Intravenous Thrombolysis before Complete Angiographic Reperfusion: Beyond Angiographic Assessment to Target Microvascular Obstruction?

OBJECTIVE: Recent data have suggested that ineffective tissue reperfusion despite successful angiographic reperfusion was partly responsible for unfavorable outcomes after endovascular therapy (EVT) and might be modulated by intravenous thrombolysis (IVT) use before EVT. To specifically decipher the effect played by IVT before EVT, we compared the clinical and safety outcomes of patients who experienced a complete reperfusion at the end of EVT according to IVT use before EVT. METHODS: The Endovascular Treatment in Ischemic Stroke (ETIS) registry is an ongoing, prospective, observational study at 21 centers that perform EVT in France. Patients were included if they had an anterior large vessel occlusion of the intracranial internal carotid artery or middle cerebral artery (M1/M2 segments) and complete reperfusion (expanded Thrombolysis in Cerebral Infarction score = 3) with EVT within 6 hours, between January 2015 and December 2021. The cohort was divided into two groups according to IVT use before EVT, and propensity score matching (PSM) was used to balance the two groups. Primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included favorable outcome (mRS 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Outcomes were estimated with multivariate logistic models adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and time from symptom onset to puncture. RESULTS: Among 5,429 patients included in the ETIS registry, 1,093 were included in the study, including 651 patients with complete recanalization treated with IVT before EVT. After PSM, 488 patients treated with IVT before EVT were compared to 337 patients without IVT. In the matched cohort analysis, the IVT+EVT group had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR] = 1.41, 95% confidence interval [CI] = 1.04-1.91, p = 0.023) and higher rates of favorable outcome (61.1% vs 48.7%, aOR = 1.49, 95% CI = 1.02-2.20, p = 0.041) at 90 days compared with the EVT alone group. Rates of symptomatic intracerebral hemorrhage were comparable between both groups (6.0% vs 4.3%, aOR = 1.16, 95% CI = 0.53-2.54, p = 0.709). INTERPRETATION: In clinical practice, even after complete angiographic reperfusion by EVT, prior IVT use improves clinical outcomes of patients without increasing bleeding risk. ANN NEUROL 2024;95:762-773.

Relevance of Brain Regions' Eloquence Assessment in Patients With a Large Ischemic Core Treated With Mechanical Thrombectomy.

OBJECTIVE: Individualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT. METHODS: We performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0-3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models. RESULTS: A total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0-3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0-3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant (p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant. CONCLUSIONS: Considering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months.