Collaterals at angiography guide clinical outcomes after endovascular stroke therapy in HERMES.

BACKGROUND: Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. METHODS: The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. RESULTS: Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. CONCLUSIONS: Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

Challenges to Widespread Implementation of Stroke Thrombectomy.

Endovascular treatment (EVT) for acute ischemic stroke is one of the most efficacious and effective treatments in medicine, yet globally, its implementation remains limited. Patterns of EVT underutilization exist in virtually any health care system and range from a complete lack of access to selective undertreatment of certain patient subgroups. In this review, we outline different patterns of EVT underutilization and possible causes. We discuss common challenges and bottlenecks that are encountered by physicians, patients, and other stakeholders when trying to establish and expand EVT services in different scenarios and possible pathways to overcome these challenges. Lastly, we discuss the importance of implementation research studies, strategic partnerships, and advocacy efforts to mitigate EVT underutilization.

Siloed mentality, health system suboptimization and the healthcare symphony: a Canadian perspective.

Measuring and optimizing a health system is challenging when patient care is split between many independent organizations. For example, patients receive care from their primary care provider, outpatient specialist clinics, hospitals, private providers and, in some instances, family members. These silos are maintained through different funding sources (or lack of funding) which incentivize siloed service delivery. A shift towards prioritizing patient outcomes and keeping the patient at the centre of care is emerging. However, competing philosophies on patient needs, how health is defined and how health is produced and funded is creating and engraining silos in the delivery of health services. Healthcare and health outcomes are produced through a series of activities conducted by diverse teams of health professionals working in concert. Health professionals are continually learning from each patient interaction; however, silos are barriers to information exchange, collaborative evidence generation and health system improvement. This paper presents a systems view of healthcare and provides a systems lens to approach current challenges in health systems. The first part of the paper provides a background on the current state and challenges to healthcare in Canada. The second part presents potential reasons for continued health system underperformance. The paper concludes with a system perspective for addressing these challenges.

Association Between Time to Treatment With Endovascular Thrombectomy and Home-Time After Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Home-time is a patient-prioritized stroke outcome that can be derived from administrative data linkages. The effect of faster time-to-treatment with endovascular thrombectomy (EVT) on home-time after acute stroke is unknown. METHODS: We used the Quality Improvement and Clinical Research registry to identify a cohort of patients who received EVT for acute ischemic stroke between 2015 and 2022 in Alberta, Canada. We calculated days at home in the first 90 days after stroke. We used ordinal regression across 6 ordered categories of home-time to evaluate the association between onset-to-arterial puncture and higher home-time, adjusting for age, sex, rural residence, NIH Stroke Scale, comorbidities, intravenous thrombolysis, and year of treatment. We used restricted cubic splines to assess the nonlinear relationship between continuous variation in time metrics and higher home-time, and also reported the adjusted odds ratios within time categories. We additionally evaluated door-to-puncture and reperfusion times. Finally, we analyzed home-time with zero-inflated models to determine the minutes of earlier treatment required to gain 1 day of home-time. RESULTS: We had 1,885 individuals in our final analytic sample. There was a nonlinear increase in home-time with faster treatment when EVT was within 4 hours of stroke onset or 2 hours of hospital arrival. There was a higher odds of achieving more days at home when onset-to-puncture time was <2 hours (adjusted odds ratio 2.36, 95% CI 1.77-3.16) and 2 to <4 hours (1.37, 95% CI 1.11-1.71) compared with ≥6 hours, and when door-to-puncture time was <1 hour (aOR 2.25, 95% CI 1.74-2.90), 1 to <1.5 hours (aOR 1.89, 95% CI 1.47-2.41), and 1.5 to <2 hours (1.35, 95% CI 1.04-1.76) compared with ≥2 hours. Results were consistent for reperfusion times. For every hour of faster treatment within 6 hours of stroke onset, there was an estimated increase in home-time of 4.7 days, meaning that approximately 1 day of home-time was gained for each 12.8 minutes of faster treatment. DISCUSSION: Faster time-to-treatment with EVT for acute stroke was associated with greater home-time, particularly within 4 hours of onset-to-puncture and 2 hours of door-to-puncture time. Within 6 hours of stroke onset, each 13 minutes of faster treatment is associated with a gain of 1 day of home-time.

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.

Adaptive Randomization Method to Prevent Extreme Instances of Group Size and Covariate Imbalance in Stroke Trials.

BACKGROUND: A recent review of randomization methods used in large multicenter clinical trials within the National Institutes of Health Stroke Trials Network identified preservation of treatment allocation randomness, achievement of the desired group size balance between treatment groups, achievement of baseline covariate balance, and ease of implementation in practice as critical properties required for optimal randomization designs. Common-scale minimal sufficient balance (CS-MSB) adaptive randomization effectively controls for covariate imbalance between treatment groups while preserving allocation randomness but does not balance group sizes. This study extends the CS-MSB adaptive randomization method to achieve both group size and covariate balance while preserving allocation randomness in hyperacute stroke trials. METHODS: A full factorial in silico simulation study evaluated the performance of the proposed new CSSize-MSB adaptive randomization method in achieving group size balance, covariate balance, and allocation randomness compared with the original CS-MSB method. Data from 4 existing hyperacute stroke trials were used to investigate the performance of CSSize-MSB for a range of sample sizes and covariate numbers and types. A discrete-event simulation model created with AnyLogic was used to dynamically visualize the decision logic of the CSSize-MSB randomization process for communication with clinicians. RESULTS: The proposed new CSSize-MSB algorithm uniformly outperformed the CS-MSB algorithm in controlling for group size imbalance while maintaining comparable levels of covariate balance and allocation randomness in hyperacute stroke trials. This improvement was consistent across a distribution of simulated trials with varying levels of imbalance but was increasingly pronounced for trials with extreme cases of imbalance. The results were consistent across a range of trial data sets of different sizes and covariate numbers and types. CONCLUSIONS: The proposed adaptive CSSize-MSB algorithm successfully controls for group size imbalance in hyperacute stroke trials under various settings, and its logic can be readily explained to clinicians using dynamic visualization.

Infarcts Due to Large Vessel Occlusions Continue to Grow Despite Near-Complete Reperfusion After Endovascular Treatment.

BACKGROUND AND PURPOSE: Infarcts in acute ischemic stroke (AIS) patients may continue to grow even after reperfusion, due to mechanisms such as microvascular obstruction and reperfusion injury. We investigated whether and how much infarcts grow in AIS patients after near-complete (expanded Thrombolysis in Cerebral Infarction [eTICI] 2c/3) reperfusion following endovascular treatment (EVT), and to assess the association of post-reperfusion infarct growth with clinical outcomes. METHODS: Data are from a single-center retrospective observational cohort study that included AIS patients undergoing EVT with near-complete reperfusion who received diffusion-weighted magnetic resonance imaging (MRI) within 2 hours post-EVT and 24 hours after EVT. Association of infarct growth between 2 and 24 hours post-EVT and 24-hour National Institutes of Health Stroke Scale (NIHSS) as well as 90-day modified Rankin Scale score was assessed using multivariable logistic regression. RESULTS: Ninety-four of 155 (60.6%) patients achieved eTICI 2c/3 and were included in the analysis. Eighty of these 94 (85.1%) patients showed infarct growth between 2 and 24 hours post-reperfusion. Infarct growth ≥5 mL was seen in 39/94 (41.5%) patients, and infarct growth ≥10 mL was seen in 20/94 (21.3%) patients. Median infarct growth between 2 and 24 hours post-reperfusion was 4.5 mL (interquartile range: 0.4-9.2 mL). Post-reperfusion infarct growth was associated with the 24-hour NIHSS in multivariable analysis (odds ratio: 1.16 [95% confidence interval 1.09-1.24], P<0.01). CONCLUSION: Infarcts continue to grow after EVT, even if near-complete reperfusion is achieved. Investigating the underlying mechanisms may inform future therapeutic approaches for mitigating the process and help improve patient outcome.

Endovascular treatment to improve outcomes for medium vessel occlusions: The ESCAPE-MeVO trial.

RATIONALE: Clinical outcomes in acute ischemic stroke due to medium vessel occlusion (MeVO) are often poor when treated with best medical management. Data from non-randomized studies suggest that endovascular treatment (EVT) may improve outcomes in MeVO stroke, but randomized data on potential benefits and risks are hitherto lacking. Thus, there is insufficient evidence to guide EVT decision-making in MeVO stroke. AIMS: The primary aim of the ESCAPE-MeVO trial is to demonstrate that acute, rapid EVT in patients with acute ischemic stroke due to MeVO results in better clinical outcomes compared to best medical management. Secondary outcomes are to demonstrate the safety of EVT, its impact on self-reported health-related quality of life, and cost-effectiveness. SAMPLE SIZE ESTIMATES: Based on previously published data, we estimate a sample size of 500 subjects to achieve a power of 85% with a two-sided alpha of 0.05. To account for potential loss to follow-up, 530 subjects will be recruited. METHODS AND DESIGN: ESCAPE-MeVO is a multicenter, prospective, randomized, open-label study with blinded endpoint evaluation (PROBE design), clinicaltrials.gov: NCT05151172. Subjects with acute ischemic stroke due to MeVO meeting the trial eligibility criteria will be allocated in a 1:1 ratio to best medical care plus EVT versus best medical care only. Patients will be screened only at comprehensive stroke centers to determine if they are eligible for the trial, regardless of whether they were previously treated at a primary care center. Key eligibility criteria are (1) acute ischemic stroke due to MeVO that is clinically and technically eligible for EVT, (2) last-known well within the last 12 h, (3) National Institutes of Health Stroke Scale > 5 or 3-5 with disabling deficit, (4) high likelihood of salvageable tissue on non-invasive neuroimaging. STUDY OUTCOMES: The primary outcome is the modified Rankin scale 90 days after randomization (shift analysis), whereby modified Rankin Score 5 and 6 will be collapsed into one category. Secondary outcomes include dichotomizations of the modified Rankin Score at 90 days, 24 h National Institutes of Health Stroke Score, difference between 24 h and baseline National Institutes of Health Stroke Score, mortality at 90 days, health-related quality of life (EQ-5D-5 L), Lawton scale of instrumental activities of daily living score, reperfusion quality (MeVO expanded Thrombolysis in Cerebral Infarction Score) and infarct volume at 24 h, and cost-effectiveness of endovascular recanalization. Safety outcomes include symptomatic and asymptomatic intracranial hemorrhage and procedural complications. DISCUSSION: The ESCAPE-MeVO trial will demonstrate the effect of endovascular thrombectomy in addition to best medical management vis-à-vis best medical management in patients with acute ischemic stroke due to MeVO and provide data for evidence-based treatment decision-making in acute MeVO stroke. DATA ACCESS STATEMENT: The raw data discussed in this mansucript will be made available by the corresponding author upon reasonable request.

In ischemic stroke, adding IV thrombolysis ≤2 h after symptom onset to thrombectomy was associated with benefit.

SOURCE CITATION: Kaesmacher J, Cavalcante F, Kappelhof M, et al; IRIS Collaborators. Time to treatment with intravenous thrombolysis before thrombectomy and functional outcomes in acute ischemic stroke: a meta-analysis. JAMA. 2024;331:764-777. 38324409.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke.

Importance: The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. Objective: To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke. Design, Setting, and Participants: Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023. Exposure: Hospital arrival to arterial puncture time and other time metrics. Main Outcomes and Measures: EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses. Results: Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean [SD] age, 69.0 [13.7] years; 527 male [50.7%]) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset. Conclusions and Relevance: Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.

Endovascular Treatment for Cerebral Venous Thrombosis: Applying Lessons Learned from Clinical Trials of Endovascular Treatment in Acute Arterial Ischemic Stroke.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare but severely disabling form of stroke. Acute treatment mainly consists of medical management, since there is no robust evidence suggesting the benefit of endovascular treatment for CVT. Given the relative lack of data to guide acute treatment decision-making, CVT treatment decisions are mostly made on a case-by-case basis. In some ways, the current status quo of endovascular treatment for CVT resembles the state of endovascular treatment for acute ischemic stroke before the wave of major positive large vessel occlusion endovascular treatment trials in 2015. SUMMARY: The current state of evidence with regard to endovascular CVT treatment is summarized, parallels to acute ischemic stroke are drawn, and it is discussed how the lessons learned from the evolution of acute ischemic stroke endovascular treatment (EVT) trials could be applied to designing a trial of endovascular treatment for CVT. The review ends by outlining possible scenarios for the future of endovascular CVT treatment. KEY MESSAGES: CVT is a serious disease, affecting young patients and their families, and harbors a considerable social and economic burden. Working toward high-level evidence for the best possible treatment strategy and exploring a possible role for EVT to improve outcomes in CVT needs to remain a high priority in stroke research.

Cost-effectiveness of endovascular thrombectomy for acute ischemic stroke with established large infarct in Germany: a decision tree and Markov model.

BACKGROUND: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5). OBJECTIVE: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective. METHODS: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups. CONCLUSIONS: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer.

Two-stage convolutional neural network for segmentation and detection of carotid web on CT angiography.

BACKGROUND: Carotid web (CaW) is a risk factor for ischemic stroke, mainly in young patients with stroke of undetermined etiology. Its detection is challenging, especially among non-experienced physicians. METHODS: We included patients with CaW from six international trials and registries of patients with acute ischemic stroke. Identification and manual segmentations of CaW were performed by three trained radiologists. We designed a two-stage segmentation strategy based on a convolutional neural network (CNN). At the first stage, the two carotid arteries were segmented using a U-shaped CNN. At the second stage, the segmentation of the CaW was first confined to the vicinity of the carotid arteries. Then, the carotid bifurcation region was localized by the proposed carotid bifurcation localization algorithm followed by another U-shaped CNN. A volume threshold based on the derived CaW manual segmentation statistics was then used to determine whether or not CaW was present. RESULTS: We included 58 patients (median (IQR) age 59 (50-75) years, 60% women). The Dice similarity coefficient and 95th percentile Hausdorff distance between manually segmented CaW and the algorithm segmented CaW were 63.20±19.03% and 1.19±0.9 mm, respectively. Using a volume threshold of 5 mm3, binary classification detection metrics for CaW on a single artery were as follows: accuracy: 92.2% (95% CI 87.93% to 96.55%), precision: 94.83% (95% CI 88.68% to 100.00%), sensitivity: 90.16% (95% CI 82.16% to 96.97%), specificity: 94.55% (95% CI 88.0% to 100.0%), F1 measure: 0.9244 (95% CI 0.8679 to 0.9692), area under the curve: 0.9235 (95%CI 0.8726 to 0.9688). CONCLUSIONS: The proposed two-stage method enables reliable segmentation and detection of CaW from head and neck CT angiography.

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.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Association between CT Perfusion Parameters and Hemorrhagic Transformation after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS: Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS: Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.