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Martin Gude,1 Hans Kirkegaard,1,2 Rolf Blauenfeldt,3 Anne Behrndtz,3 Jeppe Mainz,3 Ingunn Riddervold,4 Claus Z Simonsen,2,3 Niels Hjort,2,3 Søren P Johnsen,5 Grethe Andersen,2,3 Jan Brink Valentin5 1Department of Research and Development, Prehospital Emergency Medical Services, Central Denmark Region; and Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Danish Stroke Center, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 4Norwegian Air Ambulance Foundation, Oslo, Norway; 5Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, DenmarkCorrespondence: Martin Gude, Prehospital Emergency Medical Services, Central Denmark Region and Aarhus University Hospital, Aarhus, Denmark, Email gude@dadlnet.dkObjective: To examine the agreement between emergency medical service (EMS) providers, neurology residents and neurology consultants, using the Cincinnati Prehospital Stroke Scale (CPSS) and the Prehospital Acute Stroke Severity Scale (PASS).Methods: Patients with stroke, transient ischemic attack (TIA) and stroke mimic were included upon primary stroke admission or during rehabilitation. Patients were included from June 2018 to September 2019. Video recordings were made of patients being assessed with CPSS and PASS. The recordings were later presented to the healthcare professionals. To determine relative and absolute interrater reliability in terms of inter-rater agreement (IRA), we used generalisability theory. Group-level agreement was determined against a gold standard and presented as an area under the curve (AUC). The gold standard was a consensus agreement between two neurology consultants.Results: A total of 120 patient recordings were assessed by 30 EMS providers, two neurology residents and two neurology consultants. Using the CPSS and the PASS, a total of 1,800 assessments were completed by EMS providers, 240 by neurology residents and 240 by neurology consultants. The overall relative and absolute IRA for all items combined from the CPSS and PASS score was 0.84 (95% CI 0.80; 0.87) and 0.81 (95% CI 0.77; 0.85), respectively. Using the CPSS, the agreement on a group-level resulted in AUCs of 0.83 (95% CI 0.78; 0.88) for the EMS providers and 0.86 (95% CI 0.82; 0.90) for the neurology residents when compared with the gold standard. Using the PASS, the AUC was 0.82 (95% CI 0.77; 0.87) for the EMS providers and 0.88 (95% CI 0.84; 0.93) for the neurology residents.Conclusion: The high relative and absolute inter-rater agreement underpins a high robustness/generalisability of the two scales. A high agreement exists across individual raters and different groups of healthcare professionals supporting widespread applicability of the stroke scales.Plain Language Summary: Early stroke identification is pivotal to enable faster treatment. To aid this identification, many symptom-based stroke scales have been constructed for both stroke screening and severity assessment. In the prehospital environment, several scales have been evaluated on performance, but only few studies have evaluated the agreement between the ambulance personnel (emergency medical service (EMS) providers) and stroke physicians when interpreting the assessed symptoms in the scales. It is of great importance to know how EMS providers interpret symptoms seen in connection with the use of the scales to focus the continuous training of the EMS providers but also to aid the decision on which scale to implement in ambulances. From previous studies, we know that complex stroke scales are used to a considerably lesser extent than more simple scales, which could be caused by difficulties interpreting specific symptoms. In this study, a variety of methods was applied to determine the inter-rater agreement for two simple stroke scales using dichotomously evaluated symptoms. High inter-rater agreement between EMS providers and Stroke Neurologists exists both between individual raters and between raters grouped according to their profession and seniority. Previous studies have also found high inter-rater agreement for simple stroke scales but lesser agreement for more advanced scales. In conclusion, simple stroke scales seem to produce the highest agreement.Keywords: observer variation, prehospital emergency care, emergency medical service provider, neurologists, stroke

Background: Transcatheter patent foramen ovale (PFO) closure is the recommended treatment for patients age 18 to 60 years with cryptogenic stroke having a high probability of being PFO-related. Limited data exist on stroke recurrence after PFO closure outside clinical trials., Objectives: The purpose of this study was to examine stroke recurrence after PFO closure in routine clinical practice., Methods: We used nationwide population-based Danish registries to conduct a cohort study of all patients with PFO closure during 2008 to 2021 (n = 1,162) and a birth year and sex-matched comparison cohort from the general population (n = 11,620). We calculated absolute and relative risks of ischemic stroke within 4 years after PFO closure. We used weighted Cox regression to estimate adjusted HRs of the association between PFO closure vs the general population and ischemic stroke., Results: The absolute risks of ischemic stroke in patients with PFO closure and in the general population, respectively, were 1.4% (95% CI: 0.8%-2.3%) and 0.1% (95% CI: 0.0%-0.1%) at 1 year, 1.4% (95% CI: 0.8%-2.3%) and 0.2% (95% CI: 0.2%-0.4%) at 2 years, 2.2% (95% CI: 1.3%-3.5%) and 0.4% (95% CI: 0.2%-0.5%) at 3 years, and 2.5% (95% CI: 1.5%-4.0%) and 0.4% (95% CI: 0.3%-0.6%) at 4 years. Thus, the absolute 4-year risk of ischemic stroke was 2.1% (95% CI: 0.9%-3.3%) higher in patients with PFO closure than in the general population, corresponding to an adjusted HR of 6.3 (95% CI: 3.1-12.6)., Conclusions: The 4-year risk of ischemic stroke after routine PFO closure for cryptogenic stroke was comparable to that observed in clinical trials, but remained higher than in the general population., Competing Interests: Funding Support and Author Disclosures Dr Bonnesen was supported by research grants from the Danish Diabetes and Endocrine Academy, which is funded by the Novo Nordisk Foundation, under grant number NNF22SA0079901. Dr Schmidt was supported by the Novo Nordisk Foundation under grant number NNF19OC0054908. The funding sources had no role in the design, conduct, analysis, or reporting of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Lacunar stroke represents around a quarter of all ischemic strokes; however, their identification with computed tomography in the hyperacute setting is challenging. We aimed to validate a clinical score to identify lacunar stroke in the acute setting, independently, with data from the WAKE-UP trial using magnetic resonance imaging., Methods: We analyzed data from the WAKE-UP trial and extracted Oxfordshire Community Stroke Project (OCSP) classification. Lacunar score was defined by National Institutes of Health Stroke Scale (NIHSS) < 7 and OCSP lacunar syndrome. Assessment of lacunar infarct by two independent investigators was blinded to clinical data. We calculated sensitivity, specificity, negative and positive predictive value (NPV and PPV, respectively) of lacunar score., Results: We included 503 patients in the analysis, mean (±SD) age 65.2 (±11.6) years, 325 (65%) males, median (IQR) NIHSS = 6 (4-9); 108 (22%) lacunar infarcts were identified on magnetic resonance (MR), patients fulfilling lacunar score criteria were 120 (24%), of which 47 (44%) had a lacunar infarct. Lacunar score was negative in 322 (82%) of patients without lacunar infarct. Patients with lacunar score had lower NIHSS (4 vs 7, p < 0.001), higher systolic (157 vs 151 mmHg, p = 0.001) and diastolic (86 vs 83 mmHg, p = 0.013) blood pressure and smaller infarct volume (2.4 vs 9.5 mL, p < 0.001). Performance of lacunar score was as follows: sensitivity 0.44; specificity 0.82; PPV 0.39; NPV 0.84; and accuracy 0.73. Assuming a prevalence of lacunar stroke of 13%, PPV lowered to 0.30 but NPV was 0.90. Lacunar score performed better for supratentorial lacunar infarcts., Conclusion: Lacunar score had a very good specificity and NPV for screening of lacunar stroke. Implementation of this simple tool into clinical practice may help hyperacute management and guide patient selection in clinical trials., Data Access Statement: Data supporting the results of this paper are available upon reasonable request to the corresponding author., 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: G.T. received fees as consultant or lecturer from Acandis, Alexion, Amarin, Astra Zeneca, Bayer, Bristol Myers Squibb (BMS)/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Stryker, all outside the submitted work. M.E. reports grants from Bayer and fees paid to the Charité from Abbott, Amgen, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, BMS, Daiichi Sankyo, Sanofi, Novartis, Pfizer, all outside the submitted work. The other authors report no conflict of interest.

Background: Patent foramen ovale (PFO) has been associated with ischemic stroke and transient ischemic attack (TIA). Guidelines recommend PFO closure for stroke prevention in selected patients, but the risk of recurrent stroke remains high compared to the background population. We aimed to evaluate the causes of recurrent stroke/TIA and post-interventional complications in patients after PFO closure., Methods: Patients from the Central Denmark Region who underwent PFO closure at Aarhus University Hospital between November 5, 2018, and May 12, 2023, following an ischemic stroke, TIA, amaurosis fugax, or retinal emboli were included. Data on patient demographics, risk factors, procedural details, post-interventional complications, and recurrent stroke/TIA were collected from electronic medical records., Results: PFO closure was performed in 310 patients (median age: 49 years). During a median follow-up of 2.6 years (interquartile range: 1.5-3.6, 814 total patient-years), recurrent stroke/TIA was observed in 8 patients (2.6%), or 0.98 recurrent strokes per 100 patient-years. Recurrent stroke/TIA was more frequent in patients with hypertension (50.0% vs. 16.9%, p = 0.039). Recurrent stroke/TIA was related to thrombophilia or hematologic conditions entailing hypercoagulability in 62.5% of patients. New-onset atrial fibrillation was observed in 9.4% of patients within 45 days after the procedure. None of these patients subsequently developed an ischemic event. Other adverse outcomes were uncommon., Conclusion: Rates of recurrent ischemic stroke/TIA after PFO closure were comparable to findings in previous trials. Pre-existing vascular risk factors (hypertension), and a hypercoagulable state were associated with recurrent ischemic stroke/TIA., 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:CZS receives speaker fee from Pfizer. ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Novo Nordisk, Lundbeck Pharma, and Organon. He is an investigator in clinical studies sponsored by AstraZeneca, Idorsia, and Bayer and has received unrestricted research grants from Boehringer Ingelheim. JEN-K receives research grants from Novo Nordic Foundation, Abbott, and Boston Scientific. AA has received funding from the Karen Elise Jensen Foundation, speaker honoraria, or consultancy fees from ABBOTT, Gore Medical, Angiodynamics, EPS Vascular Jannsen, Inari Medical, and Magneto Thrombectomy Solutions. HS and JAH have no conflicts to disclose.

Introduction: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units., Patients and Methods: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights., Results: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4)., Discussion and Conclusion: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies., 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: CS: Supported by research grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region. SB, AB, MS, JN, PC, SJ TP and GA declare no conflict of interest.

Background: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial., Methods: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed., Findings: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99])., Interpretation: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients., Funding: European Union Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests MB reports funding from the European Union Horizon 2020 and Deutsche Forschungsgemeinschaft (payments to the institution); honoraria for lectures from Novartis, Boehringer Ingelheim, and Seagen; consulting fees from NeuroScios and Boehringer Ingelheim; and a role as Editor-in-Chief of Clinical Neuroradiology (Springer), outside the submitted work. JF reports funding from the European Commission; personal consulting fees from Acandis, Cerenovus, Medtronic, Microvention, Phenox, Roche, and Stryker; consulting at Philips (no payments); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Penumbra and Tonbridge; support for attending meetings or travel from Medtronic and Penumbra; and stock or stock options from Tegus medical, eppdata, and Vastrax, outside the submitted work. JF also reports participation in a Data Safety Monitoring Board (DSMB) or Advisory Board at Phenox (personal fees) and Stryker (personal fees), and a role as past president of ESMINT. SB reports funding from the EU Horizon 2020 research and innovation programme (payments made to the institution; support for attending meetings or travel), outside the submitted work. AHA reports unrestricted research grants from Boehringer Ingelheim and honoraria for lectures from BMS/Pfizer, Teva, Roche, Abbvie, Lundbeck, Novartis, outside the submitted work. AHA also reports participation in Advisory Boards for MSD, BMS/Pfizer, Lundbeck, Lilly, and Abbvie. BF reports research grants from Carlos III Institute of Health (ISCIII), personal payment for educational lectures from Servicio Madrileño de Salud, payment to the institution for lectures from Euromedice, personal payment for educational lectures from Takeda, support for attending meetings from Daichii Sankyo, and receipt of materials for research from Abbot, outside the submitted work. MDH reports funding from Nil, a grant to the University of Calgary for the TEMPO-2 trial from Boehringer Ingelheim, a grant to the University of Calgary from Biogen, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from NoNO, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from the Canadian Institute for Health Research, a grant to the University of Calgary for the HERMES collaboration from Medtronic, and a grant to the University of Calgary for the QuICR Alberta Stroke Program; some of the funds were used for the ESCAPE-NA1 trial from Alberta Innovates. MDH also reports consulting fees from Sun Pharma Brainsgate (paid work for adjudication of clinical trial outcomes), US Patent 62/086,077 (licensed to Circle NVI), US Patent 10,916,346 (licensed to Circle NVI), and private stock ownership from Circle and PUreWeb, outside the submitted work. MDH reports participation as DSMC Chair of the RACECAT trial (end 2020), participation as DSMC Chair of the Oncovir Hiltonel trial (ongoing), participation as DSMC Chair of the DUMAS trial (ongoing), participation as DSMB member of the ARTESIA trial (ongoing), participation as DSMB member of the BRAIN-AF trial (ongoing), a role as President of the Canadian Neurological Sciences Federation (not for profit), and as Board Member of the Canadian Stroke Consortium (not for profit). AK reports grants from the European Commission for the TENSION study (payment to the institution), outside the submitted work. LP reports consulting fees from Balt, consulting fees from Microvention, consulting fees from Phenox, and support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organization), outside the submitted work. CZS reports grants from Health Research Foundation of Central Denmark Region, outside the submitted work. RAB reports speakers fees from Novo Nordisk and Beyer, outside the submitted work. HD reports financial compensation for the start-up fee and the obligatory payment to the hospital administration paid by the sponsor (Medical University Heidelberg) to the Clinical Division (no personal payments), personal consulting fees from Stryker, speakers honorary from Medtronic, and support for attending meetings or travel from Medtronic, outside the submitted work. HD also reports a role as past President of the Austrian Society of Interventional Radiology and past president Austrian Society of Neuroradiology. FD reports consulting fees from Cerenovus, Balt, Cerus Endovascular, and Microvention; payment for expert testimony from Cerenovus; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Cerenovus, Stryker, Acandis, Asahi, Penumbra, Medtronic, Tonbridge, Inspire, and Q'Apel, outside the submitted work. FD also reports participation in a DSMB or Advisory Board at Cerenovus and Microvention and previous roles as Associate Editor for Journal of Interventional Surgery, Journal of Clinical Medicine, and Clinical Neuroradiology. FF reports consulting fees from eppdata and support for attending meetings or travel from Microvention, Medtronic, Cerebrovascular Research and Education Foundation, and Acandis, outside the submitted work. SG reports consulting fees from eppdata, outside the submitted work. CH reports consulting fees from Brainomix and lecture fees from Stryker, outside the submitted work. SH-J reports funding for data collection and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo, outside the submitted work. MG reports research grants from Medtronic and Cerenovus (payments to the University of Calgary); royalties or licenses from Microvention (systems of intracranial access); personal consulting fees from Microvention, Medtronic, Stryker, Mentice, Philips, and Penumbra; and stock or stock options from Circle Neurovascular, outside the submitted work. FCK was chair of the German Stroke Registry (unpaid). RM reports payments for stroke lecture from TMC Academy, outside the submitted work. MM reports grants from Balt, Medtronic, MicroVention, and Stryker; consulting fees from Siemens; and support for attending meetings or travel from Europa Group, outside the submitted work. SM-H reports consulting fees from Terumo and Boston Scientific Corporation and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo and Boston Scientific Corporation, outside the submitted work. NM reports provision of study materials, outside the submitted work. PP reports support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organisation), outside the submitted work. MP reports grants from the German Research Foundation, speaker honoraria unrelated from Merck Serono and Bayer, and support for attending meetings or travel from Merck Serono (travel reimbursement) and Bayer (travel reimbursement), outside the submitted work. VP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Daichii Sankyo, AstraZeneca and BMS, and support for attending meetings or travel from NoNo (travel reimbursement). PAR reports consulting fees to the institution from Boehringer Ingelheim and Bayer, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Bayer, Pfizer, and BMS (all made to the institution), outside the submitted work. ES reports grants from Hamburg Innovation and Hertie Foundation, outside the submitted work. DFV reports research grants from MicroVention, consulting fees from Medtronic, and paid lectures from Cerenovus/Johnson & Johnson, outside the submitted work. WW reports consulting fees to the institution from Abbvie, and consulting fees to the institution from BMS, GSK, and Servier, outside the submitted work. GT reports funding from the European Commission (EU Horizon 2020 research and innovation programme, payments to the institution); personal consulting fees from Acandis, AstraZeneca, Bayer, Boehringer Ingelheim, and Stryker; and personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, Stryker, outside the submitted work. GT also reports participation as DSMB member for the TEA Stroke Trial (no payments) and ReSCInD trial (no payments), a role as speaker of the Commission for Cerebrovascular Diseases of the German Society of Neurology (no payments), and member of the Board of Directors of the European Stroke Organisation (no payments). All other declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Competing Interests: Dr Simonsen reports grants from the Health Research Foundation of Central Denmark Region and speaker fee from Pfizer, outside the submitted work. Dr Blauenfeldt reports speaker fee from Novo Nordisk, Pfizer, and Bayer, outside the submitted work.

Importance: Patients with atrial fibrillation (AF) can have an ischemic stroke (IS) despite oral anticoagulant (OAC) treatment. Knowledge regarding the association between OAC discontinuation and the subsequent risk of recurrent IS in patients with AF is limited., Objectives: To determine the risk of recurrent IS in patients with AF receiving OAC and to evaluate the association between OAC discontinuation and the risk of recurrent IS., Design, Setting, and Participants: This is a nationwide cohort study of patients aged 50 years or older in Denmark who had AF and an IS (entry IS) and were initiating or restarting subsequent OAC treatment after being discharged between January 2014 and December 2021. Patients were followed up for recurrent IS until June 2022. Within this study cohort, a nested case-control analysis was performed in which patients with recurrent IS were matched to patients receiving OAC who had not yet experienced a stroke. Data were analyzed from May 25, 2023, to April 18, 2024., Exposure: Use of OAC at the time of recurrent IS or the equivalent date in matched controls based on redeemed prescriptions., Main Outcomes and Measures: The primary outcome was recurrent IS. Crude and adjusted cumulative incidences of recurrent IS and all-cause mortality were calculated in cohort analyses, and adjusted odds ratios (aORs) were determined for recurrent IS associated with OAC discontinuation in nested case-control analyses., Results: The study cohort included 8119 patients (4392 [54.1%] male; mean [SD] age, 78.4 [9.6] years; median (IQR) CHA2DS2-VASc score, 4.0 [3.0-5.0]). Over a mean (SD) follow-up of 2.9 (2.2) years, 663 patients had a recurrent IS, of whom 533 (80.4%) were receiving OAC at the time of their recurrent IS. The crude cumulative incidence of recurrent IS at 1 year was 4.3% (95% CI, 5.9%-7.1%), and the crude cumulative incidence of all-cause mortality was 15.4% (95% CI, 14.7%-16.2%). Adjusted analysis showed similar results. Patients who discontinued OACs had a higher risk of recurrent IS (89 cases [13.4%], 180 controls [6.8%]; aOR, 2.13; 95% CI, 1.57-2.89) compared with patients still receiving OAC., Conclusions and Relevance: The risks of recurrent IS and mortality were high in patients with AF despite secondary prevention with OAC, and OAC discontinuation doubled the risk of recurrent IS compared with patients who continued OAC. This finding highlights the importance of OAC continuation and the need for improved secondary stroke prevention in patients with AF.

Background: Hypertension and cerebral amyloid angiopathy are the most common causes of spontaneous intracerebral hemorrhage (ICH); however, these conditions do not imply macrovascular pathology. Still, computed tomography (CT) angiography (CTA) is often performed in the acute phase in patients with ICH., Purpose: To assess the diagnostic yield of CTA in the detection of secondary etiology in consecutive patients with spontaneous ICH., Material and Methods: We performed a retrospective analysis of data from a prospective single-center cohort study of 203 patients presenting with spontaneous ICH admitted to a comprehensive stroke center over a two-year period (15 October 2016 to 15 October 2018). The underlying vascular pathology was assessed using CTA., Results: CTA was performed in addition to non-contrast CT and/or magnetic resonance imaging (MRI). Vascular pathology was found in 11 of 203 (5.4%) patients and included arteriovenous malformations (n=4), aneurysms (n=4), vasospasms (n=1), cerebral venous thrombosis (n=1), and other vascular malformations (n=1). In eight cases, the finding was deemed symptomatic. Patients with vascular pathology on CTA more often had lobar located hemorrhages (63.6% vs. 36.4%, P  = 0.049). Numerically, patients with vascular pathology were younger, had smaller hematoma volumes, and lower mortality., Conclusion: Underlying macrovascular pathology was detected on CTA in only approximately 1 of 20 consecutive patients with ICH. The patients with vascular pathology more often had a hemorrhage with a lobar location and young age and the present study is supportive of a risk-based stratification approach in performing CTA., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5)., Objective: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective., Methods: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties., Results: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups., Conclusions: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer., Competing Interests: Competing interests: MB reports funding from the European Commission (European Union’s Horizon 2020 research and innovation programme, grant agreement No. 754640 – payments to the institution), and fees as consultant or lecturer from Novartis, Boehringer-Ingelheim, Guerbet, Seagen, and NeuroScios, all outside the submitted work. GT reports funding from the European Commission (European Union’s Horizon 2020 research and innovation programme, grant agreement No. 754640 – payments to the institution) for the TENSION trial, and fees as consultant or lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, Stryker, all outside the submitted work. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Subarachnoid haemorrhage (SAH) and intraventricular haemorrhage (IVH) are associated with poor patient outcomes. Intraventricular fibrinolysis is effective in clearing IVH and improving patient survival and neurological outcome. By similar rationale, cisternal irrigation has been proposed as a potential method to accelerate haematoma clearance in SAH. We aimed to provide a comprehensive review and meta-analysis evaluating the effect of intraventricular and cisternal irrigation on clinical outcomes in patients with SAH and IVH., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed preparing this systematic review and study selection was performed by multiple investigators. We extracted ORs from the individual studies and aggregated these using a random effects model. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations assessment and ROBINS-I or RoB-2., Results: 24 articles were included. In SAH, we found that cisternal irrigation with fibrinolytic agents was associated with reduced mortality (OR: 0.68, 95% CI 0.46 to 1.00), higher probability of favourable functional outcome (OR: 1.80, 95% CI 1.30 to 2.51), and reduced risks of DCI (OR: 0.28, 95% CI 0.18 to 0.42) and cerebral vasospasm (OR: 0.28, 95% CI 0.18 to 0.42), compared with conventional therapy. Cisternal irrigation with vasodilatory agents was associated with lower mortality (OR: 0.32, 95% CI 0.13 to 0.79) and reduced risk of cerebral vasospasm (OR: 0.37, 95% CI 0.17 to 0.79). The evidence for irrigation therapy of IVH was sparse and insufficient to show any significant effect., Conclusion: In this study, we found that cisternal irrigation could improve the prognosis in patients with SAH compared with conventional therapy. There is no evidence to support cisternal irrigation treatment of IVH., Competing Interests: Competing interests: ARK reports grants from IRRAS AB to Aarhus University Hospital to support the ACTIVE study and personal fees from IRRAS AB for a presentation at a scientific symposium describing his experiences with the IRRAflow technology during the conduct of the study; grants from IRRAS AB to Aarhus University Hos-pital to support the development of a neuromonitoring technology related to IRRAflow outside the submitted work; in addition, ARK has a patent for a neuromonitoring technology pending with relation to the IRRAflow technology. The remaining authors have no conflicts of interest to declare., (© 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: Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRAflow® (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRAflow® system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simultaneously monitoring and maintaining a stable intracranial pressure (ICP). We addressed important aspects of the device implementation and intracranial lavage., Method: To allow versatile investigation of multiple device parameters, we designed an ex vivo lab setup. We evaluated 1) compatibility between the IRRAflow® catheter and the Silverline f10 bolt (Spiegelberg), 2) the physiological and hydrodynamic effects of varying the IRRAflow® settings, 3) the accuracy of the IRRAflow® injection volumes, and 4) the reliability of the internal ICP monitor of the IRRAflow®., Results: The IRRAflow® catheter was not compatible with Silverline bolt fixation, which was associated with leakage and obstruction. Design space exploration of IRRAflow® settings revealed that appropriate settings included irrigation rate 20 ml/h with a drainage bag height at 0 cm, irrigation rate 90 ml/h with a drainage bag height at 19 cm and irrigation rate 180 ml/h with a drainage bag height at 29 cm. We found the injection volume performed by the IRRAflow® to be stable and reliable, while the internal ICP monitor was compromised in several ways. We observed a significant mean drift difference of 3.16 mmHg (variance 0.4, p = 0.05) over a 24-hour test period with a mean 24-hour drift of 3.66 mmHg (variance 0.28) in the pressures measured by the IRRAflow® compared to 0.5 mmHg (variance 1.12) in the Raumedic measured pressures., Conclusion: Bolting of the IRRAflow® catheter using the Medtronic Silverline® bolt is not recommendable. Increased irrigation rates are recommendable followed by a decrease in drainage bag level. ICP measurement using the IRRAflow® device was unreliable and should be accompanied by a control ICP monitor device in clinical settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haldrup et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Remote ischemic conditioning (RIC) is a simple and noninvasive procedure that has proved to be safe and feasible in numerous smaller clinical trials. Mixed results have been found in recent large randomized controlled trials. This is a post hoc subgroup analysis of the RESIST trial (Remote Ischemic Conditioning in Patients With Acute Stroke), investigating the effect of RIC in different acute ischemic stroke etiologies, and whether an effect was modified by treatment adherence., Methods: Eligible patients were adults (aged ≥18 years), independent in activities of daily living, who had prehospital stroke symptoms with a duration of less than 4 hours. They were randomized to RIC or sham. The RIC treatment protocol consisted of 5 cycles with 5 minutes of cuff inflation alternating with 5 minutes with a deflated cuff. Acceptable treatment adherence was defined as when at least 80% of planned RIC cycles were received. The analysis was performed using the entire range (shift analysis) of the modified Rankin Scale (ordinal logistic regression)., Results: A total of 698 had acute ischemic stroke, 253 (36%) were women, and the median (interquartile range) age was 73 (63-80) years. Median (interquartile range) overall adherence to RIC/sham was 91% (68%-100%). In patients with a stroke due to cerebral small vessel disease, who were adherent to treatment, RIC was associated with improved functional outcome, and the odds ratio for a shift to a lower score on the modified Rankin Scale was 2.54 (1.03-6.25); P =0.042. The association remained significant after adjusting for potential confounders. No significant associations were found with other stroke etiologies, and the overall test for interaction was not statistically significant (χ 2 , 4.33, P =0.23)., Conclusions: In patients with acute ischemic stroke due to cerebral small vessel disease, who maintained good treatment adherence, RIC was associated with improved functional outcomes at 90 days. These results should only serve as a hypothesis-generating for future trials., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777., Competing Interests: Disclosures Dr Blauenfeldt received lecture fees from Bayer, Pfizer, and Novo Nordisk, unrelated to the submitted work. Dr Hess was supported by a research grant from the National Institutes of Health. Dr Simonsen was supported by research grants from the Health Research Foundation of the Central Denmark Region. The other authors report no conflicts.

Objectives: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level., Design: This was a nationwide register-based cohort study., Setting: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System., Participants: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study., Results: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care., Conclusion: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes., 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.)

Introduction: Intraventricular haemorrhage (IVH) is associated with high morbidity and mortality. External ventricular drainage (EVD) has been shown to decrease mortality. Although EVD is widely used, outcome and complication rates in EVD-treated patients with IVH are not fully elucidated. This study aims to describe EVD complication rates and outcomes in patients with primary and secondary IVH at two university hospitals in Denmark. The study will provide a historical reference of relevant endpoints for use in future clinical trials involving patients with IVH., Methods and Analysis: This descriptive, multicentre registry study included adult patients (age 18+) with primary or secondary IVH and treated with at least one EVD between 2017 and 2021 at Aarhus University Hospital or Odense University Hospital. Patients are identified using the Danish National Patient Register. Data are collected and recorded from patient medical records. Relevant descriptive statistics and correlation analyses will be applied., Ethics and Dissemination: Ethical approval and authorisation to access, store and analyse data have been obtained (Central Denmark Region Committee on Health Research Ethics). The research lead will present the results of the study. Data will be reported according to the Strengthening the Reporting of Observational Studies in Epidemiology and results submitted for publication in peer-reviewed journals., 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.)

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

Background: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established., Methods: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score., Results: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P =0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes ( P =0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes ( P =0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively., Conclusions: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03542188., Competing Interests: Disclosures Dr Fisher reports employment by Beth Israel Deaconess Medical Center and compensation from Lumosa for consultant services. Dr Blauenfeldt reports compensation from Bayer and Novo Nordisk AS for other services. Dr Johnsen reports compensation from TrygFonden, Phizer, and Bristol Meyers Squibb for consultant services. Dr Simonsen reports employment by Aarhus University Hospital. The other authors report no conflicts.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke., Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke., Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023)., Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants., Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke., Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group., Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke., Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Importance: Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use., Objective: To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage., Design, Setting, and Participants: This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023., Interventions: Participants were randomized to receive either intraventricular lavage or standard drainage., Main Outcomes and Measures: The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency., Results: A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81; P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1; P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2]; P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control (P < .001)., Conclusions and Relevance: This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety., Trial Registration: ClinicalTrials.gov Identifier: NCT05204849.

Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting.

Competing Interests: Disclosures Dr Andersen reports to serve as a consultant for Inari Medical, Inc, and Magneto Thrombectomy Solutions. He has received grants from Abbott Vascular, AngioDynamics, Inc, EPS Vascular, Janssens Pharmaceutical, and W.L. Gore & Associates, Inc. Dr Johnsen reports to serve as a consultant for Bristol Meyers Squibb and Pfizer. He has received grants from Novo Nordisk, Pfizer, and TrygFonden. Dr Nielsen-Kudsk has received grants from Abbott Laboratories and Boston Scientific Corporation. Dr Simonsen has received grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region. The other authors report no conflicts.

Background: We aimed to investigate whether socioeconomic status (SES) was associated with functional outcome in patients with ischemic stroke treated with reperfusion therapy (intravenous thrombolysis and/or thrombectomy)., Methods: This nationwide cohort study included reperfusion-treated patients with ischemic stroke ≥18 years registered in the Danish Stroke Registry between 2015 and 2018. Functional outcome was determined by the modified Rankin Scale score 90 days after stroke. SES was defined by educational attainment, family income, and employment status before stroke. SES data were available from Statistics Denmark and linked on the individual level with data from the Danish Stroke Registry. Uni- and multivariable ordinal logistic regression was performed for each socioeconomic parameter individually (education, income, and employment) to estimate the common odds ratios (cORs) for lower 90-day modified Rankin Scale scores., Results: A total of 5666 patients were included. Mean age was 68.7 years (95% CI, 68.3-69.0), and 38.4% were female. Low SES was associated with lower odds for achieving lower 90-day modified Rankin Scale score: Low versus high education, cOR, 0.69 (95% CI, 0.61-0.79), low versus high income, cOR, 0.59 (95% CI, 0.53-0.67), and unemployed versus employed, cOR, 0.70 (95% CI, 0.58-0.83). Inequalities were reduced after adjusting for age, sex, and immigrant status, except for unemployed versus employed patients, adjusted cOR, 0.66 (95% CI, 0.54-0.80). No statistically significant differences remained after adjusting for potentially mediating variables (eg, stroke severity, prestroke modified Rankin Scale, and smoking)., Conclusions: Socioeconomic inequalities were observed in functional outcome after reperfusion treated ischemic stroke. In particular, prestroke unemployment was negatively associated with good functional outcome. A more adverse prognostic profile among patients with low SES appeared to explain the majority of these inequalities., Competing Interests: Disclosures Dr Bus reports grants from Helsefonden, TrygFonden, Aase og Ejnar Danielsens Fond, and grants from Aarhus University Department of Clinical Medicine. Dr Simonsen reports research grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region. Dr Johnsen reports compensation from Pfizer for consultant services, compensation from Bristol-Myers Squibb for consultant services, grants from Pfizer, grants from Novo Nordisk, and grants from TrygFonden. The other authors report no conflicts.

Background: White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke., Methods: The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models., Results: Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57-0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60-1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome ( P =0.443) or any hemorrhagic transformation ( P =0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19-4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80-4.81])., Conclusions: Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01525290., Competing Interests: Disclosures Dr Barow reports grants from the German Parkinson Society and ACTELION Pharmaceuticals Deutschland GmbH, outside the submitted work. Dr Boutitie reports grants from University Medical Center Hamburg-Eppendorf during the conduct of the study. Dr Ebinger reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Amgen, GlaxoSmithKlineGSK, Sanofi, Covidien, Ever, Novartis, all outside the submitted work. Dr Fiebach reports personal fees from Bioclinica, Artemida, Cerevast, and Nicolab outside the submitted work. R.L. has no personal disclosures, but reports consultancy fees paid to the institution from Ischemaview and Boehringer-Ingelheim. Dr Thijs reports personal fees and nonfinancial support from Boehringer Ingelheim, Pfizer/BMS, Bayer, Sygnis, Amgen and Allergan outside the submitted work. Dr Muir reports personal fees and nonfinancial support from Boehringer Ingelheim outside the submitted work. Dr Simonsen is supported by research grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region. CG reports personal fees from AMGEN, Bayer Vital, BMS, Boehringer Ingelheim, Sanofi Aventis, Abbott, and Prediction Biosciences outside the submitted work. GT reports personal fees from Acandis, Boehringer Ingelheim, BMS/Pfizer, Stryker, Portola, Daiichi Sankyo, grants and personal fees from Bayer, grants from Corona Foundation, German Innovation Fonds and Else Kroener Fresenius Foundation outside the submitted work. Dr Königsberg reports grants from European Union 7th Framework Program during the conduct of the study. All remaining authors declare no competing interests.

Background: We present a case illustrating evolution of symptoms and brain magnetic resonance imaging in cortical superficial siderosis., Case Presentation: A 74-year-old man with no prior medical history presented with transient focal neurological episodes with subtle imaging changes. There was no evidence of cortical superficial siderosis. Two weeks later, the patient was readmitted with new episodes, and had developed cortical superficial siderosis adjacent to a cerebral microbleed. Transient focal neurological episode secondary to cortical superficial siderosis was diagnosed together with probable cerebral amyloid angiopathy., Conclusion: Clinical symptoms may precede the development of cortical superficial siderosis prior to being detectable on brain MRI. This case highlights the temporal development of cortical superficial siderosis., (© 2023. The Author(s).)

Background: Reversibility of the diffusion-weighted imaging (DWI) lesion means that not all of the DWI lesion represents permanently injured tissue. We investigated DWI reversibility and the association with thrombolysis, reperfusion and functional outcome in patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke)., Methods: In this retrospective analysis of WAKE-UP, a randomized controlled trial (RCT) between September 2012 and June 2017 in Belgium, Denmark, France, Germany, Spain and United Kingdom, a convolutional neural network segmented the DWI lesions (b=1000 s/mm 2 ) at baseline and follow-up (24 hours). We calculated absolute and relative DWI reversibility in 2 ways: first, a volumetric (baseline volume-24-hour volume >0) and second, a voxel-based (part of baseline lesion not overlapping with 24-hour lesion) approach. We additionally defined relative voxel-based DWI-reversibility >50% to account for coregistration inaccuracies. We calculated the odds ratio for reversibility according to treatment arm. We analyzed the association of reversibility with excellent functional outcome (modified Rankin Scale score of 0-1), in a multivariable model., Results: In 363 patients, the median DWI volume was 3 (1-10) mL at baseline and 6 (2-20) mL at follow-up. Volumetric DWI reversibility was present in 19% (69/363) with a median absolute reversible volume of 1 mL (0-2) or 28% (14-50) relatively. Voxel-based DWI reversibility was present in 358/363 (99%) with a median absolute volume of 1 mL (0-2), or 22% (9-38) relatively. In 18% of the patients (67/363), relative voxel-based DWI reversibility >50% was present. Volumetric DWI reversibility and relative voxel-based DWI reversibility >50% was more frequent in patients treated with alteplase versus placebo (OR, 1.86 [95% CI, 1.09-3.17] and OR, 2.03 [95% CI, 1.18-3.50], respectively). Relative voxel-based DWI reversibility >50% was associated with excellent functional outcome (OR, 2.30 [95% CI, 1.17-4.51])., Conclusions: Small absolute volumes of DWI reversibility were present in a large proportion of randomized patients in the WAKE-UP trial. Reversibility was more often present after thrombolysis., Competing Interests: Disclosures Dr Scheldeman reports grants from Research Foundation Flanders during the conduct of the study; other (congress participation) from Daiichi Sankyo outside the submitted work. Dr Endres reports grants from Bayer Healthcare, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Foschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, fees paid to the Charité from AstraZeneca, compensations from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo Company, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer, Sanofi-Aventis U.S. LLC, Abbott Fund, all outside the submitted work. Dr Fiebach reports personal fees from Artemida, Bioclinica, Biogen, BMS, Brainomix, Cerevast, Clario (former Bioclinica), Eisai, Guerbet, Merck, Nicolab, Abbvie, AC Immune, Daiichi Sankyo, Ionis Pharmaceuticals, Julius clinical, jung diagnostics Eli Lilly, Tau Rx, outside the submitted work. Dr Gerloff reports compensations from Amgen, BMS, Boehringer Ingelheim, Abbott Canada, Prediction Biosciences, Bayer Vital Healthcare, Sanofi Aventis, Boehringer Ingelheim, Novartis, AstraZeneca, Daiichi Sankyo Europe GmbH, grants from Deutches Zentrum für Luft- und Raumfahrt, Deutsche Forschungsgemeinschaft, Gemeinnützige Hertie-Stiftung, European Union outside the submitted work. Dr Muir reports personal fees and nonfinancial support from Boehringer Ingelheim, personal fees from Biogen, Bayer, Daiichi Sankyo, AbbVieand ReNeuron, outside the submitted work. Dr Simonsen reports grants from Novo Nordisk Foundation, during the conduct of the study, employment by Aarhus Universitetshospital, grants from Health Research Foundation of Central Denmark Region. Dr Thomalla reports compensations from Acandis, grants and personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Daiichi Sankyo Europe GmbH, Portola pharmaceuticals, LLC, Amarin Pharma, Inc, and Stryker, Alexion Pharmaceuticals Inc, outside the submitted work. Dr Thijs reports personal fees from Medtronic, Boehringer Ingelheim, Bayer, Pfizer, and BMS, outside the submitted work. Dr Lemmens has no personal disclosures, but reports consultancy fees paid to the institution from Ischemaview and Boehringer Ingelheim. The other authors report no conflicts.

Background: External ventricular drainage (EVD) is a key factor in the treatment of intraventricular hemorrhage (IVH) but associated with risks and complications. Intraventricular fibrinolysis (IVF) has been proposed to improve clinical outcome and reduce complications of EVD treatment. The following review and metaanalysis provides a comprehensive evaluation of IVH treatment with external ventricular drainage (EVD) and intraventricular fibrinolysis (IVF) with regards to complications and clinical outcomes., Methods: The PRISMA guidelines were followed preparing this review. Studies included in the meta-analysis were compared using forest plots and the related odds ratios., Results: After a literature search, 980 articles were identified and 65 and underwent full-text review. Forty-two articles were included in the review and meta-analysis. We found that bolted and antibiotic-coated catheters were superior to tunnelled/uncoated catheters (P < 0.001) and antibiotic- vs. silver-impregnated catheters (P < 0.001]) in preventing infection. Shunt dependency was related to the volume of blood in the ventricles but unaffected by IVF (P = 0.98). IVF promoted hematoma clearance, decreased mortality (22.4% vs. 40.9% with IVF vs. no IVF, respectively, P < 0.00001), improved good functional outcomes (47.2% [IVF] vs. 38.3% [no IVF], P = 0.03), and reduced the rate of catheter occlusion from 37.3% without IVF to 10.6% with IVF (P = 0.0003)., Conclusions: We present evidence and best practice recommendations for the treatment of IVH with EVD and intraventricular fibrinolysis. Our analysis further provides a comprehensive quantitative reference of the most relevant clinical endpoints for future studies on novel IVH technologies and treatments., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cerebral venous thrombosis (CVT) predominantly affects young to middle-aged women. Scarce data exist regarding the long-term prognosis. We examined the clinical course of patients with CVT overall and according to their age and sex. Using Danish registries, we identified all patients with a first-time primary inpatient diagnosis of CVT from 1996-2018 (N = 653; median age, 41 years; 67% women) and individuals from the general population matched for age, sex, and calendar year (N = 65 300). Patients with CVT were at an increased risk of venous thromboembolism (VTE) at other sites, ischemic stroke, major bleeding, and mortality. For both sexes, the increased risks of VTE at other sites were most prominent among younger patients (18-54 years), whereas the increased risks of ischemic stroke, major bleeding, and mortality were most prominent among older patients (≥55 years). Among young women, the 10-year risks of VTE at other sites for patients with CVT compared with members of the matched cohort were 2.2% vs 0.4% (risk difference, 1.8%; 95% confidence interval [CI], 0.0-3.6). Among older women, compared with members of the matched cohort, the 10-year risks were 12.8% vs 3.1% (risk difference, 9.7%; 95% CI, 1.6-17.9) for ischemic stroke, 11.1% vs 4.6% (risk difference, 6.5%; 95% CI, -1.0 to 14.1) for major bleeding, and 43.1% vs 26.7% (risk difference, 16.4%; 95% CI, 3.7-29.1) for all-cause mortality. The risk of myocardial infarction was not elevated. Clinicians should be aware of the importance of age and sex heterogeneity in the prognosis of CVT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: We observed a decrease in the number of patients who were offered reperfusion therapy. We aimed to investigate if whether hospital system pressure measured as the percentage of stroke bed occupancy influenced decisions on treatment and disposition., Design: Data from a regional quality of stroke care database were obtained and linked to the organizational data monitoring of the hourly inpatient stroke bed occupancy rate. Logistic regression was used to analyze the relationship., Results: A total of 15,025 admissions were included from 1 January 2019 to 24 August 2022. Of these, 5,659 (38%) had an acute ischemic stroke. The rates of reperfusion therapy treatment were the highest in 2019 (36.2%) and 2020 (34.1%) and declined afterward (30.0% in 2021). In the logistic regression analysis, an occupancy rate of ≥85% in the hour of the first admission was associated with reduced odds of admission at the stroke unit within 3 h from the symptom onset [adjusted odds ratio: 0.80, 95% confidence interval: (0.71-0.90), p < 0.001] and a reduced odds of receiving reperfusion therapy (adjusted odds ratio: 0.83 (0.73-0.95), p = 0.007)., Conclusion: An increased bed occupancy level in the hour of the first hospital admission for stroke patients was strongly associated with decreased odds of receiving reperfusion therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Blauenfeldt, Damgaard and Simonsen.)

Background and Purpose: Sex-based differences in acute ischemic stroke are a well-known phenomenon. We aimed to explore these differences between women and men in the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial., Methods: We compared baseline demographic and imaging characteristics (visual fluid-attenuated inversion recovery [FLAIR] positivity, relative FLAIR signal intensity, collateral status) between women and men in all screened patients. In randomized patients (i.e., those with diffusion-weighted imaging (DWI)-FLAIR mismatch), we evaluated a modifying role of sex on the treatment effect of alteplase in multivariable logistic regression, with treatment adjusted for National Institute of Health Stroke Scale (NIHSS) score and age. Dependent variables were modified Rankin Scale (mRS) score of 0-1 at 90 days and distribution of mRS scores at 90 days., Results: Of 1362 screened patients, 529 (38.8%) were women. Women were older than men, had higher baseline NIHSS scores and smoked less frequently. FLAIR positivity of the DWI lesion was equally present in women (174/529, 33.1%) and men (273/833, 33.3%; p = 1.00) and other imaging variables also did not differ between the sexes. In a total of 503 randomized patients, of whom 178 were women (35.4%), sex did not modify the treatment effect of alteplase on mRS score 0-1 or on the total distribution of mRS scores., Conclusion: As in many other stroke trials, more men than women were included in the WAKE-UP trial, but the presence of a visual DWI-FLAIR mismatch and the relative FLAIR signal intensity did not differ between the sexes. The treatment effect of alteplase was not modified by sex., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Evidence-based early stroke care as reflected by fulfillment of process performance measures, is strongly related to better patient outcomes after stroke and transient ischemic attack (TIA). Detailed data on the resilience of stroke care services during the COVID-19 pandemic are limited. We aimed to examine the quality of early stroke care at Danish hospitals during the early phases of the COVID-19 pandemic., Materials and Methods: We extracted data from Danish national health registries in five time periods (11 March, 2020-27 January, 2021) and compared these to a baseline pre-pandemic period (13 March, 2019-10 March, 2020). Quality of early stroke care was assessed as fulfilment of individual process performance measures and as a composite measure (opportunity-based score)., Results: A total of 23,054 patients were admitted with stroke and 8153 with a TIA diagnosis in the entire period. On a national level, the opportunity-based score (95% confidence interval [CI]) at baseline for ischemic patients was 81.1% (80.8-81.4), for intracerebral hemorrhage (ICH) 85.5% (84.3-86.6), and for TIA 96.0% (95.3-96.1). An increase of 1.1% (0.1-2.2) and 1.5% (0.3-2.7) in the opportunity-based score was observed during the first national lockdown period for AIS and TIA followed by a decline of -1.3% (-2.2 to -0.4) in the gradual reopening phase for AIS indicators. We found a significant negative association between regional incidence rates and quality-of-care in ischemic stroke patients implying that quality decreases when admission rates increase., Conclusion: The quality of acute stroke/TIA care in Denmark remained high during the early phases of the pandemic and only minor fluctuations occurred., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RAB is supported by National Institute of Health (1R01NS112511-01A1). CK is supported from Novo Nordisk Foundation (NNF18OC0031840). DG is supported by Novo Nordisk Foundation (NNF20OC0064637). GA is supported by Novo Nordisk Foundation (NNF18OC0052924, NNF20OC0060998) Trygfoundation (120636), Lundbeck Foundation (349-2020-907), and National Institute of Health (1R01NS112511-01A1). CZS is supported by a research grant from Novo Nordisk Foundation (NNF17OC0029520) and Health Research Foundation of Central Denmark Region. Authors DD, TWS, JNH, BM, and SPJ reports no conflict of interest., (© European Stroke Organisation 2022.)