Cervical artery dissection (CAD) is a leading cause of stroke in young adults, accounting for up to 25% of strokes in this population. Despite its prevalence, management strategies vary widely due to limited large-scale randomized trials and inconsistent findings in the literature. This study aims to assess treatment practices for CAD and evaluate the consistency of clinical decision-making among stroke physicians using a structured survey. An international survey was distributed to stroke physicians and trainees, including participants in the STOP-CAD and TREAT-CAD studies. The survey explored patient characteristics influencing treatment decisions, preferred antithrombotics, treatment duration, and criteria for stopping therapy. Six case-based scenarios assessed initial treatment choices, follow-up imaging practices, and medication duration. Responses were analyzed using Krippendorff's alpha to quantify inter-rater reliability and evaluate consensus among respondents. The survey was completed by 102 stroke physicians and trainees, revealing moderate agreement, with a Krippendorff's alpha of 0.481. Significant variability was observed in CAD management, particularly in the choice of antithrombotic treatment and treatment duration. However, strong consensus was found regarding the use of follow-up imaging (99.16%), with computed tomography angiography (CTA) being the preferred modality (63.2%). The variability in CAD management highlights the need for further research to establish standardized, evidence-based guidelines.

Background: Cervical artery dissection (CeAD) accounts for nearly 25% of all ischemic strokes in young adults. CeAD can lead to the development of dissecting aneurysms (DA). However, the incidence, risk factors and outcomes of CeAD patients with DA is not well established. This study aims to identify risk factors for developing DA, subsequent growth, and impact on patient outcomes. Methods: This is a secondary analysis of the Antithrombotics for Stroke Prevention in Cervical Artery Dissection (STOP-CAD), a multicenter cross-sectional international retrospective study. CeAD patients were stratified for the presence of DA. We used multivariable regression to identify factors associated with DA. Patients with DA were further analyzed for DA growth. The primary outcome was ischemic stroke after CeAD+DA diagnosis. Secondary outcomes included ischemic stroke after CeAD+DA with DA growth. Multivariable logistic regression analysis was used to assess the association between DA and risk factors. We also performed univariate Cox regression and generated Kaplan-Meier survival curves comparing study outcomes based on presence of DA and subsequent growth. Results: Of the 4023 patients included in the STOP-CAD study, 4008 were included in this analysis and 767 (19%) patients had DA (546 with DA on initial presentation). Patients with DA had a mean age of 46 [IQR 37-55] years and 50% (383) were women. In combined adjusted analyses, DA patients were more often non-Hispanic (aOR 0.63, 95% CI 0.41-0.94, p<0.02), more commonly had a history of migraine (aOR 1.27, 95% CI 1.01-1.59, p=0.037), connective tissue disorder (aOR 2.02, 95% CI 1.22-3.36, p=0.007), minor neck trauma (aOR 1.70, 95% CI 1.29-2.26, p<0.001) and were more likely to present with ischemic stroke (aOR 1.73, 95% CI 1.05-2.87, p=0.031). DA growth was noted in 55 out of 546 (10%) patients with DA on presentation. There was no significant difference in the risk of ischemic stroke by day 180 in patients with DA (hazard ratio [HR] 0.92 [95% CI, 0.65-1.30]; P =0.63) or DA growth (HR 2.40, [95% CI, 0.79-7.24]; P =0.12). Conclusion: In this subanalysis of STOP-CAD, nearly one in five patients with CeAD developed a DA. Factors associated with a higher likelihood of DA included non-Hispanic ethnicity, history of migraine, connective tissue disorder, minor neck trauma, and ischemic stroke at presentation. DA diagnosis and DA growth did not impact the risk of subsequent ischemic stroke at 6 months.

Background and Objectives: Cervical artery dissection (CeAD) is a common cause of ischemic stroke in young adults. We aim to identify age-based differences in clinical presentation, imaging findings, and outcomes after CeAD. Methods: This was a sub-study using the STOP-CAD registry, a multicenter cross-sectional international retrospective study of patients diagnosed with CeAD and treated with an antithrombotic from January 1, 2015 to December 31, 2021. Baseline clinical and imaging characteristics were compared between younger and older adults with CeAD (≤45 versus >45 years of age) using multivariable logistic regression. We chose this age cut off due to its frequent usage in stroke in the young literature. Multiple logistic regression models were used to determine association between young age and outcomes after CeAD (ischemic stroke at 180 days, excellent functional outcome with modified Rankin Scale of 0-1 at 90 days, and mortality) after adjusting for sex, vascular risk factors, CeAD characteristics, and NIHSS on presentation. Results: Among 4023 CeAD patients included in the study, 1901 (47.3%) were ≤45 years of age. Patients were followed for a median of 307 days (IQR 102-831). Young adults with CeAD were more likely to be women (Odds Ratio [OR], 2.4; 95% CI, 2.1-2.9; p<0.001), of Hispanic ethnicity (OR, 1.8; 95% CI 1.3-2.5; p<0.001), have a history of migraines (OR, 1.6; 95% CI, 1.3-2.0; p<0.001) and recent neck trauma (OR, 1.6; 95% CI, 1.3-1.9; p<0.001) while having fewer traditional vascular risk factors. Young adults with CeAD had higher odds of a non-ischemic presentation (OR, 1.3; 95% CI, 1.1-1.5; p=0.013), vertebral artery dissection (OR 2.5; 95% CI, 2.2-3.0; p<0.001), and multivessel involvement (OR 1.5; 95% CI, 1.1-1.9; p=0.004). In adjusted analysis, younger age was not associated with an increased risk of recurrent ischemic stroke (adjusted Hazard Ratio [HR], 0.48; 95% CI 0.2-1.2; p=0.119). Younger age was associated with significantly greater odds of excellent functional outcome at 90 days (aOR, 1.48; 1.20-1.84, p<0.001) and lower risk of death at follow up (aHR, 0.37; 95% CI, 0.17-0.81; p=0.012) after CeAD. Conclusion: In a large international cohort, young adults with CeAD had a distinct clinical phenotype with higher odds of non-ischemic presentation, vertebral artery dissection, and multivessel involvement while having fewer traditional vascular risk factors. Young adults had a decreased odds of disability and mortality after CeAD.

INTRODUCTION:Endovascular thrombectomy (EVT) is the treatment of choice for LVO stroke, yet nearly half of successfully recanalised patients fail to achieve functional independence, a phenomenon termed futile recanalisation (FR). Predictors of FR remain poorly defined in large, heterogeneous populations. Therefore, we aimed to develop a predictive score for FR. PATIENTS AND METHODS:Endovascular thrombectomy-treated LVO patients from the prospective, multicentre EVATRISP collaboration were included. All patients had known pre-stroke functional status, modified thrombolysis in cerebral infarction (mTICI) score and 90-day mRS. Futile recanalisation was defined as mRS > 2 at 90 days despite mTICI ≥ 2b. Patients with FR were compared to those with successful recanalisation and mRS ≤ 2. The cohort was randomly split into derivation (70%) and validation (30%) sets. Multivariable logistic regression identified independent predictors that were used to construct the futile recanalisation following endovascular thrombectomy (FRET) score. RESULTS:Of 9909 patients, 7272 (73%) achieved successful recanalisation and 3420 (47%) of them experienced FR. In the derivation set, FR was independently associated with older age, diabetes, ischaemic heart disease, higher NIHSS, anterior cerebral artery occlusion, seizures at presentation, non-use of intravenous thrombolysis and lower Alberta Stroke Program Early CT Score (ASPECTS) or posterior circulation ASPECTS. Futile recanalisation patients had longer hospital stays and higher mortality rates. The FRET score demonstrated good discrimination (area under the curve [AUC] 0.721; 95% CI, 0.702-0.740), with FRET ≥ 3 indicating high risk. The validation cohort yielded similar performance (AUC 0.708; 95% CI, 0.680-0.737). CONCLUSION:The FRET score enables early identification of EVT patients at high risk for FR.

Impairment of the executive functions can be reduced by training, but most traditional approaches require specialized expertise. Therefore, cognitive rehabilitation is only offered to a minority of patients with a need. Computer-based Cognitive Rehabilitation (CBCR) is a low-cost intervention with rehabilitation potential. Outside of hospital rehabilitation institutions, the work is based on dysfunctions and not diagnoses, why patients after stroke, cardiac arrest, or in Parkinson’s disease were included based on their dysfunctions with the aim of potential broad implementation. This trial investigates whether specific CBCR focusing on executive functions is superior to general computer-based cognitive activities in improving working memory. Based on a statistical power calculation, 308 participants will be enrolled. A total of 291 patients are currently included in the trial. The trial is a multi-center, investigator-initiated, superiority randomized controlled trial with single blinding. Participants (≥ 18 years) with impaired working memory following stroke, cardiac arrest, or Parkinson’s disease will be randomized (1:1) to either specific CBCR using Scientific BrainTraining Pro (Happy Neuron) or an active control group performing unspecific cognitive activities. The intervention lasts eight weeks (60 min/day, 5 days/week). Six centers are involved in the trial and completion of inclusion is expected in November 2025. The primary outcome is working memory, assessed by CABPad. Secondary outcomes include instrumental activities of daily living, mood, anxiety, and quality of life measures. This trial will provide evidence on the efficacy of CBCR in enhancing executive functions, potentially guiding future clinical implementation. The trial is registered at Clinicaltrials.gov with identifier: NCT04229056. Registered on January 6, 2020.

Background and Objectives: Cervical artery dissection (CeAD) is a leading cause of ischemic stroke in younger adults, yet sex-specific variations in its clinical presentation, imaging characteristics, and outcomes remain underexplored. We aimed to evaluate these differences using data from a large, multicenter registry. Methods: We analyzed data from the STOP-CAD registry, which includes patients with radiologically confirmed non-traumatic CeAD enrolled between 2015 and 2021 across multiple centers. Clinical and imaging characteristics were compared between men and women using multivariable logistic regression. Outcomes assessed included ischemic stroke recurrence at 180 days, excellent functional outcome (modified Rankin Scale [mRS] 0–1) at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality. Results: Among 4,023 patients with CeAD, 1,783 (44.6%) were women. Compared to men, women were younger (median age: 42 vs 50 years), more likely to have a history of migraine (26.9% vs 8.3%) and connective tissue disorders (14.3% vs 5.8%), and presented more frequently with non-ischemic symptoms such as headache, neck pain, or tinnitus (adjusted OR [aOR] 2.0; 95% CI, 1.8–2.3; p<0.001). Women had significantly higher odds of vertebral artery dissection (OR, 1.3; 95% CI, 1.2-1.5; p<0.001), multivessel involvement (OR, 2.1; 95% CI, 1.7-2.5; p<0.001), and pseudoaneurysm formation (OR, 1.3; 95% CI, 1.1-1.6; p=0.003). Despite these differences, there was no significant sex-based difference in key clinical outcomes: excellent functional recovery at 90 days (OR 0.94; 95% CI 0.76-1.15 p=0.542), ischemic stroke recurrence at 180 days (OR 0.56 CI 0.23-1.3 p=0.213), or mortality (OR 0.83; 95% CI 0.47-1.48, p=0.529). Conclusion: In this large international cohort, we observed women with CeAD were younger, more likely to present with non-ischemic symptoms with distinct imaging features. These underscore the need for heightened clinical suspicion of CeAD in women presenting with atypical symptoms, even in the absence of ischemic deficits or conventional vascular risk factors, and suggest that sex-specific phenotyping may enhance diagnostic accuracy and early management.

Abstract Background and aims Whether motor recovery trajectories following intracerebral haemorrhage (ICH) and ischemic stroke (IS) differ is unknown. Methods Post-hoc analysis of the ESTREL (Enhancement of Stroke Rehabilitation with Levodopa) randomized controlled trial that enrolled patients with ICH or IS with unilateral motor hemiparesis. Primary outcome was motor recovery, assessed serially using the Fugl-Meyer motor Assessment (FMA) at baseline, 5 weeks, 3, 6 and 12 months and analyzed as repeated measure using adjusted multivariable mixed-effects models to compare trajectories over time between IS and ICH. Patients with at least two FMA evaluations during the 1-year follow-up were included. Results Of 610 participants, 34 were excluded: 14 due to death, 11 due to consent withdrawal, and 9 for other reasons, leaving 576 eligible for analysis (493 IS, 83 ICH). The median age was 73 years, 40% were female, and the median National Institutes of Health Stroke Scale score was 7. Overall, FMA total score was 34 [15–55] at baseline and increased significantly over time (p<0.001) across both groups. The trajectories of motor recovery differed according to stroke type (pinteraction<0.001), with a 5.2 (95%-CI 1.5-8.8) FMA points greater early motor recovery from baseline to 5 weeks following ICH than IS. Recovery trajectories beyond 5 weeks up to one year were comparable between both groups. Conclusions Motor recovery up to 1 year was greater following ICH than IS, mostly due to early gains within the first 5 weeks. These findings challenge prognostic pessimism in ICH and may inform delivery of care and future research. Conflict of interest Trüssel Simon: Nothing to disclose, Josefine Kaufmann: Nothing to disclose, Christopher Tränka: Nothing to disclose, Henrik Gensicke: nothing to disclose, Alexandros Polymeris: Nothing to disclose, David Seiffge: Nothing to disclose, Janis Rauch: Nothing to disclose, Stefan Engelter: Nothing to disclose Figure 1 - belongs to Results

Introduction: Posterior circulation strokes (PCS) account for one-quarter of ischemic strokes and differ from anterior circulation events in presentation, vascular anatomy, and treatment implications. Prognostic tools for PCS are scarce, and existing scores apply mainly to basilar artery occlusion, despite their potential to guide acute treatment and trial design. We aimed to develop and externally validate the Posterior Circulation Clot Burden Score (pc-CBS), a CTA/MRA-based tool to predict 3-month functional outcome across the entire posterior circulation. Methods: This investigator-initiated, retrospective cohort study included 488 consecutive PCS patients with CTA/MRA-confirmed occlusion from the ASTRAL registry (Lausanne, Switzerland) in the derivation/internal validation cohort. External validation used individual-level data from 1,340 patients across 21 stroke centers in 3 continents. Eight arterial segments (extracranial/intracranial vertebral, proximal/mid/distal basilar, P1/P2 posterior cerebral, posterior communicating arteries) were graded as patent or occluded/hairline (<1mm) and interrater reliability was tested both in CTA and MRA. The segments were then weighted via ordinal logistic regression for 3-month modified Rankin Scale (mRS). Predictive accuracy was assessed with Harrell’s C-statistics; independent contribution via likelihood ratio test (LRT). The study was registered on ClinicalTrials.gov as NCT07122934. Results: Interrater agreement was almost perfect for both CTA (n=60, κ=0.89) and MRA (n=60, κ=0.89). The 10-point pc-CBS assigns full points for complete vertebrobasilar patency and deducts for each affected segment. C-statistic were 0.70 (95%CI 0.60–0.80) for internal and 0.72 (95%CI 0.69–0.74) validation. Each 1-point decrease increased odds of unfavorable outcome (mRS 3–6) by 14% (internal) and 8% (external). Adding nine clinical outcome predictors (age, sex, prestroke mRS, NIHSS, ASPECTS, glucose, decreased consciousness, IVT, EVT) improved C-statistic to 0.84 (internal) and 0.85 (external), with pc-CBS retaining independent predictive value (LRT=6.4 and 6.3; p=0.01). Conclusions: pc-CBS is a reproducible CTA/MRA-based score for any occlusive vertebrobasilar stroke, providing independent prognostic value for functional 3-month outcome. Its simplicity, high reliability, and external validation support its use in clinical decision-making and trial stratification for PCS.

Abstract Background and aims Percutaneous device closure (PDC) is beneficial in preventing recurrent ischemic stroke in selected young patients with cryptogenic stroke and patent foramen ovale (PFO). The effect of PDC in older stroke patients with PFO and those with alternative stroke etiologies remains controversial. Methods This prospective, multicenter, international cohort study comprised 1835 patients with ischemic stroke and PFO treated either with PDC (n=793) or best medical treatment (BMT, n=1042). Inclusion was not restricted by age or stroke subtype. We assessed a composite of recurrent stroke, transient ischemic attack or another arterial embolic event as the primary outcome and performed subgroup analyses for age, stroke etiology, and PASCAL classification. Results The composite outcome was 5.3% in PDC and 6.9% in BMT treated patients (adjusted Hazard Ratio (aHR) 0.759, 95%CI 0.493–1.169, p=0.211) during a median follow-up of 36 months. This treatment effect was consistent in patients <60 years (aHR=0.727, 95%CI 0.424–1.245) and in those >60 years (aHR=0.731, 95%CI 0.376–1.421; p=0.989). In addition, subgroup analyses showed a numerical benefit of PDC over BMT in patients with higher RoPE score and high risk PFO features such as large shunt size and atrial septum aneurysm (PASCAL probable, HR 0.396; 95%CI 0.156–1.001; p=0.056). Treatment effects did not differ significantly between patients with cryptogenic or alternative etiologies. Conclusions In this large real-world cohort we showed, that PFO closure was associated with consistent beneficial treatment effects across a broad spectrum of patients, including those ≥60 years and individuals with potential alternative stroke mechanisms. Conflict of interest Nothing to disclose.

Abstract Background and aims Prior oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF) and acute ischemic stroke (AIS) may influence eligibility for intravenous thrombolysis (IVT) and clinical outcomes compared with patients without prior OAC. Methods We pooled individual patient data from two national stroke registries (Switzerland, Norway). We assessed the association of prior vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC) therapy versus no prior OAC with favourable functional outcome at 3 months (mRS 0-2), 3-month mortality and symptomatic intracranial haemorrhage (sICH). Among IVT-eligible patients, we evaluated the association of IVT with outcomes stratified by prior OAC status. Results 19,188 patients with AF and AIS were included (mean age 80 (SD 9.6)), 19.9% on VKAs, 23.5% on DOACs and 56.6% with noOAC, IVT rates 10.2% VKA, 6.3% DOAC, 27.5% noOAC. Compared with noOAC, neither prior VKA (adjusted odds ratio (aOR) 1.01, 95% CI 0.87-1.18) nor prior DOAC therapy (aOR 1.11, 95% CI 0.96-1.28) were associated with higher odds of favorable functional outcome. DOAC therapy was associated with lower odds of mortality (aOR 0.84, 95% CI 0.71-0.98), while VKA therapy showed a numerical trend toward lower odds of mortality (aOR 0.86, 95% CI 0.72–1.01). Among IVT-eligible patients, the association of IVT with outcome and mortality did not differ by prior OAC status. Rates of sICH were similar across groups. Conclusions In AIS patients with AF, preceding DOAC therapy was associated with lower mortality but not improved functional outcome. IVT was associated with favourable outcomes without heterogeneity across OAC types or safety concerns. Conflict of interest Elisabeth Forfang: nothing to disclose. Bernhard M Siepen: Reports research support from the Swiss Heart Foundation, the Swiss Academy of Medical Sciences and Bangerter-Rhyner-Foundation, and Inselspital Bern, Department of Teaching and Research, unrelated to the current project. Thomas R Meinel: is the global PI of the DO-IT RCT and registry. He reports research support of the Swiss National Science Foundation; research support of the Swiss Heart Foundation, Bangerter Rhyner Foundation and the Horten Foundation; research grants from Boehringer Ingelheim; consultancies for Medtronic, and Boehringer Ingelheim (fees paid to institution). Participation in an advisory board for Boehringer Ingelheim (fees paid to institution). Member of a clinical event committee (CEC) of the SWISS-AF study. Stefan Engelter: reports support of the Swiss National Science Foundation and of the Swiss Heart Foundation (unreacted to the current project). Torgeir Bruun Wyller: has received lecture honorary from NovoNordisk. Espen Saxhaug Kristoffersen: nothing to disclose. David Julian Seiffge: nothing to disclose. Ole Morten Rønning: nothing to disclose.

Abstract Background and aims Recent RCTs of EVT in medium- or distal-vessel occlusion (MDVO) strokes (DISTAL, ESCAPE-MeVO) reported neutral outcomes. As trials may not represent patients treated in the real world, we analyzed such patients in a large multicenter registry, comparing outcomes of bridging therapy (IVT+EVT) versus EVT-alone. Methods We retrospectively analyzed registry data from EVA-TRISP (17 stroke centers, 2014-2023). Adults with MDVO (M2–M4 MCA, ACA, PCA) treated with EVT with or without prior IVT were included. The primary outcome was the 90-day mRS distribution, analyzed with a mixed-effects proportional-odds model adjusted for age, pre-stroke mRS, baseline NIHSS, diabetes, hypertension, atrial fibrillation, and treatment year. Secondary outcomes were excellent (mRS0-1) and good (mRS0-2/return-to-premorbid) functional outcome, mortality, symptomatic intracranial haemorrhage, and successful recanalization (mTICI2b-3). Missing data were imputed; sensitivity analyses used complete-case and IPTW approaches. Results Among 3008 patients (median age 76, 45% of female sex, median NIHSS 10), 48% received bridging therapy. Adjusted analysis demonstrated better functional outcome (OR=1.60, 95%-CI 1.38-1.84, p < 0.001), higher odds of excellent (OR=1.75 95%-CI 1.45-2.11) and good (OR=1.63 95%-CI 1.36-1.96) recovery, and lower mortality (OR=0.63 95%-CI 0.50-0.78). Symptomatic intracranial hemorrhage was modestly increased (5% vs. 3%; OR=1.68 95%-CI 1.13-2.51), while recanalization rates were comparable (70% vs. 69%; OR=1.07 95%-CI 0.89-1.28). Findings were consistent across complete-case and IPTW analyses. Conclusions These results suggest that, in real-world practice, adjunctive IVT may add benefit to EVT for MDVO-patients. Conflict of interest The author(s) received no financial support for the research, authorship, and/or publication of this abstract.

BACKGROUND:After acute ischemic stroke, it is uncertain whether the time of atrial fibrillation (AF) diagnosis (before or after stroke) or AF subtype (paroxysmal or permanent) modifies the treatment effect of early versus delayed direct oral anticoagulant (DOAC) initiation. METHODS:OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke) was a randomized, parallel-group, open-label trial with blinded outcome assessment. Participants with acute ischemic stroke and AF were randomized 1:1 to early (within 4 days) or delayed (day 7-14) DOAC initiation. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, and systemic arterial embolism. In this trial subgroup analysis, the prespecified subgroup of interest was time of AF diagnosis, classified as before or after the qualifying stroke. We also investigated AF subtype classified as persistent or paroxysmal. We fitted mixed effects logistic regression models with interaction terms between each subgroup and treatment allocation. We also investigated associations between AF time of diagnosis or subtype and outcomes using multivariable logistic regression. RESULTS:We included 3619 participants (mean age 78.0±9.9 years; 45.3% women). For AF diagnosed before stroke, 37 of 918 (4.0%) participants allocated to early DOAC had a primary outcome event versus 32 of 920 (3.5%) allocated to delayed DOAC, odds ratio, 1.17 (95% CI, 0.72-1.89), while for AF diagnosed after stroke the respective primary outcome rates were 22 of 895 (2.5%) and 27 of 886 (3.0%; odds ratio, 0.79 [95% CI, 0.45-1.40], Pinteraction=0.312). AF subtype did not modify the treatment effect, with odds ratios (95% CIs) for early versus late DOAC for persistent and paroxysmal AF of 1.06 (0.71-1.58) and 0.66 (0.25-1.72), respectively, Pinteraction=0.377. AF time of diagnosis was not associated with outcome events. Compared with paroxysmal AF, persistent AF was independently associated with an increased risk of the primary outcome (adjusted odds ratio, 2.10 [95% CI, 1.19-3.68]). CONCLUSIONS:We found no evidence that AF time of diagnosis or subtype modify the effects of early DOAC treatment. Persistent AF was independently associated with approximately double the risk of the primary outcome compared with paroxysmal AF. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.

BACKGROUND:Randomized trials have demonstrated that early anticoagulation after acute atrial fibrillation-associated ischemic stroke is safe and non-inferior to delayed initiation. Whether anticoagulation should be delayed in people with larger infarcts is uncertain. AIMS:To investigate whether ischemic stroke infarct volume, measured precisely by segmentation, modifies the treatment effect of early anticoagulation with a direct oral anticoagulant (DOAC). METHODS:We did a prespecified secondary analysis of OPTIMAS (NCT: 03759938), a randomized, parallel-group, open-label trial with blinded outcome assessment which randomized people with acute ischemic stroke and atrial fibrillation to early initiation of any licensed DOAC, within 4 days of onset, or delayed initiation 7-14 days from onset. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (ICH), and systemic arterial embolism within 90 days. A central neuroimaging laboratory determined infarct volume using diffusion-weighted magnetic resonance imaging (MRI) using a validated deep learning segmentation model; on computed tomography (CT), infarcts were segmented manually. We modeled infarct volume as a continuous variable using restricted cubic splines and tested for an interaction with treatment allocation in mixed effects logistic regression. RESULTS:We included 3572 participants (mean age = 78 ± 10 years, 45% female), 98.6% of the main trial population. The effect of early versus delayed anticoagulation did not vary with infarct volume (pinteraction = 0.18). Rates of the primary outcome were 17/568 (3.0%) and 12/599 (2.0%) for early versus delayed initiation with infarcts of 0-5 mL; 6/220 (2.7%) and 11/229 (4.8%) with infarcts of 5-10 mL; 13/258 (4.6%) and 10/283 (3.5%) with infarcts of 10-25 mL; 6/145 (4.1%) and 8/145 (5.5%) with infarcts of 25-50 mL; 1/93 (1.1%) and 7/94 (7.4%) with infarcts of >50 mL; and 14/481 (2.9%) and 10/430 (2.2%) in participants with no infarct visible on clinically acquired brain imaging. Corresponding odds ratios and 95% confidence intervals were 1.52 (0.71-3.20), 0.55 (0.20-1.51), 1.29 (0.55-3.00), 0.74 (0.25-2.21), 0.13 (0.02-1.11), and 1.25 (0.55-2.86), respectively. There were no increased rates of symptomatic ICH with respect to anticoagulation timing for those with large infarcts (>25 mL); there were 3/238 (1.3%) events in the early group and 5/239 (2.1%) in the delayed group. CONCLUSION:The treatment effect of early anticoagulation with a DOAC in acute ischemic stroke associated with atrial fibrillation was not modified by infarct volume. Adverse outcomes were not increased with early anticoagulation in people with larger infarcts. Our results provide no evidence that anticoagulation initiation should be delayed beyond 4 days on the basis of infarct size.

Background and Objectives: Pregnancy and the postpartum period increase the risk of cervical artery dissection (CEAD), a notable cause of stroke in young women. We aimed to describe the clinical presentation, imaging findings, and outcomes of CEAD occurring during pregnancy or shortly after delivery. Methods: We analyzed data from the STOP-CAD registry, a large international multicenter study of patients treated with antithrombotic therapy for non-traumatic CEAD between 2015 and 2021. This sub-study focused on women who were pregnant or within 12 weeks postpartum at the time of symptom onset. We assessed baseline clinical features, imaging results, acute stroke treatments, and functional outcomes. Results: Among 1,783 women in the registry, 62 (3.5%) had pregnancy-associated CEAD, with a median age of 34 years (IQR, 30-38). One-third had a history of migraine (33.9%), one-fifth had hypertension (21.0%), while other vascular risk factors were rare. Recent minor neck trauma was reported in 17.7%. Ischemic stroke symptoms occurred in 25 (40.3%) patients, and 23 (37.1%) had acute infarcts on imaging. However, most (59.7%) presented with non-ischemic symptoms. Vertebral artery dissections were more common than carotid dissections (62.9% vs. 48.4%), and 33.9% had multivessel involvement. Among patients presenting with ischemic stroke symptoms, 4 received thrombolysis and 7 underwent thrombectomy. Remarkably, 92% had excellent functional recovery (modified Rankin Score 0–1) at 90 days, and there were no stroke recurrences at 180 days. Conclusion: Pregnancy- and postpartum-associated CEAD is uncommon and associated with ischemic stroke in nearly half of patients. A history of migraine and hypertension may be potential risk factors. Despite the severity of presentation, most patients had favorable outcomes with timely treatment.

INTRODUCTION:Whether the risk-benefit profile of once-daily versus twice-daily direct oral anticoagulants (DOAC) differs after atrial fibrillation(AF)-associated ischemic stroke is unclear. We explored this in a post-hoc analysis of ELAN trial data (NCT03148457). PATIENTS AND METHODS:We compared the risk of the primary outcome (recurrent ischemic stroke, systemic embolism, intracranial hemorrhage (ICH), major extracranial bleeding, vascular death) from treatment initiation to the trial's 90-day follow-up in participants treated with once-daily or twice-daily DOAC after AF-associated stroke using Firth's logistic and Cox proportional hazards regression in unadjusted, inverse-probability-of-treatment-weighted and augmented-inverse-probability-weighted models to address confounding. Secondary outcomes were the primary outcome components and non-major bleeding. We calculated the net clinical benefit (NCB) of twice-daily over once-daily DOAC by subtracting the weighted rate of excess bleeding attributable to twice-daily DOAC from the rate of excess ischemic events possibly prevented by twice-daily DOAC. RESULTS:We analyzed 1890/2013 (94%) participants (median age 77 years, 45% female), of whom 384 (20%) received once-daily and 1506 (80%) twice-daily DOAC. The primary outcome occurred in 64 (3.4%) participants, and did not differ between DOAC types in logistic (ORunadjusted 0.89 (95% CI 0.50-1.66); ORweighted 1.34 (0.71-2.79); ORaugmented 1.45 (0.81-3.21); twice-daily vs once-daily DOAC) nor in Cox models. We identified no clear differences in any secondary outcome. NCB analysis revealed a near-neutral net effect of twice-daily versus once-daily DOAC (+0.28 to +0.67 weighted events possibly prevented/100 person-months for ICH weights 1.5-3.3). DISCUSSION AND CONCLUSION:The risk-benefit profile of once-daily versus twice-daily DOAC after AF-associated ischemic stroke does not seem to differ.

Background: The clinical characteristics and complications associated with de novo pseudoaneurysm formation beyond the acute phase of cervical artery dissection remain poorly defined. In this study, we examined the incidence, risk factors, and related ischemic and hemorrhagic events of post-acute de novo pseudoaneurysm formation. Methods: We analyzed data from the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection). A de novo pseudoaneurysm was defined as a new (not present on initial imaging) focal enlargement in the diameter of the artery, greater than the native lumen. The incidence of de novo pseudoaneurysm was assessed at 90 days, 180 days, and beyond 180 days of follow-up. Univariate and multivariate regression analyses were conducted to identify risk factors for post-acute de novo pseudoaneurysm formation. Kaplan-Meier survival estimates were used to compare ischemic and hemorrhagic events between patients with and without de novo pseudoaneurysms. Results: Among 4008 patients, 546 were excluded as they had dissecting pseudoaneursyms on initial presentation. Therefore, 3,462 patients were included in this analysis of whom 220 patients (6.35%) developed a de novo pseudoaneurysm over a maximum follow-up of 4.4 years. Of these, 127 (57.72%) were detected within the first 90 days, and 172 (78.18%) within the first 180 days. In multivariate regression analyses, in addition to hypertension, active smoking and Hispanic ethnicity, fibromuscular dysplasia (FMD) was an independent risk factor for post-acute de novo pseudoaneurysm formation (adjusted OR: 2.160; 95% CI: 1.408–3.315; p < 0.001). Notably, the presence of a de novo pseudoaneurysm was not associated with a significant increase in ischemic (hazard ratio [HR] 1.43 [95% CI, 0.89–2.30]; P=0.14) or hemorrhagic events (hazard ratio [HR] 1.42 [95% CI, 0.43–4.69]; P=0.57). Conclusion: De novo pseudoaneurysm formation following a diagnosis of a cervical artery dissection is not uncommon and most frequently occurs within the first 180 days. FMD was independently associated with this complication. The development of a de novo pseudoaneurysm did not significantly increase the risk of subsequent ischemic or hemorrhagic events.

Abstract Background and aims The simplified CT-based Edinburgh-criteria for differential diagnosis of spontaneous lobar intracerebral hemorrhage (ICH) have been shown to identify ICH related to cerebral amyloid angiopathy (CAA). Data on ICH related to oral anticoagulation (OAC-ICH) in this context is limited. Methods Based on the NOACISP-Acute prospective single-centre registry of patients with OAC-ICH we analysed the presence and frequency of the Edinburgh CT-criteria in patients with acute lobar OAC-ICH and potentially related demographic and clinical measures. Statistical analyses were performed using Using chi-square or Fisher’s exact test, where appropriate. Results Out of 124 consecutive patients with OAC-ICH (aged 82, 42% female), 112 subjects had supratentorial ICH, with 45 lobar ICH (33 pure, 12 mixed). Hypertension was more common in patients with deep compared to lobar ICH (95% vs. 73 %, p=0.001). Of the lobar ICH, 24 subjects exhibited FLP and 35 SAH, respectively. Of these, 20 exhibited both FLP and SAH, fulfilling the simplified Edinburgh criteria for CAA. Compared to the large cohort of spontaneous ICH based on the TICH-2 cohort, our subjects with OAC-ICH were older, more frequently had lobar ICH (36 % vs 29 %; OR 1.41 [0.94 – 2.08] and positive Edinburgh-criteria (44 % vs 31 % OR 1.82 [0.93 – 3.49], albeit missing statistical significance. Conclusions As in sporadic ICH, the CT-Edinburgh-criteria for CAA can be observed in lobar OAC-ICH, potentially occurring more frequently. Future studies are warranted to determine whether the findings reflect CAA also in OAC-ICH and identify potential prognostic and therapeutic implications. Conflict of interest All authors: nothing to disclose.