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Background and Objectives: Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time., Methods: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90., Results: Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5 hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/ p = 0.03), whereas early treatment window did not modify the effect of IVT., Discussion: CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved., (© 2023 American Academy of Neurology.)

Background and Objectives: Perfusion imaging can identify adult patients with salvageable brain tissue who would benefit from thrombectomy in later time windows. The feasibility of obtaining hyperacute perfusion sequences in pediatric stroke is unknown. The aim of this study was to determine whether contrast perfusion imaging delayed time to treatment and to assess perfusion profiles in children with large vessel occlusion stroke., Methods: The Save ChildS retrospective cohort study (January 2000-December 2018) enrolled children (1 month-18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only., Results: Of 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4-7.5) perfusion+; 3.4 hours (IQR 2.5-6.5) perfusion-, p = 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5-2.0] vs 2.0 [1.5-3.0], p = 0.026) and modified Rankin Scale 1.0 [0-1] vs 2.0 [1.5-3.5], p = 0.048) in this small sample., Discussion: Automated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children., (© 2022 American Academy of Neurology.)

Background and Objectives: The effect of mechanical thrombectomy (MT) on functional outcome in patients with ischemic stroke with low ASPECTS is still uncertain. ASPECTS rating is based on the presence of ischemic hypoattenuation relative to normal; however, the degree of hypoattenuation, which directly reflects net uptake of water, is currently not considered an imaging biomarker in stroke triage. We hypothesized that the effect of thrombectomy on functional outcome in low ASPECTS patients depends on early lesion water uptake., Methods: For this multicenter observational study, patients with anterior circulation stroke with ASPECTS ≤5 were consecutively analyzed. Net water uptake (NWU) was assessed as a quantitative imaging biomarker in admission CT. The primary end point was the rate of favorable functional outcome defined as modified Rankin Scale score 0-3 at day 90. The effect of recanalization on functional outcome was analyzed according to the degree of NWU within the early infarct lesion., Results: A total of 254 patients were included, of which 148 (58%) underwent MT. The median ASPECTS was 4 (interquartile range [IQR] 3-5), and the median NWU was 11.4% (IQR 8.9%-15.1%). The rate of favorable outcome was 27.6% in patients with low NWU (<11.4%) vs 6.3% in patients with high NWU (≥11.4%; p < 0.0001). In multivariable logistic regression analysis, NWU was an independent predictor of outcome, whereas vessel recanalization (modified thrombolysis in cerebral infarction ≥2b) was only significantly associated with better outcomes if NWU was lower than 12.6%. In inverse-probability weighting analysis, recanalization was associated with 20.7% ( p = 0.01) increase in favorable outcome in patients with low NWU compared with 9.1% ( p = 0.06) in patients with high NWU., Discussion: Early NWU was independently associated with clinical outcome and might serve as an indicator of futile MT in low ASPECTS patients. NWU could be tested as a tool to select low ASPECTS patients for MT., Trial Registration Information: The study is registered within the ClinicalTrials.gov Protocol Registration and Results System (NCT04862507)., (© 2022 American Academy of Neurology.)

Background and Objectives: Robust cerebral collaterals are associated with favorable outcomes in patients with acute ischemic stroke due to large vessel occlusion treated by thrombectomy. However, collateral status assessment mostly relies on single imaging biomarkers and a more comprehensive holistic approach may provide deeper insights into the biology of collateral perfusion on medical imaging. Comprehensive collateralization is defined as blood flow of cerebral arteries through the brain tissue and into draining veins. We hypothesized that a comprehensive analysis of the cerebral collateral cascade (CCC) on an arterial, tissue, and venous level would predict clinical and radiologic outcomes., Methods: This was a multicenter retrospective cohort study of patients with acute stroke undergoing thrombectomy triage. CCC was determined by quantifying pial arterial collaterals, tissue-level collaterals, and venous outflow (VO). Pial arterial collaterals were determined by CT angiography; tissue-level collaterals were assessed on CT perfusion. VO was assessed on CT angiography using the cortical vein opacification score. Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and VO), CCC- (poor pial collaterals, tissue-level collaterals, and VO), and CCC mixed (the remainder of the patients). Primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Secondary outcome was final infarct volume., Results: A total of 647 patients met inclusion criteria: 176 CCC+, 345 CCC mixed , and 126 CCC-. Multivariable ordinal logistic regression showed that CCC+ predicted good functional outcomes (odds ratio [OR] 18.9 [95% CI 8-44.5]; p < 0.001) compared with CCC- and CCC mixed . CCC mixed patients likely had better functional outcomes compared with CCC- patients (OR 2.5 [95% CI 1.2-5.4]; p = 0.014). Quantile regression analysis (50th percentile) showed that CCC+ (β -78.5, 95% CI -96.0 to -61.1; p < 0.001) and CCC mixed (β -64.0, 95% CI -82.4 to -45.6; p < 0.001) profiles were associated with considerably lower final infarct volumes compared with CCC- profiles., Discussion: Comprehensive assessment of the collateral blood flow cascade in patients with acute stroke is a strong predictor of clinical and radiologic outcomes in patients treated by thrombectomy., (© 2022 American Academy of Neurology.)

Background and Objectives: Robust cerebrovascular collaterals in adult patients with large vessel occlusion stroke have been associated with longer treatment windows, better recanalization rates, and improved outcomes, but the role of collaterals in pediatric stroke is not known. The primary aim was to determine whether favorable collaterals correlated with better radiographic and clinical outcomes in children with ischemic stroke who underwent thrombectomy., Methods: This study analyzed a subset of children enrolled in SaveChildS, a retrospective, multicenter, observational cohort study of 73 pediatric patients with stroke who underwent thrombectomy between 2000 and 2018 at 27 US and European centers. Included patients had baseline angiographic imaging and follow-up modified Rankin Scale scores available for review. Posterior circulation occlusions were excluded. Cerebrovascular collaterals were graded on acute neuroimaging by 2 blinded neuroradiologists according to the Tan collateral score, in which favorable collaterals are defined as >50% filling and unfavorable collaterals as <50% filling distal to the occluded vessel. Collateral status was correlated with clinical and neuroimaging characteristics and outcomes. Between-group comparisons were performed with the Wilcoxon rank-sum test for continuous variables or Fisher exact test for binary variables., Results: Thirty-three children (mean age 10.9 [SD ±4.9]) years were included; 14 (42.4%) had favorable collaterals. Median final stroke volume as a percent of total brain volume (TBV) was significantly lower in patients with favorable collaterals (1.35% [interquartile range (IQR) 1.14%-3.76%] vs 7.86% [IQR 1.54%-11.07%], p = 0.049). Collateral status did not correlate with clinical outcome, infarct growth, or final Alberta Stroke Program Early CT Score (ASPECTS) in our cohort. Patients with favorable collaterals had higher baseline ASPECTS (7 [IQR 6-8] vs 5.5 [4-6], p = 0.006), smaller baseline ischemic volume (1.57% TBV [IQR 1.09%-2.29%] vs 3.42% TBV [IQR 1.26%-5.33%], p = 0.035), and slower early infarct growth rate (2.4 mL/h [IQR 1.5-5.1 mL/h] vs 10.4 mL/h [IQR 3.0-30.7 mL/h], p = 0.028)., Discussion: Favorable collaterals were associated with smaller final stroke burden and slower early infarct growth rate but not with better clinical outcome in our study. Prospective studies are needed to determine the impact of collaterals in childhood stroke., Classification of Evidence: This study provides Class II evidence that in children with ischemic stroke undergoing thrombectomy, favorable collaterals were associated with improved radiographic outcomes but not with better clinical outcomes., (© 2021 American Academy of Neurology.)

Background and Objectives: In acute stroke, early ischemic lesion hypodensity on CT is considered the imaging hallmark of brain infarction, representing a state of irreversible tissue damage with a continual increase of net water uptake. This dogma, however, is challenged by rare cases of apparently reversed early lesion hypodensity after complete reperfusion. The purpose of this study was to investigate the occurrence of reversible ischemic edema after endovascular treatment., Methods: One hundred eighty-four patients with acute ischemic anterior circulation stroke were included after consecutive screening. Ischemic brain edema was determined with quantitative lesion net water uptake (NWU) in admission CT and follow-up CT based on CT densitometry, and ΔNWU was calculated as the difference. The association of edema progression to imaging and clinical parameters was investigated. Clinical outcome was assessed with the modified Rankin Scale (mRS) scores at day 90., Results: Of 184 patients, 27 (14.7%) showed edema arrest and 3 (1.6%) exhibited significant edema reversibility. Higher degree of recanalization (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.46-6.01, p < 0.01) and shorter time from imaging to recanalization (OR per hour 0.32, 95% CI 0.18-0.54, p < 0.0001) were significantly associated with edema arrest or reversibility. Clinical outcome was significantly better in patients without edema progression (median mRS score 2 vs 5, p = 0.004)., Discussion: Although rare, lesion hypodensity considered to be representative of early infarct in acute stroke CT may be reversible after complete recanalization. Arrest of edema progression of acute brain infarct lesions may occur after successful rapid vessel recanalization, resulting in improved functional outcome. Future research is needed to investigate conditions in which early revascularization may halt or even reverse vasogenic edema of ischemic tissue., (© 2021 American Academy of Neurology.)

Objective: To determine whether thrombectomy is safe in children up to 24 hours after onset of symptoms when selected by mismatch between clinical deficit and infarct., Methods: A secondary analysis of the Save ChildS Study (January 2000-December 2018) was performed, including all pediatric patients (<18 years) diagnosed with arterial ischemic stroke who underwent endovascular recanalization at 27 European and United States stroke centers. Patients were included if they had a relevant mismatch between clinical deficit and infarct., Results: Twenty children with a median age of 10.5 (interquartile range [IQR] 7-14.6) years were included. Of those, 7 were male (35%), and median time from onset to thrombectomy was 9.8 (IQR 7.8-16.2) hours. Neurologic outcome improved from a median Pediatric NIH Stroke Scale score of 12.0 (IQR 8.8-20.3) at admission to 2.0 (IQR 1.2-6.8) at day 7. Median modified Rankin Scale (mRS) score was 1.0 (IQR 0-1.6) at 3 months and 0.0 (IQR 0-1.0) at 24 months. One patient developed transient peri-interventional vasospasm; no other complications were observed. A comparison of the mRS score to the mRS score in the DAWN and DEFUSE 3 trials revealed a higher proportion of good outcomes in the pediatric compared to the adult study population., Conclusions: Thrombectomy in pediatric ischemic stroke in an extended time window of up to 24 hours after onset of symptoms seems safe and neurologic outcomes are generally good if patients are selected by a mismatch between clinical deficit and infarct., Classification of Evidence: This study provides Class IV evidence that for children with acute ischemic stroke with a mismatch between clinical deficit and infarct size, thrombectomy is safe., (© 2020 American Academy of Neurology.)