Abstract Prothrombin complex concentrates (PCC) are used off-label to treat direct factor Xa inhibitor (FXaI)–associated bleeding or to optimize hemostasis before urgent surgery. The Global Assessment of Hemostatic TGA Indices Following the Use of Prothrombin Complex Concentrates for Major Bleeding or Urgent Surgery in Patients Treated with Factor Xa Inhibitors (GAUGE) study is a prospective observational cohort study of the effects of PCC on thrombin generation and hemostasis in FXaI-treated patients. FXaI-treated patients who presented with major bleeding or needed urgent surgery received PCC (50 IU/kg). Platelet-poor plasma was collected before and after PCC administration. Thrombin generation assay parameters, including lag time (LT), time to peak (TTP), peak thrombin generation (peak), endogenous thrombin potential (ETP), and mean velocity rate index (mVRI) were measured using calibrated automated thrombography. Hemostatic efficacy, thromboembolism, and mortality were adjudicated in duplicate. Multivariable log-linear regression was used to evaluate PCC effects on FXaI levels. Unsupervised k-means clustering was used to identify patients with the largest ETP increment. GAUGE included 101 episodes of FXaI-associated PCC use (FXaI-associated bleeding = 71; urgent surgery = 30). The median PCC dose was 48.0 IU/kg (interquartile range [IQR], 42.0-50.0). PCC did not affect FXaI levels (P> .05). PCC increased ETP (Δ868.9 ± 766.6 nM/min), peak (Δ85.7nM ± 108.2nM), and mVRI (Δ16.5 nM/min [IQR, 4.4-45.0]). PCC did not affect the LT or TTP (P> .05). Patients in cluster 1 had significantly lower pre-PCC FXaI levels (79 ng/mL [IQR, 55-93] vs 165 ng/mL [IQR, 77-219]; P = .009) and a greater ΔETP increment (P< .0001) than patients in cluster 2. Effective hemostasis was achieved in 50.0% of major bleeding events (95% confidence interval [CI], 38.4-61.6), and procedural hemostasis was normal in 76.7% of urgent surgeries (95% CI, 59.1-88.2). The 30-day risks of thromboembolism and mortality were 6.9% (95% CI, 3.4-13.6) and 12.9% (95% CI, 7.7-20.8), respectively. PCC increased quantitative thrombin generation without shortening LT or TTP, supporting a prohemostatic effect rather than true FXaI reversal.

BACKGROUND:Cerebral amyloid angiopathy (CAA) is thought to increase the risk of postthrombolytic intracranial bleeding, yet CAA neuroimaging markers and magnetic resonance imaging criteria have not been systematically evaluated in large acute stroke trials. We, therefore, examined the association of radiological Boston CAA criteria and their constituent markers with hemorrhagic risks and functional outcomes after intravenous thrombolysis in the AcT trial (Alteplase Compared to Tenecteplase). METHODS:Blinded raters recorded lobar cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity multispot sign, and centrum semiovale enlarged perivascular spaces, and classified possible and probable CAA according to radiological Boston criteria iterations, versions 1.0, 1.5, and 2.0. Multivariable logistic or ordinal regressions, adjusted for age, sex, baseline stroke severity, diabetes, hypertension, onset-to-needle time, thrombolytic agent, and endovascular therapy, assessed associations of these features/criteria with safety end points: symptomatic intracerebral hemorrhage (ICH), any ICH, Heidelberg hemorrhage grade, 90-day mortality, and functional outcomes (modified Rankin Scale score of 0-1 and ordinal modified Rankin Scale score shift). RESULTS:Among 1600 patients in the trial, 482 had suitable magnetic resonance imaging (mean age, 71 years; 47.1% female). Cortical superficial siderosis burden emerged as the dominant harmful marker: each increment was associated with increased risk of symptomatic ICH (adjusted odds ratio [aOR] per additional affected sulcus, 3.88 [95% CI, 2.87-5.26]), any ICH (aOR, 1.91 [95% CI, 1.22-2.98]), hemorrhage severity, 90-day mortality (aOR, 1.42 [95% CI, 1.18-1.71]), worse modified Rankin Scale scores (adjusted common odds ratio, 1.74 [95% CI, 1.58-1.91]), and lower odds of excellent functional recovery (aOR, 0.70 [95% CI, 0.64-0.77]). Fulfilling probable radiological Boston criteria, versions 1.0 and 1.5, increased odds of any ICH (aOR, 2.57 and 2.39 [95% CI, 2.05-3.23]; aOR, 2.39 [95% CI, 1.71-3.34], respectively), whereas fulfilling possible Boston criteria, version 1.5, was associated with worse modified Rankin Scale scores (adjusted common odds ratio, 2.34 [95% CI, 1.30-4.22]). Boston criteria, version 2.0, were not significantly associated with any hemorrhagic outcomes. CONCLUSIONS:In thrombolyzed patients with acute ischemic stroke, cortical superficial siderosis burden is strongly and consistently associated with higher risk of severe hemorrhage, disability, and death, making it a particularly relevant CAA marker when weighing thrombolytic risk versus benefit. Meeting radiological Boston criteria, versions 1.0 or 1.5, increases hemorrhagic risk, but meeting the latest 2.0 criteria does not.

Introduction: The Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion (ESCAPE-MeVO) trial did not show superiority of thrombectomy over medical management for patients with an acute ischemic stroke secondary to a medium-vessel occlusion (MeVO). The majority of patients included in this trial had an occlusion of the M2/M3 segment of the middle cerebral artery (MCA). The two main branches of the MCA differ in their anatomy and diameter: while the anterior M2/M3 branch is typically of smaller caliber and tortuous, the posterior M2/M3 branch is typically of larger caliber and more straight, making endovascular thrombectomy maneuvers easier and safer. We aimed to assess if the type of branch occlusion (anterior versus posterior branch of the MCA) had any effect on the outcomes after thrombectomy, and if there was treatment effect modification of EVT by the location of the MCA branch occlusion. Methods: This was a sub-group analysis of the ESCAPE-MeVO trial: patients harboring an MCA occlusion were classified into two groups: anterior-MCA-MeVO (occlusion of the anterior branch) and posterior-MCA-MeVO (occlusion of the posterior branch). Outcomes a) between thrombectomy patients with anterior vs. posterior MCA occlusions and b) thrombectomy and best medical care arm patients stratified by occlusion location were compared using descriptive statistics and logistic regression with adjustment for key co-variates. Thrombectomy effect modification by occlusion location was assessed with multiplicative interaction terms. Results: A total of 442 patients were therefore included in the study (170 anterior-MCA-MeVOs and 272 posterior-MCA-MeVOs). Baseline characteristics were similar between groups. Outcomes of patients with anterior-MCA-MeVO occlusion and posterior-MCA-MeVO occlusion treated with thrombectomy were similar, both in terms of angiographic outcomes and clinical outcomes at 3 months follow-up ( Figure 1 ). Finally, there was no significant difference between thrombectomy and standard medical care for patients in the anterior-MCA-MeVO group or patients in the posterior-MCA-MeVO group ( Figure 2 ), and no evidence of EVT effect modification by MCA occlusion location on 90-day mRS or any other outcome was seen. Conclusion: There was no significant association of MCA-MeVO occlusion location (anterior versus posterior) and post-thrombectomy outcomes and no EVT effect modification by occlusion location was seen in the ESCAPE-MeVO trial.

Abstract Background and aims Mobile Stroke Units (MSUs) may accelerate enrollment and early trial processes in intracerebral hemorrhage (ICH), but their impact on enrollment efficiency, feasibility, and safety in randomized trials remains incompletely defined. Methods FASTEST was a multicenter randomized trial enrolling patients with spontaneous ICH. In this secondary analysis, patients were categorized as direct MSU enrollment (enrolled entirely on MSU), MSU-facilitated enrollment (identification and initial management on MSU but enrollment in the ED), or non-MSU enrollment. Enrollment efficiency was assessed by time from symptom onset to randomization and by site-level enrollment rates during MSU-available versus MSU-unavailable periods. Issues with MSU enrollment and adverse events were evaluated. Comparisons were conducted using nonparametric tests for continuous variables and χ2 or Fisher's exact tests for categorical variables. Results Among 100 patients enrolled across 13 MSU sites, 38 were enrolled via MSU pathways (17 direct MSU; 21 MSU-facilitated). Median onset-to-randomization time was shorter for MSU-associated enrollments compared with non-MSU enrollments (93 [IQR 26] vs 111.5 [IQR 19] minutes; p<0.001), with a higher proportion enrolled within 90 minutes (36.8% vs 17.7%; p=0.032). Among MSU-associated enrollments, issues were infrequent, with isolated cases of weight estimation error and study kit issues (each 2.6%), with 94.7% having no identified issues. Rates of thromboembolic events did not differ between the two groups. At the site level, enrollment rates during MSU-available periods were higher than during MSU-unavailable periods (0.188 (SD=0.20) vs 0.057 (SD=0.04) enrollments per 10 days), representing a 0.131 relative increase. Conclusions MSUs were associated with faster enrollment, higher enrollment efficiency, and acceptable safety. Conflict of interest

BACKGROUND:To determine whether computed tomography (CT) thrombus characteristics modify the effect of intravenous (IV) thrombolysis type (tenecteplase vs alteplase) on outcomes. METHODS:This is a secondary analysis of the Alteplase compared to Tenecteplase (AcT) trial. Patients with visible intracranial occlusions on thin-slice baseline imaging were included. Key thrombus characteristics assessed by CT imaging were hyperdense artery sign, thrombus length, residual flow, clot burden score, and occlusion site. Multivariable analyses were performed to test for interactions between thrombolysis type and thrombus characteristics on clinical and angiographic outcomes. RESULTS:Of 1577 patients, 939 met inclusion criteria; 479 (51.0%) received tenecteplase and 460 (49.0%) alteplase. Among the 498 patients (53.0%) treated with endovascular thrombectomy (EVT), angiographic outcomes were comparable between treatment groups. A significant interaction was observed between thrombolysis type and thrombus length; longer thrombi were associated with reduced likelihood of modified Rankin Scale (mRS) 0-1 with alteplase (adjusted odds ratio (aOR) per 1 mm increase, 0.97 (95% confidence interval (CI): 0.95-1.00)), but not with tenecteplase (aOR: 1.00 (95% CI: 0.98-1.02); interaction p = 0.04). Similarly, the presence of residual flow within the thrombus was associated with higher odds of mRS 0-2 in the alteplase group (aOR: 2.00 (95% CI: 1.25-3.20)), but had no significant effect in the tenecteplase group (aOR: 0.93 (95% CI: 0.62-1.41); interaction p = 0.01). No other significant interactions between thrombus characteristics and thrombolysis type were identified. CONCLUSION:In the AcT trial, alteplase appeared less effective with longer thrombi and those lacking residual flow, whereas IV tenecteplase showed more consistent effectiveness across thrombus characteristics. These findings require confirmation in future prospective studies.

Abstract Background It is uncertain if the large effect size of endovascular thrombectomy (EVT) for stroke due to large vessel occlusion applies to stroke caused by medium vessel occlusions (MeVO). Two published trials examining EVT for MeVO were neutral. Methods In a multicenter, prospective, randomized, open label trial with blinded endpoint evaluation, patients with acute ischemic stroke due to MeVO presenting within 12 hours from last known well and favorable baseline non-invasive brain imaging were randomly allocated to usual care or EVT plus usual care. A key secondary outcome was the modified Rankin Score at 1 year. Results 530 patients from 5 countries were enrolled between April 2022 and June 2024. A majority (85%) had primary occlusions in a middle cerebral artery branch; 255 patients were randomized to EVT plus usual care, and 275 patients to usual care only. One patient withdrew consent immediately after randomization. At one year, 23 patients were lost to follow-up. Among 506 patients, 110/248 (44%) and 124/258 (48%) had a mRS 0-1 at 1 year [adjRR = 0.90, CI95 0.75-1.07, p=0.236]. Overall mortality was higher at 1 year in the treatment group 50/248 (20%) vs. 31/258 (12%) [adjRR = 1.89, CI95 1.28- 2.80, p=0.010]. Conclusions Endovascular treatment as compared to usual care for acute ischemic stroke due to medium vessel occlusion within 12 hours from last known did not improve outcomes at 1 year. Trial registration number: clinicaltrials.gov identifier NCT05151172 Conflict of interest Funding: Grants to the University of Calgary from the Canadian Institutes for Health Research and from Medtonic LLC

OBJECTIVE:Launched in August 2024, the ACT-GLOBAL (a multifactorial, multiarm, multistage, randomized, global adaptive platform) trial is the first multinational adaptive platform trial for acute stroke. Because it proposes to enroll participants by deferral of consent, the ACT-GLOBAL trial seeks to publish an explicit justification for this practice. METHODS:Following a standardized protocol for establishing whether it is justified to use deferral of consent, all active domains of the ACT-GLOBAL platform adaptive trial were considered according to six questions: (1) Is there evidence-based uncertainty about the research question?; (2) is the standard of care treatment included in the trial, meaning that patients are unlikely to be disadvantaged by their participation?; (3) is the trial of sufficient methodological rigor that it can result in a change of practice?; (4) Are patients eligible for enrollment in the trial likely to be incapable of providing their own consent?; (5) Will seeking to obtain consent from a surrogate decision-maker meaningfully delay treatment and impact outcomes?; and (6) Are steps taken to mitigate the compromise to individual autonomy? RESULTS:The leadership of the ACT-GLOBAL trial is able to answer affirmatively the six questions outlined above in relation to each of the trial's current domains. The results of this analysis suggest that the use of deferral of consent in the ACT-GLOBAL trial is ethically justified, where permitted by law. CONCLUSION:This exercise demonstrates the utility of following an accepted protocol for determining whether alterations to standard consent practices such as deferral of consent are ethically justified in acute stroke research.

Abstract Background and aims A Care Bundle involving early intensive blood pressure (BP) lowering improved outcome after acute spontaneous intracerebral hemorrhage (ICH) in low-resource settings. However, uncertainty remains regarding the effectiveness across diverse healthcare systems. Methods To determine whether implementation of a comprehensive, structured, evidence-based Care Bundle targeting rapid physiological stabilization and standardized referral pathways improves functional recovery after ICH. Results An international, multicenter, batched, parallel, cluster-randomized trial with an embedded implementation framework. Adults ≤24 hours of ICH receive either: a Care Bundle comprising time- and target-based management of BP, glucose, temperature; anticoagulation reversal; avoidance of early treatment limitations; and standardized pathways for intensive care and neurosurgical referral; or usual care. Hospitals are randomized in batches across 3 phases: baseline, randomized evaluation, and post-implementation. A total of 3,500 patients at 110 hospitals is estimated to provide 90% power (α=0.05) to detect a UW-mRS effect size of 0.20. Conclusions Outcomes include utility-weighted modified Rankin scale (UW-mRS, primary), mortality, 6-month health-related quality of life, and implementation outcomes (e.g. fidelity, feasibility, sustainability). Conflict of interest

Background and Purpose: Vasospasm is an important complication of subarachnoid hemorrhage (SAH) resulting in significant morbidity and mortality. Risk stratification attempts designed to identify patients most at risk of developing vasospasm have not led to significant practice changes. We sought to validate a prognostic utility criterion to identify patients at lowest risk of vasospasm. Methods: We conducted a single-centre retrospective observational study using transcranial doppler (TCD) readings of patients with SAH from 2018 to 2024. Through chart review, we extracted patient’s mean blood flow velocities in the bilateral middle cerebral artery (MCAs) throughout their admission. We defined patients at low-risk of vasospasm as: MCA velocities on TCD had to remain below 120 cm/s and velocities had to have peaked and started to decrease by the 7th day post SAH. Our primary outcome was to analyze the predictive ability of our low-risk criteria to identify patients less at risk of developing vasospasm, defined as the presence of moderate to severe vasospasm (mean velocity in the middle cerebral artery exceeding 160 cm/s). Results: We collected data on 210 consecutive patients, of whom 196 met inclusion criteria; 107 (55%) met our low-risk criteria. Only 3 (2.8%) patients meeting our low-risk criteria developed vasospasm (p < 0.001), while 46 (52%) patients not meeting our low-risk criteria developed vasospasms (RR 18.4). The Positive Predictive Value (PPV) for not developing vasospasm in our low-risk group was 97.2% (95% CI: 92.0% − 99.4%). Conclusion: Our low-risk criteria based on TCD patterns in the first 7 days since SAH can identify a cohort of patients at very low risk of moderate to severe vasospasm. Our low-risk criteria for vasospasm could be used in future prospective studies to evaluate the safety of early discharge from the intensive care unit.

Background Location‐specific hematoma‐volume thresholds are potentially important for prognostication and surgical decisions in acute intracerebral hemorrhage. We aimed to define this metric in relation to poor functional outcome in a pooled individual patient‐level data analysis of 2 large intracerebral hemorrhage clinical trials: ATACH II (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial). Methods Final hematoma volumes were measured using planimetric analysis of 24‐hour computed tomography in relation to hematoma location stratified by basal ganglia, thalamus, and lobar regions. Volume thresholds in 5‐mL increments to >50 mL and Youden's index were used to identify optimal thresholds associated with poor outcome (modified Rankin Scale scores, 4–6) and death at 3 months. Multivariable logistic regression was used to estimate adjusted odds ratio models within each location. Results There were 1691 patients included in these analyses, with 919 (54.3%), 551 (32.6%), and 221 (13.1%) located in the basal ganglia, thalamus, and lobar regions, respectively. Using Youden's index, location‐specific hematoma volume thresholds (mL) that were most predictive of poor outcome were: 22.24 for basal ganglia (sensitivity, 0.57; specificity, 0.84; adjusted odds ratio, 4.82 [95% CI, 3.19–7.27]), 8.13 for thalamus (sensitivity, 0.68; specificity, 0.75; adjusted odds ratio, 2.73 [95% CI, 1.62–4.59]), and 21.99 for lobar (sensitivity, 0.82; specificity, 0.64; adjusted odds ratio, 6.31 [95% CI, 2.53–15.74]). Hematoma volume thresholds predictive of death were 19.72 for basal ganglia, 10.06 for thalamic, and 51.94 for lobar intracerebral hemorrhage. Conclusions Hematoma volumes associated with poor outcomes and death vary by anatomic location, indicating that each brain region has a distinct volume tolerance. Location‐specific volume thresholds may guide surgical intervention to reduce hematoma burden.

Abstract Background and aims Clinical and radiographic severity of patients with spontaneous intracerebral hemorrhage (ICH) drive neurosurgical intervention. This analysis sought to identify clinical and imaging factors associated with the decision for neurosurgical intervention in the FASTEST trial. Methods Baseline clinical and CT imaging features at the time of surgical decision-making were evaluated. Multivariable logistic regression were performed to identify predictors of neurosurgical intervention, with secondary analyses assessing rFVIIa as a modifier of surgical likelihood and post-surgical outcomes. 90-day functional outcome was assessed using the modified Rankin Scale. Results Neurosurgical intervention occurred in 54/626 (8.6%) participants. Compared with non-surgical participants, those undergoing surgery were younger (57 vs 61 years, p=0.014), had greater neurological severity (median NIHSS 17 vs 12.5, p<0.001), larger baseline ICH volume (35 vs 15 mL, p<0.001), and more frequent mass effect (87% vs 67%, p<0.001) and midline shift (70% vs 33%, p<0.001). In multivariable analysis, independent predictors of neurosurgical intervention were baseline hematoma volume (adjusted OR 2.06 per 10 mL increase, 95% CI 1.62–2.62, p<0.0001) and presence of midline shift (adjusted OR 2.59, 95% CI 1.05–6.37, p=0.039). Surgical rates did not differ between rFVIIa and placebo groups (9.1% vs 8.2%, p=0.71). Post-surgical 90-day functional outcomes were similar between treatment groups (interaction p=0.41) after adjustment for baseline clinical and imaging severity. Conclusions Neurosurgical intervention for acute ICH was driven by markers of structural severity, particularly hematoma volume and midline shift. Ultra-early rFVIIa did not influence surgical decision-making or outcomes, supporting the feasibility of integrating early hemostatic therapy with standard neurosurgical care. Conflict of interest Figure 1 - belongs to Methods Figure 2 - belongs to Results

Abstract Background and aims Recent trials have shown no benefit of endovascular thrombectomy (EVT) vs. medical therapy in medium vessel occlusion (MeVO) stroke. We aimed to investigate the association between perfusion mismatch profiles and functional outcomes in MeVO stroke and to assess whether these profiles modify the treatment effect of EVT. Methods Post-hoc analysis of patients with available baseline perfusion imaging from ESCAPE-MeVO, a multicenter, randomized trial that investigated the efficacy and safety of EVT plus medical therapy compared to medical therapy alone in patients with acute MeVO stroke. Perfusion mismatch ratio and volume were defined as the ratio and difference between the critically hypoperfused area and the CTP-estimated ischemic core. The primary outcome was 90-day ordinal modified Rankin Scale (mRS). Treatment effect modification was assessed using interaction terms (perfusion mismatch*EVT). Results Of 530 enrolled patients, 309 (58.3%) had available perfusion imaging and were included in this study. Median age was 73 years (IQR = 63-82) and 141 (45.6%) were females. Median perfusion mismatch volume was 37.2 mL (IQR = 22.59 and ratio 6.1 (IQR = 2.8-10.0). Ordinal 90-day mRS was not associated with perfusion mismatch volume (adjusted OR 1.03 [95%CI = 0.99- 1.07]; per each 10-mL increase) or ratio (adjusted OR 1.03 [95%CI = 0.97- 1.09]; per each 1-unit increase). There was no modification of EVT effect by perfusion mismatch volume (p-interaction = 0.620) or ratio (p-interaction = 0.294) on ordinal 90-day mRS. Conclusions In this post-hoc analysis, perfusion mismatch was not associated with functional outcomes and did not modify the effect of EVT in MeVO stroke. Conflict of interest UP: nothing to disclose. Figure 1 - belongs to Results

Abstract Background and aims The FASTEST trial was designed to evaluate whether ultra-early administration of recombinant activated factor VII (rFVIIa) in an enriched subgroup, can improve outcomes in spontaneous intracerebral hemorrhage (ICH). Methods To determine whether rFVIIa administered within 120 minutes of symptom onset slows growth at 24 hours and improves functional outcomes at 180 days as measured by the modified Rankin Scale in patients with ICH. Results FASTEST is a phase III, international, randomized, adaptive, double-blind, placebo-controlled trial comparing rFVIIa (80 μg/kg; maximum dose 10 mg) plus best standard therapy versus placebo plus best standard therapy. In FASTEST Part 1, eligible participants were aged 18–80 years, had spontaneous ICH with a volume ≥2 cc and <60 cc, a Glasgow Coma Scale score ≥8, limited intraventricular hemorrhage, and could be treated within 120 minutes of stroke onset. Imaging included baseline and 24-hour non-contrast CT scans of the head and CT angiography (CTA) when done as standard of care. A neuroradiologist centrally assessed volume of ICH and intraventricular hemorrhage (IVH), and the presence of spot sign on CTA. Conclusions FASTEST Part 1 was stopped for futility overall in January 2025 after enrollment of 626 participants. Based upon data from FASTEST Part 1, FASTEST Part 2 began in May 2025 with the same entry criteria as Part 1, but patients must have a spot sign on CTA if treated within 120 minutes or be treated within 90 minutes. Conflict of interest

The presence of right-to-left shunt has been proposed as a prominent mechanism of paradoxical embolism in patients with active cancer. We conducted a retrospective observational study including patients presenting to the Ottawa Hospital between January 2020 and December 2022 with ischemic stroke with and without active cancer. Among 491 patients (36.9% female, median age 53), 43 (8.8%) had active cancer, with 12 (27.9%, 95% CI 15-44) having a shunt. Of 448 patients without cancer, 133 (29.7%, 95% CI 25-34) had a shunt. Overall, our finding does not support the hypothesis that cancer-associated stroke is related to right-to-left shunting.

Abstract Background and aims We report the pre-specified subgroup analysis of the rFVIIa for Acute Hemorrhagic Stroke at Earliest Time Trial (FASTEST) of patients with a CT hypodensity sign focusing on hematoma expansion and response to treatment. Methods In a prespecified analysis, we assessed the hypodensity sign as a treatment effect modifier of intravenous rFVIIa in the phase 3, multi-national, double-blind, adaptive randomized FASTEST trial. Baseline and 24-hour CTs were obtained, with CTA available in 82%; all imaging was centrally read by a blinded neuroradiologist. Effect modification was assessed for the trial’s primary outcome of 180-day disability (ordinal modified Rankin score 0-2, 3, 4-6) and, secondarily, for 24-hour growth of intracranial hemorrhage. As per the trial’s primary analysis, ordinal logistic regression was adjusted by age, baseline ICH and IVH volumes, and pre-ICH modified-Rankin-Score (mRS). Results Of 626 participants, 328 (52%) had a hypodensity sign on baseline CT. The hypodensity sign was associated with higher mean baseline ICH volumes (23.12ml, SD15.79) than those without (9.59ml, SD8.67). The hypodensity sign didn’t show evidence of interaction on the 180-day mRS (OR 1.142, 95%CI: 0.726-1.797) but did for 24-hour growth of ICH (-4.871ml, 95%CI: -7.580, -2.162). rFVIIa’s impact on hemorrhage growth and treatment effect was greatest in those with both a spot-sign and hypodensity. Conclusions Hypodense sign did not modify the clinical treatment effect of FVIIa. Having both hypodensity and spot signs at baseline was the strongest predictor of the impact of rFVIIa on reducing expansion of ICH+IVH and improving functional outcome. Conflict of interest Table 1 - belongs to Results Table 2 - belongs to Results

Abstract Background and aims Obtaining informed consent is challenging for acute stroke trials. We sought to assess the feasibility of a novel approach: advance consent, in which a person at risk of stroke provides consent to a trial in advance of experiencing an acute stroke. Methods Patients assessed in the Stroke Prevention Clinic at The Ottawa Hospital (Ottawa, Canada) were screened for diagnoses associated with a risk of acute stroke. Eligible patients completed an initial questionnaire and a follow-up questionnaire at 1 year. Participants who responded favourably to the idea of advance consent were invited to provide informed consent for 2 active acute stroke trials. Participants were followed for 1 year with regards to subsequent acute stroke and trial enrollment. Results From July 2023 to July 2024, we screened 1,547 patients; 431 met eligibility criteria, and 157 completed the initial questionnaire. Respondents overwhelmingly approved of advance consent in the initial questionnaire (96%) and at follow-up (92%). Based on their responses, 110 respondents were invited to provide advance consent; 48 participants (43%) did so, with 1 person withdrawing consent. Only 3 participants (2%) experienced any stroke, with none in the advance consent group, and no participants were enrolled into an acute stroke trial. Conclusions In this feasibility study, advance consent was strongly endorsed by participants, though ultimately this did not translate into improved trial enrollment. Conflict of interest Michel Shamy: Nothing to disclose; Ubong Udoh: Nothing to disclose; Brian Dewar: Nothing to disclose; Dar Dowlatshahi: Nothing to disclose

Abstract Background and aims Aneurysmal subarachnoid haemorrhage (aSAH) is a form of stroke frequently complicated by cerebral vasospasm. Although vasospasm is thought to occur in vessels near the ruptured aneurysm, it is not clear whether this phenomenon could be used to identify patients at low risk of subsequent vasospasm. We hypothesize that vasospasm develops earlier and is more pronounced in the artery anatomically closest to the rupture site. Methods We conducted a retrospective observational study using TCD readings from 200 patients admitted to The Ottawa Hospital from 2019-2024. We collected highest mean blood flow velocities in all vessels throughout the admission and sought to identify the artery that was the first to demonstrate an increase in velocity above standard thresholds according to Sloan's criteria ( MCA >120 cm/s, ICA > 80 cm/s, ACA >90 cm/s, PCA >60 cm/s, BA> 70 cm/s, VA> 60 cm/s). Results Of 188 patients with aSAH, 111 met inclusion criteria. In each artery tested, the most common artery to reach a ratio >1 over baseline velocities was the ipsilateral proximal vessel, though this did not occur for every aneurysm. The absence of vasospasm in the ipsilateral proximal vessel was associated with low but not very low rates of subsequent vasospasm. Conclusions Our study demonstrates a predictable pattern of vasospasm in patients with aneurysmal SAH. This could inform prospective studies aiming to rule out vasospasm risk, by identifying time points at which the absence of vasospasm in the most likely artery may reliably indicate low likelihood of later vasospasm. Conflict of interest Sanaz Biglou: nothing to disclose Laurence Poirier: nothing to disclose Vincent Brissette: nothing to disclose Dar Dowlatshahi: nothing to disclose Célina Ducroux: nothing to disclose Michel Shamy: nothing to disclose

BACKGROUND:Cancer-associated stroke has become increasingly recognized as a subcategory of embolic stroke of undetermined source (ESUS). Paradoxical embolism through a patent foramen ovale (PFO) is frequently cited as a common stroke mechanism in this population, but its prevalence in an ESUS cohort with newly diagnosed cancer is unknown. OBJECTIVE:To determine the prevalence of PFO in patients with solid organ malignancy and ESUS. METHODS:We searched the Stanford Research Repository for adults with solid organ malignancies who suffered a stroke secondary to an anterior circulation large vessel occlusion within 1 year after their cancer diagnosis. Only subjects who had an echocardiogram with bubble study were included. Chart extraction was completed for clinical/radiographic information. We used descriptive statistics to summarize the data. RESULTS:Fifty-five patients were included. Median time from cancer diagnosis to stroke was 65 days (IQR 11-182). The most common primary cancer site was lung (25.5%); 43.6% had metastases; 21/55 (38.2%) transitioned to comfort care during hospitalization. The prevalence of PFO was 20% (11/55). Paradoxical embolism was identified as a likely mechanism of stroke in 5/11 (45%) patients with PFO based on co-occurring venous thromboembolism (VTE). In 4/5 patients, VTE was asymptomatic and diagnosed based on screening studies at presentation. CONCLUSION:The prevalence of PFO among cancer patients with ESUS was 20%, and there was a high (45%) rate of co-occurring VTE. Given the high rates of asymptomatic detection of VTE identified based on screening ultrasounds, these results could support screening for VTE in this population.

Abstract Background and aims Advance consent, where a patient at risk of incapacitation provides consent before meeting the eligibility criteria for a trial, is an innovative approach that could address the challenges of obtaining informed consent in acute stroke trials. We conducted a feasibility study assessing advance consent as a means of enrolling people at risk of stroke into acute stroke trials. Here we report qualitative outcomes of the study. Methods Patients assessed in the Stroke Prevention Clinic at The Ottawa Hospital (Ottawa, Canada) were screened for diagnoses associated with a risk of acute stroke. Eligible patients completed an initial questionnaire and a follow-up questionnaire at 1 year. In both instances, participants were invited to provide free-text comments about advance consent. Qualitative data gathered from free-text responses were analysed using inductive thematic analysis. Results Of the 157 participants who entered the study, 142 provided free-text comments. In the initial questionnaire, four main themes were identified in favour of advance consent: altruism, agency, personal impact, and trust in the health care team. At one year, respondents identified three more themes: enhancing autonomy, involving family, and ease of use of advance consent. No major concerns or objections were raised. Conclusions These qualitative findings support the acceptability of advance consent for participation in acute stroke trials, both at initial assessment and one year later. Conflict of interest Michel Shamy: Nothing to disclose; Ubong Udoh: Nothing to disclose; Brian Dewar: Nothing to disclose; Dar Dowlatshahi: Nothing to disclose