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Cerebral ischemic injury occurs when blood flow drops below a critical level, resulting in an energy failure. The progressive transformation of hypoperfused viable tissue, the ischemic penumbra, into infarction is a mechanism shared by patients with ischemic stroke if timely reperfusion is not achieved. Yet, the pace at which this transformation occurs, known as the infarct growth rate (IGR), exhibits remarkable heterogeneity among patients, brain regions, and over time, reflecting differences in compensatory collateral flow and ischemic tolerance. We review (1) the pathophysiology of infarct growth, (2) the advantages and pitfalls of different approaches of IGR measurement, (3) research gaps for future studies, and (4) the clinical implications of stroke progressor phenotypes. The estimated average IGR in patients with acute large vessel occlusion stroke is 5.4 mL/h although there is wide variability based on ischemic stroke subtype, occlusion location, presence of collaterals, and patient baseline status. The IGR can be calculated using various pragmatic strategies, mostly either quantifying the extension of the infarct at a particular time and dividing this measure by the time that elapsed from symptom onset to imaging assessment or by using collateral blood flow status as a radiological surrogate marker. The IGR defines a spectrum of clinical stroke phenotypes, often dichotomized into fast and slow progressors. An IGR ≥10 mL/h and the perfusion metric hypoperfusion intensity ratio ≥0.5 are commonly used definitions of fast progressors. A nuanced understanding of the IGR and stroke progressor phenotypes could have clinical implications, including informing prognostication, acute decision-making in peripheral-to-comprehensive transfer patients eligible for thrombectomy, and selection for adjuvant neuroprotective agents., Competing Interests: Dr Nguyen is an Associate Editor of Stroke, is on the advisory board of Brainomix and Aruna Bio, and is a speaker for Genentech and Kaneka. Dr Broocks received grants or contracts from Balt. Dr Demchuk is a consultant for Boehringer Ingelheim and Hoffmann-La Roche Ltd, holds stocks in Circle NVI, is a member of the data and safety monitoring boards for Lumosa and Philips, and holds a patent for a stroke imaging software, which is licensed to Circle NVI. Dr Goyal is a consultant for Medtronic, Mentice, and MicroVention. Dr Hill received grants or contracts from Boehringer Ingelheim, Canadian Institutes of Health Research, and Medtronic and holds stock options in Basking Bioscience LLC. Dr Mitchell is a consultant for Stryker Corporation and has interests with Medtronic and Stryker Corporation. The other authors report no conflicts.

Background: A potential benefit of mechanical thrombectomy for patients with distal medium vessel occlusions is currently being investigated in randomized trials. Computed tomography perfusion imaging has not yet been tested as a method to guide mechanical thrombectomy for distal medium vessel occlusions. The purpose of this study was to assess penumbral imaging as an imaging-based method for triaging patients with ischemic stroke and acute M2-middle cerebral artery occlusion., Methods: This observational retrospective study of M2-middle cerebral artery patients with ischemic stroke triaged by multimodal computed tomography undergoing mechanical thrombectomy at a high-volume stroke center between January 2015 and January 2023. The effect of recanalization was analyzed according to computed tomography perfusion-derived lesion volumes (defined using relative cerebral blood flow <30% and T max >6 seconds) using logistic regression analysis, and interaction terms between the independent variables and recanalization were tested. The primary end point was functional independence at day 90, defined using modified Rankin Scale scores of 0 to 2., Results: A total of 140 patients with M2-middle cerebral artery occlusion were included. In multivariable logistic regression analysis, recanalization was not associated with better functional outcome (adjusted odds ratio, 1.85 [95% CI, 0.87-3.90]; P =0.11). After including interaction terms, a significant treatment effect between recanalization and computed tomography perfusion-derived lesion volumes was observed in patients with >150 mL hypoperfusion volume (adjusted odds ratio, 1.02 [95% CI, 1.00-1.03]; P =0.007) or >125 mL penumbral volumes (adjusted odds ratio, 1.02 [95% CI, 1.01-1.03]; P =0.005), as well as for baseline ischemic core volume within the range of 15 to 40 mL (adjusted odds ratio, 1.11 [95% CI, 1.01-1.22]; P =0.03)., Conclusions: Penumbral imaging might serve as a useful tool for treatment decision-making in distal medium vessel occlusions, particularly in cases of suspected non- or codominant M2-middle cerebral artery vessel occlusions. A hypoperfusion volume threshold of >150 mL emphasizes the potential value of computed tomography perfusion as a standardized tool directly showing the volumetric relevance in distal medium vessel occlusion cases., Competing Interests: Dr Broocks reports consulting for EppData GmbH and a research grant from the Foundation of the American Society of Neuroradiology. Dr Fiehler reports compensation from TG Medical for consulting services; compensation from Penumbra, Inc for consulting services; employment with Eppdata; compensation from Cerenovus for consulting services; compensation from MicroVention, Inc, for consulting services; compensation from Roche for consulting services; stock holdings in Eppdata; compensation from Tonbridge for consulting services; compensation from Medtronic USA, Inc, for consulting services; stock holdings in Eppdata; compensation from Phenox for consulting services; stock holdings in Vastrax; stock holdings in Tegus Medical; compensation from Stryker Corporation for consulting services; and compensation from Acandis for consulting services. Dr Kemmling has a research collaboration agreement with Siemens Healthcare (company involved in CT/MRI distribution). Dr Kniep: Educational presentation for Asklepios Kliniken; consulting for EppData GmbH. The other authors report no conflicts.

Background: Computed tomography perfusion (CTP) imaging is regularly used to guide patient selection for mechanical thrombectomy (MT). However, the effect of MT in patients without salvageable tissue on CTP has not been investigated. The purpose of this study was to assess the effect of MT in patients with stroke without perfusion mismatch profiles., Methods: This observational study analyzed patients with ischemic stroke consecutively treated between March 1, 2015, and January 31, 2022, triaged by multimodal-computed tomography undergoing MT. CTP lesion-core mismatch profiles were defined using a mismatch volume/ratio of ≥10 mL/1.2, respectively. The primary end point was the rate of functional independence at 90 days, defined as the modified Rankin Scale score of 0 to 2. Recanalization was evaluated with the modified Thrombolysis in Cerebral Infarction scale. The effect of baseline variables on functional outcome was assessed using multivariable logistic regression analysis. Outcomes of patients with and without CTP-mismatch profiles were compared using 1:1 propensity score matching., Results: Of 724 patients who met the inclusion criteria of this retrospective observational study, 110 (15%) patients had no CTP mismatch and were analyzed. The median age was 74 (interquartile range, 62-80) years and 53% were women. Successful recanalization (modified Thrombolysis in Cerebral Infarction score, ≥2b) was achieved in 66% (73) and associated with functional independence at 90 days (adjusted odds ratio, 7.33 [95% CI, 1.22-43.70]; P =0.03). A significant interaction was observed between recanalization and age, as well as the extent of infarction, indicating MT to be most effective in patients <70 years and with a baseline Alberta Stroke Program Early Computed Tomography Score range between 3 and 7. These findings remained stable after propensity score matching, analyzing 152 matched pairs with similar rates of functional independence between patients with and without CTP-mismatch profiles (17% versus 23%; P =0.42)., Conclusions: In patients without CTP-mismatch profiles defined according to the EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits) criteria, recanalization was associated with improved functional outcomes. This effect was associated with baseline Alberta Stroke Program Early Computed Tomography Score and age, but not with the time from onset to imaging., Competing Interests: Disclosures Dr Fiehler reports German Ministry of Science and Education, the German Ministry of Economy and Innovation, the German Research Foundation, the European Union, the Hamburgische Investitions—und Förderbank. Dr Kemmling reports Research collaboration agreement: Siemens Healthcare (company involved in computed tomography/magnetic resonance imaging distribution). Dr Kniep reports Educational presentation for Asklepios Kliniken, Consulting for EppData Gesellschaftmit beschränkter Haftung (GmbH). The other authors report no conflicts.

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: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction., Methods: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes., Results: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P =0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P =0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P =0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion., Conclusions: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03356392., Competing Interests: Disclosures The authors declared the following potential conflicts of interest with respect to the research, authorship, and publication of this article: Dr Faizy reported grants from the German Research Foundation (DFG; Project Number: 411621970). Dr Broocks reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. Dr Meyer reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. Dr Deb-Chatterji reported receiving grants from Werner Otto Stiftung outside the submitted work. Dr Hanning reported receiving personal fees from Eppdata GmbH outside the submitted work. Dr Kniep reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. Dr Maros reported receiving compensation as a speaker from Siemens Healthineers GmbH outside the submitted work. Dr Thomalla reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. Dr Fiehler reported compensation from Acandis, Cerenovus, MicroVention, Medtronic, Penumbra, Phenox, Roche, Stryker, and Tonbridge and stock holdings in Eppdata GmbH and Tegus Medical outside the submitted work. Dr Flottmann reported receiving personal fees from Eppdata GmbH outside the submitted work.

Background: Patient-specific factors associated with successful recanalization in mechanical thrombectomy (MT) have been evaluated for acute ischemic stroke with large vessel occlusion. However, MT for M2 occlusions is still a matter of debate, and predictors of successful and futile recanalization have not been assessed in detail. We sought to identify predictors of recanalization success in patients with M2 occlusions undergoing MT based on large-scale clinical data., Methods: All patients prospectively enrolled in the German Stroke Registry (May, 2015 to December, 2021) were screened (N=13 082). Inclusion criteria for the complete case analysis were isolated M2 occlusions. Standard descriptive statistics and multivariable logistic regression analysis were used to identify factors associated with successful recanalization (Thrombolysis in Cerebral Infarction [TICI]≥2b), complete recanalization (TICI=3) and futile recanalization (TICI≥2b with 90-day modified Rankin Scale [mRS] score >2)., Results: One thousand two hundred ninety-four patients were included, thereof 439 (33.9%) with TICI=2b and 643 (49.7%) with TICI=3. Five hundred sixty-nine (44%) patients had good functional outcome (90-day mRS score ≤2). In multivariable logistic regression, general anesthesia (adjusted odds ratio [aOR], 1.47 [95% CI, 1.05-2.09]; P <0.05) was associated with higher probability of TICI≥2b while intraprocedural change from local to general anesthesia (aOR, 0.49 [0.26-0.95]; P <0.05) and higher pre-mRS (aOR, 0.75 [0.67-0.85]; P <0.001) lowered probability of successful recanalization. Futile recanalization was associated with higher age (aOR, 1.05 [1.04-1.07]; P <0.001), higher prestroke mRS (aOR, 3.12 [2.49-3.91]; P <0.001), higher NIHSS at admission (aOR, 1.11 [1.08-1.14]; P <0.001), diabetes (aOR, 1.96 [1.38-2.8]; P <0.001), higher number of passes (aOR, 1.29 [1.14-1.46]; P <0.001), and adverse events (aOR, 1.82 [1.2-2.74]; P <0.01). Higher Alberta Stroke Program Early CT Score (aOR, 0.85 [0.76-0.94]; P <0.01) and IV thrombolysis (aOR, 0.71 [0.52-0.97]; P <0.05) reduced risk of futile recanalization., Conclusions: In patients with M2 occlusions, successful recanalization was significantly associated with general anesthesia and low prestroke mRS, while intraprocedural change from conscious sedation to general anesthesia increased risk of unsuccessful recanalization, presumably caused by difficult anatomy and movement of patients in these cases. Futile recanalization was associated with severe prestroke mRS, comorbidity diabetes, number of passes and adverse events during treatment. IV thrombolysis reduced the risk of futile recanalization., Competing Interests: Disclosures Drs Kniep and Flottmann are consultants for Eppdata GmbH. Dr Kniep is shareholder of Eppdata GmbH. Dr Deb-Chatterji has received research grants from the Werner Otto Stiftung and serves in the advisory board of the PRECIOUS trial (Prevention of Complications to Improve Outcome in Elderly Patients With Acute Stroke). Dr Thomalla received fees as consultant from Acandis, Boehringer Ingelheim, Bayer, and Portola and fees as lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichii Sankyo, and Portola. He serves in the board of the TEA Stroke Study and of ESO. Dr Fiehler is consultant for Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche and Tonbridge. He serves in the advisory board of Stryker and Phenox. He is stock holder of Tegus Medical, Eppdata, and Vastrax. He serves as Associate Editor at JNIS.

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: Intravenous tPA (tissue-type plasminogen activator) is often administered before endovascular thrombectomy (EVT). Recent studies have questioned whether tPA is necessary given the high rates of arterial recanalization achieved by EVT, but whether tPA impacts venous outflow (VO) is unknown. We investigated whether tPA improves VO profiles on baseline computed tomography (CT) angiography (CTA) images before EVT., Methods: Retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion undergoing EVT triage. Included patients underwent CT, CTA, and CT perfusion before EVT. VO profiles were determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on CTA as 0, not visible; 1, moderate opacification; and 2, full. Pial arterial collaterals were graded on CTA, and tissue-level collaterals were assessed on CT perfusion using the hypoperfusion intensity ratio. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analysis, we determined the correlation between tPA administration and favorable VO profiles., Results: Seven hundred seventeen patients met inclusion criteria. Three hundred sixty-five patients received tPA (tPA+), while 352 patients were not treated with tPA (tPA-). Fewer tPA+ patients had atrial fibrillation (n=128 [35%] versus n=156 [44%]; P =0.012) and anticoagulants/antiplatelet treatment before acute ischemic stroke due to large vessel occlusion onset (n=130 [36%] versus n=178 [52%]; P <0.001) compared with tPA- patients. One hundred eighty-five patients (51%) in the tPA+ and 100 patients (28%) in the tPA- group exhibited favorable VO ( P <0.001). Multivariable regression analysis showed that tPA administration was a strong independent predictor of favorable VO profiles (OR, 2.6 [95% CI, 1.7-4.0]; P <0.001) after control for favorable pial arterial CTA collaterals, favorable tissue-level collaterals on CT perfusion, age, presentation National Institutes of Health Stroke Scale, antiplatelet/anticoagulant treatment, history of atrial fibrillation and time from symptom onset to imaging., Conclusions: In patients with acute ischemic stroke due to large vessel occlusion undergoing thrombectomy triage, tPA administration was strongly associated with the presence of favorable VO profiles.

Background: Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome., Methods: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge)., Results: Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94-0.96]), prestroke modified Rankin Scale (0.48 [0.42-0.55]), admission-NIHSS (0.96 [0.94-0.98]), 24-hour NIHSS (0.83 [0.81-0.84]), diabetes (0.56 [0.43-0.72]), proximal middle cerebral artery occlusions (0.78 [0.62-0.97]), passes (0.88 [0.82-0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00-1.14]), successful recanalization (2.39 [1.68-3.43]), intracerebral hemorrhage (0.51 [0.35-0.73]), and recurrent strokes (0.54 [0.32-0.92]). Mediation analysis showed a 20 percentage points (95% CI' 17-24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI' 44%-66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI' 62%-90%) by NIHSS at hospital discharge., Conclusions: Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03356392.

Background: The optimal endovascular strategy for reperfusing distal medium-vessel occlusions (DMVO) remains unknown. This study evaluates angiographic and clinical outcomes of thrombectomy strategies in DMVO stroke of the posterior circulation., Methods: TOPMOST (Treatment for Primary Medium Vessel Occlusion Stroke) is an international, retrospective, multicenter, observational registry of patients treated for DMVO between January 2014 and June 2020. This study analyzed endovascularly treated isolated primary DMVO of the posterior cerebral artery in the P2 and P3 segment. Technical feasibility was evaluated with the first-pass effect defined as a modified Thrombolysis in Cerebral Infarction Scale score of 3. Rates of early neurological improvement and functional modified Rankin Scale scores at 90 days were compared. Safety was assessed by the occurrence of symptomatic intracranial hemorrhage and intervention-related serious adverse events., Results: A total of 141 patients met the inclusion criteria and were treated endovascularly for primary isolated DMVO in the P2 (84.4%, 119) or P3 segment (15.6%, 22) of the posterior cerebral artery. The median age was 75 (IQR, 62-81), and 45.4% (64) were female. The initial reperfusion strategy was aspiration only in 29% (41) and stent retriever in 71% (100), both achieving similar first-pass effect rates of 53.7% (22) and 44% (44; P =0.297), respectively. There were no significant differences in early neurological improvement (aspiration: 64.7% versus stent retriever: 52.2%; P =0.933) and modified Rankin Scale rates (modified Rankin Scale score 0-1, aspiration: 60.5% versus stent retriever 68.6%; P =0.4). In multivariable logistic regression analysis, the time from groin puncture to recanalization was associated with the first-pass effect (adjusted odds ratio, 0.97 [95% CI, 0.95-0.99]; P <0.001) that in turn was associated with early neurological improvement (aOR, 3.27 [95% CI, 1.16-9.21]; P <0.025). Symptomatic intracranial hemorrhage occurred in 2.8% (4) of all cases., Conclusions: Both first-pass aspiration and stent retriever thrombectomy for primary isolated posterior circulation DMVO seem to be safe and technically feasible leading to similar favorable rates of angiographic and clinical outcome.

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 Purpose: Patients presenting in the extended time window may benefit from mechanical thrombectomy. However, selection for mechanical thrombectomy in this patient group has only been performed using specialized image processing platforms, which are not widely available. We hypothesized that quantitative lesion water uptake calculated in acute stroke computed tomography (CT) may serve as imaging biomarker to estimate ischemic lesion progression and predict clinical outcome in patients undergoing mechanical thrombectomy in the extended time window., Methods: All patients with ischemic anterior circulation stroke presenting within 4.5 to 24 hours after symptom onset who received initial multimodal CT between August 2014 and March 2020 and underwent mechanical thrombectomy were analyzed. Quantitative lesion net water uptake was calculated from the admission CT. Prediction of clinical outcome was assessed using univariable receiver operating characteristic curve analysis and logistic regression analyses., Results: One hundred two patients met the inclusion criteria. In the multivariable logistic regression analysis, net water uptake (odds ratio, 0.78 [95% CI, 0.64-0.95], P =0.01), age (odds ratio, 0.94 [95% CI, 0.88-0.99]; P =0.02), and National Institutes of Health Stroke Scale (odds ratio, 0.88 [95% CI, 0.79-0.99], P =0.03) were significantly and independently associated with favorable outcome (modified Rankin Scale score ≤1), adjusted for degree of recanalization and Alberta Stroke Program Early CT Score. A multivariable predictive model including the above parameters yielded the highest diagnostic ability in the classification of functional outcome, with an area under the curve of 0.88 (sensitivity 92.3%, specificity 82.9%)., Conclusions: The implementation of quantitative lesion water uptake as imaging biomarker in the diagnosis of patients with ischemic stroke presenting in the extended time window might improve clinical prognosis. Future studies could test this biomarker as complementary or even alternative tool to CT perfusion.

Background and Purpose: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment., Methods: This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)–based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale., Results: After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group (P=0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05–1.10], P<0.001) and symptomatic intracerebral hemorrhage (adjusted odds ratio, 6.35 [95% CI, 2.08–19.35], P<0.001) were independently associated with very poor outcome. Mortality (43.5% versus 28.9%, P=0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1–2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P=0.074) compared with best medical treatment., Conclusions: In daily clinical practice, EVT for CT–based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

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.)

Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort. Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders. Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1–3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38–9.42], P=0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07–0.89], P=0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06–0.78], P=0.020) were significant protective factors against the occurrence of SICH. More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Background and Purpose: Patients with acute ischemic stroke due to large vessel occlusion and favorable tissue-level collaterals (TLCs) likely have robust cortical venous outflow (VO). We hypothesized that favorable VO predicts robust TLC and good clinical outcomes., Methods: Multicenter retrospective cohort study of consecutive acute ischemic stroke due to large vessel occlusion patients who underwent thrombectomy triage. Included patients had interpretable prethrombectomy computed tomography, computed tomography angiography, and cerebral perfusion imaging. TLCs were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (volume ratio of brain tissue with [Tmax >10 s/Tmax >6 s]). VO was determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on computed tomography angiography as 0, not visible; 1, moderate opacification; and 2, full. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analyses, we determined the association between VO and (1) favorable TLC status (defined as hypoperfusion intensity ratio ≤0.4) and (2) good functional outcome (modified Rankin Scale score, 0-2)., Results: Six hundred forty-nine patients met inclusion criteria. Patients with favorable VO were younger (median age, 72 [interquartile range (IQR), 62-80] versus 77 [IQR, 66-84] years), had a lower baseline National Institutes of Health Stroke Scale (median, 12 [IQR, 7-17] versus 19 [IQR, 13-20]), and had a higher Alberta Stroke Program Early Computed Tomography Score (median, 9 [IQR, 7-10] versus 7 [IQR, 6-9]). Favorable VO strongly predicted favorable TLC (odds ratio, 4.5 [95% CI, 3.1-6.5]; P <0.001) in an adjusted regression analysis. Favorable VO also predicted good clinical outcome (odds ratio, 10 [95% CI, 6.2-16.0]; P <0.001), while controlling for favorable TLC, age, glucose, baseline National Institutes of Health Stroke Scale, and good vessel reperfusion status., Conclusions: In this selective retrospective cohort study of acute ischemic stroke due to large vessel occlusion patients undergoing thrombectomy triage, favorable VO profiles correlated with favorable TLC and were associated with good functional outcomes after treatment. Future prospective studies should independently validate our findings.

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.)

Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort., Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders., Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0-10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7-7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8-5.6])., Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), ( P <0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time ( P <0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

Background and Purpose- The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods- The Save ChildS cohort study (January 2000-December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (<18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results- Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions- Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration- URL: https://www.drks.de/; Unique identifier: DRKS00016528.

Background and Purpose- Poor collateral flow is associated with poor clinical outcome in acute ischemic stroke and may indicate futile recanalization after successful thrombectomy. Pronounced early formation of cerebral ischemic edema may be the link between poor collateral status and declined functional outcome, but this relationship has not been investigated yet. We hypothesized that collateral status is associated with early lesion water uptake as quantitative marker for edema progression. Methods- One hundred seventy-six patients with middle cerebral artery stroke who underwent mechanical thrombectomy were analyzed. Status of cerebral collateral circulation (collaterals status [CS]) was derived using an established 5-point scoring system in admission computed tomography angiography, and good collaterals were defined as CS 3 to 4. Ischemic brain edema dynamics were quantified using early edema progression rate (EPR). EPR was derived from quantitative lesion water uptake in admission computed tomography divided by time from symptom onset to imaging. Good clinical outcome was defined as modified Rankin Scale score 0 to 2 after 90 days. Results- The median EPR was 1.4% per hour (interquartile range, 0.5-3.5%) in patients with good collaterals, which was lower than the median EPR in patients with poor collaterals of 5.8% per hour (interquartile range, 2.1-5.9%; P <0.0001). In multivariable regression analysis, lower CS was significantly and independently associated with higher EPR (1.6% EPR per 1-point CS; P =0.002). A higher EPR was associated with reduced likelihood of good clinical outcome: odds ratio 0.87; (95% CI, 0.76-0.99; P =0.03). Conclusions- Patients with poor CS had significantly higher EPR, which was associated with worse clinical outcome. These patients might benefit from adjuvant antiedematous treatment.

Background and Purpose- The introduction of stent retrievers allows for a complete extraction and histological analysis of human clots. Initial studies describe an impact of preinterventional clot migration on technical and clinical success of thrombectomy and an association with worse clinical outcome. We, therefore, performed a large study of consecutive patients whose clots have been histologically analyzed and tried to determine whether clot composition influences the rates of clot migration and thereby interventional and clinical outcome. Methods- We retrospectively evaluated data of a prospectively collected cohort of 198 consecutive patients with occlusion of the middle cerebral artery. We investigated the relationship between clot histology expressed as percentage of the main components (fibrin, erythrocytes [red blood cell], and white blood cells), the preinterventional computed tomography attenuation of the emboli, embolus length, and clot migration. We defined a binary outcome (clot migration versus no clot migration). The impact of embolus composition and computed tomography features was assessed in univariable and multivariable logistic regression models. Results- One hundred sixty-three patients fulfilled the inclusion criteria, of which 36 (22.1%) showed a clot migration. Patients with proven clot migration had significantly higher levels of red blood cells than patients without clot migration (median 50% versus 26%, P<0.001). Lower amounts of fibrin were significantly more often observed in patients in the clot migration group as compared to the no clot migration group (43.5% versus 62.0%, P<0.001). Stroke cause did not differ between migrated and stable emboli. Multivariable analysis identified a higher amount of erythrocytes (adjusted odds ratio, 1.03 per median percentage, P<0.001) and a shorter embolus length (adjusted odds ratio, 0.90 per mm, P<0.008) as independent predictors of clot migration. Conclusions- Erythrocyte-rich clots and a shorter embolus length are independent reliable predictors for clot migration. This finding is clinically important as clot migration might have a negative impact on technical and clinical outcomes of patients suffering from emergent vessel occlusions of the middle cerebral artery undergoing endovascular therapy.

Purpose: Futile recanalization with poor clinical outcome after endovascular treatment of acute ischemic stroke is poorly understood. Recently, vessel recanalization has been associated with reduced ischemic brain edema in patients with good clinical outcome. As edema volume (EV) may be quantified in computed tomography (CT), we hypothesized that higher EV after revascularization predicts futile recanalization with poor outcome., Methods: In this observational study, 67 ischemic stroke patients with M1 middle cerebral artery occlusion fulfilled all inclusion criteria and were analyzed. All patients received successful endovascular recanalization (thrombolysis in cerebral infarction scale 2b/3) and subsequent follow-up CT 24 hours later. Edema volume within the infarct lesion was calculated in follow-up CT applying lesion water uptake quantification and was used to predict clinical outcome (Modified Rankin Scale [mRS] after 90 days) compared with infarct volume., Results: The median EV after thrombectomy was 1.6 mL (interquartile range, 0.2-4.2 mL) in patients with mRS 0 to 4 and 8.6 mL (interquartile range, 2.0-49.8 mL) in patients with mRS 5 to 6 (P = 0.0008). In regression analysis, an EV increase of 1 mL was associated with an 8.0% increased likelihood of poor outcome (95% confidence interval, 2.8%-15.4%; P = 0.008). Based on univariate receiver operating characteristic curve analysis, absolute EV over 4.2 mL predicted poor outcome (mRS 5-6) with good discriminative power (area under curve, 0.74; 95% confidence interval, 0.62-0.84; specificity, 77%; sensitivity, 68%). In comparison, the area under curve for infarct volume was 0.68., Conclusions: Elevated EV after endovascular thrombectomy was associated with poor clinical outcome and may indicate futile recanalization.

Background and Purpose- The early growth of ischemic lesions has been described as being nonlinear, with lesion growth rates at their highest during the earliest period after stroke onset. We hypothesized that the time gap from imaging to revascularization results in higher lesion growth in patients with hyperacute presentation. Methods- Fifty-one patients with ischemic stroke with initial multimodal computed tomography (CT), follow-up CT after 24 hours, and successful endovascular recanalization were included and separated into 2 groups according to their median time from symptom onset to imaging (eg, hyperacute versus acute). The difference in Alberta Stroke Program Early CT Score (ASPECTS) between initial CT and follow-up CT was assessed, as well as volumetric lesion growth from early ischemic core in admission perfusion CT and total lesion volume in follow-up CT. Results- The median time from onset to imaging was 1.85 hours. There was no significant difference in admission ASPECTS (mean, 8.5 versus 8.2) or time from imaging to recanalization in both groups (median, 2.7 versus 2.4 hours; P =0.4). The mean (SD) lesion growth assessed by ASPECTS difference was 2.7 (2.3) in the hyperacute group and 1.6 (1.3) in the acute group ( P =0.03). The mean (SD) volumetric difference in the hyperacute group was 26.6 mL (43.2 mL) and 17.2 mL (26.3 mL; P =0.36) in the acute group, respectively. For every passing hour after onset, ASPECTS lesion growth was reduced by 0.4. Conclusions- Patients in the hyperacute phase showed increased ASPECTS lesion growth from imaging to recanalization suggesting a particular benefit of faster recanalization times in this group of patients with stroke.

Background and Purpose- Besides the established spot sign (SS) in computed tomography angiography (CTA), there is growing evidence that different imaging markers in noncontrast CT offer great value for outcome prediction in patients with intracerebral hemorrhage (ICH). However, it is unclear how the concurrent presence of each sign independently contributes to the predictive power of poor outcome. We, therefore, aimed to clarify the predictive value of 5 recently published noncontrast CT parameters (blend sign, black hole sign, island sign, hematoma heterogeneity, and hypodensities) and the established SS in 1 consecutive series of patients with ICH. Methods- Retrospective study of patients with ICH at 2 German tertiary stroke centers; inclusion criteria were (1) spontaneous ICH and (2) noncontrast CT and CTA performed on admission within 6 hours after onset of symptoms. We defined a binary outcome (good outcome [modified Rankin Scale score of ≤3] versus poor outcome [modified Rankin Scale score of >3]) at discharge. The predictive value of each sign was assessed in univariate and multivariable logistic regression models. Results- Of 201 patients with spontaneous ICH, 28 (13.9%) presented with black hole sign, 38 (18.9%) with blend sign, 120 (59.7%) with hypodensities, 97 (48.3%) with heterogeneous densities, 53 with island sign (26.4%), and 45 (22.4%) with SS. In univariable logistic regression, higher hematoma volume ( P<0.001), intraventricular hemorrhage ( P=0.002), and the presence of black hole sign/blend sign/hypodensities/island sign/SS/heterogeneous density (all P<0.001) on admission CT were associated with poor outcome. Multivariable analysis confirmed intraventricular hemorrhage (odds ratio, 2.20; P=0.025), higher hematoma volume (odds ratio, 1.02 per mL; P<0.019), the presence of hypodensities (odds ratio, 2.47; P=0.018), and SS (odds ratio, 12.22; P<0.001) as independent predictors of poor outcome. Conclusions- This study demonstrates the degree of interaction between 5 recent noncontrast CT imaging markers and SS and their individual contribution for outcome prediction in patients with ICH. Of the CT variables indicating poor outcome SS on CTA and hypodensities were the most reliable outcome predictors.

Background and Purpose- In acute ischemic stroke, mechanical thrombectomy allows flow restoration in the majority of cases. In case of an unsuccessful retrieval, little is known about how many retrieval attempts should be performed before stopping the procedure. This study assessed the recanalization rate and clinical outcome per retrieval maneuver. Methods- In this analysis, 330 patients with acute large vessel occlusion treated exclusively with stentrieval devices were included. Successful recanalization was defined as Thrombolysis in Cerebral Infarction 2b-3, a good clinical outcome was defined as modified Rankin Scale at 90 days of ≤2. Results- The median number of retrieval attempts was 1 (interquartile range, 1-2, maximum 8). Recanalization rates per retrieval attempt were highest for the first retrieval (46.8%) and lowest for the fifth retrieval (22.7%). After 3 retrieval attempts, 67.9% of patients were successfully recanalized. Patients with 1 to 3 retrieval attempts had higher rates of good clinical outcome (28.9% versus 7.4%; P=0.018). The number of passes was an independent negative predictor of good clinical outcome (adjusted odds ratio, 0.65; 95% CI, 0.435-0.970; P=0.035). Conclusions- Two-thirds of occlusions were successfully recanalized with up to 3 retrieval attempts. Further attempts had good recanalization rates, but the rate of favorable clinical outcome did not improve.

Objectives: Final infarct volume is regularly used as an end point of tissue outcome in stroke trials; however, the reported volumes are most commonly derived from early follow-up imaging. Those volumes are significantly impaired by ischemic edema, which causes an overestimation of the true final lesion volume. As net water uptake within ischemic brain can be quantified densitometrically in computed tomography (CT) as recently described, we hypothesized that the final lesion volume can be better estimated by correcting the lesion volume in early follow-up for the corresponding proportion of edema., Materials and Methods: After retrospective consecutive screening of the local registry, 20 patients with acute middle cerebral artery large vessel occlusion met the inclusion criteria with early and late follow-up CT; the latter acquired at least 4 weeks after admission. In early follow-up imaging 24 hours after onset, the proportion of edema contributing to the infarct lesion was calculated by quantifying the total volume of ischemic net water uptake. Edema volume was then subtracted from the total lesion volume to obtain edema-corrected lesion volumes. Finally, these corrected lesion volumes were compared with the final lesion volume on late follow-up serving as ground truth., Results: The median lesion volume in the early follow-up was 115.1 mL (range, 21.9-539.9 mL) and significantly exceeded the median final lesion volume in the late follow-up CT, which was 86.6 mL (range, 11.2-399.0 mL; p < 0.001). The calculated mean proportion of edema within the early lesion volume was 25.8% (±5.9%; range, 11.1%-35.9%. The median edema-corrected lesion volume measured after 24 hours was 87.1 mL (range, 18.2-376.3 mL). The estimation of final lesion volume in the early follow-up CT was therefore improved by a mean of 31.4% (±2.1%) when correcting for the proportion of edema and did not differ significantly from the true final infarct volume (p = 0.2)., Conclusions: Edema-corrected volumes of early follow-up infarct lesion in CT were in close agreement with the actual final infarct volumes. Computed tomography-based edema correction of subacute infarct lesions improves the estimation of final tissue outcome. This could especially improve the comparability of imaging end points and facilitate patient recruitment in clinical trials.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Objectives: Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements., Materials and Methods: We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements., Results: With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P < 0.0001; mean ± SD difference, -0.29% ± 0.39%, not different from 0, P < 0.0001). In the study cohort, the mean ± SD uptake of water within infarct measured by volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001)., Conclusions: Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging of water uptake depicts lesion pathophysiology and could serve as a quantitative imaging biomarker of acute infarct lesions.