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Background: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy., Methods: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes., Results: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (β 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (β 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence., Conclusion: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy., Competing Interests: Competing interests: TDF reports research grants from the German Research Foundation (DFG, Project Number: 411621970) for his work as a postdoctoral scholar at Stanford University. GB reports research grants from the German Research Foundation (DFG) outside of the submitted work. GWA reports equity and consulting for iSchemaView and consulting from Medtronic. MW reports grants and funding from the NIH under the grant numbers (1U01 NS086872-01, 1U01 NS087748-01 and 1R01 NS104094). He reports compensation from Subtle Medical, Magnetic Insight, Icometrix and EMTensor for consultant services and employment by the University of Texas MD Anderson Cancer Center. JF reports stock holdings in Tegus Medical and grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox and grants from Route 92 outside the submitted work. JJH reports consulting for Medtronic and MicroVention and Medical and Scientific Advisory Board membership for iSchemaView., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset., Methods: Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis., Results: A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1-17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p<0.0001) and the median Alberta Stroke Program Early CT Score (ASPECTS) was lower (5 vs 8, p<0.0001). Following IPW, there was no association between IVT and sICH in unadjusted analysis. However, after adjusting for ASPECTS and NWU, there was a significant association between IVT administration and sICH (14.6%, 95% CI: 3.3% to 25.6%, p<0.01)., Conclusion: In patients with ischaemic stroke with unknown onset, the combination of high NWU with IVT is directly linked to higher rates of sICH. Besides ASPECTS for evaluating the extent of the early infarct lesion, quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke., Competing Interests: Competing interests: JF: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB). GT: Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2). AK: research collaboration agreement: Siemens Healthcare (company involved in CT/MRI distribution). All other authors reported no relationships with commercial firms whose products could be affected by the present study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The Alberta Stroke Program Early CT Score (ASPECTS) is regularly used to guide patient selection for mechanical thrombectomy (MT). Similarly, penumbral imaging based on computed tomography perfusion (CTP) may serve as neuroimaging tool to guide treatment. Yet, patients with a large ischemic core on CTP may show only minor ischemic changes resulting in a high ASPECTS., Aim: We hypothesized twofold: (1) the treatment effect of vessel recanalization in patients with core volume > 50 mL but ASPECTS ⩾ 6 is not different compared to high ASPECTS patients with core volume < 50 mL, and (2) recanalization is associated with core overestimation., Methods: We conducted an observational study analyzing ischemic stroke patients consecutively treated with MT after triage by multimodal CT. Functional endpoint was the rate of functional independence at Day 90 defined as modified Rankin Scale (mRS) 0-2. Imaging endpoint was core overestimation, which was considered when CTP-derived core was larger than the final infarct volume assessed on follow-up imaging. Recanalization was evaluated with the extended Thrombolysis in Cerebral Infarction (eTICI) scale. Multivariable logistic regression analysis and propensity score matching (PSM) were used to assess the association of recanalization (eTICI ⩾ 2b) with functional outcome and core overestimation., Results: Of 630 patients with ASPECTS ⩾ 6, 91 patients (14.4%) had a large ischemic core. Following 1:1 PSM, the treatment effect of recanalization was not different in patients with large core and ASPECTS ⩾ 6 (+ 25.8%, 95% CI: 16.3-35.4, p < 0.001) compared to patients with ASPECTS ⩾ 6 and core volume < 50 mL (+ 14.9%, 95% CI: 5.7-24.1, p = 0.002). Recanalization (aOR: 3.46, 95% CI: 1.85-6.47, p < 0.001) and higher core volume (aOR: 1.03, 95% CI: 1.02-1.04, p < 0.001) were significantly associated with core overestimation., Conclusion: In patients with ASPECTS ⩾ 6, core volumes did not significantly modify outcomes following recanalization. Reperfusion and higher core volume were significantly associated with core overestimation which may explain the treatment effect of MT for patients with a large ischemic core but minor ischemic changes on non-enhanced CT., Data Access Statement: The data analyzed in this study will be available and shared on reasonable request from any qualified researcher for the purpose of replicating the results after clearance by the local ethics committee., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.F. received research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, MicroVention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, MicroVention, Penumbra, Route 92, Stryker, Transverse Medical; and stock holdings for Tegus.All other authors report no relevant disclosures.

Importance: Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials., Objective: To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct., Design, Setting, and Participants: This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes., Exposure: Age., Main Outcomes and Measures: Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6)., Results: A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27)., Conclusions and Relevance: In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022. The primary outcome was ischemic core overestimation, which was assumed when baseline CTP-derived ICV was larger than the final infarct volume at follow-up imaging. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 90 days after EVT. Successful vessel recanalization was defined as extended Thrombolysis in Cerebral Infarction score of 2b or higher. Categorical variables were compared between patients with ICV of 50 mL or less versus large ICV greater than 50 mL with use of the χ 2 test. Adjusted multivariable logistic regression analyses were used to assess the primary and secondary outcomes. Results In total, 721 patients (median age, 76 years [IQR, 64-83 years]; 371 female) were included, of which 162 (22%) demonstrated ischemic core overestimation. Core overestimation occurred more often in patients with ICV greater than 50 mL versus 50 mL or less (48% vs 16%; P < .001) and those with successful versus unsuccessful vessel recanalization (26% vs 13%; P < .001). In an adjusted model, successful recanalization after EVT (odds ratio [OR], 3.14 [95% CI: 1.65, 5.95]; P < .001) and larger ICV (OR, 1.03 [95% CI: 1.02, 1.04]; P < .001) were independently associated with core overestimation, while the time from symptom onset to imaging showed no association (OR, 0.99; P = .96). Core overestimation was independently associated with functional independence (adjusted OR, 2.83 [95% CI: 1.66, 4.81]; P < .001) after successful recanalization. Conclusion Ischemic core overestimation occurred more frequently in patients presenting with large CTP-derived ICV and successful vessel recanalization compared with those with unsuccessful recanalization. © RSNA, 2024 Supplemental material is available for this article.

Background: Early surrogates for functional outcome in anterior circulation stroke have been described with the National Institute of Health Stroke Scale (NIHSS) at 24 h being reported as the most accurate metric. We compare discriminatory power of established definitions of early neurological improvement (ENI) and NIHSS scores at admission and 24 h to predict functional outcome at 90 days after thrombectomy in posterior circulation stroke (PCS)., Methods: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with PCS and at least vertebral or basilar artery occlusions were included. NIHSS admission, 24 h and ENI definitions (improvement of 8/10 NIHSS points or 0/1 NIHSS points at 24 h) were compared for predicting functional outcome at 90 days. Favourable and good outcome were defined as modified Rankin Scale (mRS) 0-2 and 0-3. Multivariable logistic regression analysis was conducted to identify factors impairing predictive power., Results: Three hundred and eighty-seven patients were included. NIHSS 24 h had the highest discriminative power with receiver operator characteristics area under the curve of 0.87 (95% confidence interval: 0.83; 0.90) for good and 0.89 (0.85; 0.92) for favourable outcome; optimal cut-off values were ≤9 and ≤5. Higher age (odds ratio = 1.10 [1.05; 1.16]), adverse events during treatment (9.46 [1.52; 72.5]) and until discharge (18.34 [2.33; 172]) and high NIHSS scores at 24 h (1.29 [1.10; 1.53]) were independent predictors for turning the outcome prognosis from good (mRS ≤3) to poor (mRS ≥4)., Conclusions: NIHSS 24 h ≤9 points serves best as surrogate for good functional outcome after thrombectomy in PCS. Advanced age, severe neurological symptoms at admission and adverse events decrease its predictive value., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European 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 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.

Importance: Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse., Objective: To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice., Design, Setting, and Participants: This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching., Interventions: Mechanical thrombectomy or standard medical treatment with or without IVT., Main Outcomes and Measures: Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up., Results: Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P = .06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P = .04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P = .005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort., Conclusions and Relevance: This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.

Background: Substantial clinical evidence supporting the benefit of mechanical thrombectomy (MT) for distal occlusions within the posterior circulation is still missing. This study aims to investigate the procedural feasibility and safety of MT for isolated occlusions of the posterior cerebral artery., Methods: We retrospectively reviewed patients from three stroke centers with acute ischemic stroke attributed to isolated posterior cerebral artery occlusion (IPCAOs) who underwent MT between January 2014 and December 2019. Procedural and safety assessment included successful recanalization rates (defined as Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b), number of MT attempts and first-pass effect (TICI 3), intracranial hemorrhage (ICH), mortality, and intervention-related serious adverse events. Treatment effects were evaluated by the rate of early neurological improvement (ENI) and early functional outcome was assessed with the modified Rankin Scale (mRS) at discharge. A systematic literature review was conducted to identify and summarize previous reports on MT for IPCAOs., Results: Forty-three patients with IPCAOs located in the P1 (55.8%, 24/43), P2 (37.2%, 16/43), and P3 segment (7%, 3/43) were analyzed. The overall rate of successful recanalization (TICI ≥2b) was 86% (37/43), including a first pass-effect of 48.8% (21/43) leading to TICI 3. sICH occurred in 7% (3/43) and there were two cases with iatrogenic vessel dissection and one perforation. ENI was observed in 59% (23/39) and excellent functional outcome (mRS ≤1) in 46.2% (18/39) of patients who were discharged. The in-hospital mortality rate was 9.3% (4/43)., Conclusion: Our study suggests the technical feasibility and safety of thrombectomy for IPCAOs. Further studies are needed to investigate safety and long-term functional outcomes with posterior circulation stroke-adjusted outcome assessment., Competing Interests: Competing interests: JF: Consultant for Acandis, Boehringer Ingelheim, Codman, Microvention, Sequent, Stryker. Speaker for Bayer Healthcare, Bracco, Covidien/ev3, Penumbra, Philips, Siemens. Grants from Bundesministeriums für Wirtschaft und Energie (BMWi), Bundesministerium für Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), European Union (EU), Covidien, Stryker (THRILL study), Microvention (ERASER study), Philips. PP: Consultant for Penumbra. RC: Consultant and/or proctor for BALT, Stryker, Microvention, Rapid Medical, Siemens Medical Systems. CPS: Consultant and/or proctor for Acandis, Balt, and Rapid Medical., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

The effect of age on lesion pathophysiology in the context of thrombectomy has been poorly investigated. We aimed to investigate the impact of age on ischemic lesion water homeostasis measured with net water uptake (NWU) within a multicenter cohort of patients receiving thrombectomy for anterior circulation large vessel occlusion (LVO) stroke. Lesion-NWU was quantified in multimodal CT on admission and 24 h for calculating Δ-NWU as their difference. The impact of age and procedural parameters on Δ-NWU was analyzed. Multivariable regression analysis was performed to identify significant predictors for Δ-NWU. Two hundred and four patients with anterior circulation stroke were included in the retrospective analysis. Comparison of younger and elderly patients showed no significant differences in NWU on admission but significantly higher Δ-NWU ( p  = 0.005) on follow-up CT in younger patients. In multivariable regression analysis, higher age was independently associated with lowered Δ-NWU (95% confidence interval: -0.59 to -0.16, p  < 0.001). Although successful recanalization (TICI ≥ 2b) significantly reduced Δ-NWU progression by 6.4% ( p  < 0.001), younger age was still independently associated with higher Δ-NWU ( p  < 0.001). Younger age is significantly associated with increased brain edema formation after thrombectomy for LVO stroke. Younger patients might be particularly receptive targets for future adjuvant neuroprotective drugs that influence ischemic edema formation.

Objective: To analyze outcome and its predictors after endovascular treatment (ET) in stroke patients suffering from large vessel occlusion with large pre-treatment infarct cores defined by an Alberta Stroke Program Early CT Score (ASPECTS) <6., Methods: We analyzed data from an industry-independent, multicenter, prospective registry (German Stroke Registry - Endovascular Treatment) which enrolled consecutive patients treated by ET (June 2015-April 2018) with different devices. Multivariate logistic regression analyses identified predictors of independent outcome (IO) defined as a modified Rankin Scale (mRS) 0-2, and mortality at 90 days in patients with ASPECTS <6., Results: Of 1700 patients included in the analysis, 152 (8.9%) had a baseline ASPECTS <6. Of these, 33 patients (21.6%) achieved IO, and 68 (44.7%) were dead at 90 days. A lower age, lower baseline National Institutes of Health Stroke Scale (NIHSS) score, and successful recanalization (defined as modified Thrombolysis in Cerebral Infarction Score, mTICI 2b/3) were predictors of IO. Successful recanalization had the strongest association with IO (OR 7.0, 95% CI 1.8 to 26.8). Pre-treatment parameters predicting IO were age <70 years (sensitivity 0.79, specificity 0.69) and NIHSS <12 (0.57 and 0.94). A higher age, a pre-stroke mRS score >1, and failed recanalization were predictors of death., Conclusions: A substantial proportion of stroke patients with an ASPECTS <6 can achieve independence after thrombectomy, in particular, if they are younger, have only moderate baseline stroke symptoms, and no relevant pre-stroke disability. These results may encourage considering thrombectomy in low ASPECTS patients in clinical practice until randomized trials are available., Competing Interests: Competing interests: AA reports honoraria as speaker from Bayer Vital. JF receives research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; and serves as a consultant for Acandis, Boehringer Ingelheim, Cerenovus, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical. CG serves on scientific advisory boards for Bayer Vital, Boehringer Ingelheim, ActicorBiotech, Amgen, and Prediction Biosciences; has received funding for travel and/or speaker/ consulting honoraria from Bayer Vital, Boehringer Ingelheim, Sanofi Aventis, Amgen, EBS Technologies, GlaxoSmithKline, Lundbeck, Pfizer, Silk Road Medical, and UCB, and Abbott; serves on editorial boards for INFO Neurologie & Psychiatrie and Aktuelle Neurologie and as editor of the textbook Therapie und Verlauf neurologischer Erkrankungen; has received grants to supporting employees/ scientists of his clinic from Merz Pharmaceuticals, Allergan, Novartis, and NeuroConn; and receives research support from Deutsche Forschungsgesellschaft, the European Union, Wegener Foundation, Schilling Foundation, and Werner-Otto- Foundation. GT has received personal fees as consultant or lecturer from Acandis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daichi Sankyo, Stryker, and research grants from Bayer, Federal Ministry for Economic Affairs and Energy (BMWi), Corona-Foundation, German Research Foundation (DFG), Else Kröner-Fresenius Foundation, European Union (Horizon 2020), German Innovation Fund., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine., Methods: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively., Results: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC) NIHSS 24 hours area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROC NIHSS 24 hours AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC % change AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROC Δ change AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROC Adm AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days., Conclusion: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value., Competing Interests: Competing interests: JF: Research support from the German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions-/Förderbank (IFB), Medtronic, Microvention, Philips, Stryker; consultancy appointments; Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical; stock holdings for Tegus. GT: Consultant for Acandis, Bayer Healthcare, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Covidien, Glaxo Smith Kline; lead investigator of the WAKE-UP study; principal investigator of the THRILL study; Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2).GT: reports receiving consulting fees from Acandis, grant support and lecture fees from Bayer, lecture fees from Boehringer Ingelheim, BristolMyersSquibb/Pfizer, and DaiichiSankyo, and consulting fees and lecture fees from Portola and Stryker., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Asymptomatic intracerebral hemorrhage (aICH) is a common phenomenon in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (ET). However, the impact of aICH on the functional outcome remains widely unclear. In this study, we aimed at identifying predictors for aICH and analyzing its impact on functional outcome. Patients with AIS due to large artery occlusion in the anterior circulation treated with successful ET were enrolled in a tertiary stroke center. Patients with aICH or without intracerebral hemorrhage were included according to post-treatment CT performed within 72 h; 100 consecutive patients fulfilled the inclusion criteria and 30% classified with aICH. In logistic regression analysis, lower collateral score (OR 0.24; 95% CI 0.12-0.46, p  < 0.0001) was significantly associated with aICH. Less patients with aICH achieved an independent outcome (mRS 0-2, 16.7% vs. 44.3%, p  = 0.007). Poor outcome (mRS 4-6) was significantly higher in patients with aICH (41.4% vs. 70%, p  = 0.021). Patients with aICH had a lower ratio of independent outcome (OR 0.23, 95% CI 0.05-0.1.05, p  = 0.041) than without ICH. There were no differences concerning poor outcome ( p  = 0.5). Lower collateral status was a strong independent predictor for aICH. aICH after successful ET may decrease the likelihood of an independent functional outcome without influencing poor outcome.

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.

Importance: Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown., Objective: To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke., Design, Setting, and Participants: This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization. Median follow-up time was 16 months., Exposures: Endovascular recanalization., Main Outcomes and Measures: The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications., Results: Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40)., Conclusions and Relevance: The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians' practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.

Background and Purpose: Mechanical thrombectomy for acute ischemic stroke is performed with the patient under local anesthesia, conscious sedation, or general anesthesia. According to recent trials, up to 16% of patients require emergency conversion to general anesthesia during mechanical thrombectomy. This study investigated the procedural and clinical outcomes after emergency conversion in comparison with local anesthesia, conscious sedation, and general anesthesia., Materials and Methods: This retrospective study included 254 patients undergoing mechanical thrombectomy for acute large-vessel occlusion. The procedure was started with the patient either under local anesthesia, conscious sedation, or general anesthesia. Emergency conversion was defined as induction of general anesthesia during mechanical thrombectomy. The primary outcomes were successful reperfusion (TICI 2b/3) and functional independence (mRS at 90 days, ≤2)., Results: Twenty-five patients (9.8%) required emergency conversion to general anesthesia. The time from admission to flow restoration was increased under general anesthesia (median, 137 minutes) and emergency conversion (median, 138 minutes) compared with local anesthesia (median 110 minutes). After adjustment for confounders, emergency conversion to general anesthesia and primary general anesthesia had comparable chances of successful reperfusion (OR = 1.28; 95% CI, 0.31-5.25). Patients with emergency conversion had a tendency toward higher chances of functional independence (OR = 4.48; 95% CI, 0.49-40.86) compared with primary general anesthesia, but not compared with local anesthesia (OR = 0.86; 95% CI, 0.14-5.11) and conscious sedation (OR = 1.07; 95% CI, 0.17-6.53)., Conclusions: Patients with emergency conversion did not have lower chances of successful reperfusion or functional independence compared those with primary general anesthesia, and time to flow restoration was also similar. We found no evidence supporting the primary induction of general anesthesia in patients at risk for emergency conversion., (© 2020 by American Journal of Neuroradiology.)

The impact of endovascular vessel recanalization on patients with a low initial Alberta Stroke Program Early Computer Tomography Score (ASPECTS) is still uncertain. We hypothesized that vessel recanalization leads to an improvement in mortality and degree of disability by reducing brain oedema and malignant mass effect. In this multicentre observational study, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and an ASPECTS of ≤ 5 were analysed. Patients were assembled into two groups: successful vessel recanalization (thrombolysis in cerebral infarctions, TICI scale 2b/3) or persistent vessel occlusion (no endovascular procedure or TICI scale 0-2a). Observers were blinded to clinical data. Net water uptake within brain infarct, a quantitative biomarker based on CT densitometry, was used to quantify oedema in admission and follow-up CT and Δ-water uptake was calculated as difference between water uptake at both time points. Occurrence of malignant infarctions and secondary parenchymal haemorrhage was documented. Furthermore, modified Rankin scale score at 90 days was used for functional outcome. We included 117 patients admitted between March 2015 and August 2017 in three German stroke centres: 71 with persistent vessel occlusion and 46 with successful recanalization. The mean water uptake in the admission imaging was not different between both groups: 10.0% (±4.8) in patients with persistent vessel occlusion and 9.0% (±4.8) in patients with vessel recanalization (P = 0.4). After follow-up CT, the mean Δ-water uptake was 16.0% (±7.5) in patients with persistent vessel occlusion and 8.0% (±5.7) in patients with vessel recanalization (P < 0.001). Successful reperfusion was independently associated with a lowered Δ-water uptake of 8.0% (95% confidence interval, CI: -10.5 to -5.3%; P < 0.001) and lowered modifed Rankin scale score after 90 days of 1.5 (95% CI: -2.2 to -0.8; P < 0.001). The prevalence of malignant infarctions was 44.3% in patients with persistent vessel occlusion and 26.1% in patients with vessel recanalization. There was no significant difference for secondary haemorrhage in both groups (P = 0.7). In conclusion, successful recanalization in patients with low initial ASPECTS resulted in a significant reduction of oedema formation and was associated with a decreased prevalence of malignant infarctions and an improvement of clinical outcome., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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.

Background and purpose: It is currently unknown whether mechanical thrombectomy (MT) for ischaemic stroke patients with low initial Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is clinically beneficial or even harmful. The purpose of this study was to investigate whether failed or incomplete MT in acute large vessel occlusion stroke with an initial ASPECTS ≤ 5 is associated with worse clinical outcome compared to patients not undergoing MT. Methods: This observational cohort study included a consecutive sample of patients with anterior circulation stroke and initial ASPECTS ≤ 5 admitted between March 2015 and August 2019. Failed recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) score 0–2a, and incomplete recanalization as TICI 2b. Clinical outcome was assessed using the modified Rankin Scale (mRS) at 90 days defining very poor clinical outcome as mRS > 4. Results: One hundred and seventy patients were included. Ninety‐nine patients underwent MT and 71 patients received best medical treatment only. Clinical outcome after failed or incomplete MT (TICI 0–2b) was significantly better compared to patients with medical treatment only (median mRS 5, interquartile range 4–6 vs 5–6, P = 0.03). In multivariable logistic regression analysis, failed or incomplete MT (TICI 0–2b) showed a significantly reduced likelihood for very poor outcome (odds ratio 0.39, 95% confidence interval 0.19–0.83, P = 0.01). Failed MT (TICI 0–2a) was not associated with a worse outcome compared to best medical treatment. Conclusions: Patients with failed or incomplete recanalization results (TICI 0–2b) showed a reduced likelihood for very poor outcome compared with those who did not receive MT. Evidence from randomized trials is needed to confirm that even failed or incomplete MT is not harmful in these patients. [ABSTRACT FROM AUTHOR]