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Background: We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large-vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration., Methods and Results: We included consecutive patients with anterior circulation large-vessel occlusion from our prospective registry of thrombectomy-eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy-eligible patients (513 women; median age, 77 years [interquartile range, 67-84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0-2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32-0.75]; P =0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31-0.74]; P =0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35-point decrease in 90-day modified Rankin Scale score (ß=-0.35 [95 CI%, -0.68 to 0.01]; P =0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=-1.79 [95% CI, -3.43 to -0.15]; P =0.03) and distal thrombus migration (ß=-0.41 [95% CI, -0.69 to -0.13]; P =0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=-0.46 [95% CI, -0.74 to -0.17]; P =0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=-0.47 [95% CI, -0.96 to 0.01]; P =0.05)., Conclusions: In thrombectomy-eligible patients with anterior circulation large-vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.

Purpose: The benefit of endovascular treatment (EVT) in patients with acute symptomatic isolated occlusion of the internal carotid artery (ICA) without involvement of the middle and anterior cerebral arteries is unclear. We aimed to compare clinical and safety outcomes of best medical treatment (BMT) versus EVT + BMT in patients with stroke due to isolated ICA occlusion., Methods: We conducted a retrospective multicenter study involving patients with isolated ICA occlusion between January 2016 and December 2020. We stratified patients by BMT versus EVT and matched the groups using propensity score matching (PSM). We assessed the effect of treatment strategy on favorable outcome (modified Rankin scale ≤ 2) 90 days after treatment and compared reduction in NIHSS score at discharge, rates of symptomatic intracranial hemorrhage (sICH) and 3‑month mortality., Results: In total, we included 149 patients with isolated ICA occlusion. To address imbalances, we matched 45 patients from each group using PSM. The rate of favorable outcomes at 90 days was 56% for EVT and 38% for BMT (odds ratio, OR 1.89, 95% confidence interval, CI 0.84-4.24; p = 0.12). Patients treated with EVT showed a median reduction in NIHSS score at discharge of 6 points compared to 1 point for BMT patients (p = 0.02). Rates of symptomatic intracranial hemorrhage (7% vs. 4%; p = 0.66) and 3‑month mortality (11% vs. 13%; p = 0.74) did not differ between treatment groups. Periprocedural complications of EVT with early neurological deterioration occurred in 7% of cases., Conclusion: Although the benefit on functional outcome did not reach statistical significance, the results for NIHSS score improvement, and safety support the use of EVT in patients with stroke due to isolated ICA occlusion., (© 2023. The Author(s).)

Background: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice., Methods: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715., Findings: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone., Interpretation: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection., Funding: EU Horizon 2020., Competing Interests: Declaration of interests MB reports funding from EU Horizon 2020 and Deutsche Forschungsgemeinschaft (payments to the institution); honoraria for lectures from Novartis, Boehringer Ingelheim, and Seagen; and consulting fees from NeuroScios and Boehringer Ingelheim and is an editor in chief of Clinical Neuroradiology (Springer). JF reports funding from the European Commission; personal consulting fees from Acandis, Cerenovus, Medtronic, Microvention, Phenox, Stryker, and Roche; consulting at Philips (no payments); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Penumbra and Tonbridge; support for attending meetings or travel from Medtronic and Penumbra; stock or stock options from Tegus Medical, Eppdata, and Vastrax; and participation in a Data Safety Monitoring Board or Advisory Board at Phenox (personal fees) and Stryker (personal fees) and is a past president of ESMINT. SB reports funding from the EU Horizon 2020 research and innovation programme (754640; payments made to the institution); and support for attending meetings or travel from Medtronic and Penumbra; AHA reports unrestricted research grants from Boehringer Ingelheim; honoraria for lectures from BMS/Pfizer, Teva, Roche, Abbvie, Lundbeck, and Novartis; and participation in Advisory Boards for MSD, BMS/Pfizer, Lundbeck, Lilly, and Abbvie. BF reports research grants from Carlos III Institute of Health; personal payment for educational lectures from Servicio Madrileño de Salud; payment for lectures from Euromedice to the institution; personal payment for educational lectures from Takeda; support for attending meetings from Daiichi Sankyo; receipt of materials for research from Abbot. MDH reports funding from Nil; grants to the University of Calgary for the TEMPO-2 trial from Boehringer Ingelheim, Biogen, NoNO (ESCAPE-NA1 trial and ESCAPE-NEXT trial), Canadian Institute for Health Research (ESCAPE-NA1 trial and ESCAPE-NEXT trial), Medtronic (HERMES collaboration), Alberta Innovates (QuICR Alberta Stroke Program); that some of the funds were used for the ESCAPE-NA1 trial from Alberta Innovates; consulting fees from Sun Pharma Brainsgate (paid work for adjudication of clinical trial outcomes); US patents 62/086,077 (licensed to Circle NVI) and 10,916,346 (licensed to Circle NVI); private stock ownership from Circle and PUreWeb; participation as data and safety monitoring committee chair of the RACECAT trial (end 2020), the Oncovir Hiltonel trial (ongoing), and the DUMAS trial (ongoing); participation as a data and safety monitoring committee member of the ARTESIA trial (ongoing), and the BRAIN-AF trial (ongoing); and is president of the Canadian Neurological Sciences Federation (not for profit) and a Board member of the Canadian Stroke Consortium (not for profit). AK reports grants from the European Commission for the TENSION study (payment to the institution). LP reports consulting fees from Balt, Microvention, and Phenox; and support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organization). CZS reports grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region. RAB reports speakers fees from Novo Nordisk and Beyer. HD reports financial compensation for the start-up fee and the obligatory payment to the hospital administration paid by the sponsor (Medical University Heidelberg) to the clinical division (no personal payments); personal consulting fees from Stryker; speakers honorary from Medtronic; support for attending meetings or travel from Medtronic; and past presidency of the Austrian Society of Interventional Radiology and past presidency Austrian Society of Neuroradiology. FD reports consulting fees from Cerenovus, Phenox, Balt, Cerus Endovascular, Stryker; payment for expert testimony from Cerenovus; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Cerenovus, Stryker, Acandis, Asahi, and Penumbra; participation in a Data Safety Monitoring Board or Advisory Board at Cerenovus; and previously work as an associate editor for Journal of NeuroInterventional Surgery and Journal of Clinical Medicine. FF reports consulting fees from Eppdata and support for attending meetings or travel from Microvention, Medtronic, Cerebrovascular Research and Education Foundation (CREF), and Acandis. SG reports consulting fees from Eppdata. CH reports consulting fees from Brainomix and lecture fees from Stryker. SH-J reports funding for data collection, payment, or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Terumo. MG reports research grants from Medtronic and Cerenovus (payments to the University of Calgary); royalties or licenses from Microvention (systems of intracranial access); personal consulting fees from Microvention, Medtronic, Stryker, Mentice, Philips, and Penumbra; and stock or stock options from Circle Neurovascular. CFK was chair of the German stroke registry (unpaid). RM reports payments for a stroke lecture from TMC Academy. MM reports grants from Balt, Medtronic, MicroVention, and Stryker; consulting fees from Siemens; and support for attending meetings or travel from Europa Group. SM-H reports consulting fees from Terumo and Boston Scientific Corporation; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Terumo and Boston Scientific Corporation. NM reports the provision of study materials. PP reports support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organisation). MP reports grants from the German Research Foundation (DFG SFB 1158 A10, DFG KFO 5001 P02, DFG KFO 5001 Z, and DFG SFB TR 240 B02); speaker honoraria unrelated from Merck Serono and Bayer; and support for attending meetings or travel from Merck Serono (travel reimbursement) and Bayer (travel reimbursement). PAR reports consulting fees to the institution from Boehringer Ingelheim and Bayer; and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Bayer, Pfizer, and BMS (all made to the institution). ES reports grants from Hamburg Innovation and Hertie Foundation. DFV reports research grants from MicroVention; consulting fees from Medtronic; and paid lectures from Cerenovus and Johnson & Johnson. WW reports consulting fees to the institution from Abbvie, BMS, GSK, and Servier. GT reports funding from the European Commission (EUHorizon 2020 research and innovation programme, 754640; payments to the institution); personal consulting fees from Acandis, AstraZeneca, Bayer, Boehringer Ingelheim, and Stryker; personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Acandis, Alexion, Marin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, and Stryker; participation as DSMB member for the TEA Stroke Trial (no payments) and ReSCInD trial (no payments); work as a speaker of the Commission for Cerebrovascular Diseases of the German Society of Neurology (DGN; no payments); and membership of the Board of Directors of the European Stroke Organisation (ESO; no payments). All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window., Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others., Results: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001)., Conclusion: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion., Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale., Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002)., Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted., Competing Interests: Disclosures Dr Asdaghi reported employment by the American Heart Association. Dr Dabus reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. Dr Fifi reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. Dr Fischer reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Finitsis reports patent US11166738B2. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. Dr Herweh reported consultancy for Brainomix and Speaker with Stryker. Dr Jadhav reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Kuramatsu reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Pedro Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. Dr Michel reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Mokin reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. Dr Nolte reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. Dr Psychogios reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. Dr Puetz reported being a lecturer for Daiichi Sankyo. Dr Ribo reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Sheth reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. Dr Siddiqui reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts.

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.

The last decade's progress in demonstrating the clinical benefit of endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke has transformed the paradigm of care for these patients. This review presents the milestones in implementing EVT as standard of care, demonstrates the current state of evidence, provides guidance for identifying the candidate patient for EVT, and highlights unsolved and controversial issues. Ongoing trials investigate broadening of EVT indications for patients who present with large core infarction, adjunctive intra-arterial thrombolysis, medium vessel occlusion, low NIHSS, and tandem occlusion., Competing Interests: None declared., (Thieme. All rights reserved.)

Background:  Treatment of ischemic stroke with recombinant tissue plasminogen activator for intravenous thrombolysis (IVT) must be delivered within a narrow time window after symptom onset. This effective hyperacute treatment can be administered after ruling out active anticoagulation with direct oral anticoagulants (DOACs). Whenever this is impractical, e.g., due to aphasia, plasmatic DOAC levels are measured with a consequent delay in the IVT decision-making process ranging from 30 to 60 minutes of time. This study will test the hypothesis that hyperacute point-of-care assessment of clotting time in the patient's whole blood has sufficient diagnostic accuracy to determine immediately whether stroke patients are pretreated with DOAC., Methods and Design:  This will be a prospective single-center diagnostic accuracy study in 1,850 consecutive acute ischemic stroke patients at a tertiary stroke center in Saxony, Germany. Presence of active anticoagulation with DOAC will be determined by point-of-care quantification of clotting time via whole blood viscoelastic testing (ClotPro) using Russell venom viper and ecarin assay compared with high-performance liquid chromatography-tandem mass spectrometry as the reference standard., Discussion:  Viscoelastic point-of-care assessment of clotting time in whole blood might improve swift delivery of time-sensitive hyperacute treatment with IVT in stroke patients., Competing Interests: T.S. received grants from the German Federal Ministry of Health and Kurt Goldstein Institut, royalties from Astra-zeneca for consulting and from Dresden International University for serving as a program director and a lecturer of the Master's Program in Clinical Research. None of these activities were related to the current study. The other authors report no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Objectives: To test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset., Methods: We therefore performed the Retrospective Multicenter Hypoperfusion-Hypodensity Mismatch for The identification of Patients With Stroke Within 4.5 Hours study of patients with acute ischemic stroke and known time of symptom onset. The predictive values of hypoperfusion-hypodensity mismatch for the identification of patients with symptom onset within 4.5 hours were the main outcome measure., Results: Of 666 patients, 548 (82.3%) had multimodal CT within 4.5 hours and 118 (17.7%) beyond 4.5 hours. Hypoperfusion-hypodensity mismatch was visible in 516 (94.2%) patients with symptom onset within and in 30 (25.4%) patients beyond 4.5 hours. CT hypoperfusion-hypodensity mismatch identified patients within 4.5 hours of stroke onset with 94.2% (95% confidence interval [CI] 91.9%-95.8%) sensitivity, 74.6% (95% CI 66.0%-81.6%) specificity, 94.5% (95% CI 92.3%-96.1%) positive predictive value, and 73.3% (95% CI 64.8%-80.4%) negative predictive value. Interobserver agreement for hypoperfusion-hypodensity mismatch was substantial (κ = 0.61, 95% CI 0.53-0.69)., Discussion: Patients with acute ischemic stroke with absence of a hypodensity on native CT (NCCT) within the hypoperfused core lesion on perfusion CT (hypoperfusion-hypodensity mismatch) are likely to be within the time window of thrombolysis. Applying this method may guide the decision to use thrombolysis in patients with unknown time of stroke onset., Trial Registration Information: ClinicalTrials.gov Identifier: NCT04277728., Classification of Evidence: This study provides Class III evidence that CT hypoperfusion-hypodensity mismatch identifies patients with stroke within 4.5 hours of onset., (© 2021 American Academy of Neurology.)

Background and Purpose: Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome., Methods: We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (<36°C) and patients who were normothermic (≥36°C to <37.6°C) after EVT. Moreover, we compared the frequency of complications between these groups., Results: Among 837 patients screened, 416 patients received EVT for acLVO and fulfilled inclusion criteria (200 [48.1%] male, mean age = 76 ± 16 years, median National Institutes of Health Stroke Scale score = 16, interquartile range [IQR] = 12-20). Of these, 209 patients (50.2%) were hypothermic (median temperature = 35.2°C, IQR = 34.7-35.7) and 207 patients were normothermic (median temperature = 36.4°C, IQR = 36.1-36.7) after EVT. In multivariate analysis, hypothermia was not associated with favorable outcome (aRR = 0.99, 95% confidence interval [CI] = 0.75-1.31) and mortality (aRR = 1.18, 95% CI = 0.84-1.66). More hypothermic patients suffered from pneumonia (36.4% vs. 25.6%, p = 0.02) and bradyarrhythmia (52.6% vs. 16.4%, p < 0.001), whereas thromboembolic events were distributed evenly (5.7% vs. 6.8%, not significant)., Conclusions: Inadvertent hypothermia after EVT for acLVO is not associated with improved functional outcome or reduced mortality but is associated with an increased rate of pneumonia and bradyarrhythmia in patients with acute ischemic stroke., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT., Methods: We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted., Results: Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66-82) years, median (interquartile range), 46% men, NIHSS score 17 (13-20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6-8) vs . 8 (7-9); p  < 0.0001) and shorter door-to-groin puncture times (71 (56-84) vs . 101 (79-133) min; p  < 0.0001) than directly admitted patients. sICH (2.8% vs . 1.1%; p  = 0.58), successful reperfusion (81% vs . 77%; p  = 0.56), 90-day favourable outcome (25% vs . 29%; p  = 0.65) and 90-day survival (73% vs . 67%; p  = 0.39) rates were comparable among telestroke and direct admissions., Discussion: Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.

Background: To assess whether thrombus surface morphology has an impact on first pass reperfusion in contact aspiration (CA) and stent retriever (SR) thrombectomy., Methods: From January 2016 to December 2018, consecutive stroke patients with an occlusion of the middle cerebral artery and thrombectomy (CA or SR) were examined in this retrospective study. We assessed patients' characteristics, procedural data and clinical outcome. Thrombus surface on pretreatment digital subtraction angiography (DSA) was categorized into regular versus irregular phenotype by blinded three-reader-consensus. Primary outcome was successful reperfusion (modified treatment in cerebral ischemia (mTICI) 2b-3) after first pass. Data analysis was stratified according to thrombectomy technique and thrombus phenotype., Results: Among 203 patients (76 years (IQR 65.5-81.9), 47.3% male, National Institutes of Health Stroke Scale Score 16 (IQR 12-20)), 155 patients were treated primarily with CA and 48 with SR. 40% (n=62/155) CA and 41.7% (n=20/48) SR-treated patients had a regular thrombus phenotype. In the CA group, successful reperfusion after first pass was more frequently obtained in patients with regular compared with irregular phenotype (69.4% (n=43/62) vs 34.4% (n=32/93); P<0.0001). In contrast, in the SR group, reperfusion after first pass was achieved in 35% (n=7/20; P=0.01) of patients with regular phenotypes. In the CA group, median number of passes (1 (1-2) vs 2 (1-4); P<0.00001) and time from reaching the thrombus to reperfusion (19±27 vs 38±36 min; P=0.0001) were lower among patients with a regular phenotype., Conclusion: Direct CA is associated with higher rates of successful first pass reperfusion in patients with a regular thrombus phenotype in pretreatment DSA., Competing Interests: Competing interests: JCG received speaking fees from Penumbra Inc., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic., Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack., Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (-85%, -46%, -42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, -60%; thrombectomy, -61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers., Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

Stroke networks facilitate access to endovascular treatment (EVT) for patients with ischemic stroke due to large vessel occlusion. In this study we aimed to determine the safety of inter-hospital transfer and included all patients with acute ischemic stroke who were transferred within our stroke network for evaluation of EVT between 06/2016 and 12/2018. Data were derived from our prospective EVT database and transfer protocols. We analyzed major complications and medical interventions associated with inter-hospital transfer. Among 615 transferred patients, 377 patients (61.3%) were transferred within our telestroke network and had transfer protocols available (median age 76 years [interquartile range, IQR 17], 190 [50.4%] male, median baseline NIHSS score 17 [IQR 8], 246 [65.3%] drip-and-ship i.v.-thrombolysis). No patient suffered from cardio-respiratory failure or required emergency intubation or cardiopulmonary resuscitation during the transfer. Among 343 patients who were not intubated prior departure, 35 patients (10.2%) required medical interventions during the transfer. The performance of medical interventions was associated with a lower EVT rate and higher mortality at three months. In conclusion, the transfer of acute stroke patients for evaluation of EVT was not associated with major complications and transfer-related medical interventions were required in a minority of patients.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke., Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018., Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups., Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo., Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Endovascular therapy (EVT) trials enrolled ischemic stroke patients with good pre-stroke functional status. However, this information needed for rapid decision-making is commonly lacking in clinical practice. We hypothesized that initial misjudgment of pre-stroke functional status attenuates clinical outcomes of EVT. Data were derived from our prospective registry of ischemic stroke patients undergoing EVT for anterior circulation large vessel occlusion (01/2016-12/2017). Considering all information accumulated during hospital course, pre-stroke modified Rankin scale (mRS) was independently re-assessed and compared with pre-EVT assessments. Misjudgment was defined as any difference in mRS categories between first- and second-look assessments. Multivariable model was built to adjust for confounding variables of unfavorable outcome (mRS 3-6) and death at 90 days. Overall, we studied 217 patients: median age 75 years (IQR 64-81), 54% women, median NIHSS 17 (12-20) points. Second-look assessment of pre-stroke mRS revealed 73 (34%) cases initially being misjudged by ≥ 1 category and 17 (8%) by ≥ 2 categories. None of the second-look mRS assessments resulted in a lower mRS category than initially rated. Patients whose pre-stroke mRS score was misjudged prior to EVT showed more frequently unfavorable outcome (62/73 [84.9%] vs. 94/144 [65.3%], p = 0.002) or were deceased (30/73 [41.1%] vs. 25/144 [17.4%], p < 0.001) at 90 days than patients with consistent mRS assessments. Moreover, unfavorable outcomes occurred in nearly all patients whose initial mRS was misjudged by ≥ 2 categories (mRS 3-6: 17/17 [100%]; death: 14/17 [82.4%]; p < 0.001). In conclusion, thorough pre-EVT assessment of pre-stroke functional status appears decisive for proper selection of EVT candidates.

Background Space-occupying middle cerebral artery brain infarcts are associated with the development of brain edema, which may lead to cerebral herniation and death despite early hemicraniectomy. Aims To evaluate the benefit of therapeutic hypothermia in patients with space-occupying cerebral infarction treated with hemicraniectomy within 48 h of stroke onset. Methods Patients aged 18-60 years with space-occupying cerebral infarction treated with hemicraniectomy within 48 h and hypothermia (33-34°C) were selected from a single university hospital between 2001 and 2010 (n = 53). Patients treated with hemicraniectomy alone served as comparison group (n = 58), originating from three randomized controlled trials evaluating the effects of early decompressive surgery (DECIMAL, DESTINY, HAMLET). Primary outcome was the score on the modified Rankin scale at 12 months dichotomized between modified Rankin scale 0-3 and modified Rankin scale 4-6. Secondary outcome measures were modified Rankin scale score 0-4 and survival. Risk ratios were adjusted with Poisson regression. Results Mean patient age was 48 years. Median time from stroke onset to hemicraniectomy was 23.5 h in both treatment groups. Treatment with hypothermia had no effect on the primary outcome (modified Rankin scale 0-3 versus 4-6 (13/53 (25%) versus 24/58 (41%)); adjusted risk ratio 0.66, 95% confidence interval 0.38-1.13). Fewer patients treated with hypothermia had a modified Rankin scale score of 0-4 (21/53 (40%) versus 42/58 (72%); adjusted risk ratio 0.53, 95% confidence interval 0.37-0.76) and fewer patients survived (26/53 (49%) versus 46/58 (79%); adjusted risk ratio 0.60, 95% confidence interval 0.44-0.82). Conclusions In patients with space-occupying cerebral infarction, treatment with hypothermia had no additional benefit on functional outcome compared with treatment with hemicraniectomy alone.

Background Five randomized controlled trials recently demonstrated efficacy of endovascular treatment in acute ischemic stroke. Telestroke networks can improve stroke care in rural areas but their role in patients undergoing endovascular treatment is unknown. Aim We compared clinical outcomes of endovascular treatment between anterior circulation stroke patients transferred after teleconsultation and those directly admitted to a tertiary stroke center. Methods Data derived from consecutive patients with intracranial large vessel occlusion who underwent endovascular treatment from January 2010 to December 2014 at our tertiary stroke center. We compared baseline characteristics, onset-to-treatment times, symptomatic intracranial hemorrhage, in-hospital mortality, reperfusion (modified Treatment in Cerebral Infarction 2b/3), and favorable functional outcome (modified Rankin scale ≤ 2) at discharge between patients transferred from spoke hospitals and those directly admitted. Results We studied 151 patients who underwent emergent endovascular treatment for anterior circulation stroke: median age 70 years (interquartile range, 62-75); 55% men; median National Institutes of Health Stroke Scale score 15 (12-20). Of these, 48 (31.8%) patients were transferred after teleconsultation and 103 (68.2%) were primarily admitted to our emergency department. Transferred patients were younger (p = 0.020), received more frequently intravenous tissue plasminogen activator (p = 0.008), had prolonged time from stroke onset to endovascular treatment initiation (p < 0.0001) and tended to have lower rates of symptomatic intracranial hemorrhage (4.2% vs. 11.7%; p = 0.227) and mortality (8.3% vs. 22.6%; p = 0.041) than directly admitted patients. Similar rates of reperfusion (56.2% vs. 61.2%; p = 0.567) and favorable functional outcome (18.8% vs. 13.7%; p = 0.470) were observed in telestroke patients and those who were directly admitted. Conclusions Telestroke networks may enable delivery of endovascular treatment to selected ischemic stroke patients transferred from remote hospitals that is equitable to patients admitted directly to tertiary hospitals.

Objectives: Transesophageal echocardiography (TEE) is the diagnostic gold standard for the detection of structural heart diseases as potential sources of cardiac emboli in patients with acute cerebral ischemia. We sought to determine the diagnostic yield of TEE in patients with acute ischemic stroke or transient ischemic attack (TIA)., Methods: We retrospectively analyzed consecutive patients with acute cerebral ischemia who were admitted to our hospital between October 2008 and December 2011. TEE reports were screened for detection of cardiac source of embolism judged by the recommendation to change medical management. We performed univariate and multivariate analyses to identify predictors of clinically relevant TEE findings among baseline characteristics., Results: Of 3314 patients with ischemic stroke or TIA, TEE was performed in 791 (24%) patients (mean age 64 ± 13 years, 589 [74%] ischemic stroke, 202 [26%] TIA). A potential cardioembolic source was found in 71 (9%) patients with patent foramen ovale with atrial septal aneurysm being the most common finding (24/71 patients, 34%). In multivariate analysis, peripheral vascular disease (OR 2.57; 95%CI 1.00-6.61), imaging evidence of infarction in multiple locations (OR 4.13; 95%CI 1.36-12.58), and infarction in the posterior circulation (OR 2.11; 95%CI 1.01-4.42) were associated with the identification of a potential cardioembolic source with TEE., Conclusion: TEE identified a potential structural cardioembolic source in nearly 10% of our selected patient population with acute ischemic stroke or TIA, thus underlining its diagnostic value. Our data suggest that patients with hitherto unknown stroke etiology should be considered for additional TEE., (© 2016, Wiley Periodicals, Inc.)

Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study. We performed standard coagulation tests and specific tests for dabigatran, rivaroxaban and apixaban plasma levels. We studied 65 patients: mean age 72 ± 13 years, 30 (46 %) male, median NIHSS score 3 (IQR 6). Fifteen (23 %) were on NOAC treatment (5 dabigatran, 5 rivaroxaban, and 5 apixaban, respectively) and 50 (77 %) were not. In patients without NOAC, dabigatran was not detectable (0 ng/ml), and plasma levels of rivaroxaban (median: 10.0 ng/ml, IQR 7.0) and apixaban (7.2 ng/ml, IQR 6.7) were below our lower thresholds that allow thrombolysis. In patients with dabigatran pre-treatment, trough levels (58.0 ng/ml, IQR 143.0) were below our upper threshold that would allow thrombolysis in 3/5 patients. In patients receiving rivaroxaban, trough level (68.0 ng/ml, IQR 64.0) was below our predefined upper thresholds that would allow thrombolysis in 4/5 patients. In all patients on apixaban, trough level was above our predefined threshold of 40 ng/ml that precludes thrombolysis (98.2 ng/ml, IQR 84.3). Predefined thresholds of NOAC plasma levels in the decision of thrombolysis in NOAC treated AIS patients might supplement routine coagulation tests and should be validated in a larger study population.

Background: Selective serotonin reuptake inhibitors (SSRIs) administered in patients following acute ischemic stroke have shown to improve clinical recovery independently of changes in depression. Animal studies have demonstrated that sustained SSRI treatment is superior to short-term SSRI in evoking neurogenesis but how this benefit translates into humans remains to be answered. We hypothesized that in acute ischemic stroke patients, SSRI treatment started before the event leads to improved short-term outcomes compared to de novo SSRI treatment poststroke., Methods: We performed an exploratory analysis in consecutive acute ischemic stroke patients and compared patients already receiving fluoxetine, citalopram, or escitalopram with those who started treatment de novo., Results: Of 2653 screened patients, 239 were included (age, 69 ± 14 years; 42% men, baseline median National Institutes of Health Stroke Scale score, 7 [IQR, 10]). Of these patients, 51 started treatment with SSRI before stroke and 188 were prescribed newly SSRIs during hospitalization. In the adjusted multivariate logistic regression models, SSRI pretreatment was associated with favorable functional outcome at discharge defined as a modified Rankin Scale score of 2 or less (odds ratio [OR], 4.00; 95% confidence interval [CI], 1.68-9.57; P < .005), improved early clinical recovery (OR, 2.35; 95% CI, 1.15-4.81; P = .02), and a trend toward prediction of superior motor recovery (OR, 1.82; 95% CI, .90-3.68; P < .01)., Conclusions: Our data suggest that SSRI pretreatment may improve clinical outcomes in the early stages of acute ischemic stroke supporting the hypothesis that prolonged SSRI treatment started prestroke is superior to poststroke SSRI., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral arterial disease (PAD) is common in patients with acute cerebral ischemia. Indexes of resistance derived from the systolic and diastolic velocities are routinely used in diagnostic transcranial Doppler (TCD) to detect intracranial arterial disease. We sought to explore whether these indexes can predict the presence of PAD in acute cerebral ischemia., Methods: We prospectively evaluated consecutive patients with acute cerebral ischemia. On TCD, peak-systolic and end-diastolic velocities in both middle cerebral and basilar arteries were manually measured to calculate pulsatility index (PI) and resistance index (RI). Increased resistance was defined as PI equal to 1.2 or more and RI equal to .75 or more. Ankle-brachial index (ABI) measurements were performed and an ABI equal to .9 or more was considered predictive of definite PAD., Results: We included 95 patients (45 male, 50 female) aged 66 ± 9 years with a median National Institutes Health Stroke Scale score of 3 (interquartile range, 8) points. The ABI was abnormal and consistent with definite PAD in 24 of 95 (25.3%; 95% confidence interval [CI], 16.4-34.2) patients. Increased PI did not differ among patients with and without PAD (20.8% vs. 28.2%, P = .60). Only 1 patient with PAD had increased RI as opposed to 4 patients without PAD (4.2% vs. 5.6%, P = 1.0). Increased PI was not found to be an independent predictor of PAD (odds ratio [OR], .68; 95% CI, .22-2.12; P = .51). Increases in both PI and RI independently predicted arterial hypertension (OR, 1.62; 95% CI, 1.19-2.21; P = .002 and OR, 3.20; 95% CI, 1.51-6.77; P = .002, respectively)., Conclusions: Our findings indicate that PAD cannot be inferred from intracranial flow parameters predictive of arterial disease and risk factors such as hypertension among patients with acute cerebral ischemia., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Aims: Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition., Methods: We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day(-1) , patients additionally received either 20 mg simvastatin day(-1) or 80 mg fluvastatin day(-1) for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase., Results: Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel., Conclusions: Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2., (© 2014 The British Pharmacological Society.)

The aim of this study was to determine the importance of sleep apnea in relation to clinically silent microvascular brain tissue changes in patients with acute cerebral ischemia. Patients with acute cerebral ischemia prospectively underwent nocturnal respiratory polygraphy within 5 days from symptom-onset. Sleep apnea was defined as apnea-hypopnea-index (AHI) ≥5/h. Experienced readers blinded to clinical and sleep-related data reviewed brain computed tomography and magnetic resonance imaging scans for leukoaraiosis and chronic lacunar infarctions. Ischemic lesions were considered clinically silent when patients did not recall associated stroke-like symptoms. Functional outcome was assessed with modified Rankin Scale at discharge, 6 and 12 months. Fifty-one of 56 (91 %) patients had sleep apnea of any degree. Patients with moderate-to-severe leukoaraiosis (Wahlund score ≥5) were found to have higher mean AHI than those with none or mild leukoaraiosis (34.4 vs. 12.8/h, p < 0.001). Moderate-to-severe sleep apnea (AHI ≥15/h) was found to be an independent predictor of moderate-to-severe leukoaraiosis (adjusted OR 6.03, 95 % CI 1.76-20.6, p = 0.0042) and of moderate-to-severe leukoaraiosis associated with clinically silent chronic lacunar infarctions (adjusted OR 10.5, 95 % CI 2.19-50.6, p = 0.003). The higher the Wahlund score and the AHI, the more likely unfavorable functional outcome resulted over time (p = 0.0373). In acute cerebral ischemia, sleep apnea is associated with clinically silent microvascular brain tissue changes and may negatively influence functional outcome. Routine sleep apnea screening and further investigation of possible long-term effects of non-invasive ventilatory treatment of sleep apnea appear warranted in this at-risk population.

Objective: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke., Methods: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κ(w)) statistic was used to determine the interobserver agreement for ASPECTS., Results: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κ(w) = 0.62; 95% confidence interval 0.54-0.71)., Conclusions: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Background and Purpose: Experimental data suggest a negative interaction between x-ray contrast agents and fibrinolytic efficacy of recombinant tissue-type plasminogen activator (rtPA). We hypothesized that the application of a contrast agent before intravenous thrombolysis with rtPA reduces its clinical efficacy in acute ischemic stroke., Methods: We retrospectively studied consecutive ischemic stroke patients receiving contrast agents for computed tomography angiography before intravenous treatment with rtPA. We compared functional outcomes with an historical control group from the Canadian Alteplase for Stroke Effectiveness Study who did not receive contrast agents before thrombolysis with rtPA. Primary end point was favorable functional outcome at 90 days defined as modified Rankin Scale scores 0 to 2. We performed logistic regression analysis and a propensity score matching analysis to estimate the effect size of contrast agent use as a negative predictor of outcome., Results: We identified 111 patients for the computed tomography angiography and 1119 patients for the control group. Proportions of favorable functional outcome were 47.7% (53/111 patients) for the computed tomography angiography group and 49.5% (542/1094 patients) for the control group (P=0.77). Adjusted probabilities for favorable outcome were 0.48 (95% CI, 0.37-0.58) and 0.51 (95% CI, 0.47-0.54), respectively. Contrast use was associated with reduced odds of favorable outcome (OR, 0.62(;) 95% CI, 0.38-0.99). Propensity score matching suggested a larger effect size (OR, 10.0%; 95% CI, 0.5%-19.3%)., Conclusions: Our study did not show a significant negative clinical effect of x-ray contrast agents applied before intravenous thrombolysis with rtPA. However, to confirm a possible small negative interaction between contrast agents and rtPA, additional experimental and prospective clinical studies are needed.

Objective: A malignant profile of early brain ischemia has been demonstrated in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial. Patients with a malignant profile had a low chance for an independent functional outcome despite thrombolysis within 3-6 h. We sought to determine whether CT angiography (CTA) could identify a malignant imaging profile within 3 h from symptom onset., Methods: We studied consecutive patients (04/02-09/07) with anterior circulation stroke who received CTA before intravenous thrombolysis within 3 h. We assessed the Alberta Stroke Program Early CT Score (ASPECTS) on CTA source images (CTASI). Intracranial thrombus burden on CTA was assessed with a novel 10-point clot burden score (CBS). We analyzed percentages independent (modified Rankin Scale score < or =2) and fatal outcome at 3 months and parenchymal hematoma rates across categorized combined CTASI-ASPECTS + CBS score groups where 20 is best and 0 is worst., Results: We identified 114 patients (median age 73 years [interquartile range 61-80], onset-to-tPA time 129 min [95-152]). Among 24 patients (21%) with extensive hypoattenuation on CTASI and extensive thrombus burden (combined score < or =10), only 4% (1/24) were functionally independent whereas mortality was 50% (12/24). In contrast, 57% (51/90) of patients with less affected scores (combined score 11-20) were functionally independent and mortality was 10% (9/90; p < 0.001). Parenchymal hematoma rates were 30% (7/23) vs. 8% (7/88), respectively (p = 0.008)., Conclusion: CTA identifies a large hyperacute stroke population with high mortality and low likelihood for independent functional outcome despite early thrombolysis., (Copyright 2010 S. Karger AG, Basel.)

The introduction of brain imaging with computed tomography revolutionised the treatment of patients with acute ischaemic stroke. With the visual differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic therapy became feasible. The Alberta Stroke Program Early CT Score was devised to quantify the extent of early ischaemic changes in the middle cerebral artery territory on noncontrast computed tomography. With its systematic approach, the score is simple and reliable. However, the assessment of early ischaemic changes and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke Program Early CT Score is a strong predictor of functional outcome. Furthermore, the effectiveness of intraarterial thrombolysis in patients with middle cerebral artery occlusion shows effect modification by the Alberta Stroke Program Early CT Score. This review summarises the Alberta Stroke Program Early CT Score methodology. We illustrate current knowledge regarding Alberta Stroke Program Early CT Score applied to clinical trials and comment on how Alberta Stroke Program Early CT Score may facilitate clinical treatment decision making and future trial design. Moreover, we introduce a modification of the Alberta Stroke Program Early CT Score methodology that disregards isolated cortical swelling, i.e. focal brain swelling without associated parenchymal hypoattenuation, as early ischaemic changes in the Alberta Stroke Program Early CT Score system.

Background and Purpose: Symptomatic intracranial stenoses have a high risk for a recurrent stroke if treated medically. Although angioplasty and stent placement are proposed treatment options, data on longer-term outcome are limited., Materials and Methods: We analyzed all endovascular procedures on symptomatic intracranial stenosis at our institution from January 1998 to December 2005. We retrospectively assigned patients to group A (symptoms despite antithrombotic therapy) or group B (impaired regional cerebral blood flow [rCBF]). Primary outcome events were periprocedural major complications or recurrent ischemic strokes in the territory of the treated artery. We used the Kaplan-Meier method to calculate survival probabilities., Results: The procedural technical success rate was 92% (35/38) with periprocedural major complications in 4 cases (10.5%; group A [8.3%, 2/24], group B [14.3%, 2/14]). Median (range) follow-up for the 33 patients with technically successful procedures was 21 (0-72) months. Recurrent ischemic strokes occurred in 15% (3/20) of patients in group A and 0% (0/13) of patients in group B. Overall, there were 21% (7/33) primary outcome events (group A [25%, 5/20], group B [15%, 2/13]). There was a nonsignificant trend for better longer-term survival free of a major complication or recurrent stroke in patients with impaired rCBF compared with patients who were refractory to medical therapy treatment (Kaplan-Meier estimate 0.85 [SE 0.10] vs 0.72 [SE 0.11] at 2 years, respectively)., Conclusion: Interventional treatment of symptomatic intracranial stenosis carries significant risk for complications and recurrent stroke in high-risk patients. The observation that patients with impaired rCBF may have greater longer-term benefit than medically refractory deserves further study.

Background: The outcome of vertebrobasilar ischemia depends on the clinical presentation and the presence or absence of vascular occlusion. The aim of our study was to analyze the CT angiography (CTA) predictors of outcome in patients with suspected vertebrobasilar ischemia., Methods: We studied patients with suspected acute vertebrobasilar ischemia between April 2002 and January 2006 and had CTA done within 24 hours of symptom onset. We reviewed the final diagnosis and 3-month follow-up and analyzed the clinical and CTA predictors of outcome., Results: Of the 133 patients, 21(15%), 18 (13%), and 16 (12%) had occlusion of basilar artery (BA), vertebral artery (VA), and posterior cerebral artery (PCA) respectively. The final diagnosis was stroke in 98 (73.6%), transient ischemic attack (TIA) in 10 (7.5%), and nonischemic in 25 (18.8%). No vascular occlusion was seen on CTA in patients with TIA and nonischemic diagnosis. At 3-month follow-up, we found a mortality rate of 10.6% and good functional outcome in 71.4%. The predictors of death in the multivariable analysis were the presence of BA occlusion (odds ratio[OR] 6.7, 95% CI, 1.4-30.6) and baseline National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI, 1.06-1.2). When patients with basilar occlusion were excluded, the presence of VA occlusion (OR 6.5, 95% CI, 1.34-31.4), age (OR 1.09, 95% CI, 1.03-1.14), and baseline NIHSS (OR 1.1, 95% CI, 1.03-1.18) predicted poorer outcome., Conclusions: The presence or absence of a vascular occlusion is a critical factor for prognosis in suspected acute vertebrobasilar ischemia and is correlated with the location of occlusion.