Rate Of Symptomatic Intracranial Hemorrhage Research Articles

Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients.Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927).Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; <i>p</i>>0.999) and 3-month mortality (10.7% vs. 10.2%; <i>p</i>=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]).Conclusions: In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Endovascular Thrombectomy Versus Best Medical Management Beyond 24 Hours From Last Known Well in Acute Ischemic Stroke Due to Large Vessel Occlusion

Background The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined. Methods In this single center study, we identified patients with large vessel occlusion who were eligible for EVT based on noncontrast computed tomography (CT)/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥5, National Institutes of Health Stroke Scale of ≥6, and presenting beyond 24 hours from LKW, between January 2018 and March 2022. During the study period, EVT service limitations meant patients eligible for EVT presenting outside service hours, routinely received best medical management (BMM). Functional and safety outcomes were compared between patients receiving EVT or BMM following multivariable adjustment for age, baseline stroke severity, Alberta Stroke Program Early CT Score, time from LKW, IV thrombolysis, and clot location. Results Among 35 patients presenting beyond 24 hours from LKW and eligible for EVT, 19 (54%) were treated with EVT and 16 (46%) with BMM. Alberta Stroke Program Early CT Score were similar across both groups (EVT: 7 [6.75–8] versus BMM: 7 [6–8]), but not the baseline National Institutes of Health Stroke Scale (EVT: 17 [11–19.5] versus BMM: 20 [9.75–26]). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.3% versus 0%; P =0.28) or mortality (26.3% versus 37.5%; P =0.42) rates, respectively. The modified Rankin scale at 90 days (adjusted common odds ratio [OR], 1.94; [95% CI 0.42–8.87]; P =0.39) and functional independence rate, although numerically higher in the EVT group compared with the BMM group (modified Rankin scale≤2; 36.9% versus 18.8%; adjusted OR, 4.34; [95% CI 0.34–54.83]; P =0.25), were not significantly different. 94.7% of patients treated with EVT achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b–3). Conclusion In routine clinical practice, EVT beyond 24 hours from LKW appears safe and feasible, when performed in patients with acute ischemic stroke who were deemed eligible for EVT by noncontrast CT /CT angiography alone. A large collaborative randomized trial assessing the efficacy of EVT beyond 24 hours is warranted. Our findings provide a basis for the sample size estimate for an adequately powered trial.

Outcomes in patients with acute stroke treated at a comprehensive stroke center using telemedicine versus in-person assessments.

Telemedicine has been shown to be a safe and effective modality to assess and treat patients with acute stroke who present to a community hospital. There are no previous reports on using telemedicine to treat patients with acute stroke who present to a comprehensive stroke center. We report here the outcomes of patients with acute stroke treated in 2021 at our comprehensive stroke center using telemedicine versus an in-person assessment. Patients with acute ischemic stroke who were treated after either a telemedicine or in-person assessment at our hospital in 2021 were identified by a retrospective chart review. The primary outcomes collected were door-to-needle (DTN) time for alteplase (tPA) administration, door-to-puncture (DTP) time for endovascular thrombectomy, symptomatic intracranial hemorrhage (sICH) rates and 3-month mortality. There were 302 patients with acute stroke treated at our hospital in 2021. Of these, 18.2% (n = 55/302) were treated using telemedicine. There were no differences in any of the outcomes between patients treated using telemedicine versus an in-person assessment: DTN (35.5 min (n = 42) vs 33 min (n = 182), p < 0.76), DTP (86.5 min (n = 30) vs 85 min (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). To the best of our knowledge, this is the first study to report on outcomes for acute stroke patients treated using telemedicine at a comprehensive stroke center. In this study, there were no differences in outcomes between patients treated using telemedicine versus an in-person assessment.

From therapeutic nihilism to armamentarium: A meta-analysis of randomized clinical trials assessing safety and efficacy of endovascular therapy for acute large ischemic strokes

Three recent randomized clinical trials (RCTs) investigated the potential benefit of endovascular therapy (EVT) in acute ischemic stroke patients presenting with large infarcts. We aimed to confirm the safety and efficacy of EVT in patients presenting with large infarcts and provide more precise estimations of the treatment effects using study-level meta-analysis. Comprehensive search of MEDLINE database through PubMed till February 2023 was performed including RCTs only. The data were then extracted from the selected studies and pooled as risk ratio (RR) with 95% confidence interval (95% CI). There were a total of 1005 patients across the three qualifying RCTs. Regarding the functional outcomes assessed by modified Rankin Scale (mRS) score, the analyzed data demonstrated statistically significant differences in favor of thrombectomy for both independent ambulatory status (mRS 0-3: RR = 1.78, 95% CI [1.28, 2.48], p = 0.0006) and functional independence (mRS 0-2: RR = 2.54, 95% CI [1.85, 3.48], p < 0.001). The analyzed data did not demonstrate any statistically significant differences between EVT and medical management alone in terms of 90-day mortality (RR = 0.95, 95% CI [0.78, 1.16], p = 0.61), symptomatic intracranial hemorrhage (RR = 1.83, 95% CI [0.95, 3.55], p = 0.07), and need for hemicraniectomy (RR = 1.22, 95% CI [0.43, 3.41], p = 0.71). This study confirms the benefit of EVT on functional outcomes of patients presenting with large ischemic infarcts without significant differences in the rates of symptomatic intracranial hemorrhage, hemicraniectomy, or 90-day mortality.

A propensity score-matched comparative study of balloon guide catheters versus conventional guide catheters for concurrent mechanical thrombectomy with carotid stenting in tandem strokes: comparison of first pass effect, symptomatic intracranial hemorrhage, and 90-day functional outcomes

BackgroundExtensive clot burden in tandem strokes accounts for poor mechanical thrombectomy (MT) outcomes. Several studies have shown the benefit of balloon guide catheters (BGCs) in MT and carotid artery stenting.ObjectiveIn...

Outcomes with Endovascular Treatment of Patients with M2 Segment MCA Occlusion in the Late Time Window.

Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset. Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion. Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%, P = .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29). In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.

March 2023 Stroke Highlights.

March 2023 Stroke Highlights.

RESCUE‐ICAS: Rationale and Study Design

Background Mechanical thrombectomy (MT) failure occurs in ≈10% to 20% of MTs. Among the common causes of failed MT is residual underlying intracranial stenosis (ICAS), typically attributable to atherosclerotic disease. ICAS large‐vessel occlusion (ICAS‐LVO) remains poorly understood, and management of ICAS‐LVO is unclear. The RESCUE‐ICAS (Registry of Emergent Large Vessel Occlusion Due to Intracranial Stenosis) aims at providing better understanding of the prevalence of ICAS‐LVO, and the overall safety and efficacy of various rescue therapies. Methods RESCUE‐ICAS is a multicenter, international, prospective registry that is currently enrolling patients with ICAS‐LVO who underwent MT. All sites are required to report monthly MT cases that meet inclusion criteria. The decision of whether to use rescue therapy is up to the interventionist. Results We will collect patients’ demographic, clinical, and radiographic data at baseline. Also, we will capture variables related to the MT procedure and rescue therapy (if performed), and postprocedural clinical and imaging variables. Outcomes include the rate of successful recanalization, defined by modified Thrombolysis in Cerebral Infarction score of ≥2b, the rate of symptomatic intracranial hemorrhage, the 90‐day modified Rankin scale score, and mortality. Conclusions No strong evidence is currently available to support an optimal treatment strategy for patients with ICAS‐LVO undergoing MT. RESCUE‐ICAS is a prospective cohort study that will provide important data to help design randomized controlled trials.

Liver fibrosis-4 score predicts outcome of patients with ischemic stroke undergoing intravenous thrombolysis.

Some evidence suggests a possible influence of liver disease on stroke prognosis. We investigated the association between fibrosis-4 (FIB-4) score, a marker of liver disease, and the 3-month outcome in patients with ischemic stroke undergoing intravenous thrombolysis. We also evaluated the rate of symptomatic intracranial hemorrhage after thrombolysis. In this prospective cohort study, we enrolled consecutive patients with ischemic stroke treated with thrombolysis who had a 3-month follow-up. The FIB-4 score was calculated and the validated cut-off values were used to indicate high/low risk of advanced liver fibrosis. The primary outcome was 3-month poor prognosis estimated as a modified Rankin scale score ≥3. Of the 264 included patients, 131 (49.62%) had a 3-month mRS ≥3, with a significantly higher FIB-4 score, compared to those with a mRS <3 score (adjp <0.001). When adjusted for possible confounders by multivariate logistic regression, FIB-4 score remained a significant predictor of poor outcome (OR 1.894, p = 0.011), along with history of atrial fibrillation (OR 3.488, p = 0.017), admission NIHSS score (OR 1.305, p < 0.001), and low values of hemoglobin (OR 0.730, p < 0.001). Mechanical thrombectomy had a favorable effect on patients' outcome (OR 0.201, p = 0.005). The risk of poor 3-month outcome was significantly higher among the 32 patients (12.1%) with high risk of severe fibrosis (p = 0.007). FIB-4 score values were also related to symptomatic intracranial hemorrhage (p = 0.004), specifically among patients with high probability of advanced hepatic fibrosis (p = 0.037). FIB-4 score can be considered as a promising independent predictor of poor prognosis in patients with acute ischemic stroke undergoing intravenous thrombolysis.

Are we improving? Temporal trends in outcomes for mechanical thrombectomy for stroke: A systematic review and meta-analysis of randomized trials.

In 2015, mechanical thrombectomy (MT) was deemed the standard of care for acute ischemic stroke (AIS) in the anterior circulation due to large vessel occlusion (LVO). To determine if outcomes in patients treated with MT have changed, we conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs). A systematic literature review of the English language literature was conducted using PubMed. We included RCTs that focused on patients with AIS treated with MT. The primary outcome of interest was good functional outcome defined as modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Using Joinpoint Regression Analysis Program, we calculated the average annual percent change (AAPC) for the outcomes of interest. We included 23 RCTs with 5784 patients. The years of mid-enrollment among the included RCTs ranged from 2012-2020. There was an AAPC of +3.82% between 2012 and 2020 (95% CI 0.4 to 7.3; P-value = 0.033) in rates of good functional outcome. There was an AAPC of +6.98% between 2012 and 2020 (95% CI 0.5 to 13.9; P-value = 0.039) in rates of sICH. There was an AAPC of -0.49% between 2012 and 2020 (95% CI -4.4 to 3.5; P-value = 0.77) in rates of mortality. Between 2012 and 2020, rates of good functional outcome and sICH increased, while rates of mortality remained consistent in RCTs investigating MT for AIS. Multiple factors likely influenced our results, including increased use of MT and utilization of adjunctive therapies alongside MT.

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.

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.

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 &gt;= 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 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&lt;0.76), median DTP (86.5min (n=30) vs. 85min (n=134), p&lt;0.97), sICH (0% (n=0/55) vs. 1.6% (n=4/245, p&lt;0.59) or 3 month mortality (20.6% (n=7/34) vs. 22.1% (n=40/181), p&lt;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.

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.

Outcomes of Patients With Atrial Fibrillation Following Thrombectomy for Stroke

Patients with atrial fibrillation (AF) treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) have been reported to experience worse outcomes compared with patients without AF. To assess differences between patients with AF and their counterparts without AF treated with MT for AIS, focusing on safety outcomes, clinical outcomes, and baseline characteristics in both groups. A systematic literature review of the English language literature from inception to July 14, 2022, was conducted using Web of Science, Embase, Scopus, and PubMed databases. Studies that focused on patients with and without AF treated with MT for AIS were included. Multiple reviewers screened studies to identify studies included in analysis. Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to ensure accuracy. Data were pooled using a random-effects model. The primary outcome of interest was rate of modified Rankin Scale (mRS) scores of 0 to 2 at 90 days. Secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction (TICI) scores of 2b to 3, 90-day mortality, symptomatic intracranial hemorrhage (SICH), and baseline patient characteristics. Of 1696 initially retrieved studies, 10 studies were included, with 6543 patients. Patients with AF were a mean of 10.17 (95% CI, 8.11-12.23) years older (P < .001) and had higher rates of hypertension (OR, 1.89 [95% CI, 1.57-2.27]; P < .001) and diabetes (OR, 1.16 [95% CI, 1.02-1.31]; P = .02). Overall, there were comparable rates of mRS scores of 0 to 2 between patients with AF and patients without AF (odds ratio [OR], 0.72 [95% CI, 0.47-1.10]; P = .13), with significant heterogeneity among the included studies. After sensitivity analysis, the rate of mRS scores of 0 to 2 was significantly lower among patients with AF (OR, 0.65 [95% CI, 0.52-0.81]; P < .001). Successful reperfusion rates were similar between the groups (OR, 1.11 [95% CI, 0.78-1.58]; P = .57). The rate of SICH was similar between groups (OR, 1.05 [95% CI, 0.84-1.31]; P = .68). Mortality was significantly higher in the AF group (OR, 1.47 [95% CI, 1.12-1.92]; P = .005). In this systematic review and meta-analysis, patients with AF experienced worse 90-day outcomes, even in the setting of similar rates of successful reperfusion. This was likely associated with greater age and greater rates of comorbidities among patients with AF.