Abstract Background and aims Cortical venous opacification may reflect ischemic severity in large vessel occlusion (LVO) strokes, but its association with outcomes in tandem occlusion (cervical ICA occlusion with concurrent intracranial ICA, M1, or M2 occlusion) is unclear. Methods We performed a post-hoc analysis of the alteplase compared to tenecteplase (AcT) trial. The sphenoparietal sinus, superficial middle cerebral vein, and vein of Labbé received a Cortical Venous Opacification Score (COVES) graded 0-2 on CTA (total 0–6: lower scores indicate poorer filling). COVES+ with the internal cerebral vein (total 0-8) was also assessed. Associations with functional and safety outcomes were evaluated using regression models adjusted for age, NIHSS, ASPECTS, and door-to-needle time. Results Among 127 patients with tandem occlusion (median age 69 [IQR 60–78] years; 32% female), 17 (13.4%) had a COVES of 0 and 110 (86.6%) had COVES >0. Compared to COVES >0, patients with COVES 0 had higher NIHSS (median 20 [IQR 18–22] vs 16 [IQR 10–20], p=0.002), lower ASPECTS (median 8 [range 4–10] vs 8 [range 5–10], p=0.031), and a higher proportion with poor collaterals (29.4% vs 8.2%). COVES score was not associated with 90-day functional outcomes (ordinal mRS: acOR 1.04 [95% CI 0.86-1.26]), mortality, or symptomatic intracranial hemorrhage. COVES+ also showed no associations with outcomes. Conclusions Cortical venous opacification was not associated with functional or safety outcomes in patients with tandem occlusion in the AcT trial. These findings may reflect the small sample size or differences from the broader LVO population, warranting further study. Conflict of interest CreeAnn Phillips: nothing to disclose, Nahal Farhani: nothing to disclose, Alexandre Poppe: nothing to disclose, Bijoy Menon:nothing to disclose, Nishita Singh: nothing to disclose, Fouzi Bala: nothing to disclose, Taha Aslan: nothing to disclose, Mohammed Almekhlafi: nothing to disclose, Katrina Ignacio: nothing to disclose.

Abstract Background and aims Current treatment of symptomatic carotid stenosis relies on data that are more than 30 years old. There is limited reliable information on the stroke rate with modern, intensive medical therapy (IMT). The aim of this pragmatic registry was to provide an estimate of the ipsilateral stroke rate for patients with 50-99% symptomatic carotid stenosis who have at least one feature suggesting reduced stroke risk. Methods IMT was provided to all participants. IMT consists of dual antiplatelet therapy (short-term), high potency statins, blood pressure control, and lifestyle modification with risk factor education. Criteria for enrollment include any one of three clinical or radiologic markers. Clinical 1) Women 2) Retinal ischemic event only 3) Last symptomatic event >1 week ago. Radiologic: 1) TCD negative for emboli 2) MRI negative for intraplaque hemorrhage 3) High risk TIA with negative DWI. The primary endpoint is ipsilateral ischemic stroke within 12 months of enrollment. Results The registry completed enrollment in Sept 2025 with 114 patients (53% women), recruited from 18 centers in N America. 70% of patients qualified with stroke, 30% with TIA. All patients completed 6 month follow-up, with the ipsilateral stroke rate being 4.4%. Eight patients have died (7%). Information on stroke severity will be presented. Conclusions SCORE Registry data will allow clinicians to refine carotid stenosis decision making in symptomatic patients with >50% stenosis and potentially justify a future phase III RCT. With 6 months of follow-up in all patients, the stroke rate appears reduced compared to historical controls. Conflict of interest

Abstract Background and aims Neuroimaging is essential for acute stroke triage and decision-making; however, significant heterogeneity exists in imaging modalities and sequences due to varying socioeconomic and clinical environments. Real-world utilization patterns remain underreported. Methods We established the CRCS-K Imaging Repository, a dedicated imaging database built upon the infrastructure of the prospective multicenter CRCS-K registry from 18 centers. Through this repository, we comprehensively collected all acute neuroimaging data for consecutive ischemic stroke patients since June 2022, encompassing scans from arrival to discharge, including those from referring hospitals (Figure 1). Anonymized imaging data were linked to clinical records and validated by a central imaging lab. We analyzed door-to-treatment times and outcomes in patients receiving reperfusion therapy, comparing CT-based protocols (NCCT±CTA±CTP) versus MR-based protocols (±PWI). Results Between June 2022 and May 2025, 214,589 imaging sequences were collected from 20,789 patients. Intravenous thrombolysis (IVT) was administered to 2,258 (11%) patients, and endovascular treatment (EVT) to 2,173 (11%). In the IVT group, pre-treatment imaging consisted of CT (68.7%), MR (18.8%), and pre-arrival imaging (12.5%). In the EVT group, the modalities used were CT (39.6%), MR (51.5%), and pre-arrival imaging (8.9%). Door-to-treatment times increased stepwise with the addition of imaging sequences (Figure 2). However, comparative analysis showed no significant differences in clinical outcomes between imaging modalities (Table). Conclusions Initial neuroimaging practices vary significantly across clinical settings. While the use of advanced neuroimaging extends door-to-treatment times, it does not appear to provide additional clinical benefits for the general stroke population compared to standard protocols. Conflict of interest All authors have nothing to disclose. Figure 1 - belongs to Results Figure 2 - belongs to Results Table 1 - belongs to Results

Background Stroke rates rise steeply with age but data on tenecteplase in patients ≥80 years remain limited. This post-hoc analysis of the AcT trial compared tenecteplase with alteplase in this population.Methods The analysis included all Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT) trial participants aged 80 years or older who were randomised to tenecteplase (0.25 mg/kg single bolus) or alteplase (0.9 mg/kg over 60 min). The primary outcome was excellent functional recovery (Modified Rankin Scale (mRS) score: 0–1 at 90–120 days). Secondary outcomes included mRS score 0–2, ordinal mRS shift and safety endpoints including symptomatic intracerebral haemorrhage (sICH) and mortality. Generalised mixed-effects models adjusted for baseline covariates with site as a random effect. Exploratory analyses examined the treatment-by-time interaction using continuous onset-to-needle time (OTN), outcomes by endovascular thrombectomy (EVT) status and outcomes in patients aged≥90 years.Results Among 543 patients aged ≥80 years (286 tenecteplase, 257 alteplase; mean age 86.9 years), baseline characteristics were balanced. Rates for mRS 0–1 (22.7% vs 23.1%; adjusted RR 0.94, 95% CI 0.74 to 1.19; p=0.63) and mRS 0–2 (37.4% vs 35.5%; adjusted RR 1.02, 95% CI 0.85 to 1.13) were similar, with no significant shift across the ordinal mRS distribution. Mortality (24.5% vs 27.3%) and sICH (3.5% both groups) did not differ. Longer OTN was associated with lower functional independence (adjusted OR per 30 min delay 0.89, 95% CI 0.77 to 1.03), although this did not reach statistical significance. Outcomes were consistent across EVT (n=149) and non-EVT (n=394) subgroups and in patients aged ≥90 years (n=160).Conclusions Tenecteplase and alteplase showed comparable efficacy and safety in patients ≥80 years supporting tenecteplase as a reasonable alternative to alteplase in elderly stroke patients.

Introduction: Body weight (BW)-adapted dosing schemes for tenecteplase (TNK) and alteplase (ALT) vary. Determining whether dosing schemes affect efficacy and safety outcomes is key to facilitating treatment in emergencies where precise weight measurement is often not possible. We conducted a post hoc analysis of two BW dosing schemes (mg/kg dosing vs 10 kg BW categories) using TNK and ALT data from acute ischemic stroke (AIS) and ST-elevation myocardial infarction (STEMI) trials. Methods: Patient-level data from the STTC meta-analysis, in which ALT was dosed in mg/kg, were stratified into 10 kg BW categories used in the AcT trial (<60 to ≥90 kg), with further subcategories (<50, 50–59, 90–99, and ≥100 kg). Outcomes were compared between stratified STTC data (control vs ALT) and AcT trial data (ALT vs TNK) by BW category across datasets, and across BW categories within each dataset. This was repeated using data from key AIS (ORIGINAL, EXTEND-IA TNK, and ATTEST-2) and STEMI (ASSENT-2 and -3 and STREAM-1 and -2) trials. AIS and STEMI outcomes were not directly compared. Outcomes for AIS were modified Rankin Scale (mRS) 0–1 at Days 90–120, deaths up to Day 90, and symptomatic intracerebral hemorrhage (sICH); for STEMI, these were deaths up to Day 30, in-hospital major bleeds, and sICH up to Day 30. Forest plots were used to compare treatments by BW category; odds ratios were unadjusted unless otherwise specified. Results: Across all datasets, patients with lower BW tended to be female and elderly; those with higher BW tended to be male and younger. Outcomes were similar between STTC (N=4,361) and AcT (N=1,563) across BW groups ( Fig. 1 ), including those in which the AcT dosing scheme led to greater dose variation. For example, the <50 kg group had more deaths up to Day 90 but a similar proportion of sICH vs the other groups; findings in this group were similar between TNK and ALT. No other relationship between mRS 0–1, death, or sICH and BW was established ( Table 1 ). Findings were similar in other AIS and STEMI trials ( Fig. 2 ). Conclusions: Outcomes were comparable between the two BW dosing schemes for TNK and ALT across BW categories and were supported by other trials in AIS and STEMI. Limitations include the uncertain accuracy of BW measurements, low proportion of sICH across trials, lack of adjustment for baseline variables across trial datasets, and exploratory nature of the analysis. The safety of each dosing scheme was similar in patients with low BW.

Prognosis after acute stroke varies widely and is usually guided by imaging and clinical markers. Factors such as frailty, cognition, comorbidities, mental health, social support, and financial status strongly influence recovery but are rarely considered. To address this gap, we developed the ELAN Score, a structured 10-point tool across six domains: cognition, pre-existing disability/frailty, comorbidities, mental health, social support and financial factors. Using a global survey, we aimed to evaluate associations between individual ELAN domains and clinicians’ prediction of recovery and coping potential after a stroke. In an international online survey, stroke neurologists, neurointerventionalists, and allied specialists were randomly assigned 30 of 324 case vignettes. Each vignette described a patient with large vessel occlusion, good ASPECTS who achieved TICI 3 reperfusion, and systematically varied the severity of ELAN-specific domains. Participants were blinded to the ELAN score; scores were calculated in the background using pre-specified domain weights. Respondents were asked to estimate: the probability of return to pre-stroke functional status, and the probability of coping with an unfavorable outcome. Associations between ELAN score, individual domains, and perceived outcomes were examined using mixed-effects Poisson regression adjusted for clinician demographics, specialty, and country, with participant ID as random effect. Forty-eight participants (33% stroke neurologists, 37% interventionists; 78% >10 years’ experience; 37% women) from 18 countries completed the survey. Higher ELAN scores were significantly associated with lower probability of both respondent-predicted functional recovery and coping potential (adjIRR 0.93, 95% CI 0.91–0.95 and 0.91, 95% CI 0.90–0.93, respectively, Figure 1). In multivariable models, cognitive impairment, pre-existing disability, multiple comorbidities, and limited financial resources were consistently perceived as predictors of poor recovery, while cognition, disability, and finances were key for coping potential (Tables 1–2). Mental health and social support were not perceived as independent predictors. Clinicians in this international vignette-based survey recognized cognition, disability, and financial status as key determinants of outcome. Future work should test ELAN prospectively in diverse healthcare systems and evaluate whether structured incorporation of these factors improves prognostic accuracy.

Background: Rapid, accurate infarct identification is vital for stroke management. While follow-up non-contrast CT (NCCT) is routinely used to assess post-treatment infarct volume; its interpretation is hindered by subtle features, reader variability, and time constraints. Manual delineation is labor-intensive and inconsistent, limiting use in large trials and practice. We developed and externally validated a fully automated algorithm for infarct detection and segmentation on follow-up NCCT in the AcT (Alteplase Compared to Tenecteplase) trial, enabling consistent and efficient assessment. Methods: We employed a novel segmentation architecture combining a classic U-shaped convolutional neural network with state-of-the-art denoising diffusion probabilistic models to segment infarcts on NCCT scans. The model was trained on CT scans with manually annotated infarcts in the PRoveIT (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) study and validated using data from the AcT trial, in which patients underwent follow-up non-contrast CT after thrombolysis. Infarct presence and extent were determined by expert readers, blinded to algorithm outputs. Model performance was evaluated using standard diagnostic accuracy metrics and the Dice similarity coefficient. Results: 195 cases in PRoveIT were used for training, 1338 cases (923 infarct-positive) in AcT for testing. In testing data, the fully automated tool achieved sensitivity of 89.6% (95%CI: 87.3-91.9%), specificity of 75.0% (95%CI: 72.9-77.1%), positive predictive value of 88.8% (86.0-91.6%), negative predictive value of 76.7% (95%CI: 73.6-79.8%), and accuracy of 85.1% (82.7-87.5%) for infarct detection. The model achieved fair performance for infarct segmentation for volume calculation (Dice 0.537, 95% CI:0.488-0.585 vs 0.768, 95% CI:0.736-0.790 in training set). Some examples are illustrated in Figure 1 . Conclusions: Our automated infarct segmentation model demonstrated robust performance in detecting infarcts within this clinical trial dataset. Future work will focus on further optimizing the algorithm to improve detection and segmentation of ambiguous and challenging infarct regions.

BACKGROUND:Venous thrombosis and venous thromboembolism (VTE) are important causes and complications of stroke. They may complicate acute stroke as deep venous thrombosis or pulmonary embolism (DVT/PE), contribute causally to ischemic stroke through paradoxical embolism from a patent foramen ovale (PFO), or present directly as cerebral venous thrombosis (CVT). Despite shared pathophysiological features and overlapping antithrombotic strategies, these conditions are typically considered separately, fragmenting evidence and limiting the exchange of concepts. PURPOSE:We therefore convened experts across both stroke neurology and thrombosis medicine fields to examine these conditions under a unifying venous theme and define priorities for future clinical trials. METHODS:Thirty-two stroke and thrombosis clinicians and researchers identified research priorities across three domains: prevention of VTE after stroke, secondary prevention after PFO-related stroke, and acute and long-term management of CVT. Structured discussions were guided by the PICO (Population, Intervention, Comparison, Outcome) framework, followed by a Delphi survey to establish consensus. Priority questions centered on the balance between thrombosis prevention and bleeding risk and the optimal timing, duration, and choice of DVT/PE prophylaxis after stroke; the optimal antithrombotic strategy for patients awaiting or forgoing PFO closure; and, for CVT, the role of endovascular therapy in severe disease and the optimal duration of secondary prevention (Graphical Abstract). Across domains, the group prioritized pragmatic and platform trial designs, integration with international registries to address the rarity of CVT, and patient-oriented outcomes that extend beyond functional recovery. CONCLUSIONS:By considering these venous conditions together and bridging stroke and thrombosis disciplines, this work defines priority questions to address persistent evidence gaps, harmonize practice, and improve patient-centered outcomes.

Background: Patients with successfully recanalized large vessel occlusions by endovascular thrombectomy (EVT) may have better functional outcomes after treatment with intra-arterial thrombolytic drugs (IAT). However, the relative efficacy and safety of different IAT agents and their respective doses remain unclear. Methods: We conducted a network meta-analysis of seven randomized clinical trials (RCTs) evaluating the effects of various doses of adjunctive IA thrombolytic agents compared to controls after successful thrombectomy. The primary efficacy outcome was excellent functional recovery at 90 days, defined as a modified Rankin Scale (mRS) score of 0-1. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Between-group comparison was estimated using odds ratios with 95% credible intervals. Treatment rankings among all compared interventions were assessed using surface under the cumulative ranking curve (SUCRA) probabilities. Results: In total, we analyzed 2,193 patients across six treatment nodes: tenecteplase (0.03125 mg/kg, 0.0625 mg/kg, 0.125 mg/kg), alteplase (0.225 mg/kg), Urokinase (100,000 IU) and controls (no IA thrombolytic drug). The network diagram is shown in Fig 1. Two treatments were associated with higher odds of excellent functional outcome as compared to controls: IA alteplase at 0.225 mg/kg (OR 2.03, 95%CrI 1.37 – 3.03, Fig 2B) and IA tenecteplase at 0.125 mg/kg (OR 1.91, 95% CrI 1.13-3.28, Figure 2B). However, IA alteplase and tenecteplase at 0.125 mg/kg did not outperform other IA agents (Fig 2). SUCRA plots suggested that there is a 52.38% chance that IA alteplase is the most effective treatment, and a 39.97% chance that TNK 0.125mg/kg is the most effective (Figure 3). IA tenecteplase at 0.03125 and 0.0625 mg/kg, along with urokinase, did not show a significant benefit over the control group for excellent functional outcomes (Fig 2). For safety, no IAT agent significantly reduced or increased the risk of sICH. Conclusion: Intra-arterial alteplase 0.225mg/kg and tenecteplase 0.125 mg/kg appear most likely to improve functional recovery following successful EVT compared to controls, though our results are limited by small sample sizes in certain treatment nodes, and dichotomization of outcomes which lack granularity. Further head-to-head trials are needed.

Introduction: Treatment of in-hospital acute ischemic stroke (AIS) is challenging. We aimed to characterize in-hospital AIS and identify predictors of receiving thrombolysis and thrombectomy. Methods: We conducted an analysis of a retrospective cohort study using administrative data and chart review as part of the INPATIENTS study (Comparing In-Hospital and Community-Onset Strokes in Alberta). All in-hospital AIS patients admitted in the province between January 1, 2018, and December 31, 2022, were included. Clinical characteristics and quality of care measures were compared between treated and non-treated patients. We used multivariable logistic regression to identify predictors of acute treatment and assessed model performance using ROC curves and calibration plots. Results: Only 7.3% (158 of 2,159) in-hospital AIS patients received thrombolysis or thrombectomy between 2018 and 2022. Treated patients had higher NIHSS scores (median 12 vs. 8), fewer recent invasive procedures (42% vs. 53%), and were less likely to have altered consciousness (12.0% vs. 52.1%). Common reasons for not receiving thrombolysis included delayed recognition and recent procedures. Treated patients more often received standard stroke evaluation. The final logistic regression model included age, sex, NIHSS, altered consciousness, admitting service, and comorbidities as predictors of treatment. It showed good discrimination (AUC = 0.8371), though calibration issues may affect its generalizability. Conclusion: In-hospital AIS patients treated with thrombolysis and thrombectomy had more severe strokes, were less likely to have altered consciousness, and more often received standard stroke evaluations than non-treated patients. These differences emphasize the need to better understand barriers and develop new approaches to in-hospital stroke management.

Corticosteroids are frequently used in practice to treat patients with neurological disorders. However, its effect for stroke and traumatic brain injury (TBI) remains controversial. This study aimed to systematically review and evaluate efficacy and safety of corticosteroids for the treatment of stroke and TBI. We searched Ovid-Medline and Ovid-Embase databases for randomised controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of corticosteroids in patients with ischaemic stroke, intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or TBI. The treatment intervention was corticosteroid, and the control was placebo or routine care. Outcome measures were death, functional outcomes and adverse events. We calculated odds ratio (OR) and 95

IntroductionNumerous non-randomized studies suggest the benefit of endovascular thrombectomy (EVT) for medium vessel occlusion (MeVO) stroke, while recent randomized trials showed no benefit. In clinical practice, MeVO management remains heterogeneous. We gauged the current status quo of endovascular MeVO management and physicians' perspectives on future MeVO-EVT trials.MethodsInternational, cross-sectional survey study inquiring about practice patterns before and after publication of the MeVO trials, opinions on the design of second-generation MeVO trials, willingness to enroll in such trials, and personal opinions regarding optimal MeVO treatment strategies. Participants' anonymized responses were summarized using descriptive statistics.ResultsFour hundred fifty-six physicians responded to the survey (308 China, 55 North America, 48 Europe, and 45 other countries). 86/454 (18.9%) respondents reported treating more MeVOs with EVT since the recent MeVO-EVT trials, and 134/454 (29.5%) reported treating fewer. Four-hundred-sixteen of 454 (91.6%) reported that their willingness to enroll patients in a second-generation MeVO-EVT trial increased (282/454 [62.1%]) or remained the same (134/454 [29.5%]) compared to before the recent trial publications. Of 122/454 (26.9%) respondents who participated in a MeVO-EVT trial, 79/121 (65.3%) stated that enrolment bias occurred at their sites. Three hundred twelve of 454 (68.7%) respondents (271/378 [71.7%] interventionalists, 41/76 [53.9%] non-interventionalists, p = 0.004) expressed belief in EVT benefit despite the neutral trial results. Adjunct intra-arterial thrombolysis was anticipated to play a major role in future MeVO treatment by 290/454 (63.9%).ConclusionMost physicians think that EVT is beneficial in selected MeVO patients. Enrolment bias was thought to be a major contributor to the neutral trial results. Ninety percent were equally or more willing to enroll patients in a second-generation MeVO-EVT trial. Adjunctive intra-arterial thrombolytics were identified as a key strategy for future MeVO-EVT.

Background About 25% of patients with acute ischemic stroke have lacunar infarct on follow‐up imaging. In this secondary analysis from the AcT (Alteplase Compared With Tenecteplase) trial, we assessed if there is variation in safety or efficacy of intravenous thrombolysis by infarct type in patients with no visible occlusion. We also determined if this effect differed between tenecteplase and alteplase. Methods and Results This is a secondary analysis from the AcT trial. Lacunar infarct was defined as single, ≤15 mm, and in regions supplied by perforating arterioles on 24‐hour imaging. Outcomes included symptomatic intracerebral hemorrhage at 24 hours, any hemorrhage on imaging, and 90‐day modified Rankin Scale score. Mixed‐effects regression models adjusted for age, sex, stroke severity, thrombolytic type, and onset‐to‐needle time were used. Of 1577 patients, 456/29.9% had no visible occlusion and interpretable follow‐up imaging (magnetic resonance imaging: 41.2%). Of these 93 (20.4%) (magnetic resonance imaging: 62.3%) had lacunar infarct, 171 (37.5%) (magnetic resonance imaging: 67.4%) had nonlacunar infarct, and 192 (42.1%) (magnetic resonance imaging: 7.3%) had no visible infarct. Four patients (2.3%) in the group with nonlacunar infarct and none in the groups with lacunar infarct and no visible infarct developed symptomatic intracerebral hemorrhage. Any intracranial hemorrhage was highest (21; 12.4%) in the group with nonlacunar infarct. There was no significant interaction between thrombolytic type and treatment outcomes. Conclusions In the AcT trial, safety of intravenous thrombolysis was similar across all infarct types in patients with no visible occlusion but functional outcomes were worst in patients with nonlacunar infarct. Safety and functional outcomes after intravenous thrombolysis were better in the groups with lacunar infarct and no visible infarct as compared with the overall trial population.

INTRODUCTION:Patients who experience inhospital strokes may suffer from delays in stroke recognition, delays to acute treatment and management. We aimed to assess evidence for the difference in mortality between patients with inhospital stroke and those with community-onset stroke. METHODS:We searched MEDLINE, EMBASE, and SCOPUS (from inception to October 8, 2024) to identify studies comparing mortality outcomes for inhospital and community-onset stroke patients. We collected data on study characteristics, summarized the quality of evidence, evaluated risk of bias of studies using the Newcastle-Ottawa Scale, and investigated clinical sources of heterogeneity. We performed a random-effects meta-analysis to estimate the pooled odds of mortality of inhospital stroke versus community-onset stroke patients. RESULTS:Forty-one studies, collectively with 3,038,211 patients, of whom 3% experienced inhospital stroke, were included in the review. Inhospital stroke patients had an approximately 2.3-fold higher odds of inhospital mortality (pooled OR 2.27; 95% CI 1.80-2.86; 32 patient cohorts) and 1.9-fold higher odds of 3-month mortality (pooled OR 1.87; 95% CI 1.43-2.45; 14 patient cohorts) compared to community-onset stroke patients. Meta-analyses stratified by acute treatment received and study characteristics revealed consistently higher odds of death among inhospital stroke patients compared to community-onset stroke patients. Acute treatment received, study setting, geographic region, and components of study quality were significant sources of heterogeneity. Most concerns in study quality were due to potential risks of confounding. CONCLUSION:There was a consistently higher odds of inhospital and 3-month mortality among inhospital acute ischemic stroke patients compared to their community-onset counterparts, highlighting the need for targeted interventions to reduce this disparity.

Importance:The cumulative burden of chronic vascular and neurodegenerative changes contributes to brain frailty, which may reduce the brain's capacity to recover from acute ischemic stroke (AIS). The association between brain frailty markers and poststroke outcomes after thrombolysis is unclear. Objective:To evaluate associations between brain frailty assessed on non-contrast-enhanced computed tomography (NCCT) and magnetic resonance imaging (MRI) and functional outcome in patients with AIS treated with intravenous thrombolysis. Design, Setting, and Participants:This cohort study was a post hoc analysis of the Alteplase compared to Tenecteplase (AcT) trial, an investigator-led, registry-linked, parallel-group, open-label, randomized clinical trial that enrolled patients between December 10, 2019, and January 25, 2022, at 22 primary and comprehensive stroke centers across Canada. Participants included adults 18 years or older diagnosed with ischemic stroke causing disabling neurological deficit, presenting within 4.5 hours of symptom onset, and meeting Canadian guidelines for thrombolysis. Markers of brain frailty (cortical and subcortical atrophy, white matter changes [Fazekas score, grouped as 0, 1-2, and 3-6], lacunes, chronic infarctions, and [on MRI] microbleeds, siderosis, and enlarged perivascular spaces) were retrospectively assessed while reviewers were blinded to outcome variables. Analyses were performed from July 24, 2024, to March 25, 2025. Exposures:Patients underwent baseline NCCT and were randomized to receive intravenous thrombolysis with alteplase (0.9 mg/kg) or tenecteplase (0.25 mg/kg). Some patients also received posttreatment brain MRI. Main Outcomes and Measures:The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score of 0-1) at 90 days. Secondary outcomes included 90-day ordinal mRS score (trichotomized as 0-2, 3-4, and 5-6), symptomatic intracerebral hemorrhage, and mortality. Sensitivity analyses were performed in patients with available MRI scans. Results:Among the 1568 patients (median age, 74 [IQR, 63-83] years; 817 male [52.1%]) with interpretable NCCT findings, after correcting for multiple comparisons, higher total Fazekas score of 3 to 6 compared with 0 was associated with lower odds of a 90-day mRS score of 0 to 1 (adjusted odds ratio [OR], 0.40 [95% CI, 0.24-0.65]). Total Fazekas score (adjusted common OR [ACOR], 2.80 [95% CI, 1.88-4.16]), cortical atrophy (ACOR, 2.65 [95% CI. 1.63-4.32]), and total brain frailty score (ACOR, 3.15 [95% CI, 1.87-5.33]) were each associated with worse ordinal mRS, but were not associated with safety outcomes. Conclusions and Relevance:In this cohort study of patients with AIS treated with intravenous thrombolysis, brain frailty markers-particularly white matter changes, cortical atrophy, and total brain frailty-were associated with worse outcomes. Consideration of these neuroimaging markers may better inform clinicians and patients about treatment expectations from thrombolytic therapy.