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Background and Purpose: Successful and complete reperfusion should be the aim of every endovascular thrombectomy (EVT) procedure. However, the effect of time delays on successful reperfusion in late window stroke patients presenting 6-to-24 h from onset has not been investigated., Materials and Methods: We pooled individual patient-level data from seven trials and registries for anterior circulation stroke patients treated with EVT between 6 and 24 h from onset. We explored the impact of delays across multiple interval times, including onset to hospital arrival; hospital arrival to arterial puncture; imaging to arterial puncture; and onset to arterial puncture. Our primary outcome was successful reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2b-3. Logistic regression analyses were performed to assess the association between each of the interval times and successful reperfusion., Results: We included 608 patients. The median age was 70 years (IQR 58-79), and 307 (50.5%) were females. Successful reperfusion was achieved in 494 (81.2%) patients. Patients with successful reperfusion had lower NIHSS scores (median 15 [IQR11-19] vs 17 [11-21], p = .02) and significantly shorter hospital arrival to arterial puncture time (90 min [60-150] vs 110 min [84.5-150], p = .01) than unsuccessful reperfusion. The odds of successful reperfusion decreased by 15% for every one-hour delay in arrival-to-puncture time (adjusted odds ratio 0.85, 95% CI: 0.75-0.95). Other workflow times did not impact the rate of successful reperfusion., Conclusion: Faster hospital arrival to arterial puncture time is associated with higher odds of successful reperfusion in late window stroke patients., 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. Thornton reports personal fees (honoraria) from MicroVention, clinical advisory board and shareholder in Perfuze. Dr Hill has received grant support from Medtronic LLC and consultant fees from Boehringer Ingelheim. Dr Mangiafico acted as a consultant for CERENOVUS. Dr Patrik reports research grants from the Swiss Heart Foundation and the Swiss National Science Foundation. Dr Toni received honoraria as a member of advisory board of Abbott, Boehringer Ingelheim, Bayer, Pfizer-BMS, Medtronic, and Daiichi Sankyo. Dr Menon reports shares in Circle NVI and patents for systems of triage in acute stroke. Dr Almekhlafi reports being a member of the scientific advisory board of Palmera Medical, Inc. The other authors report no conflicts.

Background: The Carotid web (CaW) is a cause of stroke, particularly in younger individuals. However, the frequency and the radiological features of the web's morphology associated with stroke risk are uncertain. We determined the CaW radiological features on computed tomography (CT) angiography associated with ipsilateral stroke., Materials and Methods: Data from six studies of patients with acute ischemic stroke were pooled. Identification and measurement of CaWs were performed by experienced readers using baseline neck CT angiography. We assessed six 2D CaW radiological features on sagittal oblique images, namely, main axis length, thickness, height, base width, distance to wall, and angle between the web main axis and carotid wall, and CaW volume on 3D images. CaWs were divided into symptomatic if acute ischemic stroke was in the ipsilateral internal carotid artery territory and its etiology was undetermined and asymptomatic if one condition was unmet. Univariable and multivariable analyses were conducted to assess the association between each radiological CaW feature and symptomatic CaW., Results: Of the 3442 patients in the pooled data with assessable CTAs, 60 (1.7%) had CaW. In patients with CaW, median age was 59 (interquartile range [IQR]: 50-68) years, 60% were women, and 3 patients had bilateral CaWs. There were 39 (62%) symptomatic and 24 (38%) asymptomatic CaWs. Patients with symptomatic CaW were younger (55 (IQR: 49-61) years versus 69 (IQR: 52-75) years), had lower rates of hypertension (9 (25.0%) versus 12 (57.1%)) and more intracranial large vessel occlusions compared to patients with asymptomatic CaWs. After adjusting for age, hypertension, and occlusion location, CaW length (adjusted odds ratio (aOR) 1.84 (95% confidence interval [CI]: 1.03-3.28)), thickness (aOR: 2.31 (95% CI 1.08-4.97)), volume (aOR: 1.07 per 1 mm 3 increment (95% CI: 1.01-1.12)), and angle relative to the carotid wall (aOR: 0.95 (95% CI: 0.91-0.99)) were associated with symptomatic CaW., Conclusion: Radiological assessment of CaW morphology may determine its potential causal role in ischemic stroke etiology. Symptomatic CaWs tend to be longer, larger, and oriented at more acute angles relative to the carotid wall as compared to asymptomatic CaWs., 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: M.G. holds grants from Johnson & Johnson and Medtronic and is a consultant to Medtronic, Mentice, Microvention, and Philips. M.H. reports grants from Boehringer Ingelheim, consultant Grainsgate Ltd, grants from Canadian Institutes of Health Research, Medtronic, end point committee review Merck, grants Microvention, NoNO, Inc, employment university of Calgary, patent licensed (systems and methods for assisting in decision-making in acute stroke). B.M. holds stock in Circle CVI. The other authors report no conflicts.

Background: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion., Aims: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL., Methods: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed., Results: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group., Conclusion: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase., 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: A.Y.P. is the Principal investigator of the EASI-TOC trial of carotid stenting, partially funded by Stryker, Brain Canada, Heart and Stroke Foundation of Canada, and the Canadian Stroke Consortium and is in the advisory board of and receives speaker honoraria from Roche Canada. Other authors report no conflict of interest.

Background: The CHANCE-2 study compared 3 weeks of aspirin-ticagrelor to aspirin-clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin-ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown., Methods: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty., Results: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY., Conclusion: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin-ticagrelor compared to standard-of-care aspirin-clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

Background: Some patients with ischemic stroke have poor outcomes despite small infarcts after endovascular thrombectomy, while others with large infarcts sometimes fare better., Aims: We explored factors associated with such discrepancies between post-treatment infarct volume (PIV) and functional outcome., Methods: We identified patients with small PIV (volume ≤ 25th percentile) and large PIV (volume ≥ 75th percentile) on 24-48-h CT/MRI in the ESCAPE randomized-controlled trial. Demographics, comorbidities, baseline, and 24-48-h stroke severity (NIHSS), stroke location, treatment type, post-stroke complications, and other outcome scales like Barthel Index, and EQ-5D were compared between "discrepant cases" - those with 90-day modified Rankin Scale(mRS) ≤ 2 despite large PIV or mRS ≥ 3 despite small PIV - and "non-discrepant cases". Multi-variable logistic regression was used to identify pre-treatment and post-treatment factors associated with small-PIV/mRS ≥ 3 and large-PIV/mRS ≤ 2. Sensitivity analyses used different definitions of small/large PIV and good/poor outcome., Results: Among 315 patients, median PIV was 21 mL; 27/79 (34.2%) patients with PIV ≤ 7 mL (25th percentile) had mRS ≥ 3; 12/80 (15.0%) with PIV ≥ 72 mL (75th percentile) had mRS ≤ 2. Discrepant cases did not differ by CT versus MRI-based PIV ascertainment, or right versus left-hemisphere involvement ( p  = 0.39, p  = 0.81, respectively, for PIV ≤ 7 mL/mRS ≥ 3). Pre-treatment factors independently associated with small-PIV/mRS ≥ 3 included older age ( p  = 0.010), cancer, and vascular risk-factors; post-treatment factors included 48-h NIHSS ( p  = 0.007) and post-stroke complications ( p  = 0.026). Absence of vascular risk-factors ( p  = 0.004), CT-based lentiform nucleus sparing ( p  = 0.002), lower 24-hour NIHSS ( p  = 0.001), and absence of complications ( p  = 0.013) were associated with large-PIV/mRS ≤ 2. Sensitivity analyses yielded similar results., Conclusions: Discrepancies between functional ability and PIV are likely explained by differences in age, comorbidities, and post-stroke complications, emphasizing the need for high-quality post-thrombectomy stroke care., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01778335.

Background: Manual segmentations of intracranial hemorrhage on non-contrast CT images are the gold-standard in measuring hematoma growth but are prone to rater variability., Aims: We demonstrate that a convex optimization-based interactive segmentation approach can accurately and reliably measure intracranial hemorrhage growth., Methods: Baseline and 16-h follow-up head non-contrast CT images of 46 subjects presenting with intracranial hemorrhage were selected randomly from the ANNEXA-4 trial imaging database. Three users semi-automatically segmented intracranial hemorrhage to measure hematoma volume for each timepoint using our proposed method. Segmentation accuracy was quantitatively evaluated compared to manual segmentations by using Dice similarity coefficient, Pearson correlation, and Bland-Altman analysis. Intra- and inter-rater reliability of the Dice similarity coefficient and intracranial hemorrhage volumes and volume change were assessed by the intraclass correlation coefficient and minimum detectable change., Results: Among the three users, the mean Dice similarity coefficient, Pearson correlation, and mean difference ranged from 76.79% to 79.76%, 0.970 to 0.980 ( p  < 0.001), and -1.5 to -0.4 ml, respectively, for all intracranial hemorrhage segmentations. Inter-rater intraclass correlation coefficients between the three users for Dice similarity coefficient and intracranial hemorrhage volume were 0.846 and 0.962, respectively, and the corresponding minimum detectable change was 2.51 ml. Inter-rater intraclass correlation coefficient for intracranial hemorrhage volume change ranged from 0.915 to 0.958 for each user compared to manual measurements, resulting in an minimum detectable change range of 2.14 to 4.26 ml., Conclusions: We spatially and volumetrically validate a novel interactive segmentation method for delineating intracranial hemorrhage on head non-contrast CT images. Good spatial overlap, excellent volume correlation, and good repeatability suggest its usefulness for measuring intracranial hemorrhage volume and volume change on non-contrast CT images.

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.

Background: Endovascular treatment is recommended in clinical practice in Japan. However, its utilization and comprehensiveness are less well described., Aims: To report endovascular treatment utilization and overall geographical coverage in Japan and to analyze regional differences in the number of endovascular treatments, specialists, and endovascular treatment-capable hospitals., Methods: A national survey of members of the Japanese Society for NeuroEndovascular Therapy (JSNET) was conducted in 2017 and 2018. The total number of endovascular treatment cases per year was estimated, and the number of endovascular treatment cases per 100,000 people was calculated using the 2015 census. The distribution of treatment hospitals and JSNET specialists was mapped and the population coverage rate was determined., Results: The total number of endovascular treatment cases in Japan increased by 34.5% from 2016 (7702) to 2017 (10,360). The number of endovascular treatment-capable hospitals in Japan increased from 597 in 2016 to 693 in 2017, with an average annual caseload of 14.9 in 2017. The number of JSNET specialists per hospital decreased from 1.81 in 2016 to 1.76 in 2017 because of the increase in endovascular treatment-capable hospitals. Only 50 (7.2%) hospitals had > 40 endovascular treatment cases annually. The majority (97.7%) of the Japanese population lives within a 60-min drive of any endovascular treatment-capable hospital. However, only 70.4% live within a 60-min drive of a high-volume center (>40 cases annually)., Conclusions: Utilization of endovascular treatment in Japan is increasing; however, the number of cases per hospital remains low, as is the number of specialists per endovascular treatment-capable hospital. Increased number of specialists and centralization of endovascular treatment services may improve patient outcomes.

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days., (© 2014 World Stroke Organization.)

There is no consensus on how the reliability and predictive ability of noncontrast computed tomography (NCCT) and computed tomography angiography source image (CTASI) change over time from acute ischemic stroke onset. We hypothesized that the reliability for detecting early ischemic changes (EIC) would be lower in early time periods and that changes identified on CTASI would be more reliable across examiners than changes identified on NCCT. To address this, we compared the relationships between CTASI, NCCT, and final infarct in patients with initial computed tomography (CT) imaging at different time points after stroke onset. Patients with acute ischemic stroke with proximal anterior circulation occlusions (internal carotid artery, middle carotid artery M1, proximal M2) from Calgary CT Angiography (CTA) database were studied. The cohort was categorized in four groups based on time from stroke onset to baseline NCCT/CTA: 0-90 mins (n = 69), 91-180 mins (n = 88), 181-360 mins (n = 46), and >360 mins (n = 58). Median scores of NCCT-Alberta Stroke Program Early CT Score (ASPECTS), CTASI ASPECTS, and follow-up ASPECTS among different time categories were compared. To determine reliability, a subsample of NCCT brain and CTASI were interpreted at separate sessions weeks apart by two neuroradiologists and two stroke neurologists in random order. Median and mean ASPECTS ratings on NCCT and CTASI were higher than final ASPECTS in each time category (P < 0·001 for all comparisons). CTASI ASPECTS was lower than NCCT ASPECTS in each time category, and differences were significant at 0-90 mins and 91-180 mins (P < 0·001). The least agreement among readers was in detection of EIC on NCCT brain in the ultra-early phase (<90 mins) [intraclass correlation coefficient (ICC) = 0·48. By contrast, there was excellent agreement on EIC on CTASI regardless of time period (ICC = 0·87-0·96). Using ASPECTS methodology, CTASI is more reliable than NCCT at predicting final infarct extent particularly in the early time windows., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background: There is an increasing trend to treating proximal vessel occlusions with intravenous-inter-arterial (IV-IA) thrombolysis. The best dose of IV tissue plasminogen activator (tPA) remains undetermined. We compared the combination of full-dose IV recombinant tissue plasminogen activator (rtPA) and IA thrombolytic therapy to IA therapy., Methods: Between 2002 and 2009, we reviewed our computed tomographic angiography database for patients who received full-dose intravenous rtPA and endovascular therapy or endovascular therapy alone for acute ischaemic stroke treatment. Details of demographics, risk factors, endovascular procedure, and symptomatic intracranial haemorrhage were noted. Modified Rankin Scale ≤2 at three-months was used as good outcome. Recanalization was defined as Thrombolysis in Myocardial Ischaemia 2-3 flow on angiography., Results: Among 157 patients, 104 patients received IV-IA treatment and 53 patients underwent direct IA therapy. There was a higher recanalization rate with IV-IA therapy compared with IA alone (71% vs. 60%, P < 0·21) which was driven by early recanalization after IV rtPA. Mortality and independent outcome were comparable between the two groups. Symptomatic intracranial haemorrhage occurred in 8% of patients (12% in the IA group, 7% in the IV-IA group) but was more frequent as the intensity of intervention increased from device alone to thrombolytic drug alone to device plus thrombolytic drug(s). Recanalization was a strong predictor of reduced mortality risk ratio (RR) 0·48 confidence interval95 0·27-0·84) and favourable outcome (RR 2·14 confidence interval95 1·3-3·5)., Conclusions: Combined IV-IA therapy with full-dose intravenous rtPA was safe and results in good recanalization rates without excess symptomatic intracranial haemorrhage. Testing of full-dose IV tPA followed by endovascular treatment in the IMS3 trial is justified., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Whole-brain dynamic time-resolved computed tomography angiography (CTA) is a technique developed on the new 320-detector row CT scanner capable of generating time-resolved cerebral angiograms from skull base to vertex. Unlike a conventional cerebral angiogram, this technique visualizes pial arterial filling in all vascular territories, thereby providing additional hemodynamic information. Ours was a retrospective study of consecutive patients with ischemic stroke and M1 middle cerebral artery +/- intracranial internal carotid artery occlusions presenting to our center from June 2010 and undergoing dynamic time-resolved CTA and perfusion CT within 6 hours of symptom onset. Leptomeningeal collateral status was assessed by determining relative prominence of pial arteries in the ischemic region, rate and extent of retrograde flow, and various topographical patterns of pial arterial filling. Twenty-five patients were included in the study. We demonstrate the existence of the following novel properties of leptomeningeal collaterals in humans: (a) posterior (posterior cerebral artery (PCA)-MCA) dominant collateralization, (b) intra-territorial 'within MCA region' leptomeningeal collaterals, and (c) significant variability in size, extent, and retrograde filling time in pial arteries. We also describe a simple and reliable collateral grading template that, for the first time on dynamic CTA, incorporates back-filling time as well as size and extent of collateral filling.