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Background and Objectives: Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date., Methods: We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073)., Results: There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group ( p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group., Discussion: In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

Background: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion., Methods: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed., Results: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P =0.51) and mortality (17.8% versus 19.4%; P =0.76). The propensity score overlap weighting analyses showed consistent outcomes., Conclusions: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial., Registration: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167., Competing Interests: Disclosures Dr Nguyen reports being an associate editor for Stroke; compensation from Brainomix for the advisory board; compensation from Idorsia for the advisory board; pilot grant to her institution from the Society of Vascular and Interventional Neurology; compensation from Medtronic USA, Inc, for consultant services; and being a principal investigator for Route 92 Medical, Inc (no compensation). Dr Saver reports compensation from BrainQ for consultant services; stock options in Rapid Medical; stock options in Neuronics Medical; compensation from CSL Behring for consultant services; compensation from Biogen for consultant services; compensation from Roche for consultant services; compensation from Boehringer Ingelheim (prevention only) for consultant services; compensation from Abbott Laboratories for consultant services; compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services; compensation from BrainsGate for consultant services; compensation from Aeromics for consultant services; stock options in MindRhythm; compensation from MIVI Neuroscience for data and safety monitoring services; and compensation from Medtronic USA, Inc, for consultant services. Dr Nogueira reports stock options in Corindus, Inc; compensation from Viz AI for consultant services; compensation from Synchron for data and safety monitoring services; compensation from Anaconda Biomed for consultant services; stock holdings in Quantanosis AI; stock options in Brainomix; compensation from NeuroVasc Technologies, Inc, for consultant services; compensation from Ceretrieve for consultant services; compensation from Imperative Care, Inc, for consultant services; compensation from Phenox, Inc, for consultant services; compensation from Brainomix for consultant services; compensation from Philips for consultant services; compensation from RapidPulse for consultant services; compensation from Cerenovus for consultant services; compensation from Hybernia for consultant services; stock options in Truvic; compensation from Brainomix for consultant services; compensation from Perfuze for consultant services; compensation from Genentech for consultant services; compensation from Stryker Corporation for consultant services; compensation from Prolong Pharmaceuticals for consultant services; compensation from Corindus Vascular Robotics for consultant services; stock options in Vesalio; compensation from Cerebrotech for consultant services; compensation from RapidPulse for consultant services; stock options in Reist/Q’Apel Medical; compensation from Astrocyte for consultant services; stock options in Perfuze; compensation from Genentech for consultant services; compensation from Phenox for consultant services; compensation from Stryker for consultant services; stock options in Viseon, Inc; compensation from Vesalio for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Anaconda for consultant services; compensation from Cerenovus for consultant services; stock options in Viz AI; stock options in Perfuze; compensation from Imperative Care for consultant services; compensation from Biogen, Inc, for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Vesalio for consultant services; stock options in Cerebrotech; grants from Cerenovus; compensation from Viz AI for consultant services; stock options in Ceretrieve; compensation from Biogen, Inc, for consultant services; stock options in Viz AI; stock holdings in Brain4Care; grants from Stryker; compensation from Ceretrieve for consultant services; stock holdings in Piraeus Medical; compensation from Shanghai Wallaby for consultant services; compensation from Perfuze for consultant services; compensation from Corindus, Inc, for consultant services; and compensation from Prolong Pharmaceuticals for consultant services. The other authors report no conflicts.

Objective: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups., Methods: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality., Results: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, p non-inferiority =0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, p interaction ≤180 vs >180 min =0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, p interaction ICA vs MCA =0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable., Conclusions: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT., Competing Interests: Competing interests: RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze. RGN is one of the principal investigators of the ‘Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)’ trial. Funding for this project is provided by Cerenovus. RGN is the principal investigator of the ‘Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)’ trial. Funding for this project is provided by Stryker Neurovascular. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Vastrax, and Viseon., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy., Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO., Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023., Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy., Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours., Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo., Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability., Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Background: Approximately half of patients who achieve successful reperfusion do not achieve functional independence. The present study sought to investigate the clinical outcomes and safety of intraarterial or intravenous tirofiban as adjunct therapy in patients with acute basilar artery occlusion who had achieved successful recanalization with endovascular treatment., Methods and Results: In the national, prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry, 458 patients who met inclusion criteria were divided into 3 groups based on tirofiban administration (no tirofiban, n=262; intravenous tirofiban, n=101; intraarterial+intravenous tirofiban, n=95). Their clinical outcomes were compared with 90-day modified Rankin Scale scores. Adjusted odds ratios (aORs) and 95% CIs were obtained by logistic regression models and propensity score matching. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. Among 458 included patients, 184 (40.2%) achieved a favorable outcome (modified Rankin Scale score 0-3). There were no differences between the intravenous tirofiban group and the no tirofiban group in terms of safety and clinical outcomes (all P >0.05). Compared with the no tirofiban group, the intraarterial+intravenous tirofiban group had higher odds of 90-day modified Rankin Scale score 0 to 3 (aOR, 2.44 [95% CI, 1.30-4.64], P =0.006) and lower 3-month mortality (aOR, 0.38 [95% CI, 0.19-0.71], P =0.002) without an increase in any ICH (aOR, 0.34 [95% CI, 0.09-1.01], P =0.07) or symptomatic ICH (aOR, 0.23 [95% CI, 0.03-0.90], P =0.05). Similar results of intraarterial+intravenous tirofiban on improving clinical outcomes were detected in novel cohorts constructed by propensity score matching., Conclusions: Intraarterial+intravenous rather than intravenous tirofiban improved clinical outcomes without increasing the frequency of symptomatic ICH among patients with basilar artery occlusion after successful endovascular treatment. Further studies are needed to delineate the roles of intraarterial+intravenous tirofiban in patients with basilar artery occlusion receiving endovascular treatment.

Objective: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO)., Methods: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH)., Results: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence., Conclusion: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: This study aimed to evaluate the efficacy and safety of adjuvant tirofiban in patients with acute basilar artery occlusion due to large-artery atherosclerotic (LAA) receiving endovascular therapy (EVT)., Methods: This was a non-randomized, multicenter study using data from the Endovascular Treatment for Acute BASILAR Artery Occlusion (BASILAR) registry. Patients with acute basilar artery occlusion due to LAA within 24h of symptom onset who underwent EVT were included. Patients were divided into tirofiban and non-tirofiban groups according to whether tirofiban was used. The primary outcome was the ordinal modified Rankin scale score at 90 days. Safety outcomes were mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h., Results: A total of 417 patients were included, of whom 275 patients were in the tirofiban group and 142 patients in the non-tirofiban group. Compared with patients in the non-tirofiban group, patients in the tirofiban group were associated with a favorable shift in functional outcome at 90 days (6[4-6] vs 5 [2-6]; adjusted common OR, 2.51; 95 % CI, 1.64-3.83). The mortality was lower in the tirofiban group than the non-tirofiban group (40.7 % vs 58.5 %; adjusted OR, 0.35; 95 % CI, 0.21-0.56). The rate of sICH was 12.2 % in the non-tirofiban group and 5.2 % in the tirofiban group (adjusted OR, 0.37; 95 % CI, 0.17-0.80; P = 0.012)., Conclusion: Tirofiban plus EVT might improve functional outcomes with a good safety for patients with acute basilar artery occlusion due to LAA. The results need to be confirmed in a randomized trial., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: The effects of secondary collateral compensation on outcomes remain unclear in patients with acute basilar artery occlusion (BAO) after endovascular treatment (EVT). This study aimed to evaluate the benefits of the anastomosis between the posterior inferior cerebellar artery (PICA) and the superior cerebellar artery (SCA) in BAO after EVT., Methods: This cohort study was conducted using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry. Patients with acute BAO and treated with EVT were included. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (SICH) and 90-day mortality., Results: Of the 646 patients included in the study, 196 (30.3%) patients had a PICA-SCA anastomosis. The PICA-SCA anastomosis was significantly associated with independent functional outcome at 90 days (67/196 (34.2%) vs 109/450 (24.2%), adjusted OR (aOR) 1.80 (95% CI 1.13 to 2.86), p=0.01) and was significantly associated with a decreased rate of SICH (40/442 (9.0%) vs 5/193 (2.6%), aOR 0.29 (95% CI 0.11 to 0.76), p=0.01). No significant difference was found between PICA-SCA anastomosis and 90-day mortality (219/450 (48.7%) vs 80/196 (40.8%), aOR 0.72 (95% CI 0.48 to 1.08), p=0.11). Subgroup analysis showed that the association between independent functional outcome and PICA-SCA anastomosis was strongest in patients with middle BAO (27/77 (35.1%) vs 22/118 (18.6%), aOR 2.64 (95% CI 1.13 to 6.15), p=0.03)., Conclusions: The PICA-SCA anastomosis is significantly associated with better functional outcomes in patients with acute BAO after EVT, especially in those with middle BAO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke., Methods: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days., Results: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143)., Conclusions: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients., (© 2023. The Author(s).)

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window., Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others., Results: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001)., Conclusion: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs)., Methods: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232)., Results: A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, p < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, p < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95-3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH., Discussion: This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population., (© 2023 American Academy of Neurology.)

Background: Tirofiban is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to be effective in the treatment of acute coronary syndromes. However, it remains unknown whether it improves outcomes in patients with acute ischemic stroke., Objective: This trial investigates the efficacy and safety of tirofiban compared with aspirin for acute ischemic stroke within 24 h after symptom onset., Methods and Design: The Efficacy and Safety of Tirofiban Compared with Aspirin in the Treatment of Acute Ischemic Stroke (RESCUE BT 2) Trial is an investigator-initiated, prospective, randomized, double-blind, double-dummy, multicenter clinical trial. Up to 1158 eligible patients will be consecutively randomized to receive antiplatelet therapy with tirofiban or aspirin in 1:1 ratio across approximately 100 stroke centers in China., Outcomes: The primary endpoint is the proportion of patients with excellent functional outcomes defined as a modified Rankin scale score of 0 to 1 at 90 days after randomization. Lead safety endpoints include mortality at 90 days and symptomatic intracerebral hemorrhage within 48 h after treatment., Trial Registry Number: ChiCTR2000029502 (www.chictr.org.cn).

Background: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China., Methods: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows., Results: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P =0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P =0.97)., Conclusions: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows., Registration: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167., Competing Interests: Disclosures Dr Nogueira reports consulting fees for advisory roles with Anaconda Biomed, Biogen, Cerenovus, Corindus, Imperative Care, Medtronic, Genentech, NeuroVasc Technologies, Perfuze, Phenox, Prolong Pharmaceuticals, RapidPulse, Stryker, Vesalio, and Viz-AI, and stock options for advisory roles with Brainomix, Ceretrieve, Corindus, Perfuze, Vesalio, and Viz-AI, and receiving grants from Cerenovus, and Stryker. Dr Saver reports consulting fees for advisory roles with Biogen, Boehringer Ingelheim (prevention only), BrainQ, BrainsGate, Johnson & Johnson Health Care Systems Inc, Medtronic USA, Roche, and stock options for advisory roles with MindRhythm, Neuronics Medical, and Rapid Medical, and Data And Safety Monitoring fee from MIVI Neuroscience. Dr Nguyen reports research support from Medtronic/SVIN; advisory board Idorsia (unrelated). The other authors report no conflicts.

The aim of this review is to provide an overview of the use of antiplatelet medication in neurointervention, with a focus on the clinical indications for antiplatelet use in both preventing and reducing platelet aggregation. This review will cover current antiplatelet medications, pharmacokinetics, and pharmacodynamics. We will provide an overview of different endovascular devices and discuss the antiplatelet regimes in neurointervention, highlighting gaps in evidence and scope for future studies.Two randomized controlled trials have evaluated antiplatelet use in the setting of acute large vessel occlusion stroke, with neither demonstrating benefit in their overall cohorts. Evidence on antiplatelet medication for both acute and elective stenting for acute stroke and treatment of cerebral aneurysms is currently based on large case series, and practice in neurointervention has increasingly utilized dual antiplatelet regimes with clopidogrel and second-line agents like prasugrel and ticagrelor. Clopidogrel function testing has an increasing role in neurointerventional procedures, particularly for high metal surface area stents such as the braided flow diverter type stents. Intravenous glycoprotein IIB/IIIA inhibitors have been utilized for both acute bridging and rescue therapy.Antiplatelet decision making is complex, and there are few randomized control trials to guide clinical practice. Comparative trials to guide decision making remain important in both the acute and elective settings. Standardised protocols incorporating platelet function testing may play a role in assisting decision making until more robust clinical evidence is available, particularly in the context of acute neurointerventional stenting for stroke and ruptured cerebral aneurysms., Competing Interests: None declared., (Thieme. All rights reserved.)

The last decade's progress in demonstrating the clinical benefit of endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke has transformed the paradigm of care for these patients. This review presents the milestones in implementing EVT as standard of care, demonstrates the current state of evidence, provides guidance for identifying the candidate patient for EVT, and highlights unsolved and controversial issues. Ongoing trials investigate broadening of EVT indications for patients who present with large core infarction, adjunctive intra-arterial thrombolysis, medium vessel occlusion, low NIHSS, and tandem occlusion., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Objective: To investigate the efficacy and safety of IV infusion of tirofiban before endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerotic disease. The secondary objective was to identify potential mediators for the clinical effect of tirofiban., Methods: Post hoc exploratory analysis of the Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke (RESCUE BT) trial, which was a randomized, double-blinded, placebo-controlled trial at 55 centers in China from October 2018 to October 2021. Patients with occlusion of the internal carotid artery or middle cerebral artery due to intracranial atherosclerosis were included. The primary efficacy outcome was the proportion of patients achieving functional independence (defined as modified Rankin scale 0-2) at 90 days. Binary logistic regression and causal mediation analyses were used to estimate the treatment effect of tirofiban and the potential mediators., Results: This study included 435 patients, of whom 71.5% were men. The median age was 65 (interquartile range [IQR] 56-72) years, with a median NIH Stroke Scale of 14 (IQR 10-19). Patients in the tirofiban group had higher rates of functional independence at 90 days than patients in the placebo group (adjusted odds ratio 1.68; 95% CI 1.11-2.56, p = 0.02) without an increased risk of mortality or symptomatic intracranial hemorrhage. Tirofiban was associated with fewer thrombectomy passes (median [IQR] 1 [1-2] vs 1 [1-2], p = 0.004), which was an independent predictor of functional independence. Mediation analysis showed tirofiban-reduced thrombectomy passes explained 20.0% (95% CI 4.1%-76.0%) of the effect of tirofiban on functional independence., Discussion: In this post hoc analysis of the RESCUE BT trial, tirofiban was an effective and well-tolerated adjuvant medication of endovascular thrombectomy for patients with large vessel occlusion due to intracranial atherosclerosis. These findings need to be confirmed in future trials., Trial Registration Information: The RESCUE BT trial was registered on the Chinese Clinical Trial Registry: chictr.org.cn, ChiCTR-INR-17014167., Classification of Evidence: This study provides Class II evidence that tirofiban plus endovascular therapy improves 90-day outcome for patients with large vessel occlusion due to intracranial atherosclerosis., (© 2023 American Academy of Neurology.)

Background and Purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties., Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics., Results: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01)., Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey., (© 2023 American Society of Neuroimaging.)

Background: The aim of this study is to investigate the association between intravenous tirofiban and symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) receiving endovascular thrombectomy (EVT) within 24 h of time last known well (LKW)., Methods: Patients with AIS-LVO who were randomly assigned to receive intravenous tirofiban or placebo before EVT within 24 h of time LKW and had follow-up brain non-contrast computed tomography within 24 h after stopping tirofiban treatment were derived from "RESCUE BT": a multicenter, randomized, placebo-controlled, double-blind trial. All eligible patients were divided into SICH and NO-SICH groups. Subgroup analyses were performed to explore for heterogeneity., Results: Of 945 patients included in this cohort, there were 76 (8.0%) in the SICH group and 869 (92.0%) in the NO-SICH group. The incidence of SICH was not higher in patients receiving intravenous tirofiban compared with placebo (adjusted risk ratio (RR), 1.51; 95% confidence interval (CI), 0.97-2.36; P = 0.07). Subgroup analyses showed that age greater than 67-year-old (adjusted RR, 2.18; 95% CI 1.18-4.00), NIHSS greater than 16 (adjusted RR, 1.88; 95% CI 1.06-3.34), and cardioembolism (adjusted RR, 3.73; 95% CI 1.66-8.35) were associated with increased SICH risk., Conclusions: In patients with acute large vessel occlusion stroke, intravenous tirofiban before EVT within 24 h of time from last known well is not associated with increased risk of SICH. Patients who are older, have more severe neurological deficits, or with cardioembolism are at higher risk of SICH with intravenous tirofiban., Trial Registration Number: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR-INR-17014167., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Acute ischemic stroke due to basilar artery occlusion (BAO) is associated with the highest mortality in patients with large vessel occlusion. This study aimed to identify modifiable risk factors of early mortality in patients with BAO., Methods and Results: This was a cohort study of consecutive patients with BAO admitted to 47 stroke centers in China between January 2014 and May 2019. The primary outcome was all-cause mortality within 7 days after hospitalization. Of 829 patients, 164 died (0-3 days: 115; 4-7 days: 49) within 7 days after hospitalization. Among pre- and periprocedural variables, higher admission National Institutes of Health Stroke Scale (NIHSS, adjusted OR, 1.06, 95% CI: 1.04-1.09; p < 0.001), lower admission posterior circulation-Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS, adjusted OR, 0.88, 95% CI: 0.79-0.98; p = 0.02), lower Basilar Artery on Computed Tomography Angiography score (BATMAN, adjusted OR, 0.84, 95% CI: 0.76-0.93; p = 0.001), and recanalization failure (adjusted OR, 2.99, 95% CI: 2.04-4.38; p < 0.001) were independently associated with a higher risk of early mortality. Herniation (adjusted OR, 2.84, 95% CI: 1.52-5.30; p = 0.001) is an independent postprocedural predictor of early mortality. In patients dying ≤3 days, higher NIHSS (p < 0.001), lower pc-ASPECTS (p = 0.01), lower BATMAN (p = 0.004), recanalization failure (p < 0.001), herniation (p = 0.001), gastrointestinal hemorrhage (p = 0.046), and absence of pneumonia (p < 0.001) were independent predictors of early mortality. Higher NIHSS (p = 0.01), recanalization failure (p < 0.001), and pneumonia (p = 0.03) were independently associated with early mortality between 4 and 7 days., Conclusions: Recanalization failure, herniation, gastrointestinal hemorrhage, and pneumonia are potentially modifiable risk factors for early mortality in basilar artery occlusion., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The aim of this study was to test the hypothesis that intravenous tirofiban improves functional outcomes without promoting the risk of intracranial hemorrhage (ICH) in stroke secondary to basilar artery occlusion (BAO) receiving endovascular thrombectomy., Methods: Patients with acute BAO stroke who were treated with endovascular thrombectomy and had tirofiban treatment information were derived from "BASILAR": a nationwide, prospective registry. All eligible patients were divided into tirofiban and no-tirofiban groups according to whether tirofiban was used intravenously. The primary endpoint was the 90-day severity of disability as assessed by the modified Rankin scale score. Safety outcomes were the frequency of ICH and mortality., Results: Of 645 patients included in this cohort, 363 were in the tirofiban group and 282 were in the no-tirofiban group. Thrombectomy with intravenous tirofiban reduced the 90-day disability level over the range of the modified Rankin scale (adjusted common odds ratio, 2.08; 95% confidence interval (CI), 1.45-2.97; p < 0.001). The 90-day mortality of patients in the tirofiban group was lower than that in the no-tirofiban group (41.6% vs. 52.1%; adjusted hazard ratio, 0.60; 95% CI, 0.47-0.77; p < 0.001). The frequency of any ICH (6.7% vs. 13.7%; p = 0.004) and symptomatic ICH (4.8% vs. 10.1%; p = 0.01) in the tirofiban group was significantly lower than that in the no-tirofiban group., Conclusions: In patients with acute BAO stroke who underwent endovascular treatment, intravenous tirofiban might be associated with favorable outcome, reduced mortality, and a decreased frequency of ICH., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, has been shown to reduce the risk of thrombotic complications during percutaneous coronary intervention. However, it remains unknown whether tirofiban improves outcomes in large vessel occlusion stroke patients undergoing endovascular treatment., Objective: This trial aims to assess whether additional intravenous tirofiban therapy can improve the clinical outcomes in large vessel occlusion stroke patients who undergo endovascular treatment within 24 h of symptom onset., Methods and Design: The Endovascular Treatment With versus Without Tirofiban for Stroke Patients With Large Vessel Occlusion (RESCUE BT) Trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multicenter trial. Up to 930 eligible patients will be consecutively randomized to intravenous tirofiban or placebo in 1:1 ratio over 3 years across 50 endovascular-capable stroke centers in China., Outcomes: The primary end point is the disability level as measured by overall distribution of the 90-day modified Rankin Scale scores. Primary safety end points include symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days., Trial Registry Number: ChiCTR-INR-17014167 (www.chictr.org.cn).

Background: The best anesthetic management strategy for patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains uncertain. Most studies have focused on anterior-circulation stroke caused by large artery occlusion. Nevertheless, limited data are available on the appropriate choice of anesthetic for acute basilar artery occlusion (BAO). We aimed to investigate the effect of anesthetic method on clinical outcomes in patients with BAO undergoing MT., Methods: Patients undergoing MT for acute BAO in the BASILAR registry (Acute Basilar Artery Occlusion Study) were included. We divided patients into three groups according to the anesthetic technique used during MT: general anesthesia (GA), local anesthesia (LA), and conscious sedation (CS). Propensity score matching was performed to achieve baseline balance., Results: 639 patients were included. GA was used in 257 patients (40.2%), LA was used in 250 patients (39.1%), and CS was used in 132 patients (20.7%). After 1:1 matching, favorable outcome, mortality, and hemorrhagic transformation rates, as well as modified Rankin Scale (mRS) score at 90 days, did not differ between the GA, LA, and CS groups., Conclusions: The choice of anesthetic strategy, GA, LA, or CS, did not affect the clinical outcomes of patients with acute BAO treated with MT in the BASILAR registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Higher extended Thrombolysis In Cerebral Infarction (eTICI) grades are associated with better clinical outcomes after endovascular treatment (EVT) for proximal intracranial occlusion of the anterior circulation. However, the relationship between eTICI grade and outcomes after EVT in patients with acute basilar artery occlusion (BAO) remains unclear. We aimed to explore which eTICI category was the cut-off correlating with better clinical outcomes in patients with BAO undergoing EVT., Methods: We included patients treated via EVT from the BASILAR study. Multivariable logistic regression analyses were performed to assess the impact of eTICI grades on 90-day favorable functional outcomes, defined as a modified Rankin Scale (mRS) score of 0-3. Other outcomes were functional independence (mRS 0-2), all-cause mortality, and symptomatic intracranial hemorrhage., Results: Among 647 patients treated with EVT, 127 (19.6%), 128 (24.5%), 110 (21.1%), and 282 (54%) patients achieved eTICI grades of 0-2a, 2b, 2c, and 3, respectively. Compared with eTICI grades 0-2a, higher rates of favorable functional outcomes (adjusted OR (aOR) 2.96, 95% CI 1.33 to 6.57, and aOR 7.40, 95% CI 3.63 to 15.09, respectively) were observed for grades 2c and 3, not 2b (aOR 1.93, 95% CI 0.86 to 4.36). The risks of mortality and symptomatic intracranial hemorrhage were also lower for eTICI grades 2c and 3 than for grades 0-2a., Conclusions: An eTICI grade of 2c/3 may be a target for successful reperfusion after EVT in patients with acute BAO; however, further studies with larger sample sizes and clinical trials are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to investigate the efficacy and safety of endovascular treatment (EVT) plus standard medical treatment (SMT) in patients with acute basilar artery occlusion (BAO) within 6 hours of the estimated occlusion time, based on a Chinese population., Methods: The authors selected patients from the Endovascular Treatment of Acute Basilar Artery Occlusion Study (BASILAR) registry, which was a nationwide prospective registry, within 6 hours after the estimated time of onset of a stroke in acute BAO. Patients were divided into the SMT-alone group or the EVT+SMT group according to treatment modalities. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale score between 0 and 3 at 90 days. Safety outcomes included death at 90 days and symptomatic intracerebral hemorrhage., Results: The authors assessed 590 patients for eligibility. Of these patients, 127 received SMT alone and 463 were treated with EVT plus SMT. EVT was associated with a higher rate of a favorable functional outcome (adjusted OR 3.804, 95% CI 1.890-7.658; p < 0.001) and a lower proportion of deaths at 90 days (adjusted OR 0.364, 95% CI 0.223-0.594; p < 0.001). Lower age (adjusted OR 0.978, 95% CI 0.960-0.997; p = 0.022); lower baseline National Institutes of Health Stroke Scale score (adjusted OR 0.926, 95% CI 0.902-0.950; p < 0.001); higher baseline posterior circulation Alberta Stroke Program Early CT Score (adjusted OR 1.681, 95% CI 1.424-1.984; p < 0.001); absence of diabetes mellitus (adjusted OR 0.482, 95% CI 0.267-0.871; p = 0.016); and modified Thrombolysis in Cerebral Infarction scores 2b-3 (adjusted OR 5.117, 95% CI 2.304-11.367; p < 0.001) were independent factors for a favorable outcome in the EVT+SMT group., Conclusions: Based on the study design, patients with acute BAO who received EVT within 6 hours were associated with improved favorable outcome and decreased deaths compared with patients who received SMT. Predictors of desirable outcome in patients undergoing EVT included lower age, lower baseline National Institutes of Health Stroke Scale score, higher baseline posterior circulation Alberta Stroke Program Early CT Score, absence of diabetes mellitus, and modified Thrombolysis in Cerebral Infarction scores 2b-3.

Background and Purpose: Increased high-mobility group box 1 (HMGB1) levels were found in patients after acute ischemic stroke. The aim of this study was to examine whether the circulating HMGB1 levels could predict the 3-month post-stroke depression (PSD)., Methods: The subjects were first-ever ischemic stroke patients who were hospitalized during the period from July 2020 to December 2020. HMGB1 concentrations were measured by enzyme-linked immunosorbent assay after admission. A 24-item Hamilton Depression Rating Scale was performed to evaluate PSD at 3 months after stroke., Results: The analyses included 324 participants (mean age, 63.7 years; 171 male). Ninety-four patients (29.0%) were diagnosed as having PSD at 3 months. The median serum HMGB1 levels at admission was 7.5 ng/mL (IQR, 4.4-11.3 ng/mL). The PSD distribution across the HMGB1 quartiles ranged between 17.5% (first quartile) and 57.5% (fourth quartile). After covariate adjustments, the fourth quartile of HMGB1 was found to be associated with a higher risk of PSD (as compared with first HMGB1 quartile, odd ratio, 1.26; 95% confidence interval [CI], 1.17-1.35; P < 0.001). The area under the receiver operating characteristic curve of HMGB1 was 0.726 (95% CI 0.660-0.792) for PSD. Similar results were found when HMGB1 was analyzed as continuous variable. Furthermore, the optimal cutoff point of circulating HMGB1 levels was 8.6 ng/mL, with a sensitivity of 69.2% and a specificity of 73.9%., Conclusions: This study demonstrated that higher HMGB1 levels in the acute phase of ischemic stroke were associated with increased risk of PSD., (© 2021. Fondazione Società Italiana di Neurologia.)

Background and Purpose: The BASILAR registry, a nationwide prospective nonrandomized study conducted in China, enrolled consecutive patients with acute basilar artery occlusion receiving endovascular treatment or conventional-treatment from January 2014 to May 2019. This article aimed to report the results of clinical follow-up at one year among these patients., Methods: The primary outcome was the modified Rankin Scale at one year, assessed as a common odds ratio using ordinal logistic regression analysis adjusted for prespecified prognostic factors. Secondary outcomes included the modified Rankin Scale-based outcome group at one year (0-1, 0-2, or 0-3) and all-cause death., Results: Of the 829 patients enrolled in the original BASILAR registry, one-year data were available for 785 patients (94.7%). The distribution of outcomes on the modified Rankin Scale favored endovascular treatment over conventional-treatment (adjusted common odds ratio, 4.50 [95% CI, 2.81-7.29]; P <0.001). The cumulative one-year mortality rate was 54.6% in the endovascular treatment group versus 83.5% in the conventional-treatment group (adjusted odds ratio, 4.36 [95% CI, 2.69-7.29]; P <0.001)., Conclusions: The beneficial effect of endovascular treatment on functional outcome at one year in patients with acute basilar artery occlusion is similar to that reported at 90 days in the original study., Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide., Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior)., Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers., Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions., Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Background and Purpose: This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion., Methods: The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0-4 versus 5-7 versus 8-10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days., Results: In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30-14.48] and 3.20 [1.68-6.09]; respectively) and lower mortality (60.8% versus 77.6%, P =0.005 and 35.0% versus 66.2%, P< 0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94-1.02])., Conclusions: Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT. Registration: URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800014759.

Objective: The purpose of the present study is to investigate whether angiopoietin-like 4 (ANGPTL4) can promote angiogenesis and neurogenesis following stroke, as well as to explore the potential underlying mechanisms., Methods: ANGPTL4 (40 μg/kg) or a vehicle was administered via tail vein beginning 5 min prior to electrocoagulation-induced stroke in male C57/B6 J mice. Infarct volume was measured via Nissl staining at day 3 post-stroke. Angiogenesis, neurogenesis and activation of microglia were evaluated by immunofluorescence co-labelling bromodeoxyuridine (BrdU) with von Willebrand factor (vWF), doublecortin (DCX), neuronal nuclei (NeuN) and Iba1 at day 7 post-stroke. The levels of p-AKT, T-AKT, VEGF, MPO, Fas and FasL in the ipsilesional brain were detected by Western blot analysis at day 1 post-stroke., Results: Compared with the Vehicle group, ANGPTL4 reduced infarct volume significantly at day 3 post-stroke. ANGPTL4 significantly increased the number of BrdU + , BrdU + /vWF + and BrdU + /DCX + cells in the peri-infarct zone, subventricular zone and subgranular zone and inhibited BrdU + /Iba1 + cells in the peri-infarct zone at day 7 post-stroke. The level of p-AKT and the ratio of phospho-AKT to total-AKT in the ipsilesional brain were significantly elevated, the levels of MPO, Fas and FasL were significantly declined; however, there was no significant difference at day 1 post-stroke between the VEGF and total-AKT levels in both groups., Conclusions: ANGPTL4 enhances angiogenesis and neurogenesis post-stroke by upregulating the phosphorylation of AKT, reduces neuronal death and inhibits inflammatory response, which resultes from the inhibition of FasL/Fas expression and its downstream pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Eight randomized controlled trials have consistently shown that endovascular treatment plus best medical treatment improves outcome after acute anterior proximal intracranial large vessel occlusion strokes. Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation, large vessel occlusion is of any additional benefits remains unclear., Objective: This study compares the safety and efficacy of direct endovascular treatment versus intravenous recombinant tissue-type plasminogen activator bridging with endovascular treatment (bridging therapy) in acute stroke patients with intracranial internal carotid artery or middle cerebral artery-M1 occlusion within 4.5 h of symptom onset., Methods and Design: The DEVT study is a randomized, controlled, multicenter trial with blinded outcome assessment. This trial uses a five-look group-sequential non-inferiority design. Up to 194 patients in each interim analysis will be consecutively randomized to direct endovascular treatment or bridging therapy group in 1:1 ratio over three years from about 30 hospitals in China., Outcomes: The primary end-point is the proportion of independent neurological function defined as modified Rankin scale score of 0 to 2 at 90 days. The primary safety measure is symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days., Trial Registry Number: ChiCTR-IOR-17013568 (www.chictr.org.cn).

Purpose: To evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation., Methods: Consecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared., Results: A total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups., Conclusions: RS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective To compare outcomes following intracranial stent retriever-based intracranial thrombectomy (SRT) with emergency extracranial internal carotid artery (EICA) stenting or angioplasty alone in patients presenting with acute stroke due to tandem occlusions of the ICA. Methods Consecutive patients with acute anterior tandem occlusion who received an endovascular intervention within 6h of symptom onset between January 2013 and June 2016 were included in this prospective study. Demographic, radiological, procedural and clinical outcome data were compared between the stenting and the angioplasty alone groups. Results Of the 37 patients eligible for the study, 18 had angioplasty alone and 19 underwent stent placement. Successful recanalization rate was statistically significantly higher in the stenting group than in angioplasty alone group (74% vs. 39%) and although not statistically significant, more patients in the stenting group than in the angioplasty alone group had favourable outcomes (63% vs. 50%). There was no significant difference between groups in rates of symptomatic intracranial haemorrhage (SICH), cerebral herniation or mortality. Conclusion This study in a small sample size suggests that among patients with acute anterior tandem occlusion, SRT with EICA stenting tended to achieve higher recanalization and improved clinical outcomes at three months compared with SRT and angioplasty alone with a similar rate of SICH and mortality.

Hemorrhagic transformation (HT) is a major complication of ischemic stroke and further deteriorates neurological outcomes. Bradykinin 1 receptor (B1R) has been proven to mediate vasculo-toxicity in various experimental models. However, its role in the development of HT after stroke remains unclear. We detected the B1R expression in brain tissues with or without HT in a rat model of cerebral ischemia/reperfusion (I/R) with type 1 diabetes, showing higher B1R expression in the hemorrhagic areas than the ischemic tissues. Then, B1R agonist or antagonist was administrated intravenously just before reperfusion to investigate its effect on HT and the underlying molecular mechanism. Administration of low (300 nmol/kg) or high (1 μmol/kg) dose of B1R antagonist mitigated hemorrhage, improved neurobehavioral deficits, and preserved blood-brain-barrier (BBB) integrity after reperfusion for 8 h whereas the 300 nmol/kg of B1R agonist aggravated these outcomes, though only the high does of B1R antagonist affected the infarction volume. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was increased by B1R activation but decreased by B1R inhibition, which mediated B1R toxicity on BBB disruption and ischemia-related HT. Furthermore, B1R activation facilitated the mRNA and protein expressions of MMP-9 in the hemorrhagic tissues, and these increases were blocked by both ERK inhibitor U0126 and NF-κB inhibitor PDTC. U0126 also remarkably decreased the B1R-induced NF-κB/p65 activation. We concluded that upregulated B1R may contribute to early HT after I/R in type 1 diabetic rats via ERK1/2/NF-κB/MMP-9 pathway. B1R inhibition could be an encouraging therapeutic strategy to withstand HT after ischemic stroke in diabetic patients.

Guanosine (GUO) is neuroprotective when administered acutely for the treatment of cerebral ischemia. The aim of the present study was to investigate whether delayed administration of GUO improved long‑term functional recovery following stroke, as well as to explore the potential underlying mechanisms. GUO (8 mg/kg) or a vehicle was administered intraperitoneally for 7 consecutive days beginning 24 h prior to photothrombosis‑induced stroke in male C57/B6J mice. Behaviour tests were performed at days 1, 3, 7, 14 and 28 post‑stroke. Infarct volume was measured using Nissl staining at day 7 post‑stroke. Neurogenesis and angiogenesis were evaluated by co‑labelling bromodeoxyuridine (BrdU) with doublecortin (DCX), neuronal nuclei (NeuN) and von Willebrand factor, in immunohistochemical studies. Brain‑derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) levels in the ipsilesional brain at day 28 post‑stroke were detected by western blot analysis. Delayed administration of GUO did not reduce infarct volume or affect neurological function at day 7 post‑stroke; however, it did improve functional recovery from day 14 post‑stroke, when compared with the vehicle group. GUO significantly increased the number of BrdU+ and BrdU+/DCX+ cells in the subventricular zone and subgranular zone at all examined time points, the number of Brdu+/NeuN+ cells in the peri‑infarction region at days 14 and 28 post‑stroke and microvessel density in the peri‑infarction region at day 28 post‑stroke compared with the vehicle group. In addition, the BDNF and VEGF levels in the ipsilesional brain were significantly elevated. Delayed administration of GUO at 24 h post‑stroke enhanced neurogenesis and angiogenesis, and increased BDNF and VEGF levels, which likely contributes to long‑term functional recovery following stroke.

Background: Early neurological deterioration (END) is an important factor associated with worse clinical outcome in minor strokes. Early magnetic resonance imaging (MRI) findings can provide better sensitivity to delineate stroke pathophysiology and have diagnostic value associated with causative mechanisms. The aim of this study was to investigate the relationship between early MRI finding and the presence of END in minor stroke patients with lesions in the middle cerebral artery (MCA) territory., Methods: Consecutive MCA minor stroke patients who were admitted to our center within 24 hours of symptom onset were included in this study. All patients underwent MRI within 24 hours of admission. We analyzed baseline characteristics, infarction patterns, and treatment algorithms. The correlation between early MRI findings and END, defined as National Institutes of Health Stroke Scale score increasing more than 2 points during 72 hours after admission, was also determined., Results: Across 211 patients meeting entry criteria between January 2010 and December 2013, internal border-zone (IBZ) infarcts on early MRI scan were observed in 23 of 65 patients with END (35.4%) and in 18 of 146 patients without END (12.3%, P < .001). Patients with IBZ infarcts were found to have more hyperlipidemia, less perforating artery infarcts, more pial artery infarcts, more cortical border-zone infarcts and more ipsilateral large arterial stenosis. Logistic regression analysis revealed that IBZ infarct was independently associated with END after adjustment for other factors (odds ratio, 2.50; 95% confidence interval, 1.09-5.74; P = .031)., Conclusions: Early MRI patterns of IBZ infarction are associated with END in minor stroke patients with acute infarcts of the MCA territory., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design., Methods: The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models., Results: The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p < 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34(+)CD133(+)CD309(+)cells: r = 0.510, p = 0.001; CD34(+) CD133(-)CD309(+)cells: r = 0.262, p = 0.004; CD34(-)CD133(+)CD309(+)cells: r = 0.348, p < 0.001)., Conclusions: Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

Objective: To investigate the difference between the clinical effects of nasotracheal suction (NTS) mechanical ventilation and noninvasive positive pressure ventilation (CPAP) treatment of cerebral ischemic stroke (IS) induced by sleep apnea., Patients and Methods: Fifty-three patients diagnosed with cerebral IS caused by sleep apnea from February 2013 to February 2014 were selected for this study from our hospital. After the approval of the hospital's Ethics Committee and patients' signed consent, the patients were randomly divided into a test group (n=29 cases) and a control group (n=24 cases). All patients were given conventional treatment for stroke. The control group received the noninvasive ventilator application with CPAP model. The test group was treated with nasal endotracheal suction of mechanical ventilation treatment. Using the NIHSS scale and Barthel index, we compared the status of the nervous system on admission and after seven days stroke recovery treatment of the two groups. Through the comparison of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), LSaO2 and MSaO2 of the two groups on the seventh day, we compared the efficacy of the obstructive sleep apnea-hypopnea syndrome (OSAHS)., Results: The NIHSS score and Barthel index score of mild, moderate and severe were compared on the OSAHS patients at admission, and the difference was not statistically significant (p > 0.05). After treatment, all patients showed lower NIHSS score and increased Barthel scores, and the difference had statistical significance (p < 0.05). For the mild OSAHS patients, we compared the NIHSS score and Barthel index score of the test and control group, and the difference was not statistically significant (p > 0.05). For the moderate and severe OSAHS patients, the NIHSS score of the test group decreased significantly. However, the Barthel index scores increased significantly, and the difference had statistical significance (p > 0.05). The AHI, LSaO2, MSaO2, and ODI index of the two groups of patients were compared with the treatment, and the differences were not statistically significant (p > 0.05). After treatment, the AHI and the ODI index of the two groups decreased, LSaO2 and MSaO2 index increased, and AHI and ODI index of the test group decreased more than that of the control group. However, the LSaO2 and the MSaO2 index increased, and the difference had statistical significance (p > 0.05). The total effective rate of patients of the test group was higher than that of the control group, but no effectiveness and overall mortality was lower than the control group. The difference was statistically significant (p > 0.05)., Conclusions: Compared with noninvasive ventilator therapy, nasotracheal suction mechanical ventilation and noninvasive positive pressure ventilation treatment of cerebral IS induced by sleep apnea can naturally improve the prognosis of nervous system recovery, and improve the respiratory ventilation function. This may be a better treatment option for moderate and severe sleep apnea patients that is worthy of clinical application.

Objective: To inspect the feasibility and content validity of the comprehensive International Classification of Functioning, Disability and Health (ICF) core set for stroke by describing relevant aspects of functioning, disability and environmental factors affected in Chinese patients post stroke., Design: Multicentre, cross-sectional study., Setting: Department of rehabilitation medicine., Subjects: The content validity was evaluated using frequency and percentage of 208 patients with a mean age of 60 years post stroke in China., Outcome Measures: Aspects of body function and structure, activity and participation, and environmental factors in the comprehensive ICF core set for stroke., Results: Six ICF categories of body function were identified as a problem in over 90% (n = 187) of the patients (functions of the cardiovascular system and neuromusculoskeletal and movement-related functions). Impairments of brain, upper and lower extremity were identified as a problem in over 50% (n = 104) of the patients. Four ICF categories of activities and participation were documented as a problem in 100% (n = 208) of the patients (domestic and civic life). In environmental factors, nine ICF categories were documented as barriers by more than 10% (n = 20) and fewer than 50% (n = 104) of the patients (products and technology, physical geography, societal attitudes, services, systems and polices). Six ICF categories were identified as facilitators in over 90% (n = 187) of the patients (support and relationships and attitudes)., Conclusion: The findings suggest that it is feasible to apply the comprehensive ICF core set for stroke in the Chinese clinical setting, after the appropriate reduction of some categories according to Chinese patients' characteristics and culture.

ObjectiveAs the physical activator of natriuretic peptides, corin has been associated with stroke, but the underlying mechanism is not very clear. Here, we examined whether the CORIN promoter’s methylation, an epigenetic DNA modification, was associated with the risk of stroke in two independent samples.MethodsA total of 1771 participants including 853 stroke cases and 918 healthy controls were included as a discovery sample and 2,498 community members with 10 years of follow-up were included as a replication sample. DNA methylation of the CORIN promoter was quantified by target bisulfite sequencing in both samples. We first examined the single CpG association, followed by a gene-based analysis of the joint association between multiple CpG methylation and stroke, adjusting for conventional risk factors.ResultsThe single CpG association analysis found that hypermethylation at all of the 9 CpG sites assayed was significantly associated with lower odds of prevalent stroke in the discovery sample (all p