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Background: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy., Methods: Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614)., Results: In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879-0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886-0.944] and 0.909 [95% CI, 0.887-0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score <10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations., Conclusions: The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2., Competing Interests: Dr Brown reports consulting for B. Braun Interventional Systems, Inc, Medtronic, MicroVention, Inc, and the University of Calgary and is employed by BRIGHT Research Partners. Dr Goyal reports grants from Medtronic, Stryker, MicroVention, and Mentice; consulting for Stryker, Microvention, and Mentice; and a patent for systems and methods for acute stroke diagnosis with GE Healthcare. Dr Menon reports stock holdings in Circle Neurovascular Imaging and compensation from Roche and Boehringer Ingelheim. Dr Campbell reports grants from Covidien, Medtronic, and the National Health and Medical Research Council of Australia and fellowships from the National Heart Foundation of Australia, the National Stroke Foundation of Australia, and the Royal Australasian College of Physicians. Dr Mitchell reports consulting for Stryker and MicroVention and grants from Medtronic and Stryker. Dr Jovin reports consulting for Contego Medical; grants/contracts from Medtronic and Stryker; data safety monitoring board participation with Johnson & Johnson CERENOVUS; and stock holdings in Anaconda, Basking, Freeox Biotech, Galaxy, Gravity, Kandu, Methinks, Route92, StataDX, and Vizai. Dr Saver reports consulting for Abbott Laboratories, Aeromics, Biogen, Boehringer Ingelheim, BrainQ, BrainsGate, CSL Behring, Johnson & Johnson Health Care Systems, Medtronic, MindRhythm, Roche, and Stream Medical; data safety monitoring board participation with MIVI Neuroscience; and stock holdings in Neuronics Medical and Rapid Medical. Dr Muir reports consulting for Boehringer Ingelheim, Bayer, and Daiichi Sankyo. Dr White reports consulting for MicroVention and grants from the UK National Institutes for Health Research, MicroVention, Stryker, Medtronic, and Penumbra. Dr Bracard reports grants from the French Ministry of Health; others from GE Medical Systems; and nonfinancial support from MicroVention Europe. Dr Roos reports stock holdings in Nicolab. Dr van Zwam reports grants/contracts from Bayer HealthCare Pharmaceuticals, Stryker, and Johnson & Johnson; employment by Maastricht Universitair Medisch Centrum; and data safety monitoring board participation with Philips. Dr Hill reports consulting for BrainsGate; grants/contracts from Biogen, Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic MicroVention, and NoNO; end point review committee participation with Merck; employment by the University of Calgary; and a patent for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients with Circle Neurovascular Imaging. Dr Demchuk reports consulting for Boehringer Ingelheim, HLS Therapeutics, Hoffmann-La Roche, Medtronic, Nova-Signal, and Servier; data safety monitoring board participation with Philips and Lumosa; others from Novo Nordisk AS, Pfizer, and Astra Zeneca; and stock and patent for Stroke imaging software with Circle Neurovascular Imaging. The other authors report no conflicts.

Introduction: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes., Methods: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b-3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b-3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality., Results: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24-60). Arrival during working hours was independently associated with shorter NPT (p &lt; 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91-1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96-1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97-1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88-0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31-0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10-0.57]) than the longer NPT group., Conclusion: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome., (© 2023 S. Karger AG, Basel.)

Introduction: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features., Methods: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive)., Results: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092)., Conclusion: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions., Competing Interests: Declaration of Competing Interest All authors confirm there are no conflicts of interest. No part of this manuscript was created using artificial intelligence. The data in this manuscript has not been published in any other journal, (Copyright © 2023. Published by Elsevier Inc.)

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden., 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. Field receives in-kind study medication from Bayer Canada and has received honoraria for advisory board work for HLS Therapeutics and Roche Canada. She is supported by a Sauder/Heart and Stroke Professorship from the University of British Columbia, the Vancouver Coastal Health Research Institute, the Michael Smith Institute for Health Research, and the Heart and Stroke Foundation of Canada. Dr. Menon reported holding stock and a patent for systems of triage in acute stroke in Circle NVI. Dr. Dowlatshahi reported receiving a grant from Heart & Stroke Foundation of Canada and personal fees from Apopharma, BMS, and Bayer. Dr Goyal reported receiving research grants to the University of Calgary by Stryker and Cerenovus and receiving consulting fees from Stryker, Mentice, Medtronic and Microvention. Dr. Demchuk reported receiving honoraria from Medtronic and holding stock and a patent in Circle NVI, a startup stroke imaging software company. Dr Hill reports grants from Covidien (Medtronic LLC), grants from Alberta Innovates, grants from Heart & Stroke Foundation of Canada, grants from Canadian Institutes of Health Research (Canadian Stroke Prevention Intervention Network), grants from University of Calgary (Hotchkiss Brain Institute), grants from Boehringer Ingelheim Canada, grants from NoNO, Inc, and grants from Biogen. In addition, Dr Hill has a patent to US Patent office Number: 62/086,077 and is Stock owner in Pure Web Incorporated and CircleNVI. Dr. Hill is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, is a director of the Canadian Stroke Consortium, a not-for-profit group, is a director of Circle NeuroVascular, and has received public grant support to the University of Calgary from Alberta Innovates Health Solutions, Canadian Institutes of Health Research, Heart & Stroke Foundation of Canada and National Institutes of Neurological Disorders and Stroke. The other authors report no conflicts.

Introduction: Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) achieve first-pass effect (FPE). We investigated the effect of arterial tortuosity and thrombus characteristics on the relationship between first-line EVT strategy and angiographic outcomes., Patients and Methods: Patients with thin-slice baseline CT-angiography from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke) were included. Tortuosity was estimated using the tortuosity index extracted from catheter pathway, and radiological thrombus characteristics were length, non-contrast density, perviousness and hyperdense artery sign. We assessed the association of first-line EVT strategy (stent-retriever [SR] versus contact aspiration [CA] versus combined SR+CA) with FPE (eTICI score 2c/3 after one pass), final eTICI 2b/3, number of passes and procedure duration using multivariable regression. Interaction of tortuosity and thrombus characteristics with first-line technique were assessed using interaction terms., Results: Among 520 included patients, SR as a first-line modality was used in 165 (31.7%) patients, CA in 132 (25.4%), and combined SR+CA in 223 (42.9%). FPE was observed in 166 patients (31.9%). First-line strategy was not associated with FPE. Tortuosity had a significant effect on FPE only in the CA group (aOR = 0.90 [95% CI 0.83-0.98]) compared with stent-retrievers and combined first-line approach (p interaction = 0.03). There was an interaction between thrombus length and first-line strategy for number of passes (p interaction = 0.04). Longer thrombi were associated with higher number of passes only in the CA group (acOR 1.03 [95% CI 1.00-1.06])., Conclusion: Our study suggests that vessel tortuosity and longer thrombi may negatively affect the performance of first-line contact aspiration catheters in acute stroke patients undergoing EVT.

Background: Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status., Methods: Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0-49%), good (50-99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status., Results: 386 patients with collateral status classified as poor ( n = 64), good ( n = 125), and optimal ( n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78-246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8-53.0% of the observed between-patient variance in collaterals., Conclusion: Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

Purpose: Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA)., Methods: Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome., Results: Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p < 0.001)., Conclusion: This study concludes that venous opacification over time on multiphase CTA is associated with 90-day clinical outcome. There was however no added benefit of venous scoring vis-a-vis arterial collateral assessment in predicting outcome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Multiphase CTA (mCTA) is an established tool for endovascular treatment decision-making and outcome prediction in acute ischemic stroke, but its interpretation requires some degree of experience. We aimed to determine whether mCTA-based prediction of clinical outcome and final infarct volume can be improved by assessing collateral status on time-variant mCTA color maps rather than using a conventional mCTA display format., Methods: Patients from the PRove-IT cohort study with anterior circulation large vessel occlusion were included in this study. Collateral status was assessed with a three-point scale using the conventional display format. Collateral extent and filling dynamics were then graded on a three-point scale using time-variant mCTA color-maps (FastStroke, GE Healthcare, Milwaukee, WI, USA). Multivariable logistic regression was performed to determine the association of conventional collateral score, color-coded collateral extent and color-coded collateral filling dynamics with good clinical outcome and final infarct volume (volume below vs. above median infarct volume in the study sample)., Results: A total of 285 patients were included in the analysis and 53% (152/285) of the patients achieved a good outcome. Median infarct volume on follow-up was 12.6 ml. Color-coded collateral extent was significantly associated with good outcome (adjusted odds ratio [ adj OR] 0.53, 95% confidence interval [CI]:0.36-0.77) while color-coded collateral filling dynamics ( adj OR 1.30 [95%CI:0.88-1.95]) and conventional collateral scoring ( adj OR 0.72 [95%C:0.48-1.08]) were not. Both color-coded collateral extent ( adj OR 2.67 [95%CI:1.80-4.00]) and conventional collateral scoring ( adj OR 1.84 [95%CI:1.21-2.79]) were significantly associated with follow-up infarct volume, while color-coded collateral filling dynamics were not ( adj OR 1.21 [95%CI:0.83-1.78])., Conclusion: In this study, collateral extent assessment on time-variant mCTA maps improved prediction of good outcome and has similar value in predicting follow-up infarct volume compared to conventional mCTA collateral grading., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Acute strokes due to large vessel occlusion in hospitalized patients is not uncommon. We performed a systematic review and meta-analysis to investigate the timing and outcome of endovascular thrombectomy (EVT) for in-hospital stroke., Methods: We conducted a meta-analysis of clinical studies published in English until September 2020 in the MEDLINE and Cochrane databases. Studies reporting original data on the characteristics and outcomes of in-hospital stroke patients treated with EVT were included. We extracted data on the time-metrics from last known well (LKW) until reperfusion was achieved. We also collected data on procedural and functional outcomes., Results: Out of 5093 retrieved studies, 8 were included (2,622 patients). The median age was 71.4 years and median NIHSS score on admission was 16. Patients were mostly admitted to the cardiology service (27.3%). The pooled time from LKW to recognition by staff was 72.9 min (95% CI: 40.7 to 105 min). 25.6% received IV tPA. The mean time from stroke recognition to arterial puncture was 134.5 min (95% CI: 94.9 to 174.1). Successful reperfusion occurred in 82.8.% with a pooled mean time from detection to reperfusion of 193.1 min (95% CI: 139.5 to 246.7). The 90-day independent functional outcome was reported in 42% of patients (95% CI 29 to 55%)., Conclusion: EVT can be performed safely and successfully for in-hospital strokes. Noticeable delays from LKW to detection and then to puncture are noted. This calls for better stroke pathways to identify and treat these patients., Background: Stroke in hospitalized patients, referred to as in-hospital stroke (IHS), accounts for 2.2-17% of all strokes. 1 The majority of these are ischemic while intracranial hemorrhage represents 2-11% of all IHS. 1 These patients are expected to have a rapid diagnosis and treatment given the ongoing medical supervision, and therefore favorable outcomes. 1-3 However, existing studies report poor outcomes in patients with IHS with a mortality risk that exceeds that of community-onset stroke (COS): 24.7% vs 9.6%. 4 Surviving IHS patients are also less likely to be discharged home compared to COS (27.7% vs 49.9%) and to be functionally independent at 3 months (31.0% vs 50.4%). 1-4 ., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Purpose: Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation., Methods: Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0-2) based on these imaging paradigms were compared., Results: Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT., Conclusions: Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke., Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated., Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51])., Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Objective: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature., Methods: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation., Results: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions ( p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours., Conclusions: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days., Classification of Evidence: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days., (© 2020 American Academy of Neurology.)

Background: The Alberta Stroke Program Early CT Score (ASPECTS) is a systematic method of assessing the extent of early ischemic change on non-contrast computed tomography in patients with acute ischemic stroke. Our objective was to validate an automated ASPECTS scoring method we recently developed on a large data set., Materials and Methods: We retrospectively collected 602 acute ischemic stroke patients' non-contrast computed tomography scans. Expert ASPECTS readings on non-contrast computed tomography were compared to automated ASPECTS. Statistical analyses on the total ASPECTS, region level ASPECTS, and dichotomized ASPECTS (≤4 vs. >4) score were conducted., Results: In total, 602 scans were evaluated and 6020 (602 × 10) ASPECTS regions were scored. Median time from stroke onset to computed tomography was 114 min (interquartile range: 73-183 min). Total ASPECTS for the 602 patients generated by the automated method agreed well with expert readings (intraclass correlation coefficient): 0.65 (95% confidence interval (CI): 0.60-0.69). Region level analysis showed that the automated method yielded accuracy of 81.25%, sensitivity of 61.13% (95% CI: 58.4%-63.8%), specificity of 86.56% (95% CI: 85.6%-87.5%), and area under curve of 0.74 (95% CI: 0.73-0.75). For dichotomized ASPECTS (≤4 vs. >4), the automated method demonstrated sensitivity 97.21% (95% CI: 95.4%-98.4%), specificity 57.81% (95% CI: 44.8%-70.1%), accuracy 93.02%, and area under the curve of 0.78 (95% CI: 0.74-0.81). For each individual region (M1-6, lentiform, insula, and caudate), the automated method demonstrated acceptable performance., Conclusion: The automated system we developed approached the stroke expert in performance when scoring ASPECTS on non-contrast computed tomography scans of acute ischemic stroke patients.

Purpose: To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase., Methods: Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (< 2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC)., Results: Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HU max ≥ 89 measured with method 3 provided optimal sensitivity and specificity in discriminating recanalizers from non-recanalizers [recanalization 55.4% (95%CI 46.2-64.6) when HU max > 89 vs. 16.8% (95%CI 13.0-20.6) when HU max ≤ 89]. In sensitivity analyses restricted to patients with co-registered CTA/NCCT (n = 88), methods 1-4 predicted recanalization similarly (C-statistic 0.641, 0.688, 0.640, 0.648, respectively) with Method 2 having the least information loss (AIC 104.8, BIC 109.8)., Conclusion: Simple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

Correction to: Clin Neuroradiol 2018 https://doi.org/10.1007/s00062-018-0717-x Unfortunately, the author list of the original version of this article contains a mistake. The middle name of the author "Rani Gupta Sah" was erroneously tagged as part of the surname in the article's metadata.This mistake.

Purpose: Acute stroke treatment requires simple, quick and accurate detection of early ischemic changes to facilitate treatment decisions guided by published selection criteria. The aim of this study was to determine the accuracy and reliability of multiphase computed tomography angiography (mCTA) perfusion hypoattenuation for detecting early severe ischemia., Methods: Non-contrast CT (NCCT), mCTA for regional leptomeningeal score (mCTA-rLMC), and mCTA perfusion lesion visibility (mCTA-arterial and mCTA-venous) were assessed blinded to clinical information in patients treated with endovascular therapy (EVT). The extent of early ischemia defined by regions of hypoattenuation was evaluated by the Alberta Stroke Program Early CT Score (ASPECTS). The ASPECTS scores were dichotomized based on the American Heart Association (AHA) guidelines for EVT selection, ASPECTS ≥6 vs. <6. The diagnostic accuracy was calculated by comparison to 24-h magnetic resonance imaging (MRI) or CT ASPECTS. Inter-observer reliability of NCCT and mCTA ASPECTS was evaluated. Machine learning models were used to predict the clinical follow-up outcome, e.g. National Institutes of Health Stroke scale (NIHSS) and modified Rankin scale (mRS) from baseline imaging data and patient information., Results: A total of 89 acute stroke patients (68 ± 15 years of age) were analyzed (33 TICI-0, 56 TICI-2b or 3). Median baseline NIHSS was 17. The mCTA-venous had a large effect on accurately identifying early ischemia when dichotomized for ASPECTS ≥6 vs <6 (likelihood ratio [LR+] > 10 vs. [LR-] < 0.29) compared to the moderate effect of NCCT ([LR+] = 6.7; [LR-] = 0.56) and mCTA-rLMC [(LR+ = 8.0; (LR-) = 0.83)]. The inter-observer reliability in mCTA-venous was almost perfect for all ASPECTS regions except the internal capsule. The machine learning support factor regression model identified mCTA-venous as the most important imaging covariate for predicting 24-h NIHSS and 90-day mRS., Conclusion: The assessment of mCTA-venous permits a more accurate detection of early ischemia than NCCT and mCTA-rLMC score and is predictive of clinical outcome. We would recommend the inclusion of mCTA perfusion lesion in future endovascular trials aiming at extending current AHA guidelines for EVT in stroke patients with low ASPECTS.

Background and Objective: Non-Contrast Computer Tomography (NCCT) and CT angiography (CTA) are the most used and widely acceptable imaging modalities in clinical practice for the diagnosis and treatment of acute ischemic stroke (AIS) patients. Brain extraction of CT/CTA images plays an essential role in stroke imaging research. There is no robust automated brain extraction method in the literature that is well established for both NCCT and CTA images. Thus, a validated and automated brain extraction tool for CT imaging would be of great value for both research and clinical practice., Methods: The proposed brain extraction method is based on the contour evolution technique, which extracts brain tissues from acquired NCCT and CTA images in a slice-by-slice fashion. Specifically, the proposed approach makes use of a novel propagation framework, which is initialized by a localized slice with the largest brain section in axial views, followed by a geodesic level-set evolution for automatically extracting the brain section in each slice. In particular, the segmented contour propagated from the previous slice is reused to penalize the defined object function for contour evolution to enforce the shape continuity between any two adjacent contours. We show that the defined contour evolution function can be solved iteratively by globally optimal convex optimization., Results: The proposed brain extraction approach is quantitatively evaluated using 40 NCCT and CTA images acquired from 20 AIS patients and drawn from 4 different vendors, compared to manual segmentations using Dice and Jaccard coefficient metrics. The quantitative results show that the proposed segmentation algorithm is consistently accurate for both NCCT and CTA images using Dice metric. The proposed method is further validated on 1736 NCCT and CTA images of 1331 AIS patients acquired from three multi-national multi-centric clinical trials. A visual check performed on these data demonstrates a low failure rate of 0.4% for 1331 NCCT images and a zero-failure rate for 405 CTA images., Conclusions: Both quantitative and qualitative evaluation suggest that the proposed brain extraction approach for NCCT and CTA images can be used for different clinical imaging settings, thus serving to improve current image analysis in the field of neuroimaging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design., Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase., Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA)., Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA., Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion])., Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87])., Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Introduction: The Alberta Stroke Program Early CT Score on non-contrast CT is a key component of prognostication and treatment selection in acute stroke care. Previous findings show that the reliability of this scale must be improved to maximize its clinical utility. Areas covered: This review discusses technical, patient-level, and reader-level sources of variability in ASPECTS reading; relevant concepts in the psychology of medical image perception; and potential interventions likely to improve inter- and intra-rater reliability. Expert commentary: Approaching variability in medical decision making from a psychological perspective will afford cognitively informed insights into the development of interventions and training techniques aimed at improving this issue.

Background and Purpose: Intracerebral hemorrhage is a feared complication of intravenous alteplase therapy in patients with acute ischemic stroke. We explore the use of multimodal computed tomography in predicting this complication., Methods: All patients were administered intravenous alteplase with/without intra-arterial therapy. An age- and sex-matched case-control design with classic and conditional logistic regression techniques was chosen for analyses. Outcome was parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging (noncontrast computed tomography hypoattenuation degree, relative volume of very low cerebral blood volume, relative volume of cerebral blood flow ≤7 mL/min·per 100 g, relative volume of T max ≥16 s with all volumes standardized to z axis coverage, mean permeability surface area product values within T max ≥8 s volume, and mean permeability surface area product values within ipsilesional hemisphere) and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset to imaging time, baseline systolic blood pressure, blood glucose, serum creatinine, treatment type, and reperfusion status)., Results: One-hundred eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without, median baseline NIHSS score of 15) were included in the final analysis. In multivariable regression, noncontrast computed tomography hypoattenuation grade ( P <0.006) and computerized tomography perfusion white matter relative volume of very low cerebral blood volume ( P =0.04) were the only significant variables associated with parenchymal hemorrhage on follow-up imaging (area under the curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for noncontrast computed tomography hypoattenuation grade was moderate (κ=0.6)., Conclusions: Baseline hypoattenuation on noncontrast computed tomography and very low cerebral blood volume on computerized tomography perfusion are associated with development of parenchymal hemorrhage in patients with acute ischemic stroke receiving intravenous alteplase., (© 2017 American Heart Association, Inc.)

Background and Purpose: Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction., Methods: Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models., Results: Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models ( P <0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models ( P >0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score ( P <0.01) and each delay score category ( P <0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category ( P <0.05)., Conclusions: Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients., (© 2017 American Heart Association, Inc.)

Objective: To evaluate whether the use of multiphase CT angiography (CTA) improves interrater agreement for intracranial occlusion detection between stroke neurology trainees and an expert neuroradiologist., Methods: A neuroradiologist and 2 stroke neurology fellows independently reviewed 100 prospectively collected single-phase and multiphase CTA scans from acute ischemic stroke patients with mild symptoms (NIH Stroke Scale score ≤5). The presence and location of a vascular occlusion(s) were documented. Interrater agreement single- and multiphase CTA was quantified using unweighted κ statistics. We assessed for any occlusions, anterior vs posterior occlusions, and pial vessel asymmetry., Results: Using multiphase CTA, the neuroradiologist detected 50 scans with anterior circulation occlusions and 15 scans with posterior circulation occlusions. Median reading time was 2 minutes per scan. Median reading time for the neurologists was 3 minutes per multiphase CTA scan. Interrater agreement was fair between the 2 neurologists and neuroradiologist when using single-phase CTA (κ = 0.45 and 0.32). Agreement improved minimally when stratified by anterior vs posterior circulation. When using multiphase CTA, agreement was high for detection of occlusion or asymmetry of pial vessels in the anterior circulation (κ = 0.80 and 0.84)., Conclusions: Multiphase CTA improves diagnostic accuracy in minor ischemic stroke for detection of anterior circulation intracranial occlusion., Classification of Evidence: This study provides Class II evidence that multiphase CTA, compared to single-phase CTA, improves the interrater agreement between stroke neurology trainees and an expert neuroradiologist for detecting anterior circulation intracranial vascular occlusion in patients with minor acute ischemic strokes., (© 2016 American Academy of Neurology.)

Introduction: Stroke is the third leading cause of death and disability in Canada. In the hyperacute stroke setting, the treating physician must make a time critical decision on the treatment of each patient. Recent advances in imaging help the treating physician identify the subgroup of patients eligible for acute treatment of ischaemic stroke., Areas Covered: In this review we will discuss Non-Contrast Computed Tomography (NCCT), CT-Angiography (CTA), and CT-Perfusion (CTP) in assessment of patients with acute ischaemic stroke and intracerebral haemorrhage. Intravenous tPA was the only proven therapy for acute ischaemic stroke presenting within 4.5 hours, until the five recent trials proved the efficacy of EVT for acute ischaemic stroke with proximal arterial occlusion. Imaging played a major role in patient selection in all five trials. Expert commentary: The challenge of rapid clinical assessment, review of imaging and timely treatment will continue to be made easier as the development and understanding of imaging progresses.

Over the last few years, improvement in radiological imaging and treatment has changed the management of acute ischemic stroke. We have made significant advances in not only the imaging modalities themselves but also in identifying imaging parameters that can help us predict patient outcomes with both intravascular thrombolysis and endovascular thrombectomy. In this review, we describe the added utility of baseline vascular imaging including computed tomography angiography and magnetic resonance angiography in the diagnosis and management of patients with acute ischemic stroke. We focus on information these imaging modalities provide on clot characteristics, tissue state, collateral status, and endovascular planning. We also highlight the benefits of newer imaging modalities like dynamic computed tomography angiography (CTA) and multi-phase CTA. Lastly, we also describe some of the disadvantages of vascular imaging in ischemic stroke.

Background and Purpose: Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times., Methods: Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time., Results: One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters., Conclusions: Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion., (© 2015 American Heart Association, Inc.)