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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., Competing Interests: Disclosures Dr Demchuk reports receiving grant support and personal fees from Medtronic and has a patent with Circle Cardiovascular Imaging on stroke imaging software. Dr Hill reports unrestricted grant funding for the ESCAPE trial to University of Calgary from Covidien/Medtronic and active/in-kind support consortium of public/charitable sources (Heart and Stroke Foundation, Alberta Innovates Health Solutions, Alberta Health Services) and the University of Calgary (Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, and Calgary Stroke Program); grant funding from Boehringer Ingelheim, NoNo Inc, and Stryker; personal fees from Merck, nonfinancial support from Hoffmann-La Roche Canada. In addition, Dr Hill has a submitted patent for triaging systems in ischemic stroke and owns stock in Calgary Scientific, a company that focuses on medical imaging software. Dr Goyal reports receiving an unrestricted institutional grant from Medtronic; he received a grant from Stryker and consulting fees from Stryker, Microvention, Mentice; and he holds patent rights in systems and methods for acute stroke diagnosis with GE Healthcare. Dr Field is PI for the SECRET trial (Study of Rivaroxaban for Cerebral Venous Thrombosis) and receives in-kind study medication from Bayer Canada for the study. She is supported by the Vancouver Coastal Health Research Institute, the Michael Smith Foundation for Health Research, the Heart and Stroke Foundation of Canada. Dr Nogueira reports consulting fees for advisory roles with Stryker Neurovascular, Cerenovus, Medtronic, Phenox, RapidPulse, Anaconda, Perfuze, Genentech, Biogen, Prolong Pharmaceuticals, Imperative Care and stock options for advisory roles with Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte, and Cerebrotec. Dr Swartz reports Grants/Contracts from Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, National Institutes of Health, Ontario Brain Institute, and Sunnybrook Research Institute. Dr Ospel receives consulting fees from NICOLAB. Dr Poppe received research grant from Stryker for EASI-TOC study. Dr Tymianski is CEO of NoNO; patents owned by NoNO. Dr Hill received grants from Canadian Institutes for Health Research, Alberta Innovates, NoNO, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke, Covidien, Boehringer-Ingleheim, Stryker, and Medtronic; fees from Merck; patent for systems of acute stroke diagnosis; a patent issued and licensed to US Patent Office Number: 62/086,077; stock in Calgary Scientific. Dr Goyal received personal fees from Mentice, Medtronic, Microvention, Stryker; patent to systems of acute stroke diagnosis. Nonfinancial interests: Dr Poppe is PI of EASI-TOC study. Dr Demchuk is a member of the editorial board at International Journal of Stroke (Editor). Dr Nogueira is a member of the Physician Advisory Board for Cerenovus/Neuravi. Dr Hill is Director, Board of Circle Neurovascular, Director, Board of the Canadian Neuroscience Federation, and Director, Board of the Canadian Stroke Consortium. Dr Goyal is a member of the editorial board at Stroke (Consulting Editor). The other authors report no conflicts.

Background: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT., Methods: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality., Results: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P <0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P <0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P =0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P =0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P <0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P <0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P =0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P =0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes., Conclusions: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

Background and Purpose- The impact of transfer status on clinical outcomes in the DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) population is unknown. We analyzed workflow and clinical outcome differences between direct versus transfer patients in the DAWN population. Methods- The following time metrics were analyzed for each group: (1) last known well to hospital arrival, (2) hospital arrival to eligibility imaging, (3) hospital arrival to arterial puncture, (4) qualifying imaging to arterial puncture, (5) last known well to arterial puncture, (6) last known well to reperfusion. The primary end point was the rate of functional independence (90-day modified Rankin Scale [mRS] score, 0-2). Using univariate unconditional logistic regression, we calculated odds ratios and 95% CIs for the association between clinically relevant time metrics, transfer status, and functional independence (mRS 0-2). Results- A total of 206 patients were enrolled. Among these, 121 (59%) patients were transferred, and 85 (41%) patients presented directly to a thrombectomy capable center. Median time last seen well to hospital arrival time was similar between the 2 groups (678 versus 696 minutes). The time from hospital arrival to groin puncture was significantly longer in direct patients compared with transferred patients 140 minutes (interquartile range, 105.5-177.5 minutes) and 88 minutes (interquartile range, 55-125 minutes), respectively (P<0.001). Differences in treatment effect or differences in rates of mRS 0-2 in the thrombectomy treated patients were not statistically significant in direct versus transfer patients (odds ratios for mRS 0-2, thrombectomy versus control, were 5.62 in direct and 6.63 in transfer patients, respectively, Breslow-Day P=0.817). Conclusions- Although transfer patients had a faster door to puncture time, benefits of thrombectomy, and rates of mRS 0 to 2 in the treatment group were similar between direct and transferred patients in the DAWN population. These results may inform prehospital and primary stroke centers triage protocols in patients presenting in the late time window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02142283.

Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Background and Purpose: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials., Methods: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis., Results: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2., Conclusions: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640., (© 2017 American Heart Association, Inc.)

Background and Purpose: The objective of this study was to characterize demographics, treatments, and outcomes in the management of unruptured cerebral aneurysms in the United States using a national healthcare database., Methods: Clinical data were derived from the Nationwide Inpatient Sample for the years 1997 through 2006. Patients with unruptured cerebral aneurysms were identified using the appropriate International Classification of Diseases, 9th Revision code (437.3). Hospitalizations, length of stay, hospital charges, discharge pattern, age and gender distribution, and nature of intervention were analyzed. A Bureau of Labor statistics tool was used to adjust hospital and national charges for inflation. Population-adjusted rates were calculated using population estimates generated by the U.S. Census Bureau., Results: Over 100 000 records were retrieved for analysis. During the time period studied, there was a 75% increase in the number of hospitalizations associated with unruptured cerebral aneurysms. Inflation adjusted hospital charges increased by 60%, whereas the total national bill increased by 200%. Overall, length of stay decreased by 37% and in-hospital mortality rates decreased by 54%. The increasing number of hospitalizations and total national charges related to inpatient treatment of unruptured aneurysms were significantly associated with endovascular treatment rather than surgical clipping., Conclusions: Despite recent studies suggesting a low risk of rupture of incidentally diagnosed cerebral aneurysms, data from this study suggest an increasing trend of treatment for this entity in the United States. Furthermore, endovascular intervention is now the major driving force behind the increasing overall national charges. Given the current healthcare climate, the impact of these trends warrants discussion and debate.

Background and Purpose: We sought to investigate the role of the endothelial lining in aneurysmal persistence and recurrence after endovascular treatment of aneurysms., Methods: Bilateral venous pouch canine carotid aneurysms were studied by angiography and pathology 1, 2, and 3 weeks after intraoperative collagen sponge embolization, coated or not coated with fibrinogen (n=15). In 12 dogs the endothelial lining of one aneurysm was removed before embolization, and results were compared with a control aneurysm after bilateral sponge embolization. In 4 animals embolization with a sponge covered with endothelium was compared with treatment with a sponge covered with adventitia. In 4 animals an inverted venous pouch aneurysm embolized with an adventitia-covered sponge was compared with a normal aneurysm embolized with an endothelialized sponge. In 3 animals inverted venous pouch aneurysms were embolized with a sponge covered or not covered with endothelium. Control aneurysms (n=3 or 4 each) included untreated normal, inverted, and de-endothelialized venous pouch aneurysms. Angiographic results at 3 weeks were compared by Wilcoxon's test., Results: Endothelialization of the clot that forms on the sponge was complete at 1 week, forming clefts that developed into recurrences. Reversed or de-endothelialized aneurysms spontaneously thrombosed, while normal venous pouch aneurysms remained patent for at least 3 weeks. The addition of fibrinogen, endothelium, or adventitia to the sponges did not prevent recurrences, which occurred routinely after embolization of endothelialized aneurysm. De-endothelialization of the aneurysmal wall improved angiographic results at 3 weeks (P=0.02), while reversing the venous pouch before embolization led to complete healing (P=0.003)., Conclusions: The endothelial lining is essential to the persistence of residual lesions. Early endothelial invasion of the clot leads to recanalization and recurrences after embolization of aneurysms. This observation provides new opportunities to improve results of endovascular treatment of aneurysms.