Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Effect of Needle-To-Puncture Time on Reperfusion Outcome in Acute Ischemic Stroke.

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 < 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.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Distal Embolization in Relation to Radiological Thrombus Characteristics, Treatment Details, and Functional Outcome.

BACKGROUND: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE. METHODS: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models. RESULTS: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8-42.3] mm versus 24.4 [interquartile range, 17.1-32.4] mm; P<0.01). There were no statistically significant differences in the other thrombus characteristics. Factors associated with DE were thrombus length (aOR, 1.02 [95% CI, 1.01-1.04]), balloon guide catheter use (aOR, 0.49 [95% CI, 0.29-0.85]), and number of passes (aOR, 1.24 [95% CI, 1.04-1.47]). In patients with hyperdense artery sign, IVT was associated with reduced odds of DE (aOR, 0.55 [95% CI, 0.31-0.97]), P for interaction=0.04. CONCLUSIONS: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability: A Meta-Analysis.

BACKGROUND: Randomized controlled trials for the use of alteplase in acute ischemic stroke have excluded or had little representation of patients with prestroke disability, and the benefit of alteplase in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with premorbid disability. METHODS: We performed a systematic review in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines and retrieved studies reporting intravenous thrombolysis (IVT) in patients with prestroke disability (modified Rankin Scale score, 3-5) with acute ischemic stroke, either compared with untreated patients or treated patients without premorbid disability. The primary outcome was the return to premorbid disability at 90 days. Secondary outcomes included rate and odds ratio of favorable functional outcome at 90 days (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. RESULTS: Eight articles were included involving 103 988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared with those who did not receive IVT (odds ratio, 7.26 [95% CI, 2.51-21.02]). Mortality and rates of sICH were not significantly different between patients with disability treated with IVT and those not treated, although there were numerically more sICHs in the IVT group. Return to baseline function was not significantly different between patients with and without prestroke disability (odds ratio, 1.46 [95% CI, 0.75-2.83]). The rates of sICH were not significantly different in patients with and without premorbid disability. However, mortality was 3× higher in patients with premorbid disability than in those without premorbid disability (38.2% versus 12.6%). CONCLUSIONS: The use of IVT in patients with disability was associated with better outcomes compared with patients who did not receive IVT without statistically significant added risks of sICH or mortality. When compared with those without disability, there was no significant difference in the return to baseline function or sICH. High-quality data comparing treated versus untreated patients with premorbid disability are needed to clarify this issue. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

Sex-Related Differences in Outcomes After Endovascular Treatment of Patients With Late-Window Stroke.

BACKGROUND AND PURPOSE: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. METHODS: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b-3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. RESULTS: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P=0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P=0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality (Pinteraction=0.003) and symptomatic intracranial hemorrhage (Pinteraction=0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. CONCLUSIONS: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Stroke imaging prior to thrombectomy in the late window: results from a pooled multicentre analysis.

BACKGROUND AND PURPOSE: Collateral assessment using CT angiography is a promising modality for selecting patients for endovascular thrombectomy (EVT) in the late window (6-24 hours). The outcome of these patients compared with those selected using perfusion imaging is not clear. METHODS: We pooled data from seven trials and registries of EVT-treated patients in the late-time window. Patients were classified according to the baseline imaging into collateral imaging alone (collateral cohort) and perfusion plus collateral imaging (perfusion cohort). The primary outcome was the proportion of patients achieving independent 90-day functional outcome (modified Rankin Scale 'mRS' 0-2). We used the propensity score-weighting method to balance important predictors between the cohorts. RESULTS: In 608 patients, the median onset/last-known-well to emergency arrival time was 8.8 hours and 53.2% had wake-up strokes. Both cohorts had collateral imaging and 379 (62.3%) had perfusion imaging. Independent functional outcome was achieved in 43.1% overall: 168/379 patients (45.5%) in the perfusion cohort versus 94/214 (43.9%) in the collateral cohort (p=0.71). A logistic regression model adjusting for inverse-probability-weighting showed no difference in 90-day mRS score of 0-2 among the perfusion versus collateral cohorts (adjusted OR 1.05, 95% CI 0.69 to 1.59, p=0.83) or in a favourable shift in 90-day mRS (common adjusted OR 1.01, 95% CI 0.69 to 1.47, p=0.97). CONCLUSION: This pooled analysis of late window EVT showed comparable functional outcomes in patients selected for EVT using collateral imaging alone compared with patients selected using perfusion and collateral imaging. PROSPERO REGISTRATION NUMBER: CRD42020222003.

Time-resolved assessment of cortical venous drainage on multiphase CT angiography in patients with acute ischemic stroke.

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.

Validation of a machine learning software tool for automated large vessel occlusion detection in patients with suspected acute stroke.

PURPOSE: CT angiography (CTA) is the imaging standard for large vessel occlusion (LVO) detection in patients with acute ischemic stroke. StrokeSENS LVO is an automated tool that utilizes a machine learning algorithm to identify anterior large vessel occlusions (LVO) on CTA. The aim of this study was to test the algorithm's performance in LVO detection in an independent dataset. METHODS: A total of 400 studies (217 LVO, 183 other/no occlusion) read by expert consensus were used for retrospective analysis. The LVO was defined as intracranial internal carotid artery (ICA) occlusion and M1 middle cerebral artery (MCA) occlusion. Software performance in detecting anterior LVO was evaluated using receiver operator characteristics (ROC) analysis, reporting area under the curve (AUC), sensitivity, and specificity. Subgroup analyses were performed to evaluate if performance in detecting LVO differed by subgroups, namely M1 MCA and ICA occlusion sites, and in data stratified by patient age, sex, and CTA acquisition characteristics (slice thickness, kilovoltage tube peak, and scanner manufacturer). RESULTS: AUC, sensitivity, and specificity overall were as follows: 0.939, 0.894, and 0.874, respectively, in the full cohort; 0.927, 0.857, and 0.874, respectively, in the ICA occlusion cohort; 0.945, 0.914, and 0.874, respectively, in the M1 MCA occlusion cohort. Performance did not differ significantly by patient age, sex, or CTA acquisition characteristics. CONCLUSION: The StrokeSENS LVO machine learning algorithm detects anterior LVO with high accuracy from a range of scans in a large dataset.

Balloon guide catheters: use, reject, or randomize?

Thrombectomy devices played an important role in the success of endovascular treatment trials over the past five years. A balloon guide catheter (BGC) is an adjunctive device used to arrest and reverse flow by inflating the balloon at its tip, which allows for flow reversal in intracranial arteries during retrieval of thrombectomy devices by applying concomitant aspiration through its lumen. Thereby, it can decrease the risk of clot fragmentation and distal embolization. Despite the numerous benchtop and clinical observational studies showing the superiority of BGC to conventional guide catheters in improving reperfusion quality and clinical outcome, its use is still low in clinical practice. The reasons behind this reluctance might be related to technical and cost issues. Therefore, high level evidence data, i.e., a randomized clinical trial, are needed to increase its implementation in thrombectomy procedures. Nonetheless, several obstacles and challenges can prevent the completion of such a trial, and efforts are needed to overcome them. We provide an overview of the current opinions about BGCs in the neurointerventional community and discuss the feasibility and challenges of a possible randomized trial to answer the question "should a BGC be routinely used in endovascular treatment of acute ischemic stroke?"

Clinical impact of EVT with failed reperfusion in patients with acute ischemic stroke: results from the ESCAPE and ESCAPE-NA1 trials.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management. METHODS: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0-2a. Proportions of good outcome (modified Rankin scale 0-2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained. RESULTS: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81-2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56-2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00-22.97). CONCLUSION: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.

Workflow and Outcomes of Endovascular Thrombectomy for In-Hospital Stroke a Systematic Review and Meta-Analysis.

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.

Intraoperative Complications of Endovascular Treatment of Intracranial Aneurysms with Coiling or Balloon-assisted Coiling in a Prospective Multicenter Cohort of 1088 Participants: Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) Study.

Background Thromboembolic events and intraoperative rupture are the most frequent neurologic complications of intracranial aneurysm coiling. Their frequency has not been evaluated in recent series. Purpose To provide an analysis of complications, clinical outcome, and participant and aneurysm risk factors after aneurysm coiling or balloon-assisted coiling within the Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm, or ARETA, cohort. Materials and Methods Sixteen neurointerventional departments prospectively enrolled participants treated for ruptured and unruptured aneurysms between December 2013 and May 2015. Participant demographics, aneurysm characteristics, and endovascular techniques were recorded. Data were analyzed from participants within the overall cohort treated with coiling or balloon-assisted coiling for a single aneurysm. Rates of neurologic complications were analyzed, and associated factors were studied by using univariable analyses (Student t test, χ2 test, or Fisher exact test, as appropriate) and multivariable analyses (logistic regressions). Results A total of 1088 participants (mean age ± standard deviation, 54 years ± 13; 715 women [65.7%]) were analyzed. Thromboembolic events and intraoperative rupture were reported in 113 of 1088 participants (10.4%) and 34 of 1088 participants (3.1%), respectively. Poor clinical outcome (defined as modified Rankin Scale score of 3-6) was reported in 29 of 113 participants (25.7%) with thromboembolic events and in 11 of 34 participants (32.4%) with intraoperative rupture (P = .44). Factors associated with thromboembolic events were female sex (odds ratio [OR], 1.7; 95% confidence interval [CI]: 1.1, 2.8; P = .02) and middle cerebral artery location (OR, 1.9; 95% CI: 1.2, 3.0; P = .008). Factors associated with intraoperative rupture were anterior communicating artery location (OR, 2.2; 95% CI: 1.1, 4.7; P = .03) and small aneurysm size (OR, 3.0; 95% CI: 1.5, 6.3; P = .003). Conclusion During aneurysm coiling or balloon-assisted coiling, thromboembolic events were more frequent than were intraoperative rupture. Both complications were associated with poor clinical outcome in a similar percentage of participants. Risk factors for thromboembolic events were female sex and middle cerebral artery location. Risk factors for intraoperative rupture were small aneurysm size and anterior cerebral or communicating artery location. © RSNA, 2020.

Relationship Between Carotid Web Morphology on CT Angiography and Stroke: A Pooled Multicenter Analysis.

BACKGROUND: The Carotid web (CaW) is a cause of stroke particularly in younger individuals. However it's frequency, and the radiological features of the web's morphology associated with stroke risk are uncertain. We determined the CaW radiological features on CT angiography associated with ipsilateral stroke. MATERIAL AND METHODS: Data from six studies of patients with acute ischemic stroke were pooled. Identification and measurement of CaWs were performed by experienced readers on 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 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 (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%CI 1.03-3.28]), thickness (aOR 2.31 [95%CI 1.08-4.97]), volume (aOR 1.07 per 1 mm3 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.