No abstract

Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120971/-/DC1.

Computed tomography perfusion imaging in acute stroke requires further validation. We aimed to establish the optimal computed tomography perfusion parameters defining the infarct core and critically hypoperfused tissue. Sub-6-h computed tomography perfusion and 24-h magnetic resonance imaging were analysed from 314 consecutive patients with ischaemic stroke. Diffusion-weighted imaging lesion volume at 24 h was used to define the extent of critically hypoperfused tissue (in patients without reperfusion between acute and 24-h time points), and infarct core (in patients with major reperfusion at 24 h). Pixel-based analysis of co-registered computed tomography perfusion and diffusion-weighted imaging was then used to define the optimum computed tomography perfusion thresholds for critically hypoperfused at-risk tissue and infarct core. These optimized acute computed tomography perfusion threshold-based lesion volumes were then compared with 24-h diffusion-weighted imaging infarct volume, as well as 24-h and 90-day clinical outcomes for validation. Relative delay time >2 s was the most accurate computed tomography perfusion threshold in predicting the extent of critically hypoperfused tissue with both receiver operating curve analysis (area under curve 0.86), and the volumetric validation (mean difference between computed tomography perfusion and 24-h diffusion-weighted imaging lesions = 2 cm(2), 95% confidence interval 0.5-3.2 cm(2)). Cerebral blood flow <40% (of contralateral) within the relative delay time >2 s perfusion lesion was the most accurate computed tomography perfusion threshold at defining infarct core with both receiver operating characteristic analysis (area under curve = 0.85) and the volumetric validation. Using these thresholds, the extent of computed tomography perfusion mismatch tissue (the volume of 'at-risk' tissue between the critically hypoperfused and core thresholds) salvaged from infarction correlated with clinical improvement at 24 h (R(2) = 0.59, P = 0.04) and 90 days (R(2) = 0.42, P = 0.02). Patients with larger baseline computed tomography perfusion infarct core volume (>25 ml) also had poorer recovery at Day 90 (P = 0.039). Computed tomography perfusion can accurately identify critically hypoperfused tissue that progresses to infarction without early reperfusion, and the computed tomography perfusion cerebral blood flow infarct core closely predicts the final volume of infarcted tissue in patients who do reperfuse. The computed tomography perfusion infarct core and at-risk measures identified are also strong predictors of clinical outcome.