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.

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.

Endovascular Parent Vessel Occlusion Versus Flow Diversion in the Treatment of Large and Giant Aneurysms: A Randomized Comparison.

OBJECTIVE: Parent vessel occlusion (PVO) is a time-honored treatment for unclippable or uncoilable intracranial aneurysms. Flow diversion (FD) is a recent endovascular alternative that can occlude the aneurysm and spare the parent blood vessel. Our aim was to compare outcomes of FD with endovascular PVO. METHODS: This is a prespecified treatment subgroup analysis of the Flow diversion in Intracranial Aneurysms trial (FIAT). FIAT was an investigator-led parallel-group all-inclusive pragmatic randomized trial. For each patient, clinicians had to prespecify an alternative management option to FD before stratified randomization. We report all patients for whom PVO was selected as the best alternative treatment to FD. The primary outcome was a composite of core-lab determined angiographic occlusion or near-occlusion at 3-12 months combined with an independent clinical outcome (mRS<3). Primary analyses were intent-to-treat. There was no blinding. RESULTS: There were 45 patients (16.2% of the 278 FIAT patients randomized between 2011 and 2020 in 3 centers): 22 were randomly allocated to FD and 23 to PVO. Aneurysms were mainly large or giant (mean 22 mm) anterior circulation (mainly carotid) aneurysms. A poor primary outcome was reached in 11/22 FD (50.0%) compared to 9/23 PVO patients (39.1%) (RR: 1.28, 95% CI [0.66-2.47]; P = 0.466). Morbidity (mRS >2) at 1 year occurred in 4/22 FD and 6/23 PVO patients. Angiographic results and serious adverse events were similar. CONCLUSIONS: The comparison between PVO and FD was inconclusive. More randomized trials are needed to better determine the role of FD in large aneurysms eligible for PVO.

Prevalence of "Ghost Infarct Core" after Endovascular Thrombectomy.

BACKGROUND AND PURPOSE: Baseline CTP sometimes overestimates the size of the infarct core ("ghost core" phenomenon). We investigated how often CTP overestimates infarct core compared with 24-hour imaging, and aimed to characterize the patient subgroup in whom a ghost core is most likely to occur. MATERIALS AND METHODS: Data are from the randomized controlled ESCAPE-NA1 trial, in which patients with acute ischemic stroke undergoing endovascular treatment were randomized to intravenous nerinetide or placebo. Patients with available baseline CTP and 24-hour follow-up imaging were included in the analysis. Ghost infarct core was defined as CTP core volume minus 24-hour infarct volume > 10 mL). Clinical characteristics of patients with versus without ghost core were compared. Associations of ghost core and clinical characteristics were assessed by using multivariable logistic regression. RESULTS: A total of 421 of 1105 patients (38.1%) were included in the analysis. Forty-seven (11.2%) had a ghost core > 10 mL, with a median ghost infarct volume of 13.4 mL (interquartile range 7.6-26.8). Young patient age, complete recanalization, short last known well to CT times, and possibly male sex were associated with ghost infarct core. CONCLUSIONS: CTP ghost core occurred in ∼1 of 10 patients, indicating that CTP frequently overestimates the infarct core size at baseline, particularly in young patients with complete recanalization and short ischemia duration.

Direct to Angiosuite in Acute Stroke with Mobile Stroke Unit.

BACKGROUND: Early reperfusion has the best likelihood for a favorable outcome in acute ischemic stroke (AIS) with large vessel occlusion (LVO). Our experience with mobile stroke unit (MSU) for direct to angiosuite (DTAS) transfer in AIS patients with suspected LVO is presented. METHODS: Retrospective review of prospectively collected data from November 2019 to August 2022, of patients evaluated and transferred by the University of Alberta Hospital MSU and moved to angiosuite for endovascular thrombectomy (EVT). RESULT: A total of 41 cases were included. Nine were chosen for DTAS and 32 were shifted to angiosuite after stopping for computed tomography (CT) angiography of the head and neck (no-DTAS). Stroke severity measured by NIHSS (median with interquartile range (IQR)) was higher in patients of DTAS, 22 (14-24) vs 14.5 (5-25) in no-DTAS (p = 0.001). The non-contrast CT head in MSU showed hyperdense vessels in 8 (88.88%) DTAS vs 11 (34.35%) no-DTAS patients (p = 0.003). The EVT timelines (median with IQR, 90th percentile) including "door to artery puncture time" were 31 (23-50, 49.2) vs 79 (39-264, 112.8) minutes, and "door to recanalization time" was 69 (49-110, 93.2) vs 105.5 (52-178, 159.5) minutes in DTAS vs no-DTAS group, respectively. The workflow times were significantly shorter in the DTAS group (p < 0.001). Eight (88.88%) out of 9 DTAS patients had LVO and underwent thrombectomy. CONCLUSIONS: MSU for DTAS in patients with high NIHSS scores, cortical signs, and CT showing hyperdense vessel is an effective strategy to reduce the EVT workflow time.

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. METHODS: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. RESULTS: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. CONCLUSION: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.

BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. RESULTS: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13]). CONCLUSIONS: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02930018.

Treatment of wide-necked bifurcation aneurysms with the eCLIPs device: 5-year experience of a single center.

BACKGROUND: The endovascular clip system (eCLIPs) is a novel device with both neck bridging and flow-diversion properties that make it suitable for the treatment of wide-necked bifurcation aneurysms. OBJECTIVE: To describe the clinical and radiologic outcomes of the eCLIPs device, including the first-in-man use of the latest version of the device. METHODS: This is a retrospective case series on all the wide-necked bifurcation aneurysms treated with the eCLIPs device in our center. The immediate and latest radiologic and clinical outcomes were assessed. RESULTS: The device was successfully implanted in 12 of 13 patients. After a median follow-up period of 19 months (range 3-64 months), all patients with available data (11/12) had a good radiologic outcome (modified Raymond-Roy classification scores of 1 or 2). Two patients (18.2%) underwent re-treatment with simple coiling through the device. One of these had a subarachnoid hemorrhage prior to re-treatment. There were no major complications (death or permanent neurologic deficits) associated with use of the device. CONCLUSION: Our series demonstrates occlusion rates that are similar to those of standard stent-assisted coiling and intrasaccular flow diversion for wide-necked bifurcation aneurysms. Larger registry-based studies are necessary to support our findings.

How to Define Fast and Slow Progressors in Any-Type Occlusion Acute Ischemic Stroke.

The variable rate of infarct progression in acute ischemic stroke as assessed by various thresholds excludes a substantial proportion of patients due to time or core constraints. We evaluated 106 patients with any-type occlusion to compare these thresholds and assessed performance of hypoperfusion index (HI) for fast and slow rate of infarct progression. Seven (12.5%) were classified fast progressors and 23 (46%), 25 (50%), 12 (24%), and 33 (66%) slow progressors using different core and time criteria. In comparison, HI categorized 100% (n = 106) of cohort with optimal cutoff 0.5 for any-type occlusion (slow progressors: HI ≤ 0.5), sensitivity/specificity 100%/91%, AUC 0.94, and indicative of eligibility for reperfusion and clinical outcomes (median 90-day modified Rankin Scale; 2 for HI ≤ 0.5 versus 5). Estimation of progressors by HI seems comprehensive but needs external validation.

Canadian Association of Radiologists Guidance on Contrast-Associated Acute Kidney Injury.

Purpose: Iodinated contrast media is one of the most frequently administered pharmaceuticals. In Canada, over 5.4 million computed tomography (CT) examinations were performed in 2019, of which 50% were contrast enhanced. Acute kidney injury (AKI) occurring after iodinated contrast administration was historically considered a common iatrogenic complication which was managed by screening patients, prophylactic strategies, and follow-up evaluation of renal function. The Canadian Association of Radiologists (CAR) initially published guidelines on the prevention of contrast induced nephropathy in 2007, with an update in 2012. However, new developments in the field have led to the availability of safer contrast agents and changes in clinical practice, prompting a complete revision of the earlier recommendations. Information sources: Published literature, including clinical trials, retrospective cohort series, review articles, and case reports, along with expert opinions from radiologists and nephrologists across Canada. Methods: The leadership of the CAR formed a working group of radiologists and nephrologists with expertise in contrast administration and patient management related to contrast-associated AKI. We conducted a comprehensive review of the published literature to evaluate the evidence about contrast as a cause of AKI, and to inform evidence-based recommendations. Based on the available literature, the working group developed consensus recommendations. Key Findings: The working group developed 21 recommendations, on screening, choice of iodinated contrast media, prophylaxis, medication considerations, and post contrast administration management. The key changes from the 2012 guidelines were (1) Simplification of screening to a simple questionnaire, and not delaying emergent examinations due to a need for creatinine measurements (2) Prophylaxis considerations only for patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 (3) Not recommending the routine discontinuation of any drugs to decrease risk of AKI, except metformin when eGFR is less than 30 mL/min/1.73 m2 and (4) Not requiring routine follow up serum creatinine measurements post iodinated contrast administration. Limitations: We did not conduct a formal systematic review or meta-analysis. We did not evaluate our specific suggestions in the clinical environment. Implications: Given the importance of iodinated contrast media use in diagnosis and management, and the low risk of AKI after contrast use, these guidelines aim to streamline the processes around iodinated contrast use in most clinical settings. As newer evidence arises that may change or add to the recommendations provided, the working group will revise these guidelines.

Justification: Les agents de contraste iodés (ACI) sont parmi les produits pharmaceutiques les plus fréquemment administrés. Au Canada, plus de 5,4 millions d'examens de tomodensitométrie (TDM) ont été réalisés en 2019, dont 50 % ont été faits avec un ACI. L'insuffisance rénale aiguë (IRA) survenant après l'administration d'un ACI était historiquement considérée comme une complication iatrogénique fréquente qui était prise en charge par le dépistage des patients, des stratégies prophylactiques et une évaluation de suivi de la fonction rénale. L'Association canadienne des radiologistes (CAR) a publié des lignes directrices pour la prévention de la néphropathie induite par les agents de contraste en 2007 et une mise à jour en 2012. De nouveaux développements sur le terrain ont toutefois mené à la disponibilité d'agents de contraste plus sécuritaires et à des changements dans la pratique clinique, ce qui a entraîné une révision complète des recommandations antérieures. Sources: La littérature publiée, y compris les essais cliniques, les séries de cohortes rétrospectives, les articles-synthèse et les rapports de cas, de même que les opinions d'experts de radiologistes et de néphrologues de partout au Canada. Méthodologie: La direction de la CAR a formé un groupe de travail composé de radiologues et de néphrologues ayant une expertise dans l'administration d'ACI et la gestion de patients atteints d'IRA survenant après l'administration d'un ACI. Le groupe a procédé à une revue complète de la littérature publiée afin d'évaluer les données probantes sur les ACI comme cause de l'IRA et de formuler des recommandations en fonction de celles-ci. Le groupe de travail a élaboré des recommandations consensuelles en se fondant sur la documentation disponible. Principaux résultats: Le groupe de travail a élaboré 21 recommandations sur le dépistage, le choix des agents de contraste iodés, la prophylaxie, les considérations relatives aux médicaments et la gestion post-administration de l'ACI. Les principaux changements par rapport aux lignes directrices de 2012 étaient : (1) de simplifier le dépistage à un simple questionnaire et de ne pas retarder les examens émergents en raison du besoin de mesurer la créatinine; (2) d'avoir des considérations prophylactiques uniquement pour les patients dont le débit de filtration glomérulaire estimé (DFGe) est inférieur à 30 mL/min/1,73 m2; (3) de ne pas recommander l'arrêt des médicaments visant à réduire le risque d'IRA, comme c'est normalement le cas, sauf la metformine lorsque le DFGe est inférieur à 30 mL/min/1,73 m2 et; (4) ne pas demander de mesures de suivi de routine de la créatinine sérique après administration d'un agent de contraste iodé. Limites: Le groupe n'a pas procédé à une revue formelle et systématique de la littérature sur le sujet ni à une méta-analyse. Les suggestions n'ont pas été évaluées dans un environnement clinique. Conclusion: Compte tenu de l'importance des agents de contraste iodés dans le diagnostic et la prise en charge des patients, et du faible risque d'IRA encouru après leur administration, ces recommandations ne visent qu'à simplifier les processus relatifs à l'utilisation des ACI dans la plupart des milieux cliniques. Le groupe de travail révisera ces lignes directrices au fur et à mesure que des éléments de preuve plus récents seront ajoutés aux recommandations fournies.

Canadian Association of Radiologists Guidance on Contrast Associated Acute Kidney Injury.

Iodinated contrast media (ICM) is one of the most frequently administered pharmaceuticals. In Canada, over 5.4 million computed tomography (CT) examinations were performed in 2019, of which 50% were contrast enhanced. Acute kidney injury (AKI) occurring after ICM administration was historically considered a common iatrogenic complication which was managed by screening patients, prophylactic strategies, and follow up evaluation of renal function. The Canadian Association of Radiologists (CAR) initially published guidelines on the prevention of contrast induced nephropathy in 2007, with an update in 2012. However, new developments in the field have led to the availability of safer contrast agents and changes in clinical practice, prompting a complete revision of the earlier recommendations. This revised guidance document was developed by a multidisciplinary CAR Working Group of radiologists and nephrologists, and summarizes changes in practice related to contrast administration, screening, and risk stratification since the last guideline. It reviews the scientific evidence for contrast associated AKI and provides consensus-based recommendations for its prevention and management in the Canadian healthcare context. This article is a joint publication in the Canadian Association of Radiologists Journal and Canadian Journal of Kidney Health and Disease, intended to inform both communities of practice.

Association of Stent-Retriever Characteristics in Establishing Successful Reperfusion During Mechanical Thrombectomy : Results from the ESCAPE-NA1 Trial.

BACKGROUND: Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial. METHODS: Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built. RESULTS: Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46). CONCLUSION: The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

The Utility of Superselective Rotational Angiography for Frameless Stereotactic Navigation During Craniotomy for Micro-Arteriovenous Malformation.

BACKGROUND: Micro-arteriovenous malformations (AVMs) can present challenges to neurosurgeons with respect to localization during resection. We sought to describe a novel method that merges super-selective 3-dimensional angiographic images with magnetic resonance imaging (MRI) sequences to facilitate frameless stereotaxic navigation during AVM surgery. METHODS: A retrospective analysis was performed comprising cases that employed merging of angiographic and MRI images for navigation purposes. Baseline clinical and imaging features were recorded. The technique and operative experiences were analyzed descriptively and presented alongside detailed illustrative cases. RESULTS: During the review period, 11 cases were identified where this technique was employed. Successful image acquisition and merging was possible in all cases. Complete obliteration of the target pathology was achieved in all cases. Precise localization of the micro-AVMs minimized dissection in eloquent cortex. CONCLUSIONS: Superselective 3-dimensional angiographic images merged to baseline MRI sequences facilitates planning and navigation during surgery for micro-AVMs.

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial. METHODS: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling. RESULTS: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1). CONCLUSIONS: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Return on Investment in Endovascular Care: The Case of Endovascular Reperfusion Alberta.

OBJECTIVE: We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability. METHODS: We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years). RESULTS: EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at -$7,313 (-$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were -$1.26 (-$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively. CONCLUSION: The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.

Endovascular Device Choice and Tools for Recanalization of Medium Vessel Occlusions: Insights From the MeVO FRONTIERS International Survey.

Background: Endovascular treatment (EVT) for stroke due to medium vessel occlusion (MeVO) can be technically challenging. Devices and tools are rapidly evolving. We aimed to gain insight into preferences and global perspectives on the usage of endovascular tools in treating MeVOs. Methods: We conducted an international survey with seven scenarios of patients presenting A3, M2/3, M3, M3/4, or P2/3 occlusions. Respondents were asked for their preferred first-line endovascular approach, and whether they felt that the appropriate endovascular tools were available to them. Answers were analyzed by occlusion location and geographical region of practice, using multinomial/binary logistic regression. Results: A total of 263 neurointerventionists provided 1836 responses. The first-line preferences of physicians were evenly distributed among stent-retrievers, combined approaches, and aspiration only (33.2, 29.8, and 26.8%, respectively). A3 occlusions were more often treated with stent-retrievers (RR 1.21, 95% CI: 1.07-1.36), while intra-arterial thrombolysis was more often preferred in M3 (RR 2.47, 95% CI: 1.53-3.98) and M3/4 occlusions (RR 7.71, 95% CI: 4.16-14.28) compared to M2/3 occlusions. Respondents who thought appropriate tools are currently not available more often chose stent retrievers alone (RR 2.07; 95% CI: 1.01-4.24) or intra-arterial thrombolysis (RR 3.35, 95% CI: 1.26-8.42). Physicians who stated that they do not have access to optimal tools opted more often not to treat at all (RR 3.41, 95% CI: 1.11-10.49). Stent-retrievers alone were chosen more often and contact aspiration alone less often as a first-line approach in Europe (RR 2.12, 95% CI: 1.38-3.24; and RR 0.49, 95% CI 0.34-0.70, respectively) compared to the United States and Canada. Conclusions: In EVT for MeVO strokes, neurointerventionalists choose a targeted vessel specific first-line approach depending on the occlusion location, region of practice, and availability of the appropriate tools.

Association of CT-Based Hypoperfusion Index With Ischemic Core Enlargement in Patients With Medium and Large Vessel Stroke.

BACKGROUND AND OBJECTIVES: The rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset. METHODS: Core progression was assessed in 106 patients with acute stroke and CT perfusion. Using reperfusion trial core time criteria, fast progressors had core >70 mL within 6 hours of stroke onset and slow progressors had core ≤70 mL, mismatch ≥15 mL, and mismatch to core ratio ≥1.8 within 6 to 24 hours. The relationship between HI and infarct core progression (core/time) was examined using receiver operating characteristics to determine optimal HI cutoff. The HI cutoff was then tested in the overall cohort, compared between MeVO and LVO, and evaluated in patients up to 24 hours from stroke onset to differentiate fast from slow rate of core progression. HI threshold was assessed in a second independent cohort of 110 patients with acute ischemic stroke. RESULTS: In 106 patients with acute stroke, 6.6% were fast progressors, 27.4% were slow progressors, and 66% were not classified as fast or slow progressor by reperfusion trial core time criteria. HI >0.5 was associated with fast progression and able to distinguish fast from slow progressors (area under the curve [AUC] 0.94; 95% confidence interval [CI] 0.80-0.99). In MeVO (n = 26) HI >0.5 had a core progression of 0.30 mL/min compared to 0.03 mL/min for HI ≤0.5 (p < 0.001). In LVO (n = 80), HI >0.5 had a core progression of 0.26 mL/min compared to 0.02 mL/min for HI ≤0.5 (p < 0.001). In patients not classified as fast or slow progressor by reperfusion trial criteria, those with HI >0.5 had progression rate of 0.21 mL/min compared to 0.03 mL/min for those with HI ≤0.5 (p < 0.001). Validation in a second cohort of patients with acute ischemic stroke (n = 110; MeVO = 42, LVO = 68) yielded similar results for HI >0.5 to distinguish fast and slow core progression with an AUC of 0.84 (95% CI 0.72-0.97). DISCUSSION: HI can differentiate fast from slow core progression in MeVO and LVO within the first 24 hours of acute ischemic stroke. Consideration of core progression rate at time of stroke evaluation may have implications in the selection of patients with MeVO and LVO stroke for reperfusion therapy that warrant further study.

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.

Which Acute Ischemic Stroke Patients Are Fast Progressors?: Results From the ESCAPE Trial Control Arm.

BACKGROUND AND PURPOSE: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. METHODS: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. RESULTS: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, P=0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], P=0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery. CONCLUSIONS: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.