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Objective: Infarction typically develops within the borders of an initial hypoperfused tissue. We prospectively investigated whether in small subcortical stroke patients infarct growth can occur beyond the margins of the affected vascular territories.Methods: In 19 consecutive patients, stroke MRI was performed within 14 h after ictus, and at days 2 and 6 (± 1). Size of diffusion and perfusion disturbances were determined. Infarct volume measured on T2-weighted images on day 6 was considered as imaging endpoint.Results: At the initial examination, the mean diffusion lesion [apparent diffusion coefficient (ADC) lesion size, 1.82 ± 1.2 ml] was larger (p = 0.0002) than the perfusion lesion [mean transit time (MTT) lesion size, 0.72 ± 0.69 ml]. Such an "inverse mismatch" (ADC lesion > MTT lesion) was present in 14/19 patients at baseline and in all patients on day 2. Final lesion volume at day 6 was 3.2 ± 1.6 ml which was larger than the initial perfusion deficit (p = 0.02).Conclusion: In small subcortical ischaemic stroke "inverse mismatch" is frequent and infarction develops beyond the initial perfusion disturbance. This indicates that cytotoxic processes probably triggered by the infarct core are a dominant mechanism for lesion growth. Areas with normal perfusion but which are threatened by cytotoxic damage developing over several days seem prime targets for neuroprotective therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup. Methods/Design The primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. >= 0.05 μg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction. Discussion TRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of co-morbid cardiac damage in ischemic stroke patients and also to provide a basis for clinical recommendations for cardiac workup of such patients. Trial registration clinicaltrials.gov NCT01263964

Background: Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions., Methods: A large international multicentre cohort was searched for patients with intracranial ICA occlusion treated with EVT between 2014 and 2023. Patients were stratified by ICA occlusion pattern, differentiating ICA-I and ICA-L/-T occlusions. Baseline factors, technical (modified thrombolysis in cerebral infarction (mTICI) scale) and functional outcomes (modified Rankin scale [mRS] at 3 months) as well as rates of (symptomatic) intracranial hemorrhage ([s]ICH) were analyzed., Results: Of 13,453 patients, 1825 (13.6%) had isolated ICA occlusion. ICA-occlusion pattern was ICA-I in 559 (4.2%) and ICA-L/-T in 1266 (9.4%) patients. Age (years: 74 vs 73), sex (female: 45.8% vs 49.0%) and pre-stroke functional independency (pre-mRS ⩽ 2: 89.9% vs 92.2%) did not differ between the groups. Stroke severity was lower in ICA-I patients (NIHSS at admission: 14 [7-19] vs 17 [13-21] points). EVT was similarly successful with respect to technical (mTICI2b/3: 76.1% (ICA-I) vs 76.6% (ICA-L/-T); aOR 1.01 [0.76-1.35]) and functional outcome (mRS ordinal shift cOR 1.01 [0.83-1.23] in adjusted analyses. Rates of ICH (18.9% vs 34.5%; aOR 0.47 [0.36-0.62] and sICH (4.7% vs 7.3%; aOR 0.58 [0.35-0.97] were lower in ICA-I patients., Conclusion: EVT might be performed safely and similarly successful in patients with ICA-I occlusions as in patients with ICA-L/-T occlusions., 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: RRL received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Bayer.STE has received funding for travel or speaker honoraria from Bayer, Boehringer Ingelheim and Daiichi-Sankyo. He has served on scientific advisory boards for Bayer, Boehringer Ingelheim, BMS/Pfizer, and MindMaze and on the editorial board of Stroke. His institutions have received an educational grant from Pfizer, compensation from Stago for educational efforts and research support from Daiichi-Sankyo, the Science Funds [Wissenschaftsfonds] of the University Hospital Basel, the University Basel, from the “Wissenschaftsfonds Rehabilitation” of the University Hospital for Geriatric Medicine Felix Platter, the “Freiwillige Akademische Gesellschaft Basel,” the Swiss Heart Foundation, and the Swiss National Science Foundation.HG has received research support from the Swiss National Science Foundation, advisory board honoraria from Daiichi Sankyo and funding for travel from BMS/Pfizer.AZ received speaker honoraria from CSL Behring, Boehringer-Ingelheim, Alexion-Astra Zeneca and Daiichi Sankyo and advisory board honoraria from Bayer, Astra Zeneca and Daiichi Sankyo.DRJ received speaker honoraria from Medtronic and Boehringer Ingelheim.VP received speaker honoraria from Medtronic and Boehringer Ingelheim.H.J.A. reports receiving personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, and Roche that all produce products for hyperacute stroke care.MRH reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript.AS received travel grants from NovoNordiskPM received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and Faculty of Biology and Medicine of the Lausanne UniversityCHN reports receiving speaker honoraria from Abbot, Alexion, AstraZeneca, Bristol-Meyers Squibb, Pfizer and Takeda, all outside the submitted work.All further authors declare no conflicts of interest related to the presented study.

Introduction: While incident ischemic lesions (IILs) are not unusual on follow-up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown., Methods: In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months., Results: At 6 months, 78 patients (15.5%) had IILs, mostly diffusion-weighted imaging-positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: -0.31, 95% confidence interval [CI]: -0.48 to -0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition., Discussion: IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication., Highlights: Incident ischemic lesions (IILs) were assessed with registered baseline and 6-month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one-sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow-up MRI aids long-term prognostication for stroke patients., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Atrial fibrillation detected after stroke (AFDAS) is considered to be a distinct entity influenced by cardiogenic and neurogenic factors. We hypothesized that patients with AFDAS have larger stroke lesions than patients without atrial fibrillation (AF) and with known AF (KAF)., Methods and Results: Consecutive patients with magnetic resonance imaging-confirmed acute ischemic stroke admitted to a university hospital between October 2020 and January 2023 were prospectively registered. We categorized patients as AFDAS, no AF or KAF upon hospital discharge. We manually segmented diffusion-weighted imaging lesions to determine lesion volume. We analyzed 1420 patients (median age, 78; 47.2% women, median National Institutes of Health Stroke Scale score, 3; median hospital stay, 5 days). Of these, 81 had AFDAS (5.7%), 329 had KAF (23.2%) and 1010 had no AF (71.1%). Lesion volume was larger in patients with AFDAS (median, 5.4 mL [interquartile range, 1.0-21.6]) compared with patients with no AF and KAF (median, 0.7 [interquartile range,0.2-4.4] and 2.0 [interquartile range,0.3-11.1] mL, respectively; both P <0.001). Lesion volume was independently associated with AFDAS compared with no AF (adjusted odds ratio, 1.37 [95% CI, 1.20-1.58] per log mL) and KAF (adjusted odds ratio, 1.22 [95% CI, 1.07-1.41] per log mL). Patients in the highest lesion volume quartile (>6.5 mL) were more likely to be diagnosed with AFDAS compared with the lowest quartile (<0.22 mL, 13.6% versus 2.1%; adjusted odds ratio, 5.88 [95% CI, 2.30-17.40]). These associations were more pronounced when excluding 151 patients with nonembolic lesion pattern and similar when excluding 199 patients with KAF on oral anticoagulation., Conclusions: Larger stroke lesions were independently associated with AFDAS diagnosis during index stroke hospitalization highlighting a potential neurogenic contribution to AFDAS pathogenesis.

The "holy grail" of preventing and treating thrombosis and thromboembolism would be a drug that was highly effective (preventing clots) and at the same time had a low risk of bleeding. From a hemostasiological perspective, the inhibition of factor XI represents a promising target because a reduced level of factor XI protects against thrombosis without significantly increasing the risk of spontaneous bleeding. Currently, three different classes of drugs of factor XI-inhibition are tested. These are (1) monoclonal antibodies (mAbs), (2) so-called synthetic, small molecules and (3) antisense oligonucleotides (ASOs). This article provides a narrative overview of the current status of studies on all three classes of drugs. Tests with mAbs have been conducted primarily in DVT prevention after knee replacement surgery. One large phase 3 study is testing the mAbs Abelacimab in patients with atrial fibrillation. The synthetic, small molecules Asundexian and Milvexian are tested in several phase 3 trials, mainly in patients with non-cardioembolic ischemic stroke. Results can be expected in the coming years. Clinical testing of ASOs to inhibit factor XI are still in their infancies., Competing Interests: Declaration of competing interest CH Nolte has received honoraria for lectures or speaker’ bureau from Alexion, AstraZeneca, BMS, Novartis, Pfizer – all outside of the submitted manuscript., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Introduction: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results., Patients and Methods: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows., Results: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p  < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p  < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3., Discussion and Conclusion: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ivana Berisavac: speaker honoraria from Medtronic. Visnja Padjen: speaker honoraria from Medtronic and Boehringer Ingelheim. Ronen R. Leker: received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Filterlex. Andrea Zini: has received funding for speaker honoraria and consulting fees from Boehringer Ingelheim, Astra Zeneca, Daiichi Sankyo, CSL Behring, for scientific advisory board from Bayer, Astra Zeneca. Mirjam R. Heldner: reports grants from Swiss National Science Foundation, SITEM Research Support Funds and Swiss Heart Foundation, not directly related to this manuscript. Christian H Nolte: has received honoraria for lectures or speaker’s bureau from Alexion, AstraZeneca, BMS, Novartis and Pfizer. The other authors report nothing to disclose.

This topical review assesses the growing role of cardiac biomarkers beyond cardiovascular health and focuses on their importance in stroke and dementia. The first part describes blood-based cardiac biomarkers in patients with stroke and highlights applications in the setting of early diagnosis, poststroke complications, outcome prediction as well as secondary prevention. Among other applications, natriuretic peptides can be helpful in differentiating stroke subtypes. They are also currently being investigated to guide prolonged ECG monitoring and secondary prevention in patients with stroke. Elevated cardiac troponin after ischemic stroke can provide information about various poststroke complications recently termed the stroke-heart syndrome. The second part focuses on the role of cardiac biomarkers in vascular cognitive impairment and dementia, emphasizing their association with structural brain lesions. These lesions such as silent brain infarcts and white matter hyperintensities often co-occur with cardiac disease and may be important mediators between cardiovascular disease and subsequent cognitive decline. ECG and echocardiogram measurements, in addition to blood-based biomarkers, show consistent associations with vascular brain changes and incident dementia, suggesting a role in indicating risk for cognitive decline. Together, the current evidence suggests that cardiac blood-based, electrophysiological, and imaging biomarkers can be used to better understand the heart and brain connection in the setting of not only stroke but also dementia., Competing Interests: Dr Johansen received funding by the National Institute of Neurological Disorders and Stroke/National Institute on Aging and is a section editor for Stroke. She also reports compensation from the American Neurological Association for editorial services. Dr Nolte reports compensation from Boehringer Ingelheim for consultant services; compensation from Deutsches Zentrum für Herz-Kreislaufforschung for other services; compensation from Pfizer for consultant services; compensation from Portola Pharmaceuticals for other services; compensation from Novartis for other services; compensation from Abbott Canada for other services; compensation from Alexion Pharmaceuticals for consultant services; compensation from Bristol-Myers Squibb for consultant services; compensation from Deutsches Zentrum für Neurodegenerative Erkrankungen for other services; compensation from Daiichi Sankyo Europe GmbH for consultant services; and compensation from AstraZeneca for other services. Dr Bustamante received funding from Instituto de Salud Carlos III (INT22/00068) co-financed by FEDER. Dr Katan receives research support of the Swiss national Science Foundation ([182267], [213471], [198783], and [204977]); grants from the Swiss Heart Foundation and University Hospital of Zurich Foundation; participation on advisory boards and speaker honoraria for Medtronic, Bristol Myers Squibb Pfizer/Jansen, and Astra Zeneca; in kind contributions from Roche Diagnostics and Brahms Thermo Fisher Scientific.

Introduction: Thrombectomy complications remain poorly explored. This study aims to characterize periprocedural intracranial vessel perforation including the effect of thrombolysis on patient outcomes., Patients and Methods: In this multicenter retrospective cohort study, consecutive patients with vessel perforation during thrombectomy between January 2015 and April 2023 were included. Vessel perforation was defined as active extravasation on digital subtraction angiography. The primary outcome was modified Rankin Scale (mRS) at 90 days. Factors associated with the primary outcome were assessed using proportional odds models., Results: 459 patients with vessel perforation were included (mean age 72.5 ± 13.6 years, 59% female, 41% received thrombolysis). Mortality at 90 days was 51.9% and 16.3% of patients reached mRS 0-2 at 90 days. Thrombolysis was not associated with worse outcome at 90 days. Perforation of a large vessel (LV) as opposed to medium/distal vessel perforation was independently associated with worse outcome at 90 days (aOR 1.709, p  = 0.04) and LV perforation was associated with poorer survival probability (HR 1.389, p  = 0.021). Patients with active bleeding >20 min had worse survival probability, too (HR 1.797, p  = 0.009). Thrombolysis was not associated with longer bleeding duration. Bleeding cessation was achieved faster by permanent vessel occlusion compared to temporary measures (median difference: 4 min, p  < 0.001)., Discussion and Conclusion: Vessel perforation during thrombectomy is a severe and frequently fatal complication. This study does not suggest that thrombolysis significantly attributes to worse prognosis. Prompt cessation of active bleeding within 20 min is critical, emphasizing the need for interventionalists to be trained in complication management., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V. S.-Z. discloses speaker fees from Medtronic Inc. (money paid to institution). M.R.L. discloses unrestricted educational grants from Medtronic and Stryker; consulting for Medtronic, Stereotaxis, Metis Innovative and Aeaean Advisers; equity interest in Proprio, Fluid Biomed, Stroke Diagnostics, Hyperion Surgical, Apertur; editorial board of Journal of NeuroInterventional Surgery; data safety monitoring board of Arsenal Medical. M.-N.P. discloses unrestricted grants from Swiss National Science Foundation (SNF), Bangerter-Rhyner Stiftung, Stryker Neurovascular Inc., Phenox GmbH, Medtronic Inc., Rapid Medical Inc., and Penumbra Inc for the DISTAL trial, grant for SPINNERS trial from Siemens Healthineers AG (money paid to institution) and the following speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Rapid Medical Inc. and Siemens Healthineers AG (money paid to institution).

Background: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA)., Methods: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality., Results: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups., Conclusion: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar., Competing Interests: Competing interests: NA reported employment by the American Heart Association. GD reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. JTF reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. UF 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. UF reports patent US11166738B2. DCH reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. CH reported consultancy for Brainomix and Speaker with Stryker. APJ reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. JK reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. DPOK reported grants from the Joachim Herz Foundation. JBK reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. JPM reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. PM reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). MAM reported grants from Medtronic, Stryker, and MicroVention. MaM reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. SN reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. TNN reported research support from the Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. RGN 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. CHN 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. MP 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. VP reported being a lecturer for Daiichi Sankyo. MR reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. PAR reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. SAS reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. AHS 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., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation., Methods: In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0-2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t -test for unpaired samples were used for statistical analysis., Results: During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p <0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p =0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation., Conclusions: In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site., Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality., Results: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM., Conclusions: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage., Competing Interests: Disclosures Dr Dabus: consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker; stock holdings in RIST and InNeuroCo. Dr Fifi: consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; stock holdings in Imperative Care and Sim&Cure. Dr Fischer: research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Haussen: consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB for Jacobs Institute; stock options in viz AI. Dr Herweh: consultancy for Brainomix; speaker with Stryker. Dr Jadhav: consulting with Basking Biosciences; stock options in Gravity Medical Technology; a patent for a novel stent retriever device licensed to Basking Biosciences; and Editor-in-Chief for the Stroke: Vascular and Interventional Neurology journal. Dr Kaesmacher: grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser: grants from the Joachim Herz Foundation. Dr Kuramatsu: grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Marto: consulting and speaker fees from Amicus Therapeutics and Boehringer Ingelheim. Dr Michel: grants from the University of Lausanne and SNF. Dr Möhlenbruch: grants from Medtronic, Stryker, and MicroVention. Dr Mokin: stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology; consulting at MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel: consultancy for Brainomix; speaker at Boehringer Ingelheim and Pfizer. Dr Nguyen: Associate Editor of Stroke, advisory board at Aruna Bio and Brainomix. Dr Nogueira: 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; grants from Cerenovus and Stryker. Dr Nolte: research support and compensation from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen; consultancy for Alexion, Daiichi Sankyo, Novartis, AstraZeneca, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. S. Poli: research grants from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work). Dr Psychogios: 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; consultancy for Siemens Healthineers. Dr Puetz: lecturer for Daiichi Sankyo. Dr Ribo: consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb: travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Romoli: research grants from the Italian Stroke Association; consultancy for CSL Behring. Dr Sheth: consultancy for Imperative Care, viz AI, and Penumbra; compensation from Motif Neurosciences (other services); grants from the National Institutes of Health. Dr Siddiqui: 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 Ltd, Cerevatech Medical, InspireMD, PerFlow Medical; security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Inc, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. Dr Strbian: Assistant Editor of Stroke, Editorial Board of European Stroke Journal, advisory board at Boehringer Ingelheim, Alexion/AstraZeneca, and Bristol Myers Squibb/Janssen; research support from Boehringer Ingelheim; consultancies for Orion, Herantis Pharma, and CSL Behring. The other authors report no conflicts.

Importance: Elevated values of high-sensitivity cardiac troponin (hs-cTn) are common in patients with acute ischemic stroke and are associated with poor prognosis. However, diagnostic and therapeutic implications in patients with ischemic stroke remain unclear., Objective: To identify factors indicative of myocardial infarction (MI) in patients with acute ischemic stroke and hs-cTn elevation. The primary hypothesis was that a dynamic change of hs-cTn values (>50% change) in patients with acute ischemic stroke indicates MI., Design, Setting, and Participants: This cross-sectional study was a prospective, observational study with blinded end-point assessment conducted across 26 sites in Germany. Patients were included if they had acute ischemic stroke within 72 hours and either (1) highly elevated hs-cTn values on admission (>52 ng/L) or (2) hs-cTn levels above the upper limit of normal and a greater than 20% change at repeated measurements. Patients were enrolled between August 2018 and October 2020 and had 1 year of follow-up. Statistical analysis was performed between April 2022 and August 2023., Exposure: Standardized electrocardiography, echocardiography, and coronary angiography., Main Outcome and Measures: Diagnosis of MI as adjudicated by an independent end-point committee based on the findings of electrocardiography, echocardiography, and coronary angiography., Results: In total, 254 patients were included. End points were adjudicated in 247 patients (median [IQR] age, 75 [66-82] years; 117 were female [47%] and 130 male [53%]). MI was present in 126 of 247 patients (51%) and classified as type 1 MI in 50 patients (20%). Dynamic change in hs-cTn value was not associated with MI in univariable (32% vs 38%; χ2 P = .30) or adjusted comparison (odds ratio, 1.05; 95% CI, 0.31-3.33). The baseline absolute hs-cTn value was independently associated with type 1 MI. The best cutoffs for predicting type 1 MI were at hs-cTn values 5 to 10 times the upper limit normal., Conclusions and Relevance: This study found that in patients with acute ischemic stroke, a dynamic change in hs-cTn values did not identify MI, underscoring that dynamic changes do not identify the underlying pathophysiological mechanism. In exploratory analyses, very high absolute hs-cTn values were associated with a diagnosis of type 1 MI. Further studies are needed how to best identify patients with stroke who should undergo coronary angiography.

Background: Occlusion of the internal carotid artery (ICA) may extend into the middle or anterior cerebral artery (ICA-T) or be confined to the intracranial (ICA-I) or extracranial segment (ICA-E). While there is excellent evidence for endovascular therapy (EVT) in ICA-T occlusions, studies on EVT in non-tandem ICA-I or ICA-E occlusions are scarce., Objective: To characterize EVT-treated patients with ICA-I- and ICA-E occlusion by comparing them with ICA-T occlusions., Methods: The German Stroke Registry (GSR), a national, multicenter, prospective registry was searched for EVT-treated patients with isolated ICA occlusion between June 2015 and December 2021. We stratified patients by ICA occlusion site: (a) ICA-T, (b) ICA-I, (c) ICA-E. Baseline factors, procedural variables, technical (modified Thrombolysis in Cerebral Infarction (mTICI)), and functional outcomes (modified Rankin scale score at 3 months) were analyzed., Results: Of 13 082 GSR patients, 2588 (19.8%) presented with an isolated ICA occlusion, thereof 1946 (75.2%) ICA-T, 366 (14.1%) ICA-I, and 276 (10.7%) ICA-E patients. The groups differed in age (77 vs 76 vs 74 years, P trend =0.02), sex (53.4 vs 48.9 vs 43.1% female, P trend <0.01), and stroke severity (median National Institutes of Health Stroke Scale score at admission 17 vs 14 vs 13 points, P trend <0.001). In comparison with ICA-T occlusions, both ICA-I and ICA-E occlusions had lower rates of successful recanalization (mTICI 2b/3: 85.4% vs 80.4% vs 76.3%; aOR (95% CI for ICA-I vs ICA-T 0.71 (0.53 to 0.95); aOR (95% CI) for ICA-E vs ICA-T 0.57 (0.42 to 0.78)). In adjusted analyses, ICA-E occlusion was associated with worse outcome when compared with ICA-T occlusion (mRS ordinal shift, cOR (95% CI) 0.70 (0.52 to 0.93))., Conclusion: Patient characteristics and outcomes differ substantially between ICA-T, ICA-I, and ICA-E occlusions. These results warrant further studies on EVT in ICA-I and ICA-E patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca's area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca's area, during language processing., (© 2024. The Author(s).)

Importance: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients., Objective: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection., Data Sources: PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023., Study Selection: Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up., Data Extraction/synthesis: Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator., Main Outcomes and Measures: The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses., Results: Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0)., Conclusions and Relevance: This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.

Background: Endovascular treatment has become the standard care for acute basilar artery occlusion (BAO). Uncertainty persists about the optimal thrombectomy technique., Objective: To compare aspiration thrombectomy with stent retriever thrombectomy in patients with BAO in a multicenter real-world patient population., Methods: We analyzed data from the German Stroke Registry-Endovascular Treatment (GSR-ET). Patients with isolated BAO who underwent either aspiration or stent retriever thrombectomy were compared, including propensity score matching (PSM). The primary outcome measure was the modified Rankin Scale shift analysis at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), procedure complications, and metrics., Results: Of 13 082 patients in the GSR-ET, 387 patients (mean age 72.0±13.1 years; 45.0% female) fulfilled the inclusion criteria. The thrombectomy technique was aspiration only in 195 (50.4%) and stent retriever only in 192 (49.6%) patients. Functional outcome did not differ between the groups, either before (common OR (cOR) 0.94; 95% CI 0.64 to 1.38) or after PSM (cOR=1.37; 95% CI 0.90 to 2.09). There was no significant difference in sICH (2.6 vs 5.5%; P=0.231; OR=0.46; 95% CI 0.14 to 1.47), but aspiration thrombectomy demonstrated fewer procedure-related complications (4.6% vs 12.5%; P=0.017), a shorter procedure duration (24 vs 48 min; P<0.001), and higher first pass recanalization rates (75.1% vs 44.8%; P<0.001)., Conclusions: In this study both aspiration and stent retriever thrombectomy showed equal efficacy in terms of functional outcome in patients with BAO. However, procedure complications and metrics might favor aspiration over stent retriever thrombectomy., Competing Interests: Competing interests: LKel has received funding for travel or speaker honoraria from Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer outside of this study. CHN has received funding for travel or speaker honoraria from Alexion, Astra-Zeneca, Bayer Vital, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, and Takeda., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone., Methods: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0-1) and independent outcome (mRS 0-2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment., Results: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3-P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79-1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05-2.12), sICH (aOR 2.87, 95% CI 1.23-6.72), and mortality (aOR 1.77, 95% CI 1.07-2.95)., Conclusion: Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Objective: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment., Methods: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing., Results: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation., Interpretation: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital., Methods: Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany. Patients with AIS without known atrial fibrillation (AF) underwent cardiovascular MR imaging (CMR), MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic care., Results: Among 356 patients with AIS (mean age 66 years, 37.6% female), enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care (17.7% vs 5.3%; p<0.001). Consequently, fewer patients were classified as cryptogenic after enhanced diagnostic workup (38.5% vs 45.5%, p<0.001). Routine care included echocardiography in 228 (64.0%) patients. CMR was successfully performed in 292 (82.0%) patients and revealed more often a prespecified pathological finding compared with routine echocardiography (16.1% vs 5.3%). Furthermore, study-related ECG monitoring (median duration 162 hours (IQR 98-210)) detected AF in 16 (4.5%) patients, while routine monitoring (median duration 51 hours (IQR 34-74)) detected AF in seven (2.0%) patients., Conclusions: Enhanced diagnostic workup revealed a higher rate of prespecified pathological findings in patients with AIS compared with routine diagnostic care and significantly reduced the proportion of patients with cryptogenic stroke., Trial Registration Number: NCT02142413., Competing Interests: Competing interests: RW received grants from Deutsches Zentrum für Herz-/Kreislaufforschung, Deutsche Forschungsgemeinschaft, European Union, Bundesministerium für Bildung und Forschung, Medtronic and Boehringer Ingelheim as well as personal fees from Astra, Bayer, Boehringer Ingelheim, CVRx, Daiichi, BMS, Medtronic, Novartis, Pfizer, Pharmacosmos and Servier, all outside the submitted work. ME received funding from DFG under Germany's Excellence Strategy—EXC-2049—390688087, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq. ME reports grants from Bayer and fees paid to the Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, all outside the submitted work. CHN received research grants from German Ministry of Research and Education, German Center for Neurodegenerative Diseases, German Center for cardiovascular Research, and speaker and/or consultation fees from Alexion, Abbott, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer Pharma and Daiichi Sankyo. KGH reports a study grant by Bayer, lecture fees/advisory board fees from Abbott, Amarin, Alexion, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers-Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Pfizer, Portola, Sun Pharma and W. L. Gore & Associates. All other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stroke is a severe complication of infective endocarditis (IE), associated with high rates of mortality. Data on how IE patients with and without stroke differ may help to improve understanding contributing mechanisms., Methods: All patients treated for IE between 2019 and 2021 with and without associated stroke were identified from the medical records of three academic tertiary care hospitals in Germany, all part of Charité - Universitätsmedizin Berlin, Germany. Multivariable logistic regression analyses were performed to identify variables associated with the occurrence of stroke., Results: The study population consisted of 353 patients diagnosed with IE. Concomitant stroke occurred in 96/353 (27.2%) patients. Acute stroke was independently associated with co-occurring extracerebral arterial embolism [adjusted Odds ratio (aOR = 2.52; 95% confidence interval (CI) 1.35-4.71)], acute liver failure (aOR = 2.62; 95% CI 1.06-6.50), dental focus of infection (aOR = 3.14; 95% CI 1.21-8.12) and left-sided IE (aOR = 28.26; 95% CI 3.59-222.19). Stroke was found less often in IE patients with congenital heart disease (aOR = 0.20; 95% CI 0.04-0.99) and atypical pathogens isolated from blood culture (aOR = 0.31; 95% CI 0.14-0.72)., Conclusions: Stroke is more likely to occur in individuals with systemic complications affecting other organs, too. Special attention should be addressed to dental status. The low incidence of stroke in patients with congenital heart disease may reflect awareness and prophylactic measures., (© 2024. The Author(s).)

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts