Risk Of Symptomatic Intracerebral Hemorrhage Research Articles

Efficacy and safety of intravenous tenecteplase compared to alteplase before mechanical thrombectomy in acute ischemic stroke: a meta-analysis.

The benefits and risks of tenecteplase (TNK) versus alteplase (ALT) have recently been assessed in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT) with diverse results. Due to its high fibrin specificity and lack of excitotoxicity, TNK may have a higher efficacy and safety profile. This study aimed to evaluate the benefits and risks of TNK compared to ALT in AIS patients prior to thrombectomy. We systematically searched four key databases, PubMed, Embase, Web of Science and Cochrane Library until January 27, 2024 for clinical studies evaluating the effects of TNK versus ALT in patients with large vessel occlusion undergoing MT. A random-effect meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies involving 3722 patients receiving TNK (1266 patients) or ALT (2456 patients) were included (age: 69.05 ± 14.95years; 55.64% male). Compared to ALT-treated patients, TNK-treated patients demonstrated significantly higher rates of early recanalization (odds ratio 2.02, 95%-confidence interval 1.20-3.38, p = 0.008) without increased risk of symptomatic intracerebral hemorrhage (1.06, 0.64-1.76, p = 0.82) or intracerebral hemorrhage (1.21, 0.66-2.25, p = 0.54). TNK-treated patients showed similar rates of functional independence at 90days (1.13, 0.87-1.46, p = 0.37) as ALT-treated patients, but lower rates of mortality within 90days (0.65, 0.44-0.96, p = 0.03). TNK is superior to ALT in achieving early recanalization and is associated with lower mortality within 90days in AIS patients undergoing MT. Compared with ALT, TNK does not significantly alter functional independence at 90days, symptomatic intracerebral hemorrhage or intracerebral hemorrhage.

Effects of Tirofiban on Neurological Deterioration in Patients With Acute Ischemic Stroke

Evidence supports using antiplatelet therapy in patients with acute ischemic stroke. However, neurological deterioration remains common under the currently recommended antiplatelet regimen, leading to poor clinical outcomes. To determine whether intravenous tirofiban administered within 24 hours of stroke onset prevents early neurological deterioration in patients with acute noncardioembolic stroke compared with oral aspirin. This investigator-initiated, multicenter, open-label, randomized clinical trial with blinded end-point assessment was conducted at 10 comprehensive stroke centers in China between September 2020 and March 2023. Eligible patients were aged 18 to 80 years with acute noncardioembolic stroke within 24 hours of onset and had a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 20. Patients were assigned randomly (1:1) to receive intravenous tirofiban or oral aspirin for 72 hours using a central, web-based, computer-generated randomization schedule; all patients then received oral aspirin. The primary efficacy outcome was early neurological deterioration (increase in NIHSS score ≥4 points) within 72 hours after randomization. The primary safety outcome was symptomatic intracerebral hemorrhage within 72 hours after randomization. A total of 425 patients were included in the intravenous tirofiban (n = 213) or oral aspirin (n = 212) groups. Median (IQR) age was 64.0 years (56.0-71.0); 124 patients (29.2%) were female, and 301 (70.8%) were male. Early neurological deterioration occurred in 9 patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P = .002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90-day follow-up, 3 patients (1.3%) in the tirofiban group and 3 (1.5%) in the aspirin group died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P = .63), and the median (IQR) modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted odds ratio, 1.28; 95% CI, 0.90-1.83; P = .17). In patients with noncardioembolic stroke who were seen within 24 hours of symptom onset, tirofiban decreased the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systematic bleeding. ClinicalTrials.gov Identifier: NCT04491695.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial

BackgroundEndovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT.MethodsThis single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b–3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 μg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days.DiscussionThis randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden.Trial registrationClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Is Thrombectomy Worth It for Isolated Posterior Cerebral Artery Occlusion? Meta‐Analysis and Trial Sequential Analysis

Background Thrombectomy is well‐established management for acute ischemic stroke involving large vessel occlusion. However. the potential efficacy of thrombectomy for isolated posterior cerebral artery occlusion remains limited. The study aims to evaluate the benefits of thrombectomy for isolated posterior cerebral artery occlusion. Methods We searched PubMed, Cochrane, and Embase for articles published until September 2023. The primary outcome was good functional outcome at 3 months. The secondary outcomes included excellent functional outcome at 3 months and early neurological improvement. The safety outcomes were symptomatic intracerebral hemorrhage, and mortality at 3 months. Results Seven retrospective studies involving 2560 patients with isolated posterior cerebral artery occlusion were included (876 patients receiving thrombectomy). The odds ratio (OR) of good functional outcome at 3 months was 0.93 (95% CI, 0.68–1.28) between 2 groups. The OR of excellent functional outcome (OR 1.23; 95% CI 0.92–1.64) and early neurological improvement (OR 1.82; 95% CI 0.97–3.40) were not different between the 2 groups. Compared with patients with best medical management, those with thrombectomy demonstrated a significantly increased risk of mortality (OR 1.81; 95% CI 1.24–2.65), whereas the risk of symptomatic intracerebral hemorrhage (OR 2.033; 95% CI 0.996–4.148) did not show an increase. Additionally, the results of trial sequential analysis indicated all outcomes were inconclusive. Conclusion Thrombectomy stands as an available procedure for patients with isolated posterior cerebral artery occlusion; however, it shows no notable benefits in reducing symptomatic intracerebral hemorrhage risk or enhancing function and may raise mortality compared with standard medical management. Further randomized controlled trials are necessary to yield more conclusive evidence.

Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Tenecteplase versus alteplase for patients with acute ischemic stroke: a meta-analysis of randomized controlled trials.

Tenecteplase (TNK), a newer fibrinolytic agent with greater fibrin specificity and longer half-life than alteplase, may has practical advantages over alteplase in acute ischemic stroke (AIS) thrombolysis. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare different doses of TNK (0.1, 0.25, 0.4 mg/kg) and alteplase in acute ischemic stroke patients. We systematically searched PubMed, Embase and https://clinicaltrials.gov/ for RCTs comparing TNK with alteplase in this population eligible for thrombolysis. The Cochrane Risk of Bias Tool was used to assess study quality. Random-effects or fixed-effects meta-analysis models were used for evaluating all outcomes. Total 10 RCTs with 5097 patients were included. Compared with alteplase, TNK at doses of 0.25 mg/kg may associated with the greatest odds to achieve 90-day excellent independence (mRS score ≤1), but there were no significant differences between other doses of TNK (0.1 mg/kg and 0.4 mg/kg) and alteplase. Among secondary outcomes, no significant differences were found in functional outcome (mRS score ≤2) and mortality at 90 days between any dose of TNK and alteplase. Compared with alteplase, TNK was effective at doses of 0.1 mg/kg and 0.25 mg/kg without increased risk of symptomatic intracerebral hemorrhage (sICH), but patients treated with TNK 0.4 mg/kg showed increased odds of sICH. In conclusion, compared with alteplase, intravenous thrombolysis with TNK at dose of 0.25 mg/kg has a better efficacy and similar safety profile and is a reasonable option for patients with AIS.

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): Protocol for a Pragmatic, Stepped Wedge, Cluster Randomized Controlled Trial

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Tenecteplase versus alteplase for acute ischaemic stroke: a meta-analysis of phase III randomised trials

BackgroundTenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS).MethodsSystematic literature search...

Intravenous thrombolysis and endovascular therapy for acute ischemic stroke in COVID-19: a systematic review and meta-analysis.

The impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population. We searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. We included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16-2.05, p < 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97-4.31; p = 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15-3.59, p < 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51-0.86, p < 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14-2.91, p = 0.56). COVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome. PROSPERO, identifier CRD42022309785.

Abstract Number ‐ 260: Endovascular Thrombectomy for Acute Ischemic Stroke with Acute Cancer: Updated Meta‐analysis

Introduction Acute cancer is associated with poorer prognosis and death in patients with acute ischemic stroke (AIS).1 Endovascular treatment has shown to be effective and safety treatment (EVT) for AIS with large vessel occlusion2; however, the effect of acute cancer on outcomes secondary to EVT in patients with AIS remains unclear. Methods We searched PubMed, Embase, as well as Cochrane for all relevant literature until June 1, 2022. Random‐effects model was used to estimate outcomes including good functional outcome, successful reperfusion, mortality at 3‐month, and symptomatic intracerebral hemorrhage. The heterogeneity of outcomes was assessed using the Cochran Q test and I2 statistics. Results Of the 12 studies, a total of 5,944 patients with AIS were enrolled. 389 (6.5%) patients had acute cancer. A quarter of patients regained functional independence after EVT. Compared with patients without acute cancer, those with acute cancer following EVT had similar rate of successful reperfusion (76.9% versus 72.6%; OR, 0.90; 95% CI, 0.63–1.30; I2 = 27%; p = 0.18; Figure 1A) and did not increase the risk of symptomatic intracerebral hemorrhage (6.0% versus 7.7%; OR, 0.85; 95% CI, 0.51–1.42; I2 = 0%; p = 0.45; Figure 1B). However, patients with acute cancer had more functional dependence (28.2% versus 42.3%; OR, 0.53; 95% CI, 0.41–0.67; I2 = 1%; p = 0.43; Figure 1C) and death at 3‐month (39.3% versus 18.6%; OR, 3.64; 95% CI, 2.35–6.27; I2 = 64%; p &lt; 0.01; Figure 1D) than those without acute cancer. Conclusions The results of study showed that patients with acute cancer and AIS had a higher risk of functional dependence and mortality than those without acute cancer despite successful reperfusion and no increment in the occurrence of symptomatic intracerebral hemorrhage. Only 28.2% of patients with acute cancer regained functional independence, so physicians and patients should consider whether to use EVT for patients with acute cancer. There remained the need for further randomized control studies for better clinical evidence.

Association between Infarct Location and Hemorrhagic Transformation of Acute Ischemic Stroke following Successful Recanalization after Mechanical Thrombectomy.

The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy. We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation. Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10; P = .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09; P = .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82; P < .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77; P = .002). Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage.

Effect of bleeding risk prediction on decision making of intravenous thrombolysis before thrombectomy: a subgroup analysis of DIRECT-MT

BackgroundThe major concern for bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the potentially increased risk of symptomatic intracerebral hemorrhage (sICH). Thus we conducted this study to clarify whether...

Validation and comparison of multiple risk scores for prediction of symptomatic intracerebral hemorrhage after intravenous thrombolysis in VISTA.

Prediction models/scores may help to identify patients at high risk of symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis. We aimed to validate and compare the performance of different prediction models for sICH after thrombolysis using direct model estimation in the Virtual International Stroke Trials Archive (VISTA). We searched PubMed for potentially eligible prediction models from inception to 1 June 2019. Simple and practical models/scores were validated in VISTA. The primary outcome was sICH based on two criteria (National Institute of Neurological Diseases and Stroke, NINDS; Safe Implementation of Thrombolysis in Stroke-Monitoring Study, SITS-MOST) and the secondary outcome was parenchymal hematoma (PH). The discrimination performance of each model was evaluated using area under the curve (AUC) and calibration was evaluated by Hosmer-Lemeshow goodness-of-fit tests. We found 13 prediction models and five models (HAT, MSS, SPAN-100, GRASPS and THRIVE) were finally validated in VISTA. A total of 1884 participants were eligible for our study, of whom the proportion with sICH was 4.6% (87/1884) per NINDS and 3.9% (73/1884) per SITS-MOST, and with PH was 11.3% (213/1884). MSS and GRASPS had the greatest predictive ability for sICH (NINDS criteria: MSS AUC 0.7, 95% CI 0.63-0.77, p < 0.001; GRASPS AUC 0.69, 95% CI 0.63-0.76, p < 0.001; SITS-MOST criteria: MSS, AUC 0.76, 95% CI 0.68-0.85, p < 0.001; GRASPS, AUC 0.79, 95% CI 0.71-0.87, p < 0.001). Similar results were found for PH (MSS AUC 0.68, 95% CI 0.64-0.73, p = 0.017; GRASPS AUC 0.68, 95% CI 0.63-0.72, p = 0.017). The calibration of each model was almost good. MSS and GRASPS had good discrimination and calibration for sICH and PH after thrombolysis as assessed in VISTA. These two models could be used in clinical practice and clinical trials to identity individuals with high risk of sICH.

Machine learning prediction of symptomatic intracerebral hemorrhage after stroke thrombolysis: a cross-cultural validation in Caucasian and Han Chinese cohort.

Background:Previous studies found that Asians seemed to have higher risk of HT after thrombolysis than Caucasians due to its race differences in genetic polymorphism. Whether the model developed by Caucasians could predict risk of symptomatic intracerebral hemorrhage (sICH) in Asians was unknown.Objectives:To develop a machine learning–based model for predicting sICH after stroke thrombolysis in Caucasians and externally validate it in an independent Han Chinese cohort.Design:The derivation Caucasian sample included 1738 ischemic stroke (IS) patients from the Virtual International Stroke Trials Archive (VISTA) data set, and the external validation Han Chinese cohort included 296 IS patients who were treated with intravenous thrombolysis.Methods:Twenty-eight variables were collected across both samples. According to their properties, we classified them into six distinct clusters (ie, demographic variables, medical history, previous medication, baseline blood biomarkers, neuroimaging markers on initial CT scan and clinical characteristics). A support vector machine (SVM) model, which consisted of data processing, model training, testing and a 10-fold cross-validation, was developed to predict the risk of sICH after stroke thrombolysis. The receiving operating characteristic (ROC) was used to assess the prediction performance of the SVM model. A domain contribution analysis was then performed to test which cluster had the highest influence on the performance of the model.Results:In total, 85 (4.9%) patients developed sICH in the Caucasians, and 29 (9.8%) patients developed sICH in the Han Chinese cohort. Eight features including age, NIHSS score, SBP (systolic blood pressure), DBP (diastolic blood pressure), ALP (alkaline phosphatase), ALT (alanine transaminase), glucose, and creatine level were included in the final model, all of which were from demographic, clinical characteristics, and blood biomarkers clusters, respectively. The SVM model showed a good predictive performance in both Caucasians (AUC = 0.87) and Han Chinese patients (AUC = 0.74). Domain contribution analysis showed that inclusion/exclusion of clinical characteristic cluster (NIHSS score, SBP, and DBP), had the highest influence on the performance of predicting sICH in both Caucasian and Han Chinese cohorts.Conclusion:The established SVM model is feasible for predicting the risk of sICH after thrombolysis quickly and efficiently in both Caucasian and Han Chinese cohort.

Influence of Thrombocytopenia on the Outcome of Mechanical Thrombectomy in Patients with Acute Ischemic Stroke

ObjectivesMechanical thrombectomy (MT) has become leading treatment option for acute ischemic stroke (AIS) due to large vessels occlusion (LVO). Platelet counts may affect outcome in patients with AIS or transient ischemic attack. The aim of our study was to determine the influence of thrombocytopenia on the safety and efficacy of MT in patients with AIS due to anterior circulation LVO. Materials and methodsThis study included 127 consecutive adult patients with AIS due to anterior circulation LVO who underwent MT. The patients were divided into 2 groups based on initial platelet count: with thrombocytopenia (<150 × 109/L) and without thrombocytopenia (≥150 × 109/L). Primary safety outcome was symptomatic intracerebral haemorrhage (SICH), while secondary safety outcome was stroke-related mortality. Efficacy outcome was functional independence, defined as modified Rankin Scale (mRS) score 0-2. Follow- up time was 90 days. ResultsInitial thrombocytopenia (<150 × 109/L) was detected in 19 (15%) patients. Multivariable analysis showed that initial thrombocytopenia did not increase the risk of SICH and did not affect the short-term functional outcome (p = 0.587). However, initial thrombocytopenia increased the risk for stroke-related mortality (aOR 3.639, 95% CI 1.079-12.641, p = 0.037). The main cause of mortality in the group with thrombocytopenia was malignant cerebral infarction (44.4%). ConclusionsThrombocytopenia does not affect the efficacy and the risk of SICH in patients with AIS caused by anterior circulation LVO treated with MT. However, the risk of mortality is higher in patients with thrombocytopenia, mainly due to malignant cerebral infarction.

Outcomes of Mechanical Thrombectomy in Patients with Large Diffusion-Weighted Imaging Lesions.

ObjectiveDespite many advancements in endovascular treatment, the benefits of mechanical thrombectomy (MT) in patients with large infarctions remain uncertain due to hemorrhagic complications. Therefore, we aimed to investigate the efficacy and safety of recanalization via MT within 6 hours after stroke in patients with large cerebral infarction volumes (>70 mL). MethodsWe retrospectively reviewed the medical data of 30 patients with large lesions on initial diffusion-weighted imaging (>70 mL) who underwent MT at our institution within 6 hours after stroke onset. Baseline data, recanalization rate, and 3-month clinical outcomes were analyzed. Successful recanalization was defined as a modified treatment in cerebral ischemia score of 2b or 3. ResultsThe recanalization rate was 63.3%, and symptomatic intracerebral hemorrhage occurred in six patients (20%). The proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was significantly higher in the recanalization group than in the non-recanalization group (47.4% vs. 9.1%, p=0.049). The mortality rate was higher in the non-recanalization group, this difference was not significant (15.8% vs. 36.4%, p=0.372). In the analysis of 3-month clinical outcomes, only successful recanalization was significantly associated with mRS scores of 0–3 (90% vs. 50%, p=0.049). The odds ratio of recanalization for favorable outcomes (mRS 0–3) was 9.00 (95% confidence interval, 0.95–84.90; p=0.055). ConclusionDespite the risk of symptomatic intracerebral hemorrhage, successful recanalization via MT 6 hours after stroke may improve clinical outcomes in patients with large vessel occlusion.

Intravenous thrombolysis for acute ischemic stroke: why not?

The aim of this study was to summarize available evidence regarding the safety and efficacy of intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with specific comorbidities and potential contraindications to systemic reperfusion therapy. Recent advances in IVT implementation in wake-up stroke and in extended time window using advanced neuroimaging will also be highlighted. Despite theoretical concerns of a higher bleeding risk with IVT, there are no data showing increased risk of symptomatic intracerebral haemorrhage (sICH) in patients with stroke mimics, including seizures, increasing age and dual antiplatelet pretreatment. In addition, recent randomized evidence allows us to expand the time window of IVT for AIS using advanced neuroimaging both in wake-up stroke patients and in patients presenting within 4.5-9 h from symptom onset fulfilling certain neuroimaging criteria (based on DWI/FLAIR mismatch or perfusion mismatch). IVT is a highly effective systemic reperfusion therapy that counts 25 years of everyday clinical experience but still presents several challenges in its application. Appropriate patient selection and adherence to rt-PA protocol is paramount in terms of safety. The effort to simplify the indications, expand the therapeutic time window and eliminate specific initial contraindications is continuously evolving.

Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

Background and ObjectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99–5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59–1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07–2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs.Trial Registration InformationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of EvidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.

November 2021 Stroke Highlights

November 2021 <i>Stroke</i> Highlights

Cardio-cerebral infarction in left MCA strokes: a case series and literature review

The objective of this manuscript is to describe the challenges of Cardio-Cerebral Infarction (CCI) treatment and to highlight the variable approaches in management. CCI is a rare clinical presentation of simultaneous acute ischemic stroke (AIS) and acute myocardial infarction (AMI) and poses a therapeutic challenge for practitioners. Each disease requires timely intervention to prevent irreversible damage; however, optimal management remains unclear. We describe three cases of CCI. All three patients presented with symptomatic left MCA (M1) occlusion, with ST elevation myocardial infarction (STEMI) and left ventricular apical thrombus. Fibrinolysis and mechanical thrombectomy (MT) were discussed in all cases, but only one patient received alteplase (0.9 mg/kg) and none underwent MT. Percutaneous intervention (PCI) was done in only one case. The two patients that did not receive thrombolysis were treated with modified therapeutic heparin (no bolus), and all received antiplatelet therapy. Ultimately, all three patients passed away. CCI poses a clinical challenge for physicians including (1) optimal strategies to enable swift mechanical reperfusion to both the brain and myocardium; (2) difference in dosage of thrombolytics for AIS versus AMI; (3) risk of symptomatic intracerebral hemorrhage following administration of anticoagulation and/or antiplatelet therapy; and (4) caution with use of thrombolytics in the setting of acute STEMI due to the risk of myocardial rupture. In the absence of high quality evidence and clinical guidelines, treatment of CCI is highly individualized.