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Background and purpose: Intravenous (IV) lysis with alteplase is known to increase biomarkers of blood–brain barrier breakdown and has therefore been associated with secondary injuries such as hemorrhagic transformation. The impact of alteplase on brain edema formation, however, has not been investigated yet. The purpose was to examine the effects of IV alteplase on ischaemic lesion water homeostasis differentiated from final tissue infarct in patients with and without successful endovascular therapy (sET). Methods: In all, 232 middle cerebral artery stroke patients were analyzed. 147 patients received IV alteplase, of whom 106 patients received subsequent sET. Out of 85 patients without IV alteplase, 50 received sET. Ischaemic brain edema was quantified at admission and follow‐up computed tomography using quantitative lesion net water uptake (NWU) and its difference was calculated (ΔNWU). The relationship of alteplase on ΔNWU and edema‐corrected final infarct volume was analyzed using univariate and multivariate linear regression models. Results: The mean ΔNWU was 11.8% (SD 7.9) in patients with alteplase and 11.5% (SD 8.3) in patients without alteplase (P = 0.8). Alteplase was not associated with lowered ΔNWU whilst being associated with reduced edema‐corrected tissue infarct volume [−27.4 ml, 95% confidence interval (CI) −49.4 to −5.4 ml; P = 0.02], adjusted for the Alberta Stroke Program Early Computed Tomography Score and recanalization status. In patients with sET, ΔNWU was 10.5% (95% CI 6.3%–10.5%) for patients with IV alteplase and 8.4% (95% CI 9.1%–12.0%) for patients without IV alteplase. Conclusion: The application of IV alteplase did not significantly alter ischaemic lesion water homeostasis but was associated with reduced edema‐corrected tissue infarct volume, which might be directly linked to improved functional outcome. [ABSTRACT FROM AUTHOR]

Background: A sizeable proportion of stroke patients with large vessel occlusion present with minor neurological deficits. Whether mechanical thrombectomy (MT) is beneficial in these patients is controversial. We aimed to investigate factors of early neurological deterioration (END) in thrombectomy patients with minor stroke and hypothesized that END is linked to unfavorable functional outcomes., Methods: Multicenter cohort study screening all patients prospectively enrolled in the German Stroke Registry-Endovascular Treatment (n=13 082) between 2015 and 2021. Patients who underwent MT for anterior circulation vessel occlusion with baseline National Institutes of Health Stroke Scale (NIHSS) score of <6 were included. END was defined as an increase in NIHSS score of ≥4 within the first 24 hours after MT. Multivariable regression analyses were performed to investigate factors associated with END and its association with unfavorable functional outcomes 90 days after treatment (modified Rankin Scale (mRS) score ≥2)., Results: Among 817 patients included, 24% exhibited END and 48% had unfavorable functional outcomes. Prestroke mRS (adjusted odds ratio (aOR) [95% CI] 1.42 [1.13 to 1.78]), baseline NIHSS (aOR [95% CI] 0.83 [0.73 to 0.94]), time from admission to groin puncture (aOR [95% CI] 1.04 [1.02 to 1.07]), general anesthesia (aOR [95% CI] 1.68 [1.08 to 2.63]), number of passes (aOR [95% CI] 1.15 [1.03 to 1.29]), adverse events during treatment (aOR [95% CI] 1.89 [1.19 to 3.01]), successful recanalization (aOR [95% CI] 0.29 [0.17 to 0.50]), and intracranial hemorrhage on follow-up imaging (aOR [95% CI] 3.40 [1.90 to 6.07]) were independently associated with END. END was independently linked to unfavorable functional outcomes (aOR [95% CI] 7.51 [4.57 to 12.34])., Conclusions: Almost a quarter of thrombectomy patients with minor stroke developed END. These patients had twice the odds of experiencing unfavorable functional outcomes., Competing Interests: Competing interests: FF reported receiving personal fees from Eppdata GmbH outside the submitted work. HK reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. GB reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. CT reported receiving personal fees from Eppdata GmbH outside the submitted work. GT reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. JF reported an ownership stake in Eppdata GmbH and grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox, and grants from Route 92 outside the submitted work. TDF reported grants from the German Research Foundation (DFG) (Project Number: 411621970) and personal fees from Eppdata GmbH outside the submitted work., (© 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: Successful recanalization defined as modified Thrombolysis in Cerebral Infarction Score (mTICI) ≥2b is not achieved in 15%-20% of patients with acute ischemic stroke. This study aims to identify patient-specific factors associated with early stopping without successful recanalization. We hypothesized that the probability of the decision for early stopping during mechanical thrombectomy (MT) is higher in patients with an unfavorable prognosis., Methods: All patients enrolled in the German Stroke Registry (GSR) between June 2015 and December 2021 were screened. Inclusion criteria were stroke in the anterior circulation and availability of relevant clinical data. For each retrieval attempt 1-3, patients with stopping and failed reperfusion (mTICI <2b) were compared with all patients with continued retrieval attempts using descriptive statistics and multivariable logistic regression., Results: Our study included 2977 patients, 350 (12%) of which had early stopping. Higher pre-stroke Modified Rankin Scale (mRS) score (adjusted odds ratio (aOR) =1.20 (95% confidence interval (CI): 1.09; 1.32), P<0.001), higher age (aOR=1.01 (1.00; 1.02), P=0.017) and distal occlusions (aOR=1.93 (1.50; 2.47), P<0.001) as well as intraprocedural dissections/perforations (aOR=4.61 (2.95; 7.20), P<0.001) and extravasation (aOR=2.43 (1.55;3.82), P<0.001) were associated with early stopping. In patients with unsuccessful recanalization (n=622), the number of retrieval attempts (aOR=1.05 (0.94; 1.18), p=0.405) was not associated with unfavorable outcomes (90d-mRS>3)., Conclusion: The probability of early stopping was higher in patients with clinical conditions associated with: a) Favorable prognosis and assumed lower impact of recanalization success on functional status, such as distal occlusions; and b) Unfavorable prognosis, such as higher age and reduced pre-stroke functional status. Adverse events during the procedure increased the probability of early stopping. The number of recanalization attempts did not increase the risk of unfavorable outcome for patients with persistent occlusion, supporting the decision for continuation of retrieval attempts., Competing Interests: Competing interests: HK and FF are consultants for Eppdata GmbH. HK is shareholder of Eppdata GmbH. GT received consultancy fees 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. JF is consultant for Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche and Tonbridge. He serves on the advisory board of Stryker and Phenox. He is a stock holder of Tegus Medical, Eppdata and Vastrax. He serves as Associate Editor at JNIS., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Symptomatic acute occlusions of the internal carotid artery (ICA) below the circle of Willis can cause a variety of stroke symptoms, even if the major intracranial cerebral arteries remain patent; however, outcome and safety data are limited. Purpose To compare treatment effects and procedural safety of endovascular treatment (EVT) and best medical treatment (BMT) in patients with symptomatic acute occlusions of the ICA below the circle of Willis. Materials and Methods This retrospective, multicenter cohort study from 22 comprehensive stroke centers in Europe and Asia includes patients treated between January 1, 2008, and December 31, 2022. Functional (modified Rankin Scale [mRS]) and clinical (National Institutes of Health Stroke Scale [NIHSS]) outcomes, safety measures (symptomatic intracerebral hemorrhage), mortality, and procedural complications were assessed. Results A total 354 patients met the inclusion criteria (median age, 72 years [IQR, 60-81 years]; median NIHSS, 13 [IQR, 7-19]). Most frequent occlusions were in the C1 segment (243 of 354; 68.6%). Of 354 patients, 82.2% (291 patients) were administered EVT. In the overall population, favorable outcomes (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage occurred in 40.6% (108 of 266 patients), 25.2% (67 of 266 patients), and 7.1% (25 of 350 patients), respectively. After adjustment, no statistically significant difference in functional outcome was observed (adjusted odds ratio [AOR], 0.82 [95% CI: 0.31, 2.12]; average treatment effect, -12.7%; P = .19) in the EVT compared with BMT group. Symptomatic intracerebral hemorrhage (average treatment effect, -0.28%; P = .95) and mortality did not differ between both groups (average treatment effect, -17.1%; P = .07). EVT resulted in complete recanalization of the occlusion in 80.9% (229 of 283) of cases. Periprocedural distal embolization occurred in 27.8% (81 of 291 patients) and was associated with poor outcomes (AOR, 0.41; 95% CI: 0.18, 0.93; P = .03). Conclusion EVT did not reveal a favorable treatment effect over BMT, and both therapies were safe. EVT had a risk for periprocedural distal embolization associated with poor outcomes. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Daou and Chaudhary in this issue.

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: There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale (NIHSS) <6). Prior studies of patients with admission NIHSS scores ≥ 6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases., Aim: The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors., Methods: Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n = 13,082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) scores of 2b-3). FR was defined by modified Rankin Scale (mRS) scores of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR., Results: A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio (aOR) = 1.04 (95% confidence interval (CI) = 1.02-1.06)), pre-stroke mRS 1 (aOR = 2.70 (95% CI = 1.51-4.84)), transfer from admission hospital to comprehensive stroke center (aOR = 1.67 (95% CI = 1.08-2.56)), longer time from symptom onset/last seen well to admission (aOR = 1.02 (95% CI = 1.00-1.04)), MT under general anesthesia (aOR = 1.78 (95% CI = 1.13-2.82)), higher NIHSS after 24 h (aOR = 1.09 (95% CI = 1.05-1.14)), and symptomatic intracranial hemorrhage (aOR = 16.88 (95% CI = 2.03-140.14)) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI score of 2b or 3., Conclusions: Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke., Data Accessibility Statement: The data that support the findings of our study are available on reasonable request after approval of the German Stroke Registry (GSR) steering 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: The authors declared the following potential conflicts of interest: F.F. reported receiving personal fees from Eppdata GmbH outside the submitted work. H.C.K. reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. G.B. reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. C.T. reported receiving personal fees from Eppdata GmbH outside the submitted work. J.J.H. reported consulting for Medtronic and MicroVention and Medical and Scientific Advisory Board membership for iSchemaView. G.W.A. reported equity and consulting for iSchemaView and consulting from Medtronic. G.T. reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. J.F. reported an ownership stake in Eppdata GmbH and grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, and Phenox and grants from Route 92 outside the submitted work. T.D.F. reported grants from the German Research Foundation (DFG) (project no. 411621970) and personal fees from Eppdata GmbH outside the submitted work. A.H., L.W., M.S., and C.H. reported no disclosure.

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.)

Overweight/obese patients experience a lower incidence of subarachnoid hemorrhage (SAH) compared to non-overweight patients, even though elevated body mass index (BMI) has been associated with various SAH risk factors. Given that intracranial aneurysms are a primary cause of SAH, a potential protective effect of a high BMI on intracranial aneurysms is likely but remains insufficiently investigated. This population-based MRI study aims to conduct detailed analyses on risk factors associated with the incidence of unruptured intracranial aneurysms (UIA). Retrospective analysis of subjects enrolled in the prospective Hamburg City Health study who underwent intracranial magnetic resonance imaging (MRI) was done. MRI scans were screened for UIA using time-of-flight angiography. Subject data including medical history, laboratory examinations, and risk factors for UIA were collected, and a multivariable logistic regression model was used to investigate the relationship between risk factors and UIA incidence. 2688 subjects (mean (IQR) age, 65 (58-71); 1176 female (43.8%) were included. An UIA was detected in 214 subjects with an incidence of 10.6% (6.0%) in females (males). Determinants for UIA were female sex (OR 2.00, 95%CI 1.45-2.77, p < 0.001), hypertension (OR 1.48, 95%CI 1.08-2.04, p = 0.015), smoking (OR 1.41, 95%CI 1.03-1.95, p = 0.036), and BMI (OR 0.95, 95%CI 0.91-0.98, p = 0.004). Among subjects with UIA, 9.4% with a BMI > 25 had multiple aneurysms, compared to 21.6% with BMI ≤ 25 (p = 0.012). This study suggests that a high BMI exhibits a protective effect on UIA incidence and the development of multiple aneurysms. Additionally, the data confirms established risk factors for UIA development, such as female sex, hypertension, and smoking., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Landmark thrombectomy trials have provided evidence that selected patients with large ischemic stroke benefit from successful endovascular therapy, commonly defined as incomplete (modified Thrombolysis In Cerebral Infarction (mTICI) 2b) or complete reperfusion (mTICI 3). We aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in large ischemic strokes., Methods: This retrospective multicenter cohort study was conducted to compare mTICI 2b versus mTICI 3 in large ischemic strokes in the anterior circulation. Patients enrolled in the German Stroke Registry between 2015-2021 were analyzed. Large ischemic stroke was defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. Patients were matched by final mTICI grade using propensity score matching. Primary outcome was the 90-day modified Rankin Scale (mRS) score., Results: After matching, 226 patients were included. Baseline and imaging characteristics were balanced between mTICI 2b and mTICI 3 patients. There was no shift on the mRS favoring mTICI 3 compared with mTICI 2b in large ischemic strokes (adjusted common odds ratio (acOR) 1.12, 95% confidence interval (95% CI) 0.64 to 1.94, P=0.70). The rate of symptomatic intracranial hemorrhage was higher in mTICI 2b than in mTICI 3 patients (12.6% vs 4.5%, P=0.03). Mortality at 90 days did not differ between mTICI 3 and mTICI 2b (33.6% vs 37.2%; adjusted OR 0.69, 95% CI 0.33 to 1.45, P=0.33)., Conclusions: In endovascular therapy for large ischemic strokes, mTICI 3 was not associated with better 90-day functional outcomes compared with mTICI 2b. This study suggests that mTICI 2b might be warranted as the final angiographic result, questioning the benefit/risk ratio of additional maneuvers to seek for mTICI 3 in large ischemic strokes., Trial Registration Number: NCT03356392., Competing Interests: Competing interests: TDF reported grants from the German Research Foundation (DFG; Project Number: 411621970). GB reported receiving personal fees from Eppdata GmbH and compensation as a speaker from Balt outside the submitted work. HK reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. GH reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. JF reported compensation from Acandis, Cerenovus, MicroVention, Medtronic, Penumbra, Phenox, Roche, Stryker, Tonbridge and stock holdings in Eppdata GmbH and Tegus Medical outside the submitted work. FF reported receiving personal fees from Eppdata GmbH outside the submitted work., (© 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: Recent advances have highlighted the efficacy of endovascular thrombectomy (EVT) in patients with large ischemic core stroke, yet a significant portion still experience very poor outcomes, defined as a 90-day modified Rankin Score (mRS) of 5-6. This study aims to investigate the hypoperfusion intensity ratio (HIR) as a prognostic imaging parameter for these outcomes., Methods: In a multicenter retrospective cohort study, data from consecutive patients undergoing EVT for acute ischemic stroke with large vessel occlusion (AIS-LVO) at two comprehensive stroke centers were analyzed. The study included patients with an Alberta Stroke Program Early CT Score (ASPECTS) of 5 or less and utilized pretreatment perfusion imaging to calculate HIR. The primary outcome was very poor outcomes (90 days mRS 5-6)., Results: Among 102 patients included, 59 (57.8%) had very poor outcome (90 days mRS 5-6). Multivariable logistic regression analysis adjusting for multiple covariates including admission National Institutes of Health Stroke Scale (NIHSS) and EVT revealed that higher admission NIHSS (adjusted odds ratio [aOR] 1.224, 95% CI 1.089-1.374, p = 0.001) and HIR (aOR per 0.1 incremental change, 1.34, 95% CI 1.02-1.82, P = 0.042) were independently associated with very poor outcomes., Conclusion: This study demonstrates that admission NIHSS and HIR are independently associated with very poor outcome (90 days mRS 5-6) in patients with large ischemic core strokes. These findings highlight the importance of collateral status and perfusion imaging in predicting outcomes in this patient population, suggesting a potential role for HIR in the triage and management of large core stroke patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: Ischemic edema is associated with worse clinical outcomes, especially in large infarcts. Computed tomography (CT)-based densitometry allows direct quantification of absolute edema volume (EV), which challenges indirect biomarkers like midline shift (MLS). We compared EV and MLS as imaging biomarkers of ischemic edema and predictors of malignant infarction (MI) and very poor clinical outcome (VPCO) in early follow-up CT of patients with large infarcts., Materials and Methods: Patients with anterior circulation stroke, large vessel occlusion, and Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5 were included. VPCO was defined as modified Rankin scale (mRS) ≥ 5 at discharge. MLS and EV were quantified at admission and in follow-up CT 24 h after admission. Correlation was analyzed between MLS, EV, and total infarct volume (TIV). Multivariable logistic regression and receiver operating characteristics curve analyses were performed to compare MLS and EV as predictors of MI and VPCO., Results: Seventy patients (median TIV 110 mL) were analyzed. EV showed strong correlation to TIV (r = 0.91, p < 0.001) and good diagnostic accuracy to classify MI (EV AUC 0.74 [95%CI 0.61-0.88] vs. MLS AUC 0.82 [95%CI 0.71-0.94]; p = 0.48) and VPCO (EV AUC 0.72 [95%CI 0.60-0.84] vs. MLS AUC 0.69 [95%CI 0.57-0.81]; p = 0.5) with no significant difference compared to MLS, which did not correlate with TIV < 110 mL (r = 0.17, p = 0.33)., Conclusion: EV might serve as an imaging biomarker of ischemic edema in future studies, as it is applicable to infarcts of all volumes and predicts MI and VPCO in patients with large infarcts with the same accuracy as MLS., Clinical Relevance Statement: Utilization of edema volume instead of midline shift as an edema parameter would allow differentiation of patients with large and small infarcts based on the extent of edema, with possible advantages in the prediction of treatment effects, complications, and outcome., Key Points: • CT densitometry-based absolute edema volume challenges midline shift as current gold standard measure of ischemic edema. • Edema volume predicts malignant infarction and poor clinical outcome in patients with large infarcts with similar accuracy compared to MLS irrespective of the lesion extent. • Edema volume might serve as a reliable quantitative imaging biomarker of ischemic edema in acute stroke triage independent of lesion size., (© 2024. The Author(s).)

Introduction: Managing blood pressure in patients with large vessel occlusion affects infarct size and clinical outcomes. We examined how restoring blood flow impacts systemic blood pressure during mechanical thrombectomy., Patients and Methods: Patients with large vessel occlusion in the anterior circulation undergoing mechanical thrombectomy between June 2016 and January 2018 were screened. We included those treated under local anesthesia or conscious sedation and analyzed standardized anesthesia protocols to assess systolic and diastolic blood pressure levels throughout the procedure. The primary outcome was the change of blood pressure, compared 5 min before versus 5 min after the last recanalization attempt. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction score ⩾ 2b., Results: Of 134 patients, 117 (87%) achieved successful angiographic reperfusion, showing a notable systolic blood pressure drop 5 min after flow restoration (10.2 ± 14.6 vs 3.24 ± 8.65 mm Hg, p  = 0.009). Successful angiographic reperfusion was a significant predictor for this decrease in multivariable logistic regression: OR = 1.34 (95% CI: 1.03-1.73, p  = 0.0299). Among 66 patients not given circulation-affecting meds, a significant systolic pressure reduction was also observed (155 ± 17 mm Hg to 148 ± 17 mm Hg ; p  < 0.001). No diastolic pressure changes were significant., Discussion and Conclusions: Flow restoration was associated with an immediate reduction of systolic blood pressure values in patients undergoing mechanical recanalization under local anesthesia or conscious sedation. This suggests a complex interplay between endovascular stroke therapy and cardiovascular hemodynamics., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AAK: The corresponding author reports no disclosures.CB: The Co-author reports no disclosures.LM: The Co-author reports no disclosures.HG: The Co-author reports no disclosures.GB: The Co-author reports no disclosures.SK: The Co-author reports no disclosures.TF: The Co-author reports no disclosures.CH: The Co-author reports no disclosures.MI: The Co-author reports no disclosures.JF: The Co-author reports personal fees from Consultant for Microvention, Stryker, Cerenovus, Acandis, Penumbra and Medtronic outside the submitted work. He is a member of the Executive Board of the scientific societies DGNR and ESMINT.FF: The Co-author reports no disclosures.

Objectives: Medical devices based on X-ray imaging, such as computed tomography, are considered notable sources of artificial radiation. The aim of this study was to compare the computed tomography dose volume index, the dose length product, and the effective dose of the brain non-contrast enhanced examination on two CT scanners to determine the current state in terms of radiation doses, compare doses to the reference values, and possibly optimize the examination., Materials and Methods: Data from January 2020 to the second half of 2021 were retrospectively obtained by accessing dose reports from the Picture Archiving and Communication System (PACS). Data were collected and analyzed in Microsoft Excel. The effective dose was estimated using the dose-length product parameter and the normalized conversion factor for a given anatomical region. For statistical analysis, a two-sample t -test was used., Results: The first data set consists of 200 patients (100 and 100 for older and newer CT scanners) regardless of the scan technique; the average CTDI vol and DLP for the older CT scanner were 57.61 ± 2.89 mGy and 993.28 ± 146.18 mGy cm, and for the newer CT scanner, 43.66 ± 11.15 mGy and 828.14 ± 130.06 mGy cm. The second data set consists of 100 patients (50 for the older CT scanner and 50 for the newer CT scanner) for a sequential scan; the average CTDI vol and DLP for the older CT scanner were 58.63 ± 3.33 mGy and 949.42 ± 80.87 mGy.cm, and for the newer CT, 57.25 ± 3.4 mGy and 942.13 ± 73.05 mGy cm. The third data set consists of 40 patients (20 and 20 for older and newer CT scanners) for the helical scan - the average CTDI vol and DLP for the older CT scanner were 54.6 ± 0 mGy and 1252.2 ± 52.11 mGy.cm, and for the newer CT, 37.18 ± 2.52 mGy and 859.66 ± 72.04 mGy cm. The difference between the older and newer CT scanners in terms of dose reduction was approximately 30 % in favor of the newer scanner for noncontrast enhanced brain examinations performed using the helical scan technique., Conclusion: A non-contrast enhanced brain examination scanned with newer CT equipment was associated with a lower radiation burden on the patient., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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.)

Background: Hematoma volume is a major pathophysiological hallmark of acute intracerebral hemorrhage (ICH). We investigated how the variance in functional outcome induced by the ICH volume is explained by neurological deficits at admission using a mediation model., Methods: Patients with acute ICH treated in three tertiary stroke centers between January 2010 and April 2019 were retrospectively analyzed. Mediation analysis was performed to investigate the effect of ICH volume (0.8 ml (5% quantile) versus 130.6 ml (95% quantile)) on the risk of unfavorable functional outcome at discharge defined as modified Rankin Score (mRS) ≥ 3 with mediation through National Institutes of Health Stroke Scale (NIHSS) at admission. Multivariable regression was conducted to identify factors related to neurological improvement and deterioration., Results: Three hundred thirty-eight patients were analyzed. One hundred twenty-one patients (36%) achieved mRS ≤ 3 at discharge. Mediation analysis showed that NIHSS on admission explained 30% [13%; 58%] of the ICH volume-induced variance in functional outcome at smaller ICH volume levels, and 14% [4%; 46%] at larger ICH volume levels. Higher ICH volume at admission and brainstem or intraventricular location of ICH were associated with neurological deterioration, while younger age, normotension, lower ICH volumes, and lobar location of ICH were predictors for neurological improvement., Conclusion: NIHSS at admission reflects 14% of the functional outcome at discharge for larger hematoma volumes and 30% for smaller hematoma volumes. These results underscore the importance of effects not reflected in NIHSS admission for the outcome of ICH patients such as secondary brain injury and early rehabilitation., (© 2024. The Author(s).)

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P  < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging ( β estimate, 5.50, 95% CI, 3.81-7.19, P  < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location., 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: Dr Laurens WINKELMEIER reports no disclosure.Dr Jeremy J. HEIT reports consulting for Medtronic and MicroVention and Medical and Scientific Advisory Board membership for iSchemaView.Dr Gabriel BROOCKS reported receiving personal fees from Eppdata GmbH and compensation as a speaker from Balt outside the submitted work.Julia PRÜTER reports no disclosure.Dr Christian HEITKAMP reports no disclosure.Maximilian SCHELL reports no disclosure.Dr Gregory W. ALBERS reports equity and consulting for iSchemaView and consulting from Medtronic.Dr Maarten G. LANSBERG reports no disclosure.Dr Max WINTERMARK reports grants and funding from the NIH under the grant numbers (1U01 NS086872-01, 1U01 NS087748-01 and 1R01 NS104094).Dr André KEMMLING reports a research collaboration agreement with Siemens Healthcare (company involved in CT/MRI distribution).Dr Christian Paul STRACKE reports no disclosure.Dr Adrien GUENEGO reports no disclosure.Dr Daniel PAECH reports no disclosure.Dr Jens FIEHLER reports grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox and grants from Route 92 outside the submitted work.Dr Tobias D. FAIZY reports grants from the German Research Foundation (DFG) during the conduct of the study.

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: 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: Follow-up infarct volume (FIV) is used as surrogate for treatment efficiency in mechanical thrombectomy (MT). However, previous works suggest that MT-related FIV reduction has only limited association with outcome comparing MT independently of recanalization success versus medical care. It remains unclear to what extent the relationship between successful recanalization versus persistent occlusion and functional outcome is explained by FIV reduction., Objective: To determine whether FIV mediates the relationship between successful recanalization and functional outcome., Methods: All patients from our institution enrolled in the German Stroke Registry (May 2015-December 2019) with anterior circulation stroke; availability of the relevant clinical data, and follow-up-CT were analyzed. The effect of FIV reduction on functional outcome (90-day modified Rankin Scale (mRS) score ≤2) after successful recanalization (Thrombolysis in Cerebral Infarction ≥2b) was quantified using mediation analysis., Results: 429 patients were included, of whom, 309 (72 %) had successful recanalization and 127 (39%) had good functional outcome. Good outcome was associated with age (OR=0.89, P<0.001), pre-stroke mRS score (OR=0.38, P<0.001), FIV (OR=0.98, P<0.001), hypertension (OR=2.08, P<0.05), and successful recanalization (OR=3.57, P<0.01). Using linear regression in the mediator pathway, FIV was associated with Alberta Stroke program Early CT Score (coefficient (Co)=-26.13, P<0.001), admission National Institutes of Health Stroke Scale score (Co=3.69, P<0.001), age (Co=-1.18, P<0.05), and successful recanalization (Co=-85.22, P<0.001). Successful recanalization increased the probability of good outcome by 23 percentage points (pp) (95% CI 16pp to 29pp). 56% (95% CI 38% to 78%) of the improvement in good outcome was explained by FIV reduction., Conclusion: 56% (95% CI 38% to 78%) of outcome improvement after successful recanalization was explained by FIV reduction. Results corroborate pathophysiological assumptions and confirm the value of FIV as an imaging endpoint in clinical trials. 44% (95% CI 22% to 62%) of the improvement in outcome was not explained by FIV reduction and reflects the remaining mismatch between radiological and clinical outcome measures., Competing Interests: Competing interests: HK and FF are consultants for Eppdata GmbH. HK has financial interest in Eppdata GmbH. MD-C has received research grants from the Werner Otto Stiftung and serves on the advisory board of the PRECIOUS Trial. GT 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 on the board of the TEA Stroke Study and of ESO. JF is consultant for Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche, and Tonbridge. He serves on the advisory board of Stryker and Phenox. He is stock holder of Tegus Medical, Eppdata, and Vastrax. He is associate editor at JNIS., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions., Aim: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO)., Methods: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group., Results: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts ( p  < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p  = 0.02) and LVO (7.2% vs 3.5%, p  < 0.001)., Conclusion: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions., Data Access Statement: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee., Clinical Trial Registration Information: ClinicalTrials.gov Identifier: NCT03356392., 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: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.W., C.H., M.B., C.B., and M.S. reported no disclosure. T.D.F. reported grants from the German Research Foundation (DFG; Project No. 411621970). G.B. and L.M. reported receiving compensation as a speaker from Balt and personal fees from Eppdata GmbH outside the submitted work. H.K. reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. U.H. reported receiving personal fees from Eppdata GmbH outside the submitted work. G.T. reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. J.F. reported compensation from Acandis, Cerenovus, MicroVention, Medtronic, Penumbra, Phenox, Roche, Stryker, Tonbridge, and stock holdings in Eppdata GmbH and Tegus Medical outside the submitted work. F.F. reported receiving personal fees from Eppdata GmbH outside the submitted work.

Introduction: In acute ischemic stroke, prediction of the tissue outcome after reperfusion can be used to identify patients that might benefit from mechanical thrombectomy (MT). The aim of this work was to develop a deep learning model that can predict the follow-up infarct location and extent exclusively based on acute single-phase computed tomography angiography (CTA) datasets. In comparison to CT perfusion (CTP), CTA imaging is more widely available, less prone to artifacts, and the established standard of care in acute stroke imaging protocols. Furthermore, recent RCTs have shown that also patients with large established infarctions benefit from MT, which might not have been selected for MT based on CTP core/penumbra mismatch analysis., Methods: All patients with acute large vessel occlusion of the anterior circulation treated at our institution between 12/2015 and 12/2020 were screened ( N  = 404) and 238 patients undergoing MT with successful reperfusion were included for final analysis. Ground truth infarct lesions were segmented on 24 h follow-up CT scans. Pre-processed CTA images were used as input for a U-Net-based convolutional neural network trained for lesion prediction, enhanced with a spatial and channel-wise squeeze-and-excitation block. Post-processing was applied to remove small predicted lesion components. The model was evaluated using a 5-fold cross-validation and a separate test set with Dice similarity coefficient (DSC) as the primary metric and average volume error as the secondary metric., Results: The mean ± standard deviation test set DSC over all folds after post-processing was 0.35 ± 0.2 and the mean test set average volume error was 11.5 mL. The performance was relatively uniform across models with the best model according to the DSC achieved a score of 0.37 ± 0.2 after post-processing and the best model in terms of average volume error yielded 3.9 mL., Conclusion: 24 h follow-up infarct prediction using acute CTA imaging exclusively is feasible with DSC measures comparable to results of CTP-based algorithms reported in other studies. The proposed method might pave the way to a wider acceptance, feasibility, and applicability of follow-up infarct prediction based on artificial intelligence., Competing Interests: HK and FF are consultants for Eppdata GmbH. HK has financial interest in Eppdata GmbH. NF has financial interest in Eppdata GmbH. JF is consultant for Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche and Tonbridge, serves in the advisory board of Stryker and Phenox, is stock holder of Tegus Medical, Eppdata and Vastrax., and serves as Associate Editor at JNIS. Author FP was employed by company deCODE Genetics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Palsson, Forkert, Meyer, Broocks, Flottmann, Maros, Bechstein, Winkelmeier, Schlemm, Fiehler, Gellißen and Kniep.)

Introduction: Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (END unexplained ) with regard to the cerebral collateral status., Patients and Methods: Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. END unexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of END unexplained and unfavorable functional outcome (modified Rankin Scale score 3-6)., Results: A total of 620 patients met the inclusion criteria. END unexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with END unexplained exhibited more often unfavorable VO (81% vs. 53%; P  < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P  = 0.045) was an independent predictor of END unexplained . END unexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P  = 0.001)., Discussion and Conclusion: Unfavorable VO on admission CTA was associated with END unexplained . END unexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of END unexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes., 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: Dr J.J. HEIT reports consulting for Medtronic and MicroVention and Medical and Scientific Advisory Board membership for iSchemaView. Dr G.W. ALBERS reports equity and consulting for iSchemaView and consulting from Medtronic. Dr H. KNIEP reports an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services. Dr M. WINTERMARK reports grants and funding from the National Institutes of Health under the grant numbers (1U01 NS086872-01, 1U01 NS087748-01, and 1R01 NS104094). Dr J. FIEHLER reports grants and personal fees from Acandis, Cerenovus, MicroVention, Medtronic, Stryker, Phenox and grants from Route 92 outside the submitted work. Dr T. D. FAIZY reports grants from the German Research Foundation (DFG) during the conduct of the study (Project Number: 411621970). Dres M.G. LANSBERG, G. BROOCKS, C.P. STRACKE, A. GUENEGO, D. PAECH, L. WINKELMEIER, M. SCHELL and C. HEITKAMP report no disclosures relevant to the manuscript.

Background and Purpose: In ischemic stroke, the impact of short- versus long-term blood glucose level (BGL) on early lesion pathophysiology and functional outcome has not been assessed. The purpose of this study was to directly compare the effect of long-term blood glucose (glycated hemoglobin [HbA1c]) versus serum BGL on early edema formation and functional outcome., Methods: Anterior circulation ischemic stroke patients who underwent mechanical thrombectomy after multimodal computed tomography (CT) on admission were analyzed. Endpoints were early ischemic cerebral edema, measured by quantitative net water uptake (NWU) on initial CT and functional independence at Day 90., Results: A total of 345 patients were included. Patients with functional independence had significantly lower baseline NWU (3.1% vs. 8.3%; p < 0.001) and lower BGL (113 vs. 123 mg/dL; p < 0.001) than those without functional independence, while HbA1c levels did not differ significantly (5.7% vs. 5.8%; p = 0.15). A significant association was found for NWU and BGL (ß = 0.02, 95% confidence interval [CI] 0.006-0.03; p = 0.002), but not for HbA1c and NWU (ß = -0.16, 95% CI -0.53-0.21; p = 0.39). Mediation analysis showed that 67% of the effect of BGL on functional outcome was mediated by early edema formation., Conclusion: Aggravated early edema and worse functional outcome was associated with elevated short-term serum BGL, but not with HbA1c levels. Hence, the link between short-term BGL and early edema development might be used as a target for adjuvant therapy in patients with ischemic stroke., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)