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 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.

Background: The existence of cerebral reperfusion injury in human beings remains controversial. Thus, we aimed to explore the presence of reperfusion injury in acute ischemic stroke patients with recanalization after mechanical thrombectomy and analyzed its impact on neurological outcome. Methods: We reviewed our prospectively collected database CIPPIS (Comparison Influence to Prognosis of CTP and MRP in AIS Patients, NCT03367286), and enrolled anterior circulation large artery occlusion patients with recanalization after mechanical thrombectomy who underwent (1) computed tomography (CT) perfusion on admission and immediately after recanalization to determine reperfusion region, and (2) CT and/or magnetic resonance imaging (MRI) immediately and 24 hours after recanalization to determine lesion areas. The expansion of lesion between recanalization and 24 hours within reperfusion region was potentially caused by reperfusion, thus termed as radiological observed reperfusion injury (RORI). Based on the imaging modality immediately after recanalization, RORI was further divided into RORI _CT and RORI _MRI . We first included a small cohort who had performed both CT and MRI immediately after recanalization to validate the consistency between RORI _CT and RORI _MRI (Study 1). Then the association with RORI _CT and poor outcome, defined as 3-month modified Rankin Scale score of 3 to 6, was explored in a larger cohort (Study 2). Results: Study 1 included 23 patients and good consistency was found between RORI _CT and RORI _MRI (intraclass correlation=0.97, P <0.001). Among 226 patients included in Study 2, a total of 106 (46.9%) were identified with RORI. The ratio of RORI to reperfusion region was 30.1 (16.2, 51.0)% and was independently associated with poor outcome (odds ratio=1.55 per 10% [95% CI‚ 1.30–1.84]; P <0.001). Conclusions: Our findings suggested that RORI was relatively frequent in stroke patients with recanalization after mechanical thrombectomy and associated with poor outcome despite successful recanalization. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03367286.

The effects and risks of the use of intravenous thrombolysis between 4.5 and 24 hours after the onset of a posterior circulation ischemic stroke are not well studied. In a trial conducted in China, we randomly assigned patients with posterior circulation stroke, without extensive early hypodensity on computed tomography and with no planned thrombectomy, to receive alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg) or standard medical treatment 4.5 to 24 hours after the onset of symptoms. The primary outcome was functional independence (defined as a score of 0 to 2 on the modified Rankin scale; scores range from 0 to 6, with higher scores indicating greater disability) at 90 days. The key safety outcomes were symptomatic intracranial hemorrhage and death. A total of 234 patients were enrolled; 117 were assigned to the alteplase group and 117 to the standard-treatment group. The median score on the National Institutes of Health Stroke Scale was 3 (interquartile range, 2 to 6) (scores range from 0 to 42, with higher scores indicating greater neurologic deficit). A higher percentage of patients in the alteplase group than in the standard-treatment group had functional independence at 90 days (89.6% vs. 72.6%; adjusted risk ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.30; P = 0.01). The incidence of symptomatic intracranial hemorrhage within 36 hours was 1.7% in the alteplase group and 0.9% in the standard-treatment group. At 90 days, 5.2% of the patients in the alteplase group and 8.5% of those in the standard-treatment group had died. Among Chinese patients with mainly mild posterior circulation stroke who did not receive thrombectomy, alteplase administered 4.5 to 24 hours after stroke onset resulted in a higher frequency of functional independence at 90 days than standard medical care. (Funded by the National Natural Science Foundation of China; EXPECTS ClinicalTrials.gov number, NCT05429476.).

Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden’s Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.