Rate Of Intracranial Hemorrhage Research Articles

General anesthesia vs. non-general anesthesia for vertebrobasilar stroke endovascular therapy.

The optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT). Patients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0-3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0-2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8). In the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06-12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found. Patients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8). URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

Abstract 93: Effect Of Intravenous Tirofiban Following Successful Endovascular Thrombectomy On Functional Outcomes In Large Artery Atherosclerotic Stroke: Secondary Analysis Of A Randomized Clinical Trial

Background: Incomplete reperfusion contributes to reduced neurological recovery of patients with acute large vessel occlusion and successful reperfusion after endovascular thrombectomy. Intravenous tirofiban might enhance macrocirculatory and microcirculatory reperfusion in these patients, especially in those with large artery atherosclerotic stroke. We aimed to investigate whether treatment with adjunct intravenous tirofiban is associated improved outcomes following successful reperfusion in patients with acute large artery atherosclerotic stroke. Methods: In this subgroup analysis of RESCUE BT trial, patients with intracranial large artery atherosclerotic stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 were included. The primary outcome was the difference in proportion of independent functional outcome, defined as a modified Rankin score of 0 to 2 at 90 days. Safety outcomes included the rates of symptomatic intracranial hemorrhage and 90-day mortality. Results: Among the 382 patients with intracranial large artery atherosclerosis stroke and successful reperfusion (median [IQR] age, 65 (55-72) years; 105 [27.5%] women), 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95/175) with tirofiban and 44.0% (91/207) with placebo (adjusted odds ratio [aOR], 1.59; 95% CI, 1.03-2.45; P = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of symptomatic intracranial hemorrhage within 48 hours (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; P = 0.44) or 90-day mortality (21/175 [12.0] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; P = 0.27). Conclusions: Among patients with acute large artery atherosclerotic stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of symptomatic intracranial hemorrhage or mortality. Confirmatory randomized trials in these patients are desirable.

Abstract TMP6: Association Of Tirofiban With Outcomes After Thrombectomy In Stroke Due To Atherosclerosis: An Exploratory Analysis Of The RESCUE BT Placebo-controlled Randomized Trial

Background: The efficacy and safety of tirofiban, as an adjuvant medication of endovascular therapy (EVT), in patients with large vessel occlusion due to atherosclerotic thrombosis was still unclear. Methods: The Endovascular Treatment With versus Without Tirofiban in Stroke (RESCUE BT) trial was a randomized, double-blinded, placebo-controlled trial that was performed at 55 centers in China from October 10, 2018 to October 31, 2021. This was a post hoc exploratory analysis of the RESCUE BT trial and 435 patients were included in the intention-to-treat analysis. The primary outcome was the proportion of functional independence (defined as modified Rankin Scale 0-2) at 90 days. We estimated the efficacy and safety of EVT plus placebo versus EVT plus tirofiban using binary logistic regression analysis. A causal mediation analysis was also performed to assess the potential mediators of tirofiban on functional outcome. Results: This study included 435 patients, including 197 patients assigned to the tirofiban group and 238 patients assigned to the placebo group. The median age was 65 [IQR, 56-72] years, and 311 (71.5%) patients were men. Tirofiban was associated with higher rates of functional independence at 90 days compared with the placebo (adjusted odds ratio with 95% CI, 1.68 [1.11–2.56], P = 0.014). There was no significant difference in mortality and symptomatic intracranial hemorrhage between the two groups, thought the rate of intracranial hemorrhage was numerically higher in the tirofiban group (29.1% versus 23.2%, P = 0.165). Tirofiban was also associated with fewer number of thrombectomy passes (beta, -0.48; 95% CI, -0.62 to -0.34; P < 0.001). Treatment-reduced passes explains 20.0% (95% CI, 4-76) of the beneficial effect of tirofiban on functional independence. Conclusion: Tirofiban plus EVT might be an effective and well-tolerated option for patients with anterior large vessel occlusion due to atherosclerosis. These findings are needed to be confirmed in future trials.

Abstract WP168: Percutaneous Left Atrial Appendage Closure Device For Patients With Atrial Fibrillation In New York

Introduction: Trials have shown that WATCHMAN left atrial appendage closure (LAAC) for stroke is noninferior to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). Since the approval of WATCHMAN, real world clinical outcome of LAAC is still limited. We performed a state wide analysis to evaluate clinical outcomes for AF patients undergo LAAC. Methods: Using the Healthcare Cost and Utilization Project (HCUP) State Inpatient Database, we included New York state adult patients, who had AF diagnosis with and without LAAC procedure from 2011 to 2017. Patients who had acute ischemic stroke (AIS) or history of AIS prior or during index admission were excluded. AF, AIS and other diagnosis were identified based on standard ICD-9 CM and ICD-10 CM codes. We compared rates of AIS, intracranial hemorrhage (ICH) and death between patients with and without LAAC. We also constructed a Cox regression model to determine hazard ratios (HR) of LAAC associated with each outcome. Results: Of the 627,972 patients with AF admitted, the mean age was 75.8 and 33.1% were female, and 773 (0.1%) underwent LAAC. AIS readmission occurred in 0.030% of AF patients without LAAC while it occurred in 0.012% of patients underwent LAAC. In the Cox regression model, LAAC had similar AIS readmission (HR 0.84, 95% CI 0.44-1.62, P = 0.602) and ICH readmission (HR 1.688, 95% CI 0.63-4.50, P = 0.296), but LAAC was associated with less death (HR 0.295, 95% CI 0.20-0.43, P < 0.001). These outcomes remained the same despite adjustment with common risk factors and insurance type, or adjustment with CHADS 2 VASC 2 scores. In sensitivity analysis, after restricting to patients that had ICH prior to index admission, LAAC again had similar AIS readmission (HR 1.884, 95% CI 0.26-13.46, P = 0.528) compared to non-LAAC group but still marginally associated with less death (HR 0.289, 95% CI 0.07-1.16, P = 0.080). Conclusion: In New York state, AF patients underwent LAAC procedural are less likely to have death during follow up despite adjustment of common risk factors or CHADS 2 VASC 2 score, while AIS and ICH readmission appears to be similar. However, given potential underlying confounding by treatment indication, these findings need confirmation by ongoing randomized control trials.

Effect of implementing care protocols on acute ischemic stroke outcomes: a systematic review.

Implementing stroke care protocols has intended to provide better care quality, favor early functional recovery, and achieving long-term results for the rehabilitation of the patient. To analyze the effect of implementing care protocols on the outcomes of acute ischemic stroke. Primary studies published from 2011 to 2020 and which met the following criteria were included: population should be people with acute ischemic stroke; studies should present results on the outcomes of using protocols in the therapeutic approach to acute ischemic stroke. The bibliographic search was carried out in June 2020 in 7 databases. The article selection was conducted by two independent reviewers and the results were narratively synthesized. A total of 11,226 publications were retrieved in the databases, of which 30 were included in the study. After implementing the protocol, 70.8% of the publications found an increase in the rate of performing reperfusion therapy, such as thrombolysis and thrombectomy; 45.5% identified an improvement in the clinical prognosis of the patient; and 25.0% of the studies identified a decrease in the length of hospital stay. Out of 19 studies that addressed the rate of symptomatic intracranial hemorrhage, 2 (10.5%) identified a decrease. A decrease in mortality was mentioned in 3 (25.0%) articles out of 12 that evaluated this outcome. We have identified the importance of implementing protocols in increasing the performance of reperfusion therapies, and a good functional outcome with improved prognosis after discharge. However, there is still a need to invest in reducing post-thrombolysis complications and mortality.

Endovascular Thrombectomy with or without Intravenous Thrombolysis for Anterior Circulation Large Vessel Occlusion in the Imperial College London Thrombectomy Registry.

Background and purpose. Mechanical thrombectomy (MT) is the standard of care for eligible patients with a large vessel occlusion (LVO) acute ischemic stroke. Among patients undergoing MT there has been uncertainty regarding the role of intravenous thrombolysis (IVT) and previous trials have yielded conflicting results regarding clinical outcomes. We aim to investigate clinical, reperfusion outcomes and safety of MT with or without IVT for ischemic stroke due to anterior circulation LVO. Materials and Methods. This observational, prospective, single-centre study included consecutive patients with acute LVO ischemic stroke of the anterior circulation. The primary outcomes were the rate of in-hospital mortality, symptomatic intracranial haemorrhage and functional independence (mRS 0-2 at 90 days). Results. We enrolled a total of 577 consecutive patients: 161 (27.9%) were treated with MT alone while 416 (72.1%) underwent IVT and MT. Patients with MT who were treated with IVT had lower rates of in-hospital mortality (p = 0.037), higher TICI reperfusion grades (p = 0.007), similar rates of symptomatic intracranial haemorrhage (p = 0.317) and a higher percentage of functional independence mRS (0-2) at 90 days (p = 0.022). Bridging IVT with MT compared to MT alone was independently associated with a favorable post-intervention TICI score (>2b) (OR, 1.716; 95% CI, 1.076-2.735, p = 0.023). Conclusions. Our findings suggest that combined treatment with MT and IVT is safe and results in increased reperfusion rates as compared to MT alone.

Abstract WMP2: Acute Stroke Treatment In Patients With Pre-exiting Disability: A Secondary Analysis Of The BEST-MSU Trial

Background: Few data exists on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. Methods: A pre-specified subgroup analysis of tPA-eligible patients with PD enrolled in a prospective multicenter trial of Mobile Stroke Units (MSUs) vs standard management by emergency medical services (EMS). All patients had baseline mRS scores. Co-primary outcomes were mean utility-weighted modified Rankin Scale score (uw-mRS) and return to baseline mRS at 90 days. Linear and logistic regression models compared outcomes in patients with vs without PD, and patients with PD treated by MSU vs EMS. Time metrics, safety, quality of life, and health-care utilization were also compared. Results: Of 1047 patients, 254 had baseline mRS >= 2 (159 MSU, 95 EMS; 31% mRS 2, 52% mRS 3, 17% mRS 4). Compared to patients without disability, patients with PD were older, had higher NIHSS, more comorbidities, less often lived at home, were treated slower, and had less thrombectomy. Patients with PD had worse 90-day uw-mRS (0.39 vs 0.80), higher mortality, more health-care utilization and worse quality of life than patients without PD. However, rates of symptomatic intracranial hemorrhage and final diagnoses of stroke mimics were similar between groups, and 52% of patients with PD returned to their baseline mRS. Patients with PD treated within the first hour had better 90-day uw-mRS than those treated later (0.48 vs 0.36, p=0.01). Comparing patients with PD treated by MSU vs EMS, time from last-known-well to tPA bolus was shorter (82 vs 111 min), and 24% vs 0% were treated in the first hour. Among patients with PD, MSU patients had non-significantly better 90-day uw-mRS (0.41 vs 0.35, p=0.09) and higher rate of returning to baseline mRS (56% vs 44%, p=0.09) than EMS patients. There was no interaction between either time to treatment (p=0.24) or MSU vs EMS group assignment (p= 0.42), 90-day uw-mRS, and PD vs no disability status. Conclusion: Although outcomes after stroke are less favorable in patients with vs without PD, in a large, controlled trial, we found no interaction between baseline disability and the benefit of MSU treatment. Our data support the earliest treatment of acute stroke patients regardless of premorbid functional status.

Abstract TP3: Network-wide Incidence Of Intracranial Hemorrhage In Patients With Acute Ischemic Stroke Receiving Tenecteplase

Background: Intravenous tenecteplase (TNK) is currently being used as a thrombolytic agent in acute ischemic stroke (AIS) and has has been shown to be non-inferior to intravenous alteplase according to recent studies. Intracranial hemorrhage (ICH) as a complication of alteplase is approximately at 6%. The aim of our study was to determine the rate of significant ICH in patients receiving TNK indicated for AIS in a real world setting. Methods: A network-wide (3 CSCs, 6 PSCs), multicenter retrospective chart review of patients receiving TNK from February 2020 to January 2022 was performed using the Get With The Guidelines database. TNK bolus dose of 0.25mg/kg was used according to a network-wide policy. ICH was categorized using ECASS-3 criteria. Fisher exact test statistic was used to determine if a significant association existed between the presence of ICH and baseline ASPECTS score, endovascular treatment (EVT), and IV eptifibatide use. A benchmark less than 2% PH-2 incidence was set based on historical alteplase related PH-2 rates within our network. Social science statistics software was used for data analysis. Results: Out of 180 patients who received TNK, 25 subjects (13.89%) developed hemorrhagic transformation. Mean age was 71.88 (95% CI 65.54, 78.22). Forty-eight percent of subjects were female. Median ASPECTS score was 8 (95% CI 7.54, 8.78). Median 90 day mRS was 3 (95% CI 2.1, 3.9). Hemorrhagic transformation was classified as HI-1 in 5% (n=9), HI-2 in 1.7% (n=3), PH-1 in 3.8% (n=7), and PH-2 in 3.3% (n=6) subjects. No significant difference between subjects with other subtypes versus PH-2 was identified when adjusting for ASPECTS score >=7 versus <7 (Fisher value=1), EVT versus no EVT (Fisher value=0.65), or use of IV eptifibatide (Fisher value=0.06). Conclusion: Tenecteplase is associated with higher rates of PH-2 intracranial hemorrhage when compared with our benchmark rates of alteplase-related PH-2. This study is significantly limited by small sample size, retrospective nature, and uncontrolled variables. Larger, prospective studies are needed to validate our results.

Abstract TMP86: Clinical Outcomes Of Endovascular Thrombectomy Versus Acute Medical Treatment In Acute Ischemic Strokes Secondary To Medium Vessel Occlusion

Introduction: Acute ischemic stroke (AIS) from arterial occlusions are treated with emergent endovascular thrombectomy (EVT) when clinically appropriate. Clinical outcomes of EVT in medium vessel occlusion (MVO) compared to large vessel occlusion (LVO) have neither been well established nor compared to alternate medical management. Our aim was to evaluate outcomes of patients with AIS secondary to MVO undergoing EVT. Methods: We conducted a retrospective chart review of patients presenting to with MVO-associated AIS undergoing EVT or aggressive intra-arterial thrombolytic treatment with concurrent administration of IV eptifibatide. We assessed occlusion site, NIHSS (presentation, 7 day or discharge, 3 months), mRS (baseline, 90-day), and intracranial hemorrhage (ICH) rate. MVO was defined as occlusion of pure M2 middle cerebral artery without M1 segment involvement, anterior cerebral artery A1 segment or more distal, and posterior cerebral artery P1 segment or more distal. Mann-Whitney U test, Fisher exact test statistic, and T-test statistic were used for analysis. Results: From August 2020 to December 2021, out of 175 patients who underwent EVT, 50 had MVO (n=33 M2 occlusion, n=12 M3 occlusion, n=1 for P1, P2, A1, A2, A3 each). Twelve subjects with MVO received aggressive medical management with concurrent IV eptifibatide. Subjects between arms were similar at baseline (median NIHSS 11 [95% CI 10.75, 14.32]; mean age 71.5 [95% CI 69.24, 73.77]; male 48.39% [n=30]). The difference between initial NIHSS and discharge NIHSS was statistically significant in the EVT arm (Z-Score=4.03; p-value < .00001) but not in the medical arm (Z-score=1.96; p-value 0.05). Hemorrhagic transformation occurred in 28% (n=14) of EVT arm and 16.67% (n=2) of medical arm. This was not statistically significant (Fisher value: 0.71). Median 90 day mRS was 1 (95% CI [0.89, 2.11]). The difference between 90 day mRS was not significantly different (Z-score=-1.20; p-value 0.23). Conclusion: In our patient cohort, endovascular therapy was safe in medium vessel occlusion and may have more favorable clinical outcomes as illustrated by higher delta NIHSS in the endovascular thrombectomy group. Larger, prospective studies are needed to validate our results.

Abstract WP11: Outcomes Associated With Iv Tenecteplase And Iv Alteplase For Acute Ischemic Stroke With Or Without Thrombectomy In Real-world Settings In The United States

Background and Purpose: Although many stroke centers in United States are using intravenous (IV) tenecteplase (TNK) for acute ischemic stroke patients, there is paucity of comparative data between IV TNK and IV alteplase from real-world settings. Materials and Methods: We analyzed the data from 122 healthcare facilities to determine the effect of IV TNK (compared with IV alteplase) on occurrence of two outcomes in acute ischemic stroke patients stratified by use of thrombectomy: non-routine discharge or death, and intracranial hemorrhage after adjusting for potential confounders. Results: Among 30,643 acute ischemic stroke patients analyzed, 29,480 (96.2%) and 1,163 (3.8%) patients received IV alteplase and IV TNK, respectively. The proportion of patients who received thrombectomy was significantly higher among patients who received IV TNK compared with those who received IV alteplase (16.7% versus 11.0%, p<0.001). Occurrence of intracranial hemorrhage was higher more common among patients treated with IV TNK among acute ischemic stroke patients who received thrombectomy (20.1% versus 16.8%, p=0.234) or did not receive thrombectomy (7.9% versus 5.1%, p<0.001). In the logistic regression analysis, patients treated with IV TNK who did not receive thrombectomy were at higher risk of intracranial hemorrhage (OR, 1.34, 95% CI 1.05-1.72, p=0.02) after adjusting for potential confounders. There was no difference in the rate of non-routine discharge or death between patients treated with IV TNK and those treated with IV alteplase in the multivariate analyses. Conclusions: In an analysis of real-world data, IV TNK was associated with higher rates of intracranial hemorrhage compared with IV alteplase in patients with acute ischemic stroke.

Abstract TP44: No Differences In Outcomes For Stroke Patients Presenting To A Comprehensive Stroke Center And Treated Using Telestroke Vs. In-person Assessments During The Covid-19 Pandemic.

Introduction: Telestroke is the use of videoconferencing technology by a stroke specialist to assess and treat acute ischemic stroke patients who present elsewhere. It has been well-studied previously in a “Hub-and-Spoke” model. In 2021, Telestroke was used to assess and treat acute ischemic stroke patients who presented primarily after-hours to our comprehensive stroke center because we were concerned the COVID-19 pandemic could affect the timeliness of in-person code stroke assessments. After implementation, we determined the efficacy and safety outcomes for patients treated with Telestroke versus in-person assessments. Hypothesis: We hypothesized that there will be no difference in the efficacy or safety outcomes between patients treated using Telestroke vs. in-person assessments. Methods: A retrospective chart review identified acute ischemic stroke patients who presented to our center in 2021, who were assessed and treated using either Telestroke or an in-person assessment. The primary outcomes for efficacy were door-to-needle (DTN) time for alteplase administration and door to puncture (DTP) time for endovascular thrombectomy. The primary safety outcomes were 3-month mortality and symptomatic intracranial hemorrhage rates (sICH). Results: We treated 302 acute stroke patients in 2021, with 18.2% (n=55/302) of patients treated using Telestroke. There were no differences in clinical outcomes between patients treated using Telestroke vs. in-person assessments: median DTN (35.5min (n=42) vs. 33min (n=182), p<0.76), median DTP (86.5min (n=30) vs. 85min (n=134), p<0.97), sICH (0% (n=0/55) vs. 1.6% (n=4/245, p<0.59) or 3 month mortality (20.6% (n=7/34) vs. 22.1% (n=40/181), p<0.29). Conclusion: This is the first study to our knowledge that reports on using Telestroke at a comprehensive stroke center. In this study, there were no differences in the clinical outcomes between stroke patients treated with Telestroke vs. in-person assessments. These results support using Telestroke to meet the increasing demands for acute stroke assessments at other comprehensive stroke centers.

Abstract 53: Long-term Treatment Risk Of Hemorrhage In Unruptured Brain Arteriovenous Malformation Patients

Introduction: The long-term effects of interventional treatment (with surgery, stereotactic radiosurgery, or endovascular embolization) for unruptured brain arteriovenous malformations (uBAVM) are uncertain. We address this in a large multi-center international cohort study comparing risk of intracranial hemorrhage (ICH) in the treated and untreated course of uBAVM patients. Methods: We pooled individual patient data (n=3,291) from 10 cohorts and imputed missing data. Survival analysis was performed from time of uBAVM diagnosis to intracranial hemorrhage (ICH) using Cox models, stratified by cohort, censoring at death or last follow-up, and including BAVM interventional treatment as a time-varying covariate. We tested for an interaction of treatment with follow-up time, then estimated the association of interventional treatment with ICH, adjusting for propensity quintile. Individual treatment propensity scores were calculated using logistic regression with Spetzler-Martin grade, sex, diagnosis age and year, cohort, and presence of presenting symptoms (seizures, headaches, and/or deficits). Results: Median cohort age was 36 years, 48% were female, and 77% received ≥1 treatment modality for uBAVM during follow-up. 373 ICH occurred during 32,054 person-years of follow-up (median=6.6y), for an ICH rate of 1.16 per 100 P-Y. Overall, treatment was not associated with risk of ICH (HR=1.12, 95% CI=0.89-1.51, p=0.33). However, we observed a strong interaction between treatment and follow-up time (p<0.001): between 0-1 year, treatment was associated with higher risk of ICH (HR=3.48, 95% CI: 2.26-5.37, p<0.001); between 1-10 years, we found no association between treatment and risk of ICH (HR=1.02, 95% CI: 0.73-1.45, p=0.87); after 10 years, treatment was associated with a lower risk of ICH (HR=0.46, 95% CI: 0.30-0.70, p<0.001). Survival curves for untreated and treated courses crossed around 17 years. Conclusion: After accounting for treatment propensity for uBAVM, we found an initial increased risk of ICH in the treated relative to untreated course, which continually declined over time with survival curves crossing around 17 years. These results require confirmation in a randomized controlled trial of uBAVM with long-term follow-up.

The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz (RODIN) Trial: Protocol for a Double-Blinded Clinical Trial of Nelonemdaz in Patients with Hyperacute Ischemic Stroke and Endovascular Thrombectomy.

Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients. The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset. The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran-Mantel-Haenszel shift test. The secondary endpoints include functional independence (mRS 0-2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).

Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation.

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials.

Several randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs. A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model. Nine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0-1 at 90 days (RR = 1.03; 95% CI = 0.97-1.10; P-value = 0.359) and mRS 0-2 at 90 days (RR = 1.03; 95% CI = 0.87-1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0-1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0-2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81-1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75-1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0-1, mRS 0-2, sICH, and mortality) compared to alteplase. Based on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS.

Comparing Tigertriever 13 to other thrombectomy devices for distal medium vessel occlusion: A systematic review and meta-analysis.

There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO. Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0-2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5-96.7%]) versus other devices (81.6% [95% CI: 75.3-88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1-12.5%]) versus other devices (6.9% [95% CI: 5.5-8.8%]). There was significant heterogeneity in the reporting of mortality and mRS. Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.

Asymptomatic Postoperative Cerebral Venous Sinus Thrombosis After Posterior Fossa Tumor Surgery: Incidence, Risk Factors, and Therapeutic Options.

Cerebral venous sinus thrombosis (CVST) is a known complication of posterior fossa surgery near the sigmoid and transverse sinus. The incidence and treatment of postoperative asymptomatic CVST are controversial. To analyze incidence, risk factors, and management of asymptomatic postoperative CVST after posterior fossa tumor surgery. In this retrospective, single-center study, we included all patients who underwent posterior fossa tumor surgery in the semisitting position between January 2013 and December 2020. All patients underwent preoperative and postoperative imaging using MRI with/without additional computed tomography angiography. We analyzed the effect of demographic and surgical data on the incidence of postoperative CVST. Furthermore, therapeutic anticoagulation or conservative treatment for postoperative CVST and the incidence of intracranial hemorrhage were investigated. In total, 266 patients were included. Thirty-three of 266 (12.4%) patients developed postoperative CVST. All patients were asymptomatic. Thirteen of 33 patients received therapeutic anticoagulation, and 20 patients did not. Univariate analysis showed that age ( P = .56), sex ( P = .20), American Society of Anesthesiology status ( P = .13), body mass index ( P = .60), and length of surgery ( P = .176) were not statistically correlated with postoperative CVST. Multivariate analysis revealed that meningioma ( P < .001, odds ratio 11.3, CI 95% 4.1-31.2) and vestibular schwannoma ( P = .013, odds ratio 4.4, CI 95% 1.3-16.3) are risk factors for the development of new postoperative CVST. The use of therapeutic anticoagulation to treat postoperative CVST was associated with a higher rate of intracranial hemorrhage (n = 4, P = .017). Tumor entity influences the incidence of postoperative CVST. In clinically asymptomatic patients, careful decision making is necessary whether to initiate therapeutic anticoagulation or not.

Effect of intra-arterial nimodipine on iatrogenic vasospasms during endovascular stroke treatment – angiographic resolution and infarct growth in follow-up imaging

PurposeThe treatment of vasospasms during endovascular stroke treatment (EST) with intra-arterial nimodipine (NM) is routinely performed. However, the efficacy of resolving iatrogenic vasospasms during the angiographic intervention and the infarct development in follow-up imaging after EST has not been studied yet.MethodsRetrospective single-center analysis of patients receiving EST for anterior circulation vessel occlusion between 01/2015 and 12/2021. The primary endpoint was ASPECTS in follow-up imaging. Secondary endpoints were the clinical outcome (combined endpoint NIHSS 24 h after EST and difference between modified Rankin Scale (mRS) before stroke and at discharge (delta mRS)) and intracranial hemorrhage (ICH) in follow-up imaging. Patients with vasospasms receiving NM (NM+) or not (NM-) were compared in univariate analysis.ResultsVasospasms occurred in 79/1283 patients (6.2%), who consecutively received intra-arterial NM during EST. The targeted vasospasm angiographically resolved in 84% (66/79) under NM therapy. ASPECTS was lower in follow-up imaging after vasospasms and NM-treatment (NM – 7 (6–9), NM + 6 (4.5-8), p = 0.013) and the clinical outcome was worse (NIHSS 24 h after EST was higher in patients treated with NM (median, IQR; NM+: 14, 5–21 vs. NM-: 9, 3–18; p = 0.004), delta-mRS was higher in the NM + group (median, IQR; NM+: 3, 1–4 vs. NM-: 2, 1–2; p = 0.011)). Any ICH (NM+: 27/79, 34.2% vs. NM-: 356/1204, 29.6%; p = 0.386) and symptomatic ICH (NM+: 2/79, 2.5% vs. NM-: 21/1204, 1.7%; p = 0.609) was equally distributed between groups.ConclusionIntra-arterial nimodipine during EST resolves iatrogenic vasospasms efficiently during EST without increasing intracranial hemorrhage rates. However, patients with vasospasms and NM treatment show higher infarct growth resulting in lower ASPECTS in follow-up imaging.

Safety and Efficacy of Prasugrel Administration in Emergent Endovascular Treatment for Intracranial Atherosclerotic Disease.

Intracranial atherosclerosis disease (ICAD) is one of the most common causes of acute ischemic stroke. In endovascular treatment (EVT) for acute large vessel occlusion stroke-related ICAD, reocclusion of the recanalized artery due to in situ thrombosis is problematic. In this study, the safety and efficacy of prasugrel administration to avoid reocclusion of emergent EVT for ICAD was investigated. All consecutive emergent EVTs for ICAD between September 2019 and December 2022 were included in this study. The procedures were divided into two groups as receiving periprocedural prasugrel (PSG group) or not (non-PSG group). Target vessel patency on follow-up, postprocedural intracranial hemorrhage (ICH), and clinical outcome were compared between PSG and non-PSG groups. A total of 27 procedures were included in this analysis. Nineteen target vessels were patent on follow-up and eight were non-patent. Fifteen patients received prasugrel (18.75 mg: 11 cases, 11.25 mg: 4 cases), and twelve patients did not receive prasugrel. The target vessel patency rate was better in the PSG group vs. non-PSG group (100% vs. 33.3%, respectively; p = 0.0002). The postprocedural ICH rate was not different between the groups (PSG: 40.0% vs. non-PSG: 25.0%; p = 0.68), and all ICHs were asymptomatic. Good clinical outcome (modified Rankin Scale score of 0 to 3 at discharge) was more frequent in the PSG group than that in the non-PSG group (66.7% vs. 16.7%, respectively; p = 0.019). Prasugrel administration was significantly associated with target vessel patency and good clinical outcome after emergent EVT for ICAD without increasing the symptomatic ICH rate. Prasugrel administration might be safe and effective to avoid reocclusion during and after emergent EVT for ICAD.

Cancer-Associated Stroke and Acute Endovascular Reperfusion Therapy.

Since stroke is often associated with cancer, acute stroke patients with cancer undergoing endovascular therapy (EVT) are not uncommon. Reportedly, the proportion of such cases is approximately 6%-7% of all stroke EVT cases. Ischemic stroke in patients with active cancer (cancer-associated stroke) includes not only strokes caused by cancer-related hypercoagulability but also coincident strokes due to common etiologies, strokes associated with tumor emboli, direct tumor invasion of blood vessels, and strokes associated with cancer therapy. Stroke caused by cancer-related hypercoagulability itself encompasses various entities, including paradoxical embolism, stroke due to nonbacterial thrombotic endocarditis, and in situ arterial occlusion due to disseminated intravascular coagulation or thrombotic microangiopathy. Thus, diverse mechanisms contribute to cancer-associated stroke, emphasizing the need to consider individualized treatment strategies for acute cases involving large vessel occlusion. Observational studies have shown that EVT for cancer-associated stroke results in poorer clinical outcomes, but with comparable rates of successful reperfusion and symptomatic intracranial hemorrhage when compared with stroke patients without cancer. This suggests that denying patients EVT solely on the basis of comorbid active cancer is inappropriate, and decision-making should be shared with the patients and their families, preferably through a multidisciplinary team approach. Thrombi retrieved from patients with stroke caused by cancer-related hypercoagulability have unique characteristics, being predominantly platelet rich and difficult to retrieve. Preprocedural imaging and serum biomarkers, including the hyperdense vessel sign on non-contrast CT, susceptibility vessel sign on T2* or susceptibility-weighted MRI, three-territory sign on MRI, and D-dimer levels, are valuable in evaluating the stroke subtype and thrombus features. Thrombectomy techniques, such as contact aspiration and stent retriever monotherapy, have shown varying degrees of effectiveness for stroke caused by cancer-related hypercoagulability, warranting further study. After reperfusion therapy, appropriate treatment for the prevention of stroke recurrence should be initiated, considering the specific stroke subtypes. In conclusion, cancer-associated stroke encompasses diverse subtypes, and thrombi associated with stroke caused by cancer-related hypercoagulability present various challenges for thrombectomy. Individualized treatment approaches based on underlying mechanisms are essential for improving outcomes in acute stroke patients with active cancer. Optimization of preprocedural diagnosis, EVT techniques, and secondary prevention of stroke caused by cancer-related hypercoagulability will lead to better management of these patients and enhance their quality of life.