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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.

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 Aim: To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO)., Methods: We performed a prospective analysis of patients with intracranial LVO who underwent successful MT and received a 1.5 T MRI including diffusion-weighted imaging (DWI) in standard- and high-resolution as well as susceptibility-weighted imaging (SWI) on the day following the intervention. Reperfusion grade was assessed on post-thrombectomy digital subtraction angiography (DSA) using the expanded thrombolysis in cerebral infarction (eTICI) scale. Punctuate DWI lesions distal to the DWI core lesion were classified as peripheral emboli. DWI lesions outside the primary affected vascular territory were classified as emboli into new territories. Additionally, SWI and post-thrombectomy DSA were analyzed and correlated to findings on DWI., Results: Twenty-eight patients undergoing successful MT met the inclusion criteria. In 26/28 patients (93%), a total of 324 embolic lesions were detected in DWI representing 2.1% of the cumulated ischemic core volume. 151 peripheral emboli were detected in standard-resolution DWI, 173 additional emboli were uncovered in high-resolution DWI. Eight out of nine patients with an eTICI 3 reperfusion had embolic lesions (29 DWI lesions). 9.6% (31/324) of peripheral emboli were observed in vascular territories not affected by the LVO. SWI lesions were observed in close proximity to 10.2% (33/324) of DWI lesions., Conclusions: Peripheral emboli are frequent after MT even after complete reperfusion. These emboli occur rather in the vascular territory of the occluded vessel than in other territories. A large proportion of peripheral emboli is only detected by high-resolution DWI.

Studies evaluating the effect of reperfusion on ischemic edema in acute stroke described conflicting results. Net water uptake (NWU) per brain volume is a new quantitative imaging biomarker of space-occupying ischemic edema, which can be measured in computed tomography (CT). We sought to investigate the effects of vessel recanalization on the formation of ischemic brain edema using quantitative NWU. In this multicenter observational study, acute ischemic stroke patients with a large vessel occlusion (LVO) in the anterior circulation were consecutively screened. Patients with vessel recanalization (thrombolysis in cerebral infarction (TICI) 2 b or 3) versus persistent vessel occlusion (no thrombectomy, TICI 0-1) were compared. Lesion-NWU was quantified in multimodal admission CT and follow-up CT (FCT), and ΔNWU was calculated as difference. Of 194 included patients, 150 had successful endovascular recanalization and 44 persistent LVO. In FCT after treatment, the mean (standard deviation) ΔNWU was 15.8% (5.7) in patients with persistent LVO and 9.8% (5.8) with vessel recanalization ( p  < 0.001). In multivariate regression analysis, vessel recanalization was independently associated with a lowered ΔNWU by 6.3% compared to LVO (95% confidence interval: 3.7-9.0, p  < 0.001). Successful vessel recanalization was associated with a significantly reduced formation of ischemic brain edema. Quantitative NWU may be used to compare the treatment effects in acute stroke.

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]