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Background: Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort., Methods: This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers., Results: Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes., Conclusions: In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov., Registration Number: NCT00878813.

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy., Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset., Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313)., Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone., Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT., Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes., Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

Background: There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques., Methods: We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c‑3 reperfusion (FPR)., Results: This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54)., Conclusion: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters., Methods: We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status., Results: In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83)., Conclusion: Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable., (© 2023. The Author(s).)

Background and Purpose: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status., Materials and Methods: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI ( n  = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4)., Results: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26)., Conclusions: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite., (© 2024 by American Journal of Neuroradiology.)

Determining the optimal transportation for each stroke patient is critically important to achieve the best possible outcomes. In border regions the next comprehensive stroke center may be just across an international border, but bureaucratic and financial hurdles may prevent a simple transfer to the next stroke center. We hypothesized that in regions close to international borders, patients may benefit from an "open border, closed transfer scenario", meaning that patients in whom a large vessel occlusion (LVO) is detected in the primary stroke center will benefit from a transfer to the nearest stroke center offering endovascular thrombectomy-even if this may be across a national border. We used the Swiss-German-French trinational region as an example for a region with several international borders within close proximity to one another, and compared two feasible scenarios; (a) a "closed borders, open transfer" scenario, where the patient is transported to any center in the same country, (b) an "open border, closed transfer" scenario, where patients are always transported to the nearby primary stroke center first and then to the nearest comprehensive stroke center in either the same or a neighboring country and (c) and "open borders, open transfer" scenario. The outcome of interest was the predicted probability of acute ischemic stroke patients to achieve a good outcome using a conditional probability model which predicts the likelihood of excellent outcome (modified Rankin scale score of 0-1 at 90 days post-stroke) for patients with suspected LVO. Results were modeled in a virtual map from which the ideal transport concept emerged. For an exemplary LVO stroke patient in Germany, the probability of a good outcome was higher in an open border, closed transfer scenario than with closed borders, open transfer (33.1 vs. 30.1%). Moreover, time to EVT would decrease from 232 min in the first scenario to 169 min in an open border, closed transfer scenario. The catchment area of the University Hospital Basel was almost double the size in an open border, closed transfer scenario compared to closed borders (1674 km 2 vs. 2897 km 2 ) and would receive transfers from 3 primary stroke centers in other countries (2 in Germany and 1 in France). Stroke patients showed a higher likelihood of good outcome in the "open border" scenarios without transfer restrictions to a specific healthcare system. This probably has implications for stroke treatment in all border regions where EVT eligible stroke patients may benefit from transport to the closest EVT capable center whenever possible, regardless of whether this hospital is located in the same or a neighboring country/jurisdiction., (© 2024. The Author(s).)

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors., Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay., Results: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses., Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Deep perforator arteriolopathy (DPA) causes intracerebral haemorrhage (ICH) and lacunar strokes (LS). We compare patient characteristics, MRI findings and clinical outcomes among patients with deep ICH and LS., Patients and Methods: We included patients with MRI-confirmed LS or ICH in the basal ganglia, thalamus, internal capsule or brainstem from the Bernese Stroke Registry. We assessed MRI small vessel disease (SVD) markers, SVD burden score, modified Rankin Scale (mRS) and ischaemic stroke or ICH at 3 months., Results: We included 716 patients, 117 patients (16.3%) with deep ICH (mean age (SD) 65.1 (±15.2) years, 37.1% female) and 599 patients (83.7%) with LS (mean age (SD) 69.7 (±13.6) years, 39.9% female). Compared to LS, deep ICH was associated with a higher SVD burden score (median (IQR) 2 (1-2) vs 1 (0-2)), aOR shift 3.19, 95%CI 2.15-4.75). Deep ICH patients had more often cerebral microbleeds (deep ICH: 71.6% vs LS: 29.2%, p  < 0.001, median count (IQR) 4(2-12) vs 2(1-6)) and a higher prevalence of lacunes (deep ICH: 60.5% vs LS: 27.4% p  < 0.001). At 3 months, deep ICH was associated with higher mRS (aOR shift 2.16, 95%CI 1.21-3.87). Occurrence of ischaemic stroke was numerically but not significantly higher in deep ICH (4.3% vs 2.9%; p  = 0.51). One patient (1.1%) with ICH but none with LS suffered ICH recurrence., Discussion/conclusion: DPA manifesting as ICH is associated with more severe MRI SVD burden and worse outcome compared to LS. The short-term risks of subsequent ischaemic stroke and recurrent ICH are similar in ICH and LS patients. This implies potential consequences for future secondary prevention strategies., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Goeldlin: Grants from Swiss Academy of Medical Sciences/Bangerter-Rhyner-Foundation, Mittelbauvereinigung der Universität Bern (outside the submitted work), Swiss Stroke Society (Förderpreis), European Stroke Organisation (department to department visit grant), Insel Gruppe, and Pfizer congress grant (outside the submitted work). Dr. Siepen: Funding by the Bangerter-Rhyner-Foundation (outside the submitted work). Dr. Fischer: research support from Swiss National Science Foundation, Swiss Heart Foundation, Medtronic (BEYOND SWIFT, SWIFT DIRECT), Stryker, Rapid medical, Penumbra, Phenox (DISTAL), consultancies for Medtronic, Stryker, and CSL Behring (fees paid to institution), participation in an advisory board for Alexion/Portola and Boehringer Ingelheim (fees paid to institution).Dr. Seiffge: Advisory board for Bayer and Portola/Alexion, Research grant from the Bangerter-Rhyner Foundation. All other authors do not report conflicts of interest.

Background: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT., Methods: SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses., Results: Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion., Conclusion: Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials., Trial Registration Number: clinicaltrials.gov NCT03192332., Competing Interests: Competing interests: GM reports consulting fees from Stryker Neurovascular, and paid lectures for Medtronic and Microvention Europe. ON reports funding from a Stryker research grant, and payment or honoraria for Phenox lecture and Stryker lecture. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips, and Apta Targets; payment or honoraria from Ischemia View; participates on a data safety monitoring board or advisory board of Sensome; and has stock or stock options in Anaconda Biomed, CVAid, and Methinks. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical as imaging core laboratory. JG reports a Swiss National Funds grant for MRI in stroke. UF reports financial support for the present study from Medtronic; research grants from Medtronic BEYOND SWIFT registry, the Swiss National Science Foundation, and the Swiss Heart Foundation; consulting fees from Medtronic, Stryker, and CSL Behring (fees paid to institution); has membership of a data safety monitoring board for the IN EXTREMIS trial and the TITAN trial; was on the advisory board for Portola (Alexion; fees paid to institution); is an editor at the Journal of Neurointerventional Surgery; and is Vice President of the Swiss Neurological Society. JK reports financial support from Medtronic for the BEYOND SWIFT registry (fees paid to institution), and research grants from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution), Swiss Academy of Medical Sciences supporting MRI research (fees paid to institution), and Swiss Heart Foundation supporting cardiac MRI in the etiological work-up of stroke patients (fees paid to institution)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The RACECAT (Transfer to the Closest Local Stroke Center vs Direct Transfer to Endovascular Stroke Center of Acute Stroke Patients With Suspected Large Vessel Occlusion in the Catalan Territory) trial was the first randomized trial addressing the prehospital triage of acute stroke patients based on the distribution of thrombolysis centers and intervention centers in Catalonia, Spain. The study compared the drip-and-ship with the mothership paradigm in regions where a local thrombolysis center can be reached faster than the nearest intervention center (equipoise region). The present study aims to determine the population-based applicability of the results of the RACECAT study to 4 stroke networks with a different degree of clustering of the intervention centers (clustered, dispersed). Methods and Results Stroke networks were compared with regard to transport time saved for thrombolysis (under the drip-and-ship approach) and transport time saved for endovascular therapy (under the mothership approach). Population-based transport times were modeled with a local instance of an openrouteservice server using open data from OpenStreetMap.The fraction of the population in the equipoise region differed substantially between clustered networks (Catalonia, 63.4%; France North, 87.7%) and dispersed networks (Southwest Bavaria, 40.1%; Switzerland, 40.0%). Transport time savings for thrombolysis under the drip-and-ship approach were more marked in clustered networks (Catalonia, 29 minutes; France North, 27 minutes) than in dispersed networks (Southwest Bavaria and Switzerland, both 18 minutes). Conclusions Infrastructure differences between stroke networks may hamper the applicability of the results of the RACECAT study to other stroke networks with a different distribution of intervention centers. Stroke networks should assess the population densities and hospital type/distribution in the temporal domain before applying prehospital triage algorithms to their specific setting.

Background: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment., Methods: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986., Findings: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly., Interpretation: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment., Funding: Stryker and Amsterdam University Medical Centers, University of Amsterdam., Competing Interests: Declaration of interests CBM reports grants from CardioVasculair Onderzoek Nederland by the Dutch Heart Foundation, TWIN Foundation, the European Commission, Healthcare Evaluation Netherlands, and Stryker (all paid to institution); and is a minority interest shareholder of Nicolab. YBR reports being a minor shareholder of Nicolab. JG reports consultancy funds from Medtronic as Global Principal Investigator of STAR (NCT01327989) and Swift Direct (NCT03192332) and from Cerenovus (now part of Johnson & Johnson) and participation on a data safety monitoring board or advisory board (clinical ethics committee member of the Promise Study) for Penumbra. CC reports consulting fees from Microvention, Medtronic, Cerenovus, MIVI, and Stryker. TD reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Microvention. BJE reports institutional funding from HealthHolland Top Sector Life Sciences and Nicolab. RGN reports funding from Cerenovus as Principal Investigator of the ENDOLOW trial and from Stryker Neurovascular as Principal Investigator of the DUSK trial; consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze; and being an investor in Viz-AI, Perfuze, Cerebrotech, Reist–Q’Apel Medical, Truvic, Vastrax, and Viseon. UF reports funding from Medtronic, Stryker, Rapid Medical, Phenox, Penumbra, Swiss National Science Foundation, CSL Behring, Portola (now part of Alexion), Boehringer Ingelheim, and Biogen. SD reports institutional funding from the National Health and Medical Research Council and funding from Medtronic, Abbott, and CSL Behring for participation on data safety monitoring boards or advisory boards. PM reports institutional funding from Stryker and Medtronic. BY reports institutional research grants from Stryker and Medtronic. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT., Methods: In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3-6) and recurrent ischaemic stroke at 3 months using regression models., Results: Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA ( n  = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% ( n  = 3416), cardiac embolism in 23.6% ( n  = 4059), small vessel disease in 11.7% ( n  = 2011), other causes in 7.4% ( n  = 1267), more than one cause in 6.3% ( n  = 1078) and unknown cause in 31.3% ( n  = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98-1.14; p  = 0.135) or death (aOR = 1.10; 95% CI: 0.99-1.21; p  = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11-1.44; p  < 0.001)., Conclusions: One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.

Background and Purpose: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging., Materials and Methods: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion., Results: The median age of the final study population ( n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics ( n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1)., Conclusions: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials., (© 2023 by American Journal of Neuroradiology.)

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.)

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020., Patients and Methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively., Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000. Rates of SUs, IVT and EVT were stable in 2020. There was an increase in mean rates of SUs, IVT and EVT compared to similar data from 2016., Conclusion: Although there was an increase in reperfusion treatment rates in many countries between 2016 and 2019, this was halted in 2020. There are persistent major inequalities in acute stroke treatment in the European region. Tailored strategies directed to the most vulnerable regions should be prioritised.

Background: Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce., Methods: We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed., Results: Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p  = 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p  < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause., Conclusion: In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients., Clinical Trial Registration: NCT03826927.

Background: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT)., Methods: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours., Results: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short., Conclusions: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials., Trial Registration Number: URL: https://www., Clinicaltrials: gov ; Unique identifier: NCT03192332., Competing Interests: Competing interests: MA reports honoraria for lectures from AstraZeneca, Bayer, Covidien, Medtronic and Sanofi; Participation on Scientific Advisory Boards of Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Pfizer. CC reports consulting fees from Medtronic (payment made to CC). EC reports grants from the Swiss Heart Foundation and Swiss National Science Foundation, not related to present study. HCD reports that in the last 3 years, he received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, BMS, Boehringer Ingelheim, Daiichi Sankyo, Novo-Nordisk, Pfizer, Portola and WebMD Global. Boehringer Ingelheim provided financial support for research projects. HCD also received research grants from the German Research Council (DFG) and German Ministry of Education and Research (BMBF). HCD serves as editor of Neurologie up2date, Info Neurologie & Psychiatrie, Arzneimitteltherapie, as co-editor of Cephalalgia and on the editorial board of Lancet Neurology and Drugs. MTF reports research grants from Medtronic, Siemens, Genentech, Idorsia, and Vesalio; consulting fees from Genentech, Balt USA, Cerenovus, and Oculus Imaging; participation on a Data Safety Monitoring Board or Advisory Board for Balt USA, Jacobs Institute, and Imperative Care. UF reports financial support for the present study from Medtronic. SWIFT DIRECT is an investigator-initiated trial. The sponsor was not involved in the final study design, protocol, conduct, evaluation of results or preparation of the manuscript. UF also reports research grants from Medtronic BEYOND SWIFT registry, Swiss National Science Foundation, Swiss Heart Foundation; consulting fees from Medtronic, Stryker and CSL Behring (fees paid to institution); membership of a Data Safety Monitoring Board for the IN EXTREMIS trial and TITAN trial and Portola (Alexion) Advisory board (fees paid to institution); and Vice Presidency of the Swiss Neurological Society. UF is a member of the editorial board of JNIS. JG reports a Swiss National Funds (SNF) grant for MRI in stroke. JK reports financial support of Medtronic for the BEYOND SWIFT Registry (fees paid to institution); research grant from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution); Swiss Academy of Medical Sciences research grant supporting MRI research (fees paid to institution); Swiss Heart Foundation research grant supporting cardiac MRI in the etiological workup of stroke patients (fees paid to institution). AL reports grants from the University of Zurich, the LOOP Zurich, and P&K Pühringer Foundation; consulting fees from Bayer AG; and a lecture honorarium from Moleac Pte, Singapore. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical as imaging core lab. GM reports consulting fees from Stryker Neurovascular; paid lectures for Medtronic and Microvention Europe. PM reports research funding (fees paid to institution) from the Swiss National Science Foundation, Swiss Heart Foundation and Medtronic Research Grant. PM reports grants from the Swiss National Science Foundation; Consulting fees Medtronic, Stryker; payment or honoraria from Medtronic, Stryker; participation on a Data Safety Monitoring Board or Advisory Board of MicroVention. ON reports funding from a Stryker Research grant; payment or honoraria for Phenox lecture and Stryker lecture. WP reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses STROKE TEAM-Training (LAERDAL medical); payment or honoraria from LAERDAL medical, Alexion, Pfizer-BMS, Stryker Neurovascular; support for attending meetings and/or travel from LAERDAL medical, Alexion, Pfizer-BMS and Stryker Neurovascular. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips and Apta Targets; payment or honoraria from Ischemia View; participation on a Data Safety Monitoring Board or Advisory Board of Sensome; stock or stock options in Anaconda Biomed, CVAid and Methinks. AHS reports being a co-investigator for NIH - 1R01EB030092-01, Project Title: High Speed Angiography at 1000 frames per second; Mentor for Brain Aneurysm Foundation Carol W. Harvey Chair of Research, Sharon Epperson Chair of Research, Project Title: A Whole Blood RNA Diagnostic for Unruptured Brain Aneurysm: Risk Assessment Prototype Development and Testing; receipt of consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Inc, Boston Scientific, Canon Medical Systems USA, Inc, Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc, Cerenovus, Cerevatech Medical, Inc, Cordis, Corindus, Inc, Endostream Medical, Ltd, Imperative Care, InspireMD, Ltd, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc, Peijia Medical, Penumbra, Q’Apel Medical, Inc, Rapid Medical, Serenity Medical, Inc, Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc, VasSol, Viz.ai, Inc (payments made to AHS); Secretary – Board of the Society of NeuroInterventional Surgery 2020-2021 (unpaid) Chair – Cerebrovascular Section of the AANS/CNS 2020-2021 (unpaid); stock or stock options Adona Medical, Inc, Amnis Therapeutics, Bend IT Technologies, Ltd, BlinkTBI, Inc, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc, Cognition Medical, CVAID Ltd, E8, Inc, Endostream Medical, Ltd, Galaxy Therapeutics, Inc, Imperative Care, Inc, InspireMD, Ltd, Instylla, Inc, International Medical Distribution Partners, Launch NY, Inc, NeuroRadial Technologies, Inc, NeuroTechnology Investors, Neurovascular Diagnostics, Inc, Peijia Medical, PerFlow Medical, Ltd, Q’Apel Medical, Inc, QAS.ai, Inc, Radical Catheter Technologies, Inc, Rebound Therapeutics Corp (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc (Purchased 2020 by Medtronic), Sense Diagnostics, Inc, Serenity Medical, Inc, Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, Inc, StimMed, LLC, Synchron, Inc, Three Rivers Medical, Inc, Truvic Medical, Inc, Tulavi Therapeutics, Inc, Vastrax, LLC, VICIS, Inc, Viseon, Inc (payments made to AHS); Other financial or non-financial interests: National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial & CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial (payments made to AHS). IS reports consulting fees (paid to IS) from Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, AstraZeneca, Novonordisk and Medtronic; payment or honoraria (paid to IS) from Sanofi Synthé-Labo, Medtronic, Boheringer Ingelheim, AstraZeneca and BMS-Pfizer. JS reports funding for the present manuscript from Medtronic (paid to JS); consulting fees from Cerenovus (paid to JS); participation on a Data Safety Monitoring Board or Advisory Board – MIVI (paid to JS), Phillips (paid to JS); stock or stock options in Rapid Medical (paid to JS). MW reports a grant from Stryker Neurovascular; consulting fees from Stryker Neurovascular (payments to MW); payment or honoraria from Stryker Neurovascular, Bracco Imaging (payments to MW); German Society of Neuroradiology (DGNR) Board member (no payments); receipt of equipment, materials, drugs, medical writing, gifts or other services from ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice AB, Phenox, Stryker Neurovascular (support to institution). All other authors report no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Mechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO)., Objective: To assist physicians in their clinical decisions with regard toMT., Methods: These guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach., Results: We found high-quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelinesdetails aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities., Conclusions: MT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision-making with regard tothe mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume., Competing Interests: Competing interests: Competing interests for the authors can be found in the file entitled ESO-ESMINT Thrombectomy Guidelines Suppl appendix., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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: The DEFUSE-3 and DAWN trials showed that mechanical thrombectomy (MT) improves the outcome of selected patients with anterior circulation large vessel occlusions (LVO) up to 24 h after stroke onset. However, it is unknown whether only those patients fulfilling the trial inclusion criteria benefit, or whether benefit is seen in a broader range of patients presenting between 6 and 24 h., Aims: We determined whether fulfilling the DEFUSE-3 and DAWN selection criteria affects outcomes in MT patients in clinical practice., Methods: We reviewed adult patients with LVO treated with MT between 6 and 24 h after stroke onset at five Swiss stroke centers between 2014 and 2021. We compared two groups: (1) patients who satisfied neither DEFUSE-3 nor DAWN criteria (NDND) and (2) those who satisfied DEFUSE-3 or DAWN criteria (DOD). We used logistic regression to examine the impact of trial eligibility on two safety outcomes (symptomatic intracranial hemorrhage [sICH] and all-cause mortality at 3 months) and two efficacy outcomes (modified Rankin Score [mRS] shift toward lower categories and mRS of 0-2 at 3 months)., Results: Of 174 patients who received MT, 102 (59%) belonged to the NDND group. Rates of sICH were similar between the NDND group and the DOD group (3% vs. 4%, p  =  1.00). Multivariable regression revealed no differences in 3-month all-cause mortality (aOR 2.07, 95% CI 0.64-6.84, p  = 0.23) or functional outcomes (mRS shift: acOR 0.81, 95% CI 0.37-1.79, p  = 0.60; mRS 0-2: aOR 0.91, 95% CI 0.31-2.57, p  = 0.85 )., Conclusion: Among adult patients with LVO treated with MT between 6 and 24 h, safety and efficacy outcomes were similar between DEFUSE-3/DAWN eligible and ineligible patients. Our data provide a compelling rationale for randomized trials with broader inclusion criteria for MT.

Background: Despite evolving treatments, functional recovery in patients with large vessel occlusion stroke remains variable and outcome prediction challenging. Can we improve estimation of functional outcome with interpretable deep learning models using clinical and magnetic resonance imaging data?, Methods: In this observational study, we collected data of 222 patients with middle cerebral artery M1 segment occlusion who received mechanical thrombectomy. In a 5-fold cross validation, we evaluated interpretable deep learning models for predicting functional outcome in terms of modified Rankin scale at 3 months using clinical variables, diffusion weighted imaging and perfusion weighted imaging, and a combination thereof. Based on 50 test patients, we compared model performances to those of 5 experienced stroke neurologists. Prediction performance for ordinal (modified Rankin scale score, 0-6) and binary (modified Rankin scale score, 0-2 versus 3-6) functional outcome was assessed using discrimination and calibration measures like area under the receiver operating characteristic curve and accuracy (percentage of correctly classified patients)., Results: In the cross validation, the model based on clinical variables and diffusion weighted imaging achieved the highest binary prediction performance (area under the receiver operating characteristic curve, 0.766 [0.727-0.803]). Performance of models using clinical variables or diffusion weighted imaging only was lower. Adding perfusion weighted imaging did not improve outcome prediction. On the test set of 50 patients, binary prediction performance between model (accuracy, 60% [55.4%-64.4%]) and neurologists (accuracy, 60% [55.8%-64.21%]) was similar when using clinical data. However, models significantly outperformed neurologists when imaging data were provided, alone or in combination with clinical variables (accuracy, 72% [67.8%-76%] versus 64% [59.8%-68.4%] with clinical and imaging data). Prediction performance of neurologists with comparable experience varied strongly., Conclusions: We hypothesize that early prediction of functional outcome in large vessel occlusion stroke patients may be significantly improved if neurologists are supported by interpretable deep learning models., Competing Interests: Disclosures Dr Heldner reports grants from the Bangerter Foundation, the Swiss National Science Foundation, SITEM (Center for Translational Medicine and Biomedical Entrepreneurship) Support Funds, and the Swiss Heart Foundation, all outside the submitted work. Dr Antonenko reports a grant from the Swiss National Science Foundation. Dr Dobrocky reports consultant fees for MicroVention, Inc. Dr Fischer reports grants from Alexion, CSL Behring, Medtronic, Penumbra, Inc, Phenox, Inc, Rapid Medical, Ltd, and Stryker. Dr Gralla reports interests with Medtronic USA, Inc. Dr Arnold reports consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Pfizer, Boehringer Ingelheim, Covidien, Medtronic, and Novo Nordisk. Dr Luft reports consultancy fees from Amgen and Moleac, Ltd. Susanne Wegener received research funds by the Swiss National Science Foundation, the UZH Clinical research priority program (CRPP) stroke, the Swiss Heart foundation, the Zurich Neuroscience Center (ZNZ), speaker honoraria from Springer, Teva Pharma, and consultancy fees from Bayer and Novartis. The other authors report no conflicts.

Purpose: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone., Methods: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models., Findings: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p  = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p  = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%)., Conclusion: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

Importance: Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce., Objective: To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke., Design, Setting, and Participants: Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching., Interventions: Mechanical thrombectomy with or without IVT., Main Outcomes and Measures: Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death., Results: After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01)., Conclusions and Relevance: These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.

Aim: To compare safety and functional outcomes of intravenous thrombolysis (IVT) between females and males with acute ischaemic stroke (AIS) in relation to preadmission use of antiplatelets., Methods: Multicentre cohort study of patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry, presenting with AIS and receiving IVT. Primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). Primary functional outcome was functional independence at 3 months after discharge. Multivariable logistic regression models were fitted to assess the association between sex and each outcome according to preadmission use of antiplatelets., Results: The study included 4996 patients (42.51 % females, older than males, median age 79 vs 71 years, p < 0.0001). Comparable proportions of females (39.92 %) and males (40.39 %) used antiplatelets before admission (p = 0.74). In total, 3.06 % females and 2.47 % males developed in-hospital sICH (p = 0.19), with similar odds (adjusted odds ratio, [AOR] 0.93, 95 % confidence interval, [CI] 0.63-1.39). No interaction was found between sex and preadmission use of either single or dual antiplatelets in relation to in-hospital sICH (p = 0.94 and p = 0.23). Males had higher odds of functional independence at 3 months (AOR 1.34, 95 % CI 1.09-1.65), regardless of preadmission use of antiplatelets (interaction between sex and preadmission use of either single or dual antiplatelets p = 0.41 and p = 0.58)., Conclusion: No sex differences were observed in the safety of IVT regarding preadmission use of antiplatelets. Males showed more favourable 3-month functional independence than females; however, this sex difference was apparently not explained by a sex-specific mechanism related to preadmission use of antiplatelets., (© 2023. The Author(s).)

Purpose: Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT., Methods: Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed., Results: In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively)., Conclusion: A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required., (© 2022. The Author(s).)

Background: We assessed the efficacy and safety of mechanical thrombectomy (MT) in adult stroke patients with anterior circulation large vessel occlusion presenting in the late time window not fulfilling the DEFUSE-3 (Thrombectomy for Stroke at 6 to 16 Hours With Selection by Perfusion Imaging trial) and DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct trial) inclusion criteria., Methods: Cohort study of adults with anterior circulation large vessel occlusion admitted between 6 and 24 hours after last-seen-well at 5 participating Swiss stroke centers between 2014 and 2021. Mismatch was assessed by computer tomography or magnetic resonance imaging perfusion with automated software (RAPID or OLEA). We excluded patients meeting DEFUSE-3 and DAWN inclusion criteria and compared those who underwent MT with those receiving best medical treatment alone by inverse probability of treatment weighting using the propensity score. The primary efficacy end point was a favorable functional outcome at 90 days, defined as a modified Rankin Scale score shift toward lower categories. The primary safety end point was symptomatic intracranial hemorrhage within 7 days of stroke onset; the secondary was all-cause mortality within 90 days., Results: Among 278 patients with anterior circulation large vessel occlusion presenting in the late time window, 190 (68%) did not meet the DEFUSE-3 and DAWN inclusion criteria and thus were included in the analyses. Of those, 102 (54%) received MT. In the inverse probability of treatment weighting analysis, patients in the MT group had higher odds of favorable outcomes compared with the best medical treatment alone group (modified Rankin Scale shift: acOR, 1.46 [1.02-2.10]; P =0.04) and lower odds of all-cause mortality within 90 days (aOR, 0.59 [0.37-0.93]; P =0.02). There were no significant differences in symptomatic intracranial hemorrhage (MT versus best medical treatment alone: 5% versus 2%, P =0.63)., Conclusions: Two out of 3 patients with anterior circulation large vessel occlusion presenting in the late time window did not meet the DEFUSE-3 and DAWN inclusion criteria. In these patients, MT was associated with higher odds of favorable functional outcomes without increased rates of symptomatic intracranial hemorrhage. These findings support the enrollment of patients into ongoing randomized trials on MT in the late window with more permissive inclusion criteria.

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Background: Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown., Objective: To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers., Methods: A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results., Results: There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67)., Conclusion: Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT., Competing Interests: Competing interests: CBLMM reports grants from CVON/Dutch Heart Foundation, TWIN Foundation, European Commission, Health Evaluation Netherlands, and Stryker outside the submitted work (all paid to institution); and is shareholder of Nico-lab. YBWEMR is a shareholder of Nico-lab. UF reports grants during the conduct of the study from Medtronic, Stryker, and CSL Behring, unrelated to the submitted work, and his board membership at the Journal of NeuroInterventional Surgery. JG is a global principal investigator of STAR (Solitaire FR Thrombectomy for Acute Revascularisation), Clinical Event Committee member of the PROMISE study (Prospective, Multicenter, Observational, Single-Arm European Registry on the ACE Reperfusion Catheters and the Penumbra System in the Treatment of Acute Ischemic Stroke; Penumbra), and a principal investigator and consultant for the SWIFT DIRECT study (Solitaire With the Intention for Thrombectomy Plus Intravenous tPA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke; Medtronic) and receives Swiss National Science Foundation grants for magnetic resonance imaging in stroke. JK reports grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, Swiss National Science Foundation, and the Clinical Trials Unit Bern during the conduct of this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO., Methods: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days)., Results: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR., Discussion: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management., Classification of Evidence: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function., (© 2022 American Academy of Neurology.)

Background This study was conducted to explore the association of different phenotypes, count, and location of chronic covert brain infarctions (CBIs) with detection of atrial fibrillation (AF) on prolonged post-stroke cardiac rhythm monitoring (PCM). Methods and Results We conducted a cohort single-center study of consecutive first-ever ischemic stroke or transient ischemic attack patients undergoing PCM between January 2015 and December 2017. We blindly rated CBI phenotypes according to established definitions and white matter hyperintensities (WMHs) according to the age-related white matter changes rating scale. We used (multiple) regression models to assess the association of the imaging biomarkers and incident AF on PCM. A total of 795 patients (median [interquartile range]) aged 69 (57-78) years, 41% women, median National Institutes of Health Stroke Scale score 2 (0-5), median PCM duration 14 (7-14) days, and AF detection in 61 patients (7.7%) were included. On univariate analysis, WMHs (per point odds ratio, 1.35 [95% CI, 1.03-1.78]) but not CBIs (odds ratio, 0.90 [95% CI, 0.52-1.56]) were associated with AF detection. Neither CBI phenotype, count, nor location were associated with AF detection. After adjustment for age, hypertension, and stroke severity, neither increasing WMHs (per point adjusted odds ratio, 0.85 [95% CI, 0.60-1.20]) nor CBIs (adjusted odds ratio, 0.60 [95% CI, 0.33-1.09]) were independently associated with AF detection. Conclusions Although WMHs and CBIs represent surrogate biomarkers of vascular risk factors, neither WMHs nor CBIs, including their phenotypes, count, and location, were independently associated with AF detection on PCM. In patients with manifest ischemic stroke or transient ischemic attack, the presence of imaging biomarkers of chronic ischemic injury does not seem promising to further refine prediction tools for AF detection on PCM.

Background: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients., Methods: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3)., Results: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH., Conclusions: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04096248.

Background and Purpose: To investigate the association of different phenotypes, count, and locations of chronic covert brain infarctions (CBI) with long-term mortality in patients with first-ever manifest acute ischemic stroke (AIS) or transient ischemic attack (TIA). Additionally, to analyze their potential interaction with white matter hyperintensities (WMH) and predictive value in addition to established mortality scores., Methods: Single-center cohort study including consecutive patients with first-ever AIS or TIA with available MRI imaging from January 2015 to December 2017. Blinded raters adjudicated CBI phenotypes and WMH (age-related white matter changes score) according to established definitions. We compared Cox regression models including prespecified established predictors of mortality using Harrell's C and likelihood ratio tests., Results: A total of 2236 patients (median [interquartile range] age: 71 [59-80] years, 43% female, National Institutes of Health Stroke Scale: 2 [1-6], median follow-up: 1436 days, 21% death during follow-up) were included. Increasing WMH (per point adjusted Hazard Ratio [aHR] = 1.29 [1.14-1.45]), but not CBI (aHR = 1.21 [0.99-1.49]), were independently associated with mortality. Neither CBI phenotype, count, nor location was associated with mortality and there was no multiplicative interaction between CBI and WMH (p &gt; .1). As compared to patients without CBI or WMH, patients with moderate or severe WMH and additional CBI had the highest hazards of death (aHR = 1.62 [1.23-2.13]). The Cox regression model including CBI and WMH had a small but significant increment in Harrell's C when compared to the model including 14 clinical variables (0.831 vs. 0.827, p &lt; .001)., Discussion: WMH represent a strong surrogate biomarker of long-term mortality in first-ever manifest AIS or TIA patients. CBI phenotypes, count, and location seem less relevant. Incorporation of CBI and WMH slightly improves predictive capacity of established risk scores., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c)., Methods: Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome., Results: In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P =0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P =0.01)., Conclusions: Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies.

Background and Purpose: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice., Methods: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared., Results: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR] adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, OR adjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, OR adjusted  = 1.75, p = 0.002; mRS shift: p adjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: OR adjusted  = 0.52, p = 0.005; death: OR adjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (p adjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, OR adjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, OR adjusted  = 1.80, p = 0.001; mRS shift: p adjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: OR adjusted  = 0.38, p < 0.0001; death: OR adjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: OR adjusted  = 0.58, p = 0.004; death: OR adjusted  = 1.57, p = 0.014; mRS shift: p adjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped., Conclusions: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Since 2015, a series of endovascular trials transformed the management of patients with large vessel occlusion stroke. Most thrombectomy trials used restrictive eligibility criteria to optimize the chances of showing that thrombectomy could work. The problem arises when generalizing trial results into evidence-based recommendations. Many organizations, oblivious of this problem, translated verbatim restrictive trial eligibility criteria into authoritative guidelines, which limit the use of thrombectomy to highly selected patients. The clinical problem becomes as follows: what to do for all other stroke patients equally in need of care? The cycle of restrictive trial eligibility criteria, corresponding restrictive guidelines, observational studies of unvalidated practices showing other patients benefit, a new trial is needed, has been repeated often. Thrombectomy trials ought to have included all patients that could potentially benefit. If the signal that was looked for by restricting eligibility is at risk of being lost in the noise generated by the heterogeneity of patients, D. Sackett proposed a solution: to use the same criteria, not to select some patients and exclude others but to prespecify the subgroup of patients most likely to benefit. In this commentary, we propose a tiered approach, where the boundaries of treatment beneficiaries can be more rigorously tested and confirmed. Identification of these patients before the development of guidelines, which would have otherwise neglected these individuals, may open innumerable treatment opportunities to those who will instead be denied of them.

Purpose: Incomplete reperfusion after mechanical thrombectomy (MT) is associated with a poor outcome. Rescue therapy would potentially benefit some patients with an expanded treatment in cerebral ischemia score (eTICI) 2b50/2b67 reperfusion but also harbors increased risks. The relative benefits of eTICI 2c/3 over eTICI 2b50/67 in clinically important subpopulations were analyzed., Methods: Retrospective analysis of our institutional database for all patients with occlusion of the intracranial internal carotid artery (ICA) or the M1/M2 segment undergoing MT and final reperfusion of ≥eTICI 2b50 (903 patients). The heterogeneity in subgroups of different time metrics, age, National Institutes of Health Stroke Scale (NIHSS), number of retrieval attempts, Alberta Stroke Programme Early CT Score (ASPECTS) and site of occlusion using interaction terms (p i ) was analyzed., Results: The presence of eTICI 2c/3 was associated with better outcomes in most subgroups. Time metrics showed no interaction of eTICI 2c/3 over eTICI 2b50/2b67 and clinical outcomes (onset to reperfusion p i  = 0.77, puncture to reperfusion p i  = 0.65, onset to puncture p i  = 0.63). An eTICI 2c/3 had less consistent association with mRS ≤2 in older patients (>82 years, p i  = 0.038) and patients with either lower NIHSS (≤9) or very high NIHSS (>19, p i  = 0.01). Regarding occlusion sites, the beneficial effect of eTICI 2c/3 was absent for occlusions in the M2 segments (aOR 0.73, 95% confidence interval [CI] 0.33-1.59, p i  = 0.018)., Conclusion: Beneficial effect of eTICI 2c/3 over eTICI 2b50/2b67 only decreased in older patients, M2-occlusions and patients with either low or very high NIHSS. Improving eTICI 2b50/2b67 to eTICI 2c/3 in those subgroups may be more often futile., (© 2022. The Author(s).)

Objective: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door-to-needle (DTN) time, door-to-puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT)., Methods: An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss-Stroke-Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed-effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0-2) at 90 days., Results: Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0-6] vs 4 [1-11]), and presented later after symptom onset (150 vs 123 min, p < 0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73-0.96), but not with MT (aOR 1.11, 0.93-1.34); longer adjusted DTN (+22 min [13-30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30-1.81)., Interpretation: We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue-based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184-194., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Rationale: Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear., Aim: To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers., Sample Size: To randomize 404 patients 1:1 to direct MT or combined IVT+MT., Methods and Design: A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design., Outcomes: The primary efficacy endpoint is functional independence (modified Rankin Scale 0-2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days., Discussion: SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT., Trial Registration: ClinicalTrials.gov Identifier: NCT03192332.

Intravenous thrombolytics and endovascular thrombectomy for ischemic stroke have evolved in parallel. However, the best approach to combine these reperfusion therapies in patients eligible for both strategies remains uncertain. Initial randomized trials of endovascular thrombectomy included administration of intravenous thrombolytics to all eligible patients. However, whether that is of net benefit has been questioned and parallels drawn with treatment of ST-segment-elevation myocardial infarction, where intravenous thrombolytics are only given if first medical contact to percutaneous intervention is expected to be >90 minutes. Six randomized trials of a direct thrombectomy approach versus intravenous thrombolytics followed by endovascular thrombectomy have now reported their results. With exception of a minority of patients in one trial, the trials all used alteplase rather than potentially more effective tenecteplase. This review examines the current state of evidence and implications for clinical practice. Importantly, these trials only apply to patients who present to a hospital with immediate access to endovascular thrombectomy and are not relevant to patients who receive thrombolytic and are then transferred to an endovascular-capable hospital. Although 2 of the 6 randomized trials met their prespecified noninferiority margin, these margins were large compared with the absolute benefit of alteplase. Overall, functional outcome was similar, with slight trends favoring bridging thrombolytics and a significant increase in final reperfusion. Symptomatic hemorrhage was increased by ≈1.8% in the bridging group but death was nonsignificantly lower. The workflow in direct thrombectomy trials involved delaying thrombolytic administration until eligibility for thrombectomy and the trials was established and randomization completed. This reduced the time available for thrombolytics to occur prethrombectomy compared with standard practice. We conclude that, pending individual-patient data meta-analyses, intravenous thrombolytics retain an important role alongside endovascular thrombectomy. Further efforts to accelerate and enhance reperfusion with thrombolytics and perform individual patient-level pooled subgroup analyses are warranted.

Background and Purpose: Randomized controlled trials have challenged the assumption that reperfusion success after mechanical thrombectomy varies depending on the retrieval techniques applied; however, recent analyses have suggested that acute ischemic stroke (AIS) patients showing susceptibility vessel sign (SVS) may respond differently. We aimed to compare different stent retriever (SR)-based thrombectomy techniques with respect to interventional outcome parameters depending on SVS status., Methods: We retrospectively reviewed 497 patients treated with SR-based thrombectomy for anterior circulation AIS. Imaging was conducted using a 1.5 T or 3 T magnetic resonance imaging (MRI) scanner. Logistic regression analyses were performed to test for the interaction of SVS status and first-line retrieval technique. Results are shown as percentages, total values or adjusted odds ratio (aOR) with 95% confidence intervals (CI)., Results: An SVS was present in 87.9% (n = 437) of patients. First-line SR thrombectomy was used to treat 293 patients, whereas 204 patients were treated with a combined approach (COA) of SR and distal aspiration. An additional balloon-guide catheter (BGC) was used in 273 SR-treated (93.2%) and 89 COA-treated (43.6%) patients. On logistic regression analysis, the interaction variable of SVS status and first-line retrieval technique was not associated with first-pass reperfusion (aOR 1.736, 95% CI 0.491-6.136; p = 0.392), overall reperfusion (aOR 3.173, 95% CI 0.752-13.387; p = 0.116), periinterventional complications, embolization into new territories, or symptomatic intracerebral hemorrhage. The use of BGC did not affect the results., Conclusion: While previous analyses indicated that first-line SR thrombectomy may promise higher rates of reperfusion than contact aspiration in AIS patients with SVS, our data show no superiority of any particular SR-based retrieval technique regardless of SVS status., (© 2021. The Author(s).)

Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain., Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥ 3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥ 4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias., Results: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42-2.16]; P <0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 [1.08-2.36]; P =0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20-2.15]; P =0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59-4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30-3.75]), dependency or death (OR, 1.42 [0.91-2.23]), or mortality (OR, 1.65 [0.94-2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76-5.04]), dependency or death (OR, 1.49 [1.07-2.07]), and mortality (OR, 1.65 [1.11-2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73-4.29])., Conclusions: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Introduction: The DAWN trial demonstrated the effectiveness of late endovascular treatment in acute ischemic stroke patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of endovascular treatment patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late endovascular treatment., Methods: We retrospectively analyzed all consecutive acute ischemic stroke patients admitted 6-24 h after last proof of good health in two stroke centers, with initial National Institutes of Health Stroke Scale (NIHSS) ≥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSS ≥ 10 and ASPECTS ≥ 7, or NIHSS ≥ 20 and ASPECTS ≥ 5. We assessed the interaction between the presence of the clinical-ASPECTS mismatch and late endovascular treatment using ordinal shift analysis of the three-month modified Rankin Scale and adjusting for multiple confounders., Results: The included 337 patients had a median age of 73 years (IQR = 61-82), admission NIHSS of 18 (15-22), and baseline ASPECTS of 7 (5-9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late endovascular treatment. Among 141 (41.8%) mismatch negative patients, late endovascular treatment was performed in 72 (51.1%) patients. In the adjusted analysis, late endovascular treatment was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted odd ratio, aOR = 2.83; 95% confidence interval, CI: 1.48-5.58) but not in its absence (aOR = 1.32; 95%CI: 0.61-2.84). The p -value for the interaction term between clinical-ASPECTS mismatch and late endovascular treatment was 0.073., Conclusions: In our retrospective two-site analysis, late endovascular treatment seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late endovascular treatment decisions, obviating the need for advanced imaging.

Background: Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable., Objective: To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions., Methods: This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT- group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome-that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days., Results: Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0-1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days., Conclusions: Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT., Competing Interests: Competing interests: AMS reports support from Penumbra, Stryker, Medtronic; and consulting fees from: Terumo, Stryker, Penumbra, Siemens. BL reports grants from Stryker, Penumbra, and Microvention. MM reports personal fees from Acticor Biotech, Air liquide, Amgen, and Boerhinger. RGN: principal investigator, Stryker Neurovascular (DAWN trial (no compensation), Trevo-2 trial), Cerenovus/Neuravi (ENDOLOW trial, no compensation); consultant to Stryker Neurovascular; steering committee member, Stryker Neurovascular(no compensation), Medtronic (SWIFT trial, SWIFT Prime trial (no compensation)), Cerenovus/Neuravi (ARISE-2 trial, no compensation); angiographic core lab, Medtronic (STAR trial); executive committee member, Penumbra (no compensation); physician advisory board, Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, Allm Inc.(no compensation), Viz-AI (stock options). AHS: financial interest/investor/stock options/ownership: Amnis Therapeutics, Apama Medical,Blink TBI, Inc., Buffalo Technology Partners, Inc., Cardinal Health, Cerebrotech Medical Systems, Inc., Claret Medical, Cognition Medical, Endostream Medical, Ltd., Imperative Care, International Medical Distribution Partners, Rebound Therapeutics Corp., Silk Road Medical, StimMed, Synchron, Three Rivers Medical, Inc., Viseon Spine, Inc; consultant/advisory board: Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Inc., Cerebrotech Medical Systems, Inc., Cerenovus, Claret Medical, Corindus, Inc., Endostream Medical, Ltd., Guidepoint 15Global Consulting, Imperative Care, Integra, Medtronic, MicroVention, Northwest University—DSMB Chair for HEAT Trial, Penumbra, Rapid Medical, Rebound Therapeutics Corp., Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc.,VasSol, W.L. Gore & Associates; national PI/steering committees: Cerenovus LARGE Trial and ARISE II Trial, Medtronic SWIFTPRIME and SWIFT DIRECT Trials, MicroVention FRED Trial & CONFIDENCE Study, MUSC POSITIVE Trial,Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial; principal investigator: Cummings Foundation grant., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The degree of reperfusion is the most important modifiable predictor of 3 month functional outcome and mortality in ischemic stroke patients treated with mechanical thrombectomy. Whether the beneficial effect of reperfusion also leads to a reduction in long term mortality is unknown., Methods: Patients undergoing mechanical thrombectomy between January 2010 and December 2018 were included. The post-thrombectomy degree of reperfusion and emboli in new territories were core laboratory adjudicated. Reperfusion was evaluated according to the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Vital status was obtained from the Swiss population register. Adjusted hazard ratios (aHRs) using time split Cox regression models were calculated. Subgroup analyses were performed in patients with borderline indications., Results: Our study included 1264 patients (median follow-up per patient 2.5 years). Patients with successful reperfusion had longer survival times, attributable to a lower hazard of death within 0-90 days and for >90 days to 2 years (aHR 0.34, 95% CI 0.26 to 0.46; aHR 0.37, 95% CI 0.22 to 0.62). This association was homogeneous across all predefined subgroups (p for interaction >0.05). Among patients with successful reperfusion, a significant difference in the hazard of death was observed between eTICI2b50 and eTICI3 (aHR 0.51, 95% CI 0.33 to 0.79). Emboli in new territories were present in 5% of patients, and were associated with increased mortality (aHR 2.3, 95% CI 1.11 to 4.86)., Conclusion: Successful, and ideally complete, reperfusion without emboli in new territories is associated with a reduction in long term mortality in patients treated with mechanical thrombectomy, and this was evident across several subgroups., Competing Interests: Competing interests: UF reports grants during the conduct of the study from Medtronic, Stryker, and CSL Behring, unrelated to the submitted work. JG is a global principal investigator of STAR (Solitaire FR Thrombectomy for Acute Revascularisation), Clinical Event Committee member of the PROMISE study (Prospective, Multicenter, Observational, Single-Arm European Registry on the ACE Reperfusion Catheters and the Penumbra System in the Treatment of Acute Ischemic Stroke; Penumbra), and a principal investigator and consultant for the SWIFT DIRECT study (Solitaire With the Intention for Thrombectomy Plus Intravenous tPA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke; Medtronic) and receives Swiss National Science Foundation grants for magnetic resonance imaging in stroke. JK reports grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern during the conduct of the study. MA reports personal fees from Bayer, Bristol-Myers Squibb, Medtronic, Amgen, Daiichi Sankyo, Nestlé Health Sciences, Boehringer Ingelheim, and Covidien during the conduct of the study. TRM reports research support from the Bangerter Rhyner Foundation, Swiss National Foundation, and the Swiss Heart Foundation. MRH reports research support from the Bangerter Foundation, scientific advisory board honoraria from Amgen, and personal fees from Bayer., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial fibrillation, which is a relevant risk factor for stroke., Methods: PubMed was searched for 'migraine' AND 'atrial fibrillation' and selected original investigations on the association of migraine and atrial fibrillation for our analysis. Articles without original data, such as guidelines, narrative reviews, editorials and others, were excluded., Results: In all, 109 publications were found. Twenty-two were included and analysed for this review. The population-based Atherosclerosis Risk in Communities study showed a significant association of migraine with visual aura and incident atrial fibrillation (hazard ratio 1.30, 95% confidence interval 1.03-1.62, p = 0.02), but not for migraine without aura, compared to non-headache persons after multivariable adjustment for vascular risk factors. An even larger population-based study in Denmark confirmed this association (odds ratio 1.25, 95% confidence interval 1.16-1.36). Studies investigating patients with ischaemic stroke and migraine are methodologically insufficient and provide contradictory results. Ablation therapy for atrial fibrillation in patients with migraine might reduce migraine attacks, but transient post-ablation new-onset migraine-like headaches in persons without a history of migraine have also been reported., Conclusion: Population-based studies indicate a significant association of migraine with aura and atrial fibrillation. In practical terms, screening for atrial fibrillation in patients who have a long history of migraine might be reasonable, whereas in patients with stroke or other disorders and migraine extensive screening for atrial fibrillation should be performed as in all patients without migraine., (© 2021 European Academy of Neurology.)

Purpose of Review: Direct oral anticoagulants (DOAC) are the mainstay of anticoagulant therapy for stroke prevention in patients with nonvalvular atrial fibrillation. Persistent uncertainties remain in different areas, and this review discusses current dilemmas based on selected studies., Recent Findings: Optimal timing of DOAC initiation after a recent ischaemic stroke in patients with atrial fibrillation is currently unknown and subject of ongoing randomized controlled trials. Ischaemic stroke despite anticoagulant therapy in patients with atrial fibrillation is frequent, constitutes heterogeneous causes (competing stroke cause, medication error and cardioembolism despite anticoagulation) and optimal treatment is currently unknown. Thorough etiological work-up is justified. Recent randomized controlled trials found no beneficial effect of DOAC therapy in unselected patients with embolic stroke of undetermined source (ESUS). Currently ongoing trials targeting subgroup of ESUS patients with additional atrial cardiopathy will provide novel data. Cerebral mircobleeds combined in a novel risk score (MICON score) provide good predictive value to stratify the risk of intracranial haemorrhage in patients taking anticoagulants. Use of DOAC after intracerebral haemorrhage in patients with atrial fibrillation is subject of ongoing trials., Summary: There are still significant uncertainties in anticoagulant management in patients with stroke. Ongoing trials will soon provide novel data to improve management of these patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse., Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days)., Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics., Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty., Competing Interests: Competing interests: Related: UF and JG are global PIs for the SWIFT DIRECT study (Solitaire With the Intention for Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-Retriever Thrombectomy in Acute Anterior Circulation Stroke) supported by Medtronic. Unrelated: JG is a global PI of STAR (Solitaire FR Thrombectomy for Acute Revascularisation Observational study), Clinical Event Committee member of the PROMISE study (European Registry on the ACE Reperfusion Catheters and the Penumbra System in the Treatment of Acute Ischemic Stroke; Penumbra), Consultancy, and receives Swiss National Science Foundation (SNSF) grants for MRI in stroke. UF receives research grants from SNSF and serves as a consultant for Medtronic and Stryker. MA received speaker honoraria from Bayer, Boehringer Ingelheim, and Covidien; advisory board honoraria from Amgen Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Covidien, Daichy Sankyo and Nestlé Health Science; research grant provided by the Swiss Heart Foundation. JK reports grants from SAMW / Bangerter Foundation, the Swiss Stroke Society and non-financial support from Stryker and Pfizer outside the submitted work. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from AngioCare BV, Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Top Medical/Concentric, Stryker, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. MG reports licensing agreement for systems of acute stroke diagnosis for GE Healthcare and Consultancy for Medtronic, Stryker, MicroVention and Mentice as well as unrestricted research grant by Stryker for the UNMASK-EVT study. MDH has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US patent office number 62/086077 and owns stock in Calgary Scientific, Inc—a company that focuses on medical imaging software., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group., Materials and Methods: Six hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs., Results: The susceptibility vessel sign was present in 87.5% ( n  = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P  = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P  = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P  = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P  = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications., Conclusions: The susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates., (© 2021 by American Journal of Neuroradiology.)