Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis.

Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

[Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis].

OBJECTIVE: To assess the impact of cerebral microbleeds (CMBs) on clinical outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis. METHODS: The clinical data of 225 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 were reviewed. The severity of CMBs and hemorrhagic transformation (HT) after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months were evaluated. Favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. Multivariate logistic-regression analysis and binary logistic-regression were used to determine independent risk factors of HT and favorable outcome. RESULTS: The mean age of 225 patients was (66.29±13.01) y, 73 (32.4%) patients were women, mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 11.40±5.89, and onset-to-needle time was (238.40±89.16) min. Totally, 522 CMBs were detected in 91 patients (36.1%). Postlytic radiological HT was found in 64 patients (28.4%), among which 43 (19.1%) were hemorrhagic infarction and 21 (9.3%) were parenchymal hematoma. Univariate analysis showed that patients with HT had higher NIHSS score and more incidence of atrial fibrillation and that patients with unfavorable outcome were older and had higher NIHSS score and more CMBs. Multivariate logistic regression analysis showed that multiple CMBs (>=3) was independently associated with parenchymal hematoma (OR=4.957, 95%CI 1.306-18.811, P=0.019), but not with hemorrhagic infarction (OR=1.204, 95%CI 0.386-3.754, P=0.749). Binary logistic regression analysis showed that multiple CMBs (>=3) was independently associated with unfavorable outcome (OR=3.496, 95%CI 1.381-8.849, P=0.008). CONCLUSION: Multiple CMBs are correlated with parenchymal hematoma and unfavorable neurological outcome after thrombolytic therapy in patients with acute ischemic stroke.

[Impact of atrial fibrillation on clinical outcome in patients with acute ischemic stroke undergoing thrombolytic therapy].

OBJECTIVE: To investigate the impact of atrial fibrillation (AF) on clinical outcomes in patients with acute ischemic stroke undergoing thrombolytic therapy. METHODS: The clinical data of 330 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine between June 2009 and August 2013 were reviewed. Clinical outcomes in AF and non-AF groups were evaluated by univariate and multivariate analysis. Favorable outcome was defined as a modified Rankin Scale (mRS) 0-2 on day 90. Hemorrhagic transformation (HT) was classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH) within the first 24h according to ECASS II criteria. Hypoperfusion and severe hypoperfusion were defined as Tmax >6 s and >8 s, respectively. The rate of reperfusion was compared between AF and non-AF groups. RESULTS: Among 330 patients, 137(41.5%) had AF. Compared with non-AF patients, patients with AF were older [(71.7±11.5)y vs (63.4±13.2)y, P<0.001], had higher baseline National Institutes of Health Stroke Scale [IQR, 13(8-16) vs 9(5-15), P<0.001], higher rate of HT(HI: 28.5% vs 17.1%, P=0.015; PH: 13.9% vs 4.1%, P=0.002), and lower rate of favorable outcome (41.5% vs 58.0%, P=0.005) at d 90. After adjustment, AF was not a risk factor for favorable outcome (OR=0.920, 95%CI:0.533-1.586; P=0.763) and mortality (OR=1.381, 95%CI:1.096-1.242; P=0.466) on day 90. AF was also not associated with HI (OR=1.676, 95%CI: 0.972-3.031; P=0.088), but it increased the rate of PH (OR=3.621, 95%CI: 1.403-9.344; P=0.008). Among 94 patients with pre- and post-thrombolytic perfusion-weighted image, AF was not associated with increased rate of reperfusion for hypoperfusion (Tmax >6 s, OR=1.12, 95%CI: 0.35-3.63, P=0.849), but was correlated with increased rate of reperfusion for severe hypoperfusion (Tmax>8 s, OR=10.57, 95%CI:1.16-96.50, P=0.037). CONCLUSION: The presence of AF has no independent impact on neurological outcome in thrombolytic patients with acute ischemic stroke. It is associated with increased reperfusion rate of more severe hypoperfusion area and higher frequency of PH.

Prediction factors and clinical significance of different types of hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in acute ischemic stroke seriously affects the prognosis of patients. This study aimed to investigate the risk factors of different types of HT and their correlation with prognosis after IVT. METHODS: Based on the CASE II registry, we included patients with acute ischemic stroke who received IVT within 4.5 h of onset. HT was further divided into hemorrhagic infarction (HI) and parenchymal hemorrhage (PH). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months. Multivariate logistic regression analysis was used to determine the independent influencing factors of HT subtypes and clinical outcome. RESULTS: Among 13108 included patients, 541 (4.1%) developed HI and 440 (3.4%) developed PH. In multivariate analysis, age (OR 1.038, 95% CI 1.028 to 1.049, p < 0.001), atrial fibrillation (OR 1.446, 95% CI 1.141 to 1.943, p = 0.002), baseline diastolic pressure (OR 1.012, 95% CI 1.004 to 1.020, p = 0.005), baseline NIHSS score (OR 1.060, 95% CI 1.049 to 1.071, p < 0.001) and onset to treatment time (OR 1.002, 95% CI 1.000 to 1.004, p = 0.020) independently predicted PH after IVT. In the patients with HT, PH (OR 3.611, 95% CI 2.540 to 5.134, p < 0.001) and remote hemorrhage (OR 1.579, 95% CI 1.115 to 2.235, p = 0.010) were independently related to poor outcome. CONCLUSIONS: Different types of HT after IVT had different risk factors and clinical significance. The occurrence of PH and remote hemorrhage independently increased the risk of poor outcome.

Endovascular Treatment for Minor Acute Ischemic Strokes With Large Vessel Occlusion.

Background It remains uncertain whether patients with minor acute ischemic stroke with large vessel occlusion benefit from endovascular treatment (EVT). We aim to evaluate the outcomes of EVT in minor acute ischemic stroke with anterior circulation large vessel occlusion. Methods and Results Based on a nationwide prospective stroke registry, patients with minor acute ischemic stroke with anterior circulation large vessel occlusion within 24 hours of onset were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Primary outcome was excellent functional outcome defined as modified Rankin Scale score 0 to 1 at 90 days. In addition, a multivariable logistic regression model was used to analyze the effect of EVT guided by perfusion imaging. A total of 572 patients with median age 68 years (interquartile range=60-77) and median National Institutes of Health Stroke score 3 (interquartile range =2-4) were identified and 123 patients were treated with standard medical treatment plus EVT. EVT was not associated with excellent functional outcome (unadjusted odds ratio [OR], 0.771 [95% CI, 0.516-1.151]; adjusted OR, 0.793 [95% CI, 0.515-1.219]; P=0.290). However, therapy selection guided by perfusion imaging was a modifier of EVT effect on outcomes, as EVT was significantly associated with excellent functional outcome (60.0% versus 50.8%, unadjusted OR, 1.451 [95% CI, 0.643-3.272]; adjusted OR, 2.849 [95% CI, 1.006-8.067]; P=0.049) but not with symptomatic intracerebral hemorrhage in the imaging-guided group. Conclusions Although functional outcomes in minor acute ischemic stroke caused by anterior circulation large vessel occlusion were not improved from the routine use of EVT, our results suggested that EVT guided by perfusion imaging could be beneficial for those patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04487340.

Clinical Outcome in Acute Ischemic Stroke Patients With Microbleeds After Thrombolytic Therapy: A Meta-Analysis.

It remains unclear whether preexisting cerebral microbleeds (CMBs) increase the risks of worse functional outcome after thrombolytic therapy. We performed a systematic review and meta-analysis to assess the risk of unfavorable outcome in patients with acute ischemic stroke and CMBs.We searched EMBASE, PubMed, and Web of Science for relevant studies assessing functional outcome in the patients with CMBs following thrombolytic therapy. Fixed-effects and random-effects models were performed.Five eligible studies including 1974 patients were pooled in meta-analysis. The prevalence of CMBs was 24.3%. The pooled analysis demonstrates odds ratio for preexisting CMBs and the achievement of favorable outcome to be 0.69 (95% CI 0.56-0.86; P = 0.001) with no evidence of statistical heterogeneity (I = 46.7%, P = 0.112).Our meta-analysis of available published data demonstrates an increased risk of worse functional outcome after thrombolytic therapy for acute ischemic stroke in patients with pre-existing CMBs. Future studies are needed to determine whether the risk outweigh the expected benefit of reperfusion therapies.