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Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain., Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect., Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022., Intervention: EVT vs MM., Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI., Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled., Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased., Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking., Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever., Design, Setting, and Participants: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset., Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever., Main Outcomes and Measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers., Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis., Conclusions and Relevance: In this study, among patients with LVO stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke.

Background: Mechanical thrombectomy (MT) is the standard-of-care treatment for stroke patients with emergent large vessel occlusions. Despite this, little is known about physician decision making regarding MT and prognostic accuracy., Methods: A prospective multicenter cohort study of patients undergoing MT was performed at 11 comprehensive stroke centers. The attending neurointerventionalist completed a preprocedure survey prior to arterial access and identified key decision factors and the most likely radiographic and clinical outcome at 90 days. Post hoc review was subsequently performed to document hospital course and outcome., Results: 299 patients were enrolled. Good clinical outcome (modified Rankin Scale (mRS) score of 0-2) was obtained in 38% of patients. The most frequently identified factors influencing the decision to proceed with thrombectomy were site of occlusion (81%), National Institutes of Health Stroke Scale score (74%), and perfusion imaging mismatch (43%). Premorbid mRS score determination in the hyperacute setting accurately matched retrospectively collected data from the hospital admission in only 140 patients (46.8%). Physicians correctly predicted the patient's 90 day mRS tertile (0-2, 3-4, or 5-6) and final modified Thrombolysis in Ischemic Cerebral Infarction score preprocedure in only 44.2% and 44.3% of patients, respectively. Clinicians tended to overestimate the influence of occlusion site and perfusion imaging on outcomes, while underestimating the importance of pre-morbid mRS., Conclusions: This is the first prospective study to evaluate neurointerventionalists' ability to accurately predict clinical outcome after MT. Overall, neurointerventionalists performed poorly in prognosticating patient 90 day outcomes, raising ethical questions regarding whether MT should be withheld in patients with emergent large vessel occlusions thought to have a poor prognosis., Competing Interests: Competing interests: KMF, MC, JAH, FCA, MM, and PK serve on the editorial board of JNIS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Loss of retinal ganglion cells after occipital lobe damage is known to occur through transsynaptic retrograde degeneration in congenital lesions; however, studies of this phenomenon in acquired pathology, such as strokes affecting postgenicular visual pathway, are scant. We studied a cohort of adult patients with known onset of occipital lobe stroke to look for the presence, rate, and timing of macular ganglion cell loss on optical coherence tomography., Methods: Retrospective review of patients seen in tertiary neuro-ophthalmology practice with homonymous hemianopia secondary to occipital lobe stroke of known onset. Optical coherence tomography of the macular ganglion cell complex (GCC) was performed, and hemifields corresponding to the side of the visual field (VF) defect were compared with the control retinal hemifield., Results: Fifteen patients with homonymous VF defects were included in the study, and 8 of these (53.3%) demonstrated GCC hemifield thickness of less than 90% on the side corresponding to VF loss including 2/9 (22%) patients who had a stroke less than 2.5 years ago and 6/6 (100%) patients who had a stroke longer than 2.5 years ago. The amount of hemifield atrophy correlated to the logarithm of time since stroke onset ( P =0.030) but not age ( P = 0.95) or mean deviation on VF ( P = 0.19). Three patients with longitudinal data showed GCC thinning rates of 1.99, 5.13, and 5.68 µm per year., Conclusion: Transsynaptic retrograde degeneration occurs after occipital lobe stroke as early as 5.5 months after injury and was observed in all patients 2.5 years after stroke., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Competing Interests: Competing interests: None declared.

Background: Endovascular treatment (EVT) for stroke due to medium vessel occlusion (MeVO) can be technically challenging and specific endovascular tools are needed to safely and effectively recanalize these relatively small and fragile vessels. We aimed to gain insight into availability and desired qualities of endovascular devices used in MeVO stroke and examined barriers to adoption of MeVO EVT in clinical practice on a global scale., Methods: We conducted a case-based international survey among neurointerventionalists. As a part of the survey, participants were asked whether they felt appropriate endovascular tools for MeVO stroke exist and are available to them in their clinical practice. We then examined barriers to adopting MeVO EVT and analyzed them by geographic regions., Results: A total of 263 neurointerventionists participated, of which 178 (67.7%) and 83 (31.6%) provided responses on desired qualities of MeVO EVT tools and on barriers to their adoption in local practice, respectively. The majority 121/178 (68%) felt there was substantial room for improvement regarding existing tools. A large proportion 131/178 (73.6%) felt they had appropriate access to existing tools. The most commonly mentioned barrier for adopting MeVO EVT in North America was "awaiting better tools" (9/28 responses, 32.1%), while "awaiting better evidence" (8/26 responses, 30.8%), and the need for improved "funding" (7/26 responses, 26.9%) were important barriers in Europe., Conclusion: The majority of surveyed neurointerventionalists felt that dedicated MeVO EVT tools can be substantially improved upon. Different regions face various challenges in adoption of MeVO EVT, but overall, physicians are mostly awaiting better MeVO EVT tools., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: There is a paucity of data and a belief that endovascular thrombectomy (EVT) has low efficacy for acute ischemic stroke (AIS) in patients with cancer. We aimed to critically compare the clinical outcomes of EVT for AIS in patients with and without cancer., Methods: Records of all patients undergoing EVT for AIS between January 2015 and 2020 were screened for cancer at the time of EVT. Active cancer was defined as patients who were diagnosed with cancer and were undergoing or refused treatment for that cancer. Baseline modified Rankin Scale (mRS), age and sex were used in a 1:5 propensity score matching ratio. After matching we evaluated for any change in the National Institutes of Health Stroke Scale (NIHSS) from baseline to discharge, hemorrhagic transformation (HT), and 90-day mRS and mortality., Results: There were 19 patients with cancer and 95 matched controls. The mean±SD age was 70.89±11.16 years, and 17 (89.47%) were female. The baseline NIHSS was 22 ± 7.5 and baseline mRS was 1 (IQR 1). There was no significant difference in change in baseline to discharge NIHSS, 90-day mRS or mortality; 90-day mRS 0-2 was 45.2% in the non-cancer group versus 46.7% in cancer group (p=0.54). HT was significantly higher in patients with cancer (57.89% vs 6.49%, p<0.001)., Conclusions: In propensity matched analysis of patients undergoing EVT for AIS with and without cancer, 90-day functional outcomes and mortality were similar. However, there was a significantly higher rate of HT in cancer patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch., Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVT pri ) were compared to those who received primary MM (MM pri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality)., Results: Of 540 patients, 286 (53%) received EVT pri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MM pri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MM pri : 3 [2-4], p < 0.001). Functional independence was similar (EVT pri : 77.4% vs MM pri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVT pri : 16.3% vs MM pri : 1.3%, p < 0.001) and neurological worsening (EVT pri : 19.6% vs MM pri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVT pri : 77.4% vs MM pri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVT pri : 77.4% vs MM pri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (p interaction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation., Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378., (© 2022 American Neurological Association.)

Introduction: The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians' approaches to anaesthesia during EVT for MeVO stroke., Methods: In a worldwide, case-based, online survey, physicians' preferred anaesthesia approach during EVT for MeVO stroke was categorized as "initial GA", "initial GA if necessary" (depending on patient cooperation), "no initial GA, but conversion if necessary" (start with local anaesthesia or conscious sedation), and "no GA". Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics., Results: A total of 366 survey participants provided 1464 responses to 4 primary MeVO EVT case-scenarios. One-third of responses (489/1464 [33%]) favoured no initial GA, but conversion if necessary. Both initial GA and initial GA if necessary were preferred in 368/1464 (25%) of responses respectively. No GA was favoured in 244/1464 (17%). Occlusion location, respondent specialization (interventional neuroradiology), higher age, and female respondent sex were significantly associated with GA preference. GA was more often used in Europe than in other parts of the world ( p  < 0.001)., Conclusions: Anaesthesia approaches in MeVO EVT vary across world regions and patient and physician factors. Most physicians in this survey preferred to start with local anaesthesia or conscious sedation and convert to GA if necessary.

Background: M2 segment occlusions represent approximately one-third of non-lacunar ischemic stroke and can lead to permanent neurological deficits. Various techniques are available for mechanical thrombectomy beyond the circle of Willis, but data evaluating their effectiveness and safety are lacking., Methods: A retrospective review of patients with ischemic stroke undergoing mechanical thrombectomy for M2 occlusions from 13 centers in North American and Europe was performed. Tandem or multiple-territory occlusions were excluded. The primary outcome was 90-day modified Rankin Scale and reperfusion rates across stent-retriever, direct aspiration and combined techniques., Results: There were 465 patients (mean age 71.48±14.03 years, 53.1% female) with M2 occlusions who underwent mechanical thrombectomy. Stent-retriever alone was used in 133 (28.6%), direct aspiration alone in 93 (20.0%) and the combined technique in 239 (51.4%) patients. Successful reperfusion was achieved with the combined technique in 198 (82.2%; OR 2.6 (1.1-6.9)), with stent-retriever alone in 112 (84.2%; OR 9.2 (1.9-44.6)) and with direct aspiration alone in 62 (66.7%; referencecategory). Intraprocedural subarachnoid hemorrhages (iSAH) were 36 (7.7%) and were more likely to occur in patients treated with the stent-retrievers (OR 5.0 (1.1-24.3)) and combined technique (OR 4.6 (1.1-20.9)). Good clinical outcome was achieved in 260 (61.8%) patients, while 59 (14.0%) patients died. Older age, higher baseline NIHSS (National Institutes of Health Stroke Scale), parenchymal hemorrhage and iSAH were associated with poor outcome while successful recanalization and higher baseline ASPECTS (Alberta Stroke Program Early CT Score) were associated with good outcome. No differences were found among the three techniques in terms of clinical outcome., Conclusion: Stent-retrievers and a combined approach for M2 occlusions seem more effective than direct aspiration, but with higher rates of iSAH. This leads to no detectable difference in clinical outcome at 3 months., Competing Interests: Competing interests: MC is a member of the JNIS editorial board., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians' decision-making for EVT in primary MeVO stroke., Methods: In an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions ("immediate EVT", "no EVT", or "wait for alteplase effect" [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivariable logistic regression was performed to assess the effect of alteplase on treatment decision., Results: The survey was completed by 366 physicians from 44 countries, resulting in 2196 responses included in this study. In alteplase-treated cases, 641/1098 (58.4%) responses favored immediate EVT, (279/1098 [25.4%]) favored no EVT and 178/1098 (16.2%) opted to wait for alteplase effect. In non-alteplase-treated case scenarios, 846/1098 (78.7%) were in favor of and 252/1098 (21.3%) against EVT. Intravenous alteplase was associated with a lower chance of a decision in favor of immediate EVT (adjusted OR 0.38 [95%CI 0.31 to 0.46])., Conclusions: Intravenous alteplase is an important factor in EVT decision-making for MeVO stroke. However, even in alteplase-treated patients, more than half of the physicians decided to proceed with EVT without waiting for alteplase effect., Competing Interests: Competing interests: Dr. Menon reports editorial board membership at Stroke (Assistant Editor). Dr. Fiehler reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. Dr. Chen reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Ceronovus, Penumbra, outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). Dr. Sakai has nothing to disclose. Dr. Goyal reports personal fees from Stryker, personal fees from Mentice, personal fees from Microvention, personal fees from Medtronic, outside the submitted work; and editorial board membership at Stroke (Consulting Editor); in addition, Dr. Goyal has a patent for systems of acute stroke diagnosis issued and licensed., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: We aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients., Methods: In the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making., Results: Overall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patient age (incidence rate ratio (IRR) 1.24, 99% CI 1.19 to 1.30), higher National Institutes of Health Stroke Scale (NIHSS) score (IRR 1.69, 99% CI 1.57 to 1.82), and small core volume (IRR 1.35, 99% CI 1.24 to 1.46) were positively associated with the decision to treat with EVT. Interventionalists (IRR 1.26, 99% CI 1.01 to 1.56) were more likely to treat patients with MeVO immediately with EVT. In the dominance analysis, factors influencing the decision in favor of EVT were (in order of importance): baseline NIHSS, core volume, alteplase use, patients' age, and occlusion site., Conclusions: Most physicians in this survey were interventionalists and would treat patients with MeVO stroke immediately with EVT. This finding supports the need for robust clinical evidence., Competing Interests: Competing interests: AMD reports editorial board membership at International Journal of Stroke (Editor). BKM reports editorial board membership at Stroke (Assistant Editor). MC reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Cerenovus, Penumbra outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). JF reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and Executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. MG reports personal fees from Stryker, personal fees from Mentice, Microvention, and Medtronic outside the submitted work; and editorial board membership at Stroke (Consulting Editor). In addition, NG has a patent for Systems of acute stroke diagnosis issued and licensed. PC, MK, NS, NK, JMO, RM, NS have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Patients with acute ischemic stroke due to medium vessel occlusion (MeVO) make up a substantial part of the acute stroke population, though guidelines currently do not recommend endovascular treatment (EVT) for them. A growing body of evidence suggests that EVT is effective in MeVOs, including observational data but no randomized studies. We aimed to explore willingness of physicians worldwide to randomize MeVO stroke patients into a hypothetical trial comparing EVT in addition to best medical management versus best medical management only., Methods: In an international cross-sectional survey among stroke physicians, participants were presented with 4 cases of primary MeVOs (6 scenarios each). Each subsequent scenario changed one key patient characteristic compared to the previous one, and asked survey participants whether they would be willing to randomize the described patient. Overall, physician- and scenario-specific decision rates were calculated. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to randomize., Results: Overall, 366 participants (56 women) from 44 countries provided 8784 answers to 24 MeVO case scenarios. The majority of responses (78.3%) were in favor of randomizing. Most physicians were willing to accept patients transferred for EVT from a primary center (82%) and the majority of these (76.5%) were willing to randomize these patients after transfer. Patient age > 65 years, A3 occlusion, small core volume, and patient intravenous alteplase eligibility significantly influenced the physician's decision to randomize (adjOR 1.24, 95%CI 1.13-1.36; adjOR 1.17, 95%CI 1.01-1.34; adjOR 0.98, 95%CI 0.97-0.99 and adjOR 1.38, 95%CI 1.21-1.57, respectively)., Conclusions: Most physicians in this survey were willing to randomize acute MeVO stroke patients irrespective of patient characteristics into a trial comparing EVT in addition to best medical management versus best medical management only, suggesting there is clinical equipoise., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Purpose of the Review: This article aims to provide an update on the designation of stroke centers, neurointerventionalist demand, and cost-effectiveness of stroke thrombectomy in the United States., Recent Findings: There are now more than 1,660 stroke centers certified by national accrediting bodies in the United States, 306 of which are designated as thrombectomy-capable or comprehensive stroke centers. Considering the amount of nationally certified centers and the number of patients with acute stroke eligible for thrombectomy, each center would be responsible for 64 to 104 thrombectomies per year. As a result, there is a growing demand placed on neurointerventionalists, who have the ability to alter the trajectory of large vessel occlusive strokes. Numbers needed to achieve functional independence after stroke thrombectomy at 90 days range from 3.2 to 7.4 patients in the early time window and 2.8 to 3.6 patients in the extended time window in appropriately selected candidates. With the low number needed to treat, in a variety of valued-based calculations and cost-effectiveness analyses, stroke thrombectomy has proved to be both clinically effective and cost-effective., Summary: Advancements in the early recognition and treatment of stroke have been paralleled by a remodeling of health care systems to ensure best practices in a timely manner. Stroke center-accrediting bodies provide oversight to safeguard these standards. As successful trial data from high volume centers transform into real-world experience, we must continue to re-evaluate cost-effectiveness, strike a balance between sufficient case volumes to maintain clinical excellence vs the burden and burnout associated with call responsibilities, and improve access to care for all., (© 2021 American Academy of Neurology.)

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide., Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior)., Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers., Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions., Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Competing Interests: Competing interests: AS reports serving as the Principal Investigator (PI) for SELECT, SELECT2, a site PI for DEFUSE 3, and a speaker bureau and advisory board member in Stryker. MR reports serving as a site PI and steering committee member for SELECT2, and holds consulting agreement for Medtronic, Stryker, Cerenovus, Anaconda Biomed, Apta Targets, Sanofi, and reports serving as a speakers bureau member for: Philips, UCB Pharma, Ischemia View, and reports ownership in Anaconda Biomed, and Methinks. MSH reports receiving fees for consulting for Cerenovus, and reports serving as a member on DSMB for Rapid Medical, and DSMB for Cerenovus, and a steering committee member and a site PI for SELECT2. MGL reports serving as a steering committee member for SELECT2, and PI for DEFUSE 3. BY reports serving as a co-PI for SELECT2 and DIRECTS SAFE. JFA reports having received honoraria as speaker/consultant for the following companies: BI, Pfizer, Daiichi, Bayer, Amgen, and Medtronic; and reports serving as a site PI on SELECT2. The institutions where JFA works have received research funding from Spanish Ministry of Economy, European Comission, and Castilla y León Departments of Health and Education. JMO receives consulting fees from Aptoll, Abbvie, Medtronic, and reports receiving speaker fees from Pfizer, Bristol Myers Squibb. LE reports serving as a site PI on SELECT2 and a sonsultant for Cerenovus, Medtronic, VizAI, Microvention, and Scientia. AA reports serving as a speaker bureau member and consultant for NovaSignal, Longeviti, and Siemens. NW Manning reports serving as a site PI on SELECT2, and a consultant for Balt, Stryker, Microvention and Medtronic. CWS reports serving as an Imaging Core Lab member for SELECT and SELECT2. SEK reports serving as a site PI on SELECT2, and reports receiving consultant fees from Medtronic, receiving grants non-relevant to this work from WL Gore, Medtronic, Bristol-Myers Squibb, and other fees from Bristol-Myers Squibb (consultant), Abbvie (consultant), UpToDate (royalties), and Elsevier (royalties). ASA reports serving as a consultant for Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker, and reports receiving research support from Balt, Medtronic, Microvention, Penumbra, and Siemens, and is a shareholder at Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Marblehead, Mentice, Neurogami, Serenity, Synchron, Triad Medical, and Truvic. MP reports research partnership with Siemens, Apollo Medical Imaging, and Canon; and reports serving as an advisory boards member for Medtronic, Boehringer Ingelheim. AEH reports serving as a consultant/speaker for Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt; a site PI on SELECT2 and COMPLETE study – Penumbra, LVO SYNCHRONISE; steering committee/publication committee member for SELECT, DAWN, SELECT2, EXPEDITE II, EMBOLISE, CLEAR; a Proctor for Pipeline, FRED, Wingspan, and Onyx; and is supported by grants from GE Healthcare, Valley Baptist. GWA reports serving as a steering committee member for SELECT2, PI for DEFUSE 3, and reports receiving consulting fees for iSV and Genentech and has equity interest in iSV. BC, MGA, MC, SB, RFB, NPO, TW, JB, MM, JS, JPT, NS, OK, DG, SW, DC, and TJK report serving as site PIs for SELECT2. VMP, GT, PJ, and JCG report no relevant disclosures and no conflicts of interest to this work.

Few clinical situations in medical practice are as time-sensitive and and have such profound ramifications as selection of patients with acute stroke for mechanical thrombectomy (MT). Emergent large vessel occlusion has become a treatable disease with minimal numbers needed to treat to achieve a functional, long-term neurologic outcome. However, MT carries risk and many patients who are appropriately reperfused continue to have significant neurologic deficits and disability despite a successful procedure. The decision to offer or withhold MT can be complex. Frequently decisions must be made based on incomplete information or emergently while the physician is awoken from sleep or distracted while performing other procedures. A growing number of studies have examined cognitive errors and biases as they pertain to patient diagnosis and treatment in medicine. Dual process theory identifies two decision-making processes as system 1 ('implicit') and system 2 ('explicit') and describes the patterns through which decisions are formulated. The implicit system is the default pathway as it requires little effort or focus, uses mental short cuts, and is rapid; however, this pathway is subject to considerable bias and error. This manuscript reviews the mechanisms underlying the way in which physician decisions about MT are made, specifically highlighting prominent biases that may affect judgment, and reviews other important principles, such as confidence in decisions, aggressiveness to pursue MT, and strategies to improve decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Leptomeningeal anastomoses or pial collateral vessels play a critical role in cerebral blood flow (CBF) restoration following ischemic stroke. The magnitude of this adaptive response is postulated to be controlled by the endothelium, although the underlying molecular mechanisms remain under investigation. Here we demonstrated that endothelial genetic deletion, using EphA4fl/fl/Tie2-Cre and EphA4fl/fl/VeCahderin-CreERT2 mice and vessel painting strategies, implicated EphA4 receptor tyrosine kinase as a major suppressor of pial collateral remodeling, CBF, and functional recovery following permanent middle cerebral artery occlusion. Pial collateral remodeling is limited by the crosstalk between EphA4-Tie2 signaling in vascular endothelial cells, which is mediated through p-Akt regulation. Furthermore, peptide inhibition of EphA4 resulted in acceleration of the pial arteriogenic response. Our findings demonstrate that EphA4 is a negative regulator of Tie2 receptor signaling, which limits pial collateral arteriogenesis following cerebrovascular occlusion. Therapeutic targeting of EphA4 and/or Tie2 represents an attractive new strategy for improving collateral function, neural tissue health, and functional recovery following ischemic stroke.

Introduction: Despite the increasing national adoption of automated computed tomography perfusion (CTP) to select thrombectomy patients 6 hours after last known well, reliability issues have been anecdotally reported. Unreliable diagnostic tests add time and confusion to a process that requires efficiency. Our study aims to critically assess an automated CTP program in a contemporary cohort of patients presenting with large vessel occlusion (LVO) in the extended time window by evaluating the rate of unreliable automated CTP maps and whether this influences clinical outcomes., Methods: A retrospective review of consecutive thrombectomy candidates undergoing CTP imaging in the extended time window was performed. All automated CTP maps using RAPID software (iSchemaView, Menlo Park, CA) were assessed for reliability. Clinical outcomes were compared between patients with and without reliable RAPID reports., Results: Ninety-nine consecutive thrombectomy candidates underwent automated CTP imaging from February 2017 to December 2018. Of these, 78 (79%) had LVO determined by CT angiographyand were included in the study population. Automated CTP maps were unreliable in 13% of cases as a result of motion artifact (n = 3) and contrast bolus flow issues (n = 7). Heart failure was more frequent in patients with unreliable studies. Clinical outcomes did not significantly differ between patients with and without unreliable studies., Conclusions: Thirteen percent of CTP maps generated by automated software were unreliable, with an increased frequency among patients with heart failure. Given the rate of unreliable automated CTP maps, further studies are warranted to not only establish the true necessity of currently available CTP software, but also more reliable methods to select patients for thrombectomy presenting in the extended time window., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background and Purpose: Identifying a last known well (LKW) time surrogate for acute stroke is vital to increase stroke treatment. Diffusion-weighted imaging (DWI) signal intensity initially increases from onset of stroke but mapping a reliable time course to the signal intensity has not been demonstrated., Methods: We retrospectively reviewed stroke code patients between 1/2016 and 6/2017 from the prospective; Institutional review board (IRB) approved University of California San Diego Stroke Registry. Patients who had magnetic resonance imaging of brain from onset, with or without intervention, are included. All ischemic strokes were confirmed and timing from onset to imaging was calculated. Raw DWI intensity is measured using IMPAX software and compared to contralateral side for control for a relative DWI intensity (rDWI). LKW and magnetic resonance imaging (MRI) time were collected by chart review. Correlation is assessed using Pearson correlation coefficient between DWI intensity, rDWI, and time to MRI imaging. 1.5T, 3T, and combined modalities were examined., Results: Seventy-eight patients were included in this analysis. Overall, there was statistically significant positive correlation (.53, P < .001) between DWI intensity and LKW time irrespective of scanner strength. Using 1.5T analyses, there was good correlation (.46, P < .001). 3T MRI analysis further showed comparatively stronger positive correlation (.66, P < .001)., Conclusions: There is good correlation between DWI intensity and minutes from onset to MRI. This suggests a time-dependent DWI intensity response and supports the potential use of DWI intensity measurements to extrapolate an LKW time. Further studies are being pursued to increase both experience and generalizability., (© 2019 by the American Society of Neuroimaging.)

Background: Compared with males, females consistently fare worse following mechanical thrombectomy for large vessel ischemic strokes. Understanding why this gender disparity occurs may guide improvements in future treatment strategies. In this study, we aim to determine whether gender differences in cerebral arterial diameter correlate with clinical outcomes following stroke thrombectomy., Methods: We performed an observational study of consecutive acute ischemic stroke patients undergoing mechanical thrombectomy at a single, urban tertiary care medical center. Catheter angiographic images were used to manually measure proximal segment arterial diameters in a standardized fashion. Medical record review was used to obtain relevant independent and dependent variables., Results: Ninety two patients (42 females) between June 2013 and August 2016 met inclusion criteria. Internal carotid artery (ICA) terminus diameters for males and females were 3.08 mm (SD=0.46) and 2.81 mm (SD=0.45), respectively (P=0.01). M1 segment middle cerebral artery (MCA) diameters for males and females were 2.47 mm (SD=0.30) and 2.18 mm (SD=0.31), respectively (P<0.0001). 48% of patients in the upper MCA caliber tertile attained a favorable mRS 90 day value compared with 35% in each of the lower and middle tertiles (P=0.51). Larger MCA diameters correlated with favorable discharge disposition (P=0.21)., Conclusions: These results provide limited evidence that males have larger cerebral arterial diameters than females and that larger arterial diameters may improve the odds for favorable clinical outcomes. If future studies validate these findings, arterial diameter may become a relevant variable in the design of improved thrombectomy strategies., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose- Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS, <6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods- A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS <6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results- Two hundred fourteen patients (EVT, 124; medical management, 90) were included from 8 US and Spain centers between January 2012 and March 2017. The groups were similar in age, Alberta Stroke Program early computed tomographic score, IV alteplase rate and time last seen normal to presentation. There was no difference in mRS of 0 to 1 between EVT and medical management (55.7% versus 54.4%, respectively; adjusted odds ratio, 1.3; 95% CI, 0.64-2.64; P=0.47). Similar results were seen for mRS of 0 to 2 (63.3% EVT versus 67.8% medical management; adjusted odds ratio, 0.9; 95% CI, 0.43-1.88; P=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5% EVT, 48.4% medical management; odds ratio, 1.17; 95% CI, 0.54-2.52; P=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance ( P=0.07). Symptomatic intracerebral hemorrhage rates were higher with thrombectomy (5.8% EVT versus 0% medical management; P=0.02). Conclusions- Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS, <6) receiving thrombectomy irrespective of thrombus location, with increased symptomatic intracerebral hemorrhage rates, consistent with the guidelines recommending the treatment for NIHSS ≥6. There was a signal toward benefit with EVT only in M1 occlusions; however, this needs to be further evaluated in future randomized control trials.

Competing Interests: Competing interests: None declared.

Importance: The treatment effects of individual mechanical thrombectomy devices in large-vessel acute ischemic stroke (AIS) remain unclear., Objective: To determine whether the novel 3-dimensional (3-D) stent retriever used in conjunction with an aspiration-based mechanical thrombectomy device (Penumbra System; Penumbra) is noninferior to aspiration-based thrombectomy alone in AIS., Design, Setting, and Participants: This randomized, noninferiority clinical trial enrolled patients at 25 North American centers from May 19, 2012, through November 19, 2015, with follow-up for 90 days. Adjudicators of the primary end points were masked to treatment allocation. Patients with large-vessel intracranial occlusion AIS presenting with a National Institutes of Health Stroke Scale (NIHSS) score of at least 8 within 8 hours of onset underwent 1:1 randomization to 3-D stent retriever with aspiration or aspiration alone. The primary analyses were conducted in the intention-to-treat population., Interventions: Mechanical thrombectomy using intracranial aspiration with or without the 3-D stent retriever., Main Outcomes and Measures: The primary effectiveness end point was the rate of a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2 to 3 with a 15% noninferiority margin. Device- and procedure-related serious adverse events at 24 hours were the primary safety end points., Results: Of 8082 patients screened, 198 patients were enrolled (111 women [56.1%] and 87 men [43.9%]; mean [SD] age, 66.9 [13.0] years) and randomized, including 98 in the 3-D stent retriever with aspiration group and 100 in the aspiration alone group; an additional 238 patients were eligible but not enrolled. The median baseline NIHSS score was 18.0 (interquartile range, 14.0-23.0). Eighty-two of 94 patients in the 3-D stent retriever and aspiration group (87.2%) had an mTICI grade of 2 to 3 compared with 79 of 96 in the aspiration alone group (82.3%; difference, 4.9%; 90% CI, -3.6% to 13.5%). None of the other measures were significantly different between the 2 groups. Device-related serious adverse events were reported by 4 of 98 patients in the 3-D stent retriever with aspiration group (4.1%) vs 5 of 100 patients in the aspiration only group (5.0%); procedure-related serious adverse events, 10 of 98 (10.2%) vs 14 of 100 (14.0%). A 90-day modified Rankin Scale score of 0 to 2 was reported by 39 of 86 patients in the 3-D stent retriever with aspiration group (45.3%) vs 44 of 96 patients in the aspiration only group (45.8%)., Conclusions and Relevance: The present study provides class 1 evidence for the noninferiority of the 3-D stent retriever with aspiration vs aspiration alone in AIS. Future trials should evaluate whether these results can be generalized to other stent retrievers., Trial Registration: clinicaltrials.gov Identifier: NCT01584609.

Background: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy., Methods: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days., Results: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00)., Conclusions: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Background: Most patients with large vessel occlusion (LVO) stroke need to be transferred to receive thrombectomy. To save time, the decision to transfer often relies on clinical scales as a surrogate for LVO rather than imaging. However, clinical scales have been associated with high levels of diagnostic error. The aim of this study is to define the susceptibility to overdiagnosis of our current transfer decision process by measuring the rate of non-treatment transfers, the most common reasons for no treatment and potential predictors., Methods: Clinical and transfer data on consecutive patients transferred to a single endovascular capable centre for possible thrombectomy via stroke code activation were retrospectively reviewed. Whether patients underwent the procedure, why they did not undergo the procedure, and other clinical and logistical predictors were recorded. χ 2 tests and multivariate logistic regression analysis were performed., Results: From 2015 to 2016, 105/192 transferred patients (54%) did not undergo thrombectomy and the most common reason was absence of a LVO found on CTA after transfer (71/104 (68%)). 14/16 (88%) with a National Institutes of Health Stroke Scale (NIHSS) score <10 did not undergo thrombectomy while 41/78 (52%) with a NIHSS>20 underwent thrombectomy (p<0.001). Helicopter use was associated with no treatment (p=0.004) while arrival within 5 hours was associated with treatment (p<0.001)., Conclusions: Clinical scales appear to overdiagnose LVO and may be responsible for the majority of our stroke code transfers not undergoing thrombectomy. Primary stroke centres therefore have reason to develop the capability to rapidly acquire and interpret a CTA in patients with suspected LVO prior to transfer. Such efforts may reduce the costs associated with unnecessary thrombectomy transfers., Competing Interests: Competing interests: MC is a consultant for Genentech, Penumbra, Stryker and Medtronic., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Purpose: Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy., Methods: Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality., Results: There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001)., Conclusions: Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The promising results of the Solitaire Flow Restoration (FR) With the Intention for Thrombectomy (SWIFT) trial recently led to Food and Drug Administration (FDA) approval of the Solitaire FR stent retriever device for recanalization of cerebral vessels in patients with acute ischemic stroke., Objective: To report the early postmarket experience with this device since its FDA approval in the United States, which has not been previously described., Methods: We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between March 2012 and July 2012 at 10 United States centers where the Solitaire FR was used as a single device or in conjunction with other intraarterial endovascular approaches., Results: A total of 101 patients were identified (mean age, 64.7 years; mean admission National Institutes of Health Stroke Scale [NIHSS] score, 17.6). Intravenous thrombolysis was administered in 39% of cases; other endovascular techniques were utilized in conjunction with the Solitaire FR in 52%. Successful recanalization (Thrombolysis in Myocardial Infarction 2/3) was achieved in 88%. The rate of symptomatic intracranial hemorrhage within the first 24 hours was 15%. In-hospital mortality was 26%. At 30 days, 38% of patients had favorable functional outcome (modified Rankin scale score ≤2). Severity of NIHSS score on admission was a strong predictor of poor outcome., Conclusion: Our study shows that a variety of other endovascular approaches are used in conjunction with Solitaire FR in actual practice in the United States. Early postmarket results suggest that Solitaire FR is an effective tool for endovascular treatment of acute ischemic stroke.

Though rarely considered in the clinical decision algorithm, issues of cost-effectiveness assume critical importance for the sustainability of a widely used therapy that entails considerable cost and has unproven benefit. Although current data are limited, we review the studies that have demonstrated via modeling that endovascular stroke treatment may generate significant future economic benefits, even if these treatments have a high price and result in relatively small initial reductions in disability. We highlight important considerations that, on the basis of the logistics and protocols of current neuroendovascular practices, should be included in future cost-effectiveness analyses of endovascular therapy for acute ischemic stroke.

Background: Reperfusion therapy for acute ischemic stroke (AIS) is rapidly evolving, with the development of multiple endovascular modalities that can be used alone or in combination., Objective: To determine which pharmacologic or mechanical modality may be associated with increased rates of recanalization., Methods: A cohort of 1122 patients with AIS involving the anterior circulation treated at 13 stroke centers underwent intra-arterial (IA) therapy within 8 hours of symptom onset. Demographic information, admission National Institutes of Health Stroke Scale (NIHSS), mechanical and pharmacologic treatments used, recanalization grade, and hemorrhagic complications were recorded., Results: The mean age was 67 ± 16 years and the median NIHSS was 17. The sites of arterial occlusion before treatment were M1 middle cerebral artery (MCA) in 561 (50%) patients, carotid terminus in 214 (19%) patients, M2 MCA in 171 (15%) patients, tandem occlusions in 141 (13%) patients, and isolated extracranial internal carotid artery occlusion in 35 (3%) patients. Therapeutic interventions included multimodal therapy in 584 (52%) patients, pharmacologic therapy only in 264 (24%) patients, and mechanical therapy only in 274 (24%) patients. Patients treated with multimodal therapy had a significantly higher Thrombolysis in Myocardial Infarction 2 or 3 recanalization rate (435 patients [74%]) compared with pharmacologic therapy only (160 patients, [61%]) or mechanical only therapy (173 patients [63%]), P<.001. In binary logistic regression modeling, independent predictors of Thrombolysis in Myocardial Infarction 2 or 3 recanalization were use of IA thrombolytic OR 1.58 (1.21-2.08), P<.001 and stent deployment 1.91 (1.23-2.96), P<.001., Conclusion: Multimodal therapy has significantly higher recanalization rates compared with pharmacologic or mechanical therapy. Among the individual treatment modalities, stent deployment or IA thrombolytics increase the chance of recanalization., (Copyright © 2011 by the Congress of Neurological Surgeons)

Background and Purpose: The development of comprehensive stroke centers within hub-and-spoke stroke networks offers the opportunity to increase the proportion of acute ischemic stroke patients treated with intra-arterial therapies (IAT). Interhospital transfer delays will be critical in evaluating the success of this strategy., Methods: We collected data on consecutive patients who were transferred to our institution for possible IAT. We defined transfer time as time elapsed from initial transfer call to arrival at our hospital and assessed whether transfer time was a predictor of emergent angiography using multivariable logistic regression., Results: Among 132 patients referred for IAT, 53 (40.2%) were excluded on clinical grounds. The remaining 79 (59.8%) patients (mean age, 61 years; median National Institutes of Health Stroke Scale score, 18; 49.4% male) were analyzed. Sixty-one of 79 (77%) patients underwent emergent angiography for IAT. The median hospital-to-hospital distance was 14.7 (interquartile range, 8.5-21.9) miles and median transfer time was 104 (interquartile range, 80-135) minutes. Transfer time was 33% lower among those who underwent emergent angiography (100.6 versus 149.0 minutes; P<0.001). Adjusting for relevant covariates, transfer time remained an independent predictor of emergent angiography (OR, 0.975; 95% CI, 0.956-0.995; P=0.014). The odds of treatment decrease by 2.5% for every minute of transfer time., Conclusions: Delay in hospital-to-hospital transfer is a common reason that acute ischemic stroke patients are excluded from interventional therapy. The likelihood of receiving IAT decreases rapidly by increasing transfer time. Specific goals for transfer time should be considered in future quality standards for hub-and-spoke-organized stroke networks.

The burden of ischemic stroke in the United States continues to increase each year. Patients with stroke with the most severe disability require a disproportionately large share of healthcare resources. Acute endovascular stroke therapy has the potential to reduce the disability associated with large vessel occlusions and diminish the tremendous economic and emotional burden. This article serves to provide a backdrop on acute stroke therapy focusing on the role, limitations, and benefits of an endovascular approach. We review the rationale, current literature, and future directions of mechanical devices for stroke thrombolysis. We also review pertinent issues related to thrombolysis-related intracerebral hemorrhage and appropriate patient selection.

Background and Purpose: Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT., Methods: A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death., Results: The mean age was 66+/-15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63-3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23-2.30; P<0.0001) compared with conscious sedation., Conclusions: Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

The past decade has witnessed an explosion of devices available for treating acute ischemic stroke. Here, we review a range of recently patented devices and the data supporting their use. These include devices to enhance thrombolysis, thrombectomy devices, stents, devices for augmenting global brain tissue perfusion, and devices that provide neuroprotection after stroke. We discuss specific design elements of these devices and directions for future research. Ultimately, individually tailored combinations of these devices will likely prove most useful in treating patients with acute ischemic stroke.

Objective: Studies on animal models have shown that apoptosis plays a role in acute ischemic stroke, but the clinical significance of apoptosis in human stroke has not been well established., Design and Methods: Acute ischemic stroke patients who had been examined by magnetic resonance imaging (MRI) were recruited, and their blood samples were collected after informed consent obtained. Sixteen samples were taken from 7 patients and 4 control subjects. DNA was extracted from the plasma and analyzed. The plasma level of tumor necrosis factor-alpha (TNF-alpha) was analyzed by western blot, and relative caspase 3/7 activity was assayed., Results: Soluble and membrane-associated TNF-alpha were found to be higher in the plasma from ischemic stroke patients than in that from the controls. Further, this result was more significant in patients with grey matter lesions than white matter lesions., Conclusions: Apoptotic factors are detected in the plasma of patients with acute ischemic stroke and might be related to infarct area., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective and Importance: We report the histopathologic examination of Wingspan stent in acute ischemic stroke., Clinical Presentation: A 75-year-old female presented with acute left-hemiplegia due to right carotid terminus occlusion. Mechanical embolectomy was unsuccessful., Intervention: A Wingspan stent was placed from the distal intracranial carotid artery to the proximal middle cerebral artery stem and established partial antegrade flow. The patient died of malignant infarction on post-stroke day 7. At autopsy, embolized calcified atherosclerotic plaque fragments were noted within a non-occlusive thrombus over which the Wingspan stent was deployed. There was no evidence of intimal or media dissection or perforator ostium occlusion., Conclusion: Our case provides a rare pathological description of intracranial stent placement in the setting of acute ischemic stroke.

Purpose: To determine if radiology residents who used a structured reporting system (SRS) produced higher quality reports than residents who used conventional free-text dictation to report cranial magnetic resonance (MR) imaging in patients suspected of having a stroke., Materials and Methods: The study was approved by an institutional review board and was HIPAA compliant; informed consent was obtained. This study included residents, with 16 in the control group and 18 in the intervention group. For phase 1, each subject reviewed the same set of 25 brain MR imaging cases and dictated the cases by using free-text conventional dictation. For phase 2, 4 months later, the control group repeated the same process, whereas the intervention group reread the same MR imaging cases by using SRS to create reports. Resident-generated reports were graded for accuracy and completeness by a neuroradiologist on the basis of consensus interpretations and criterion standard diagnoses as established with at least 6 months of clinical follow-up, imaging follow-up, and/or histologic examination where appropriate. Accuracy and completeness scores were analyzed by using a Wilcoxon signed rank test for paired data and a Mann-Whitney U test for nonpaired data. Intervention group residents were surveyed regarding their opinions of SRS., Results: For phase 1 reports, no significant difference in accuracy or completeness scores between control and intervention groups was found. Decreases in accuracy (91.5 to 88.7) and completeness (68.7 to 54.3) scores for phase 2 compared with phase 1 for the intervention group were found; increases in accuracy (91.4 to 92.4) and completeness (67.8 to 71.7) scores for phase 2 compared with phase 1 for the control group were found (all P values < .001). The most common complaints were that the SRS was overly constraining with regard to report content and was time-consuming to use., Conclusion: While there are many potential benefits of structuring radiology reports, such changes cannot be assumed to improve report accuracy or completeness. Any SRS should be tested for effect on intrinsic report quality.

A 58-year-old man admitted to the hospital with an acute stroke was found to have a left atrial mass attached to the interatrial septum via a stalk. Although initially thought to be a myxoma, the mass was pathologically proved to be a thrombus. Clues pointing to thrombus as the etiology were a history of atrial fibrillation, the absence of anticoagulation, an enlarged left atrium, and the presence of spontaneous echo contrast.

This article focuses on the medical diseases that not only lead to cerebrovascular complications, but at times initially manifest as cerebral infarction. Specifically, I examine the relationships between stroke and various medical diseases (inflammatory disease, migraine and other vasoconstrictive disorders, congenital heart disease, connective tissue disorders, infectious disease, malignancy, and polycystic kidney disease). Many of these conditions may cause cerebrovascular ischemia via nonatherosclerotic mechanisms. Understanding these relationships between stroke and medical disease will allow the reader to better recognize etiologic relationships, and thereby reach more accurate diagnoses.

Background: We aimed to identify the rate of major neurologic improvement (MNI) at 24 h following endovascular recanalization therapy (ERT) for acute ischemic stroke and its association with short-term outcome., Methods: We retrospectively reviewed consecutive acute ischemic stroke patients presenting to our institution over 4 years and undergoing ERT. Angiograms were independently reviewed. Data on demographics, medical history, initial NIHSS score, 24-hour NIHSS score, site of acute vascular lesion, pre- and posttreatment Thrombolysis in Myocardial Infarction scores, symptomatic intracerebral hemorrhage (within 36 h of intervention that was associated with a 4-point decline in NIHSS score) and discharge disposition were collected. We used logistic regression analysis to identify predictors of MNI (defined as >or=8-point improvement in NIHSS or a score of 0-1 at 24 h) and favorable discharge status (defined as home or acute rehabilitation)., Results: Sixty-eight patients were included (median age = 71 years, 60% women, median NIHSS score = 19.5, anterior circulation = 75%). The modes of ERT were pharmacologic only (28%), mechanical only (35%) and multimodal therapy (37%). Thrombolysis in Myocardial Infarction 2 or 3 recanalization was achieved in 64.7% (mechanical only 46%, pharmacologic only 63% and multimodal 84%). The outcomes were: symptomatic intracerebral hemorrhage (11.8%), MNI (26.5%) and favorable discharge (41.2%). Age (OR = 0.93, p = 0.003) and cardioembolic stroke subtype (OR = 6.0, p = 0.018) were independent predictors of MNI. MNI was a strong predictor of favorable discharge status (OR = 46.4, p < 0.001)., Conclusions: Despite initial stroke severity, MNI occurred in over one fourth of the patients and independently and strongly predicted favorable discharge outcome., ((c) 2008 S. Karger AG, Basel.)

Recent research demonstrates the complexity and variety of pathophysiologic processes underlying cerebral ischemia. This review will focus on the multimodal effects of the various drugs currently used for stroke prevention. The most recent clinical studies of each will also be reviewed, and the implications for clinical use and future research discussed. An evolving approach for stroke prevention will include a combination of antiplatelets, increased use of statins, ACE inhibitors and possibly vitamin therapy., ((c) 2005 Prous Science. All rights reserved.)

BackgroundThe pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale.MethodsPREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated.ResultsAs per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series.ConclusionsThe PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture.Trial registrationNCT02186561.