loop. These findings suggest that ICP elevation is neither necessary nor sufficient for diagnosing CVOI. A multidimensional diagnostic framework, integrating symptomatology, venographic morphology, and venous flow dynamics, is essential to improve diagnostic accuracy and guide individualized management. Recognizing the complexity of this condition may prevent underdiagnosis and optimize outcomes for patients with CVOI.

While cardiac abnormalities are well-documented in epilepsy patients, the underlying mechanisms mediating epilepsy-heart interplay remain incompletely understood. This study aimed to investigate epilepsy- related structural and functional cardiac alterations, and to assess the potential mediating role of inflammation from a genetic standpoint. We conducted a two-step Mendelian randomization (MR) analysis in this study, with epilepsy and its two subtypes (generalized epilepsy and focal epilepsy) as exposures, 82 cardiac traits (76 cardiac phenotypes based on cardiac magnetic resonance imaging and 6 electrocardiogram - based characteristics) as outcomes, as well as 91 plasma inflammatory proteins as mediators. The MR results demonstrated causal correlations of epilepsy and generalized epilepsy on cardiac traits. Epilepsy and its two subtypes can causally induce alterations in plasma inflammatory protein levels. Mediation analysis identified C-X-C motif chemokine ligand (CXCL) 1 and CXCL9 as potential mediators of epilepsy’s effect on regional end-diastolic left ventricular wall thickness, accounting for 9.3

RATIONALE:Adjunctive neuroprotection is a promising strategy for improving functional recovery in patients with acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT). Remote ischaemic conditioning (RIC) has been shown to be safe and effective in patients with AIS; however, its specific impact on neurological outcomes in patients undergoing MT remains to be established. AIM:To evaluate the safety and efficacy of adjunctive RIC in improving 90-day functional outcomes in patients with AIS treated with MT, and to compare two treatment durations (14 days vs 30 days). METHODS AND DESIGN:Safety and Efficacy of Remote Ischaemic Conditioning for Acute Ischaemic Stroke Treated with Mechanical Thrombectomy (RECAST-MT) is a multicentre, randomised, controlled, open-label trial with blinded end-point assessment conducted in China. Patients with AIS caused by large-vessel occlusion in the anterior circulation who are scheduled to undergo MT will be enrolled and randomly assigned in a 1:1:1 ratio to receive 14-day RIC, 30-day RIC or standard treatment alone. To allow for early termination due to futility, an interim analysis will be conducted. Total enrolment will range from a minimum of 1526 patients (if one arm is terminated early) to a maximum of 2105 patients (if all arms reach full recruitment). RIC is performed by intermittently inflating cuffs on the upper arm to a pressure of 200 mm Hg. STUDY OUTCOMES:The primary end point is the proportion of patients achieving functional independence (modified Rankin Scale (mRS) score 0-2) at 90 days. Secondary end points include a shift analysis of mRS scores, early neurological improvement and infarct volume on imaging. The primary safety outcome is the incidence of any intracranial haemorrhage within 14 days or at discharge. DISCUSSION:The RECAST-MT trial will provide phase III evidence on the efficacy of RIC in combination with MT for patients with AIS. If successful, this approach could offer a safe, easy-to-implement and cost-effective neuroprotective therapy in this population. TRIAL REGISTRATION NUMBER:NCT06559241.

Abstract Background and aims To determine whether the efficacy and safety of endovascular therapy (EVT) for basilar artery occlusion are modified by the presence of intracranial atherosclerotic disease (ICAD). Methods We performed an individual patient data meta-analysis pooling randomized controlled trial data from BASICS, BEST, ATTENTION, and BAOCHE. Patients were classified by ICAD status. The primary outcome was a favorable functional outcome (mRS 0–3) at 90 days. Secondary outcomes included functional independence (mRS 0–2), ordinal mRS shift, and 90-day mortality. Mixed-effects logistic regression models adjusted for baseline covariates were used, with trial included as a random effect. Effect modification by ICAD status was assessed using interaction testing. Results Among 832 patients with known ICAD status, 491 had no ICAD, and 341 had ICAD. EVT was associated with higher odds of favorable outcome (mRS 0–3) in both non-ICAD (adjusted odds ratio [aOR] 2.52, 95% CI 1.66–3.83) and ICAD patients (aOR 2.50, 95% CI 1.47–4.25), with no evidence of effect modification (p-interaction = 0.98). Consistent benefit was observed for functional independence (non-ICAD: aOR 2.75; ICAD: aOR 3.22; p-interaction = 0.68) and ordinal mRS shift (non-ICAD: aOR 2.15; ICAD: aOR 2.24;p-interaction = 0.89). EVT was also associated with reduced 90-day mortality in both groups (non-ICAD: aOR 0.53; ICAD: aOR 0.64; p-interaction = 0.56). Symptomatic intracranial hemorrhage was more frequent with EVT in both non-ICAD (3.9%vs.0.9%) and ICAD patients (6.0%vs.0.0%). Conclusions Endovascular therapy confers substantial and consistent benefit in basilar artery occlusion regardless of ICAD status. The presence of ICAD should not preclude patients from EVT. Conflict of interest No relevant disclosures to this work.

Abstract Background and aims While the efficacy of endovascular therapy (EVT) for vertebrobasilar artery occlusion (VBAO) is established, the magnitude of individual benefit remains highly variable. Average treatment effects often mask patients who may derive exceptional benefit or those for whom intervention may be futile. We developed VERITAS Nexus, a causal ML framework designed to shift the paradigm from population-level averages to Individualized Conditional Average Treatment Effects (CATE). Methods We performed a pooled analysis of individual patient data from four landmark RCTs (BASICS, BEST, ATTENTION, BAOCHE). Utilizing an ensemble of causal ML architectures, we conducted an as-treated analysis to model counterfactual outcomes. The primary endpoint was the individual probability of a favorable outcome (mRS 0-3 at 90 days) under both EVT and medical management (MM). Results Among the 988 patients analyzed (EVT: 574; MM: 414), the median age was 67 years (IQR 58–74) and median NIHSS was 22 (IQR 13–35). VERITAS Nexus revealed a spectrum of individualized responses, with CATE ranging from negligible to highly significant (mean 13.0%). Individualized benefit profiling showed that 62.6% derived moderate benefit (>5%) and 44.9% derived strong benefit (>15%). The model-driven NNT was 3.1, while the outcome models achieved an AUC of 0.75(95% CI0.694–0.801)for MM and 0.68(95% CI 0.635–0.725)for EVT. Conclusions VERITAS Nexus demonstrates that BAO treatment response is individualistic. By quantifying the specific "benefit margin" for each patient, this tool moves beyond binary "treat vs. no-treat" logic. It provides a robust clinical decision support framework to facilitate tailored intervention and high-precision shared decision-making. Conflict of interest Nothing to disclose