Background Susceptibility-weighted imaging (SWI) reveals three forms of cerebral hemorrhagic burden: cerebral microbleeds (CMB), chronic parenchymal hemorrhage, and cortical superficial siderosis (cSS). Prior work has focused on CMB counts, whereas the other two are rarely quantified at scale; their prognostic value in ischemic stroke is thus uncertain. An artificial intelligence (AI) tool to quantify all three at registry scale was developed and tested to determine whether the resulting total hemorrhagic burden (THB) score stratifies risk. Methods The tool was applied to the Clinical Research Collaboration for Stroke in Korea registry (16 sites). After restricting to first-ever ischemic stroke without intravenous thrombolysis or thrombectomy and pre-stroke modified Rankin Scale (mRS) ≤1, 6,124 patients were included in the analysis. THB summed the z-transformed logged values of the three components. Results CMB, parenchymal hemorrhage, and cSS were positive in 45.8%, 17.1%, and 3.4% of patients, respectively, with distinct clinical determinants. THB was associated with 3-month poor outcome (mRS ≥3): adjusted odds ratio (OR) per standard deviation 1.19 (95% CI, 1.11–1.27; P<0.001). The ordinal mRS shift was driven by parenchymal hemorrhage volume (joint-model OR, 1.23 per log unit) and CMB count (OR, 1.19); cSS was directionally consistent but non-significant. Poor-outcome rates rose monotonically across THB tiers, from 18.6% in the lowest to 36.8% in the highest tier. Conclusion An AI tool feasibly quantified all three SWI hemorrhagic findings at the registry scale. The resulting THB composite stratified patients by 3-month functional outcome with a tier-based gradient, thus supporting its use for risk stratification.

BACKGROUND:Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect. METHODS:Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and the effect of M2 laterality, division occlusion and procedure time were assessed. RESULTS:About 1734 patients with M2 occlusions underwent either frontline aspiration (n = 711) or SR/combined (n = 958) thrombectomy between 2013 and 2024. PSM analysis favored aspiration for functional independence (49.9% vs 44.0%, OR 1.27 (1.03-1.57)), complete recanalization (61.2% vs 48.7%, OR 1.66 (1.34-2.05)), complete first pass effect (35.0% vs 27.6%, OR 1.42 (1.13-1.78)), and sICH (3.5% vs 6.2%, OR 0.55 (0.33-0.91)), with no difference in mortality. Frontline aspiration had significantly shorter procedural times (median 28 [IQR 15-49.5] vs 51 [IQR 35-78] minutes; p < 0.001). For every minute increase in procedure time, the probability of functional independence decreased significantly (p < 0.001) less with frontline aspiration (0.35%) compared to SR/combined (1.61%). CONCLUSION:Frontline aspiration for M2 occlusions resulted in better clinical and angiographic outcomes compared to SRs. Future trials for MeVO with a focus on contact aspiration thrombectomy may succeed where recent trials have failed.

BACKGROUND:Recent trials established the efficacy of thrombectomy for large-core stroke by utilizing the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as a pragmatic tool. However, whether this topographical scoring captures the therapeutic ceiling, or the upper threshold of infarct volume where the benefit of reperfusion diminishes, remains unclear. METHODS:Leveraging a nationwide multicenter registry in Korea (2022-2024), we compared the prognostic value of quantitative volumetry and ASPECTS in thrombectomy-treated patients. We analyzed discordance between ASPECTS and volumetry derived from diffusion-weighted imaging, computed tomography perfusion, and noncontrast computed tomography. The primary outcome was poor functional outcome (90-day modified Rankin Scale score 5-6). To estimate treatment effects across specific volume spectra, we conducted target trial emulations that stratified causal estimates by volumetric thresholds, with the ordinal 90-day modified Rankin Scale score shift as the primary outcome. RESULTS:Among 552 patients, the mean age was 70.4±12.6 years, and 319 (57.8%) were men. Patients classified as large core by ASPECTS but not by diffusion-weighted imaging volumetry (ASPECTS-only large core) had poor outcome proportions comparable to the both small-core group (11.8% versus 11.7%), with no excess risk after adjustment. Conversely, volumetric confirmation of large core across diffusion-weighted imaging, computed tomography perfusion, and noncontrast computed tomography consistently predicted poor prognosis regardless of ASPECTS (adjusted odds ratio, 6.92 [95% CI, 2.58-19.34] for the diffusion-weighted imaging-only large-core group). In the target trial emulations, the overall benefit of thrombectomy was attenuated (common odds ratio, 0.56 [95% CI, 0.31-1.03]). Stratified analyses delineated a therapeutic ceiling, with benefit in the 50 to 110 mL range (common odds ratio, 0.38 [95% CI, 0.15-0.97]) disappearing in extensive infarctions >110 mL. CONCLUSIONS:Quantitative volumetry provided better prognostic discrimination and identified ≥110 mL as a therapeutic ceiling where the benefit of thrombectomy becomes negligible. These findings advocate integrating volumetric thresholds into patient selection to minimize futile reperfusion and prioritize safety, serving as a critical refinement to current topographical scoring.

INTRODUCTION:Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear. PATIENTS AND METHODS:This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in the Stroke Thrombectomy and Aneurysm Registry. Patients selected for EVT by advanced imaging (CTP or MR) were matched with those selected by conventional imaging using propensity score matching (PSM) accounting for possible confounders. Primary outcome was functional independence at 90 days. Other outcomes include bedridden state or death at 90-days and symptomatic intracranial hemorrhage (sICH). RESULTS:268 patients were included. 150 patients were selected for BAO EVT by conventional imaging, 86 by CTP, and 32 by MR. Patients selected by advanced imaging were significantly older than those selected by conventional imaging (median age 71 vs 64 years, p = 0.001); patient characteristics were otherwise similar between cohorts. After PSM, 90-day outcomes were similar between the two cohorts (p = 0.56), with similar rates of functional independence (39.4% vs 35.1%, p = 0.65), bedridden state or death (40.4% vs 44.7%, p = 0.66), and sICH (3.3% vs 5.7%, p = 0.49) for conventional and advanced imaging groups, respectively. Results were similar across treatment time windows (all p > 0.05). CONCLUSIONS:Selecting patients for basilar EVT using conventional versus advanced imaging did not result in different clinical outcomes, regardless of treatment time windows. Conventional imaging appears sufficient as a first-line tool for selecting basilar EVT patients in routine clinical practice.

BACKGROUND:Hemorrhagic transformation (HT) after recanalization therapy remains a critical concern in acute ischemic stroke management. While severe hemorrhages clearly worsen outcomes, the prognostic impact of mild HT and its optimal prediction methods remain uncertain. In this study, we aimed to evaluate the clinical significance of all HT subtypes and develop automated HT prediction models based on noncontrast computed tomography (CT) images. METHODS:We analyzed 2211 patients receiving intravenous thrombolysis and endovascular thrombectomy from the multicenter Clinical Research Collaboration for Stroke in Korea Imaging repository (2022-2024). HT was classified on follow-up imaging of magnetic resonance or CT. Baseline ischemic lesion volume and Alberta Stroke Program Early CT Score-based net water uptake were quantified on baseline noncontrast CT. Multivariable regression was used to assess the association of HT and 90-day modified Rankin Scale scores. The performance of HT prediction models was compared, the automated imaging model versus established scores (hemorrhage after thrombolysis score and SEDAN), using the area under the curve. RESULTS:HT occurred in 41.2% of patients (hemorrhagic infarction [HI] 1: 13.8% and HI2: 16.8%, parenchymal hematoma [PH] 1: 6.5% and PH2: 4.1%). All HT subtypes independently predicted worse functional recoveries with stepwise increasing odds ratios: HI1 (1.77 [95% CI, 1.40-2.22]), HI2 (2.83 [95% CI, 2.27-3.53]), PH1 (4.65 [95% CI, 3.41-6.36]), and PH2 (14.76 [95% CI, 9.61-22.90]). This association persisted across treatment modalities and vascular territories. For PH prediction, the automated imaging model (noncontrast CT imaging markers combined with clinical variables) achieved superior performance (area under the curve, 0.77 [95% CI, 0.73-0.80]) compared with hemorrhage after thrombolysis score (0.71 [95% CI, 0.68-0.75]) and SEDAN (0.72 [95% CI, 0.69-0.76]) scores (both P<0.01 for area under the curve comparison). CONCLUSIONS:Even mild HI was independently associated with poor functional outcomes after reperfusion therapy. Automated noncontrast CT-derived biomarkers provide superior HT risk prediction compared with conventional scores, offering a practical tool for individualized stroke management in the reperfusion era.

BACKGROUND:The ATTENTION (0-12 hours) and BAOCHE (6-24 hours) trials demonstrated the efficacy of endovascular treatment (EVT) for basilar artery occlusion (BAO) in highly selected populations, but real-world generalizability remains uncertain. PATIENTS AND METHODS:We analyzed patients with acute BAO presenting within 24 hours of last known well from a nationwide, multicenter, prospective stroke registry. Patients were categorised as ATTENTION-eligible, BAOCHE-eligible, and ineligible based on clinical and neuroimaging criteria from both trials. The primary outcome was the distribution of 3-month modified Rankin Scale (mRS). Secondary outcomes included 3-month mRS of 0-3 and 0-2, 90-day mortality, and symptomatic hemorrhagic transformation. Inverse probability of treatment weighting was applied to adjust for baseline differences. RESULTS:Among 49,471 patients with acute ischemic stroke, 2.0% (n = 1012) had BAO. Of these, 24% met ATTENTION-criteria, 6% met BAOCHE-criteria, and 72% were ineligible for both. Endovascular treatment was performed in 75%, 59%, and 43% of these groups, respectively. In ATTENTION-eligible patients, EVT was associated with more favourable mRS distribution (cOR, 1.73; 95% CI, 1.03-2.93) and lower 3-month mortality (RR, 0.52; 95% CI, 0.33-0.80). In BAOCHE-eligible patients, adjusted models did not reach statistical significance due to limited sample size. Among ineligible patients, EVT was associated with lower mortality (RR, 0.77; 95% CI, 0.60-0.99). Symptomatic haemorrhage rates did not differ across groups. CONCLUSION:Most BAO patients were ineligible for pivotal EVT trials, and eligibility for the more stringent BAOCHE criteria was particularly rare in real-world practice. Endovascular treatment was associated with reduced mortality even in ineligible patients. These findings highlight the practical limitations of current trial-based selection criteria and support broader application of EVT for BAO.

OBJECTIVE:Endovascular thrombectomy (EVT) for acute large-vessel occlusion stroke is well established, yet its role in patients presenting with minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score < 6) remains unclear. Prior studies have not accounted for intraprocedural factors that may influence outcomes in this subgroup. METHODS:The authors analyzed 5693 patients from the STAR (Stroke and Thrombectomy and Aneurysm Registry), including 398 with low NIHSS scores, to evaluate the association between procedure time (PT) and outcomes. Among patients with low NIHSS scores, propensity score matching was used to compare outcomes between those with PT ≤ 35 versus > 35 minutes, a cutoff defined using receiver operating characteristic curve analysis. The authors performed a meta-analysis of studies reporting best medical management (BMM) outcomes in patients with low NIHSS scores. To compare these with EVT-treated patients, a matched BMM comparator cohort using stratification on pooled baseline characteristics was constructed. Outcomes included 90-day functional independence (modified Rankin Scale [mRS] scores 0-2), intracranial hemorrhage, and mortality. RESULTS:PT had a stronger negative effect on outcomes in patients with low NIHSS scores compared with those with high scores, with a steeper decline in functional independence per minute of PT (slope: -0.45% vs -0.21%; p = 0.03 for interaction). Among patients with low scores, PT ≤ 35 minutes was associated with higher 90-day functional independence compared with the propensity score-matching cohort with PT > 35 minutes (82.6% vs 59.0%, p < 0.001). When benchmarked against BMM (75.2% mRS scores 0-2), patients undergoing EVT within 35 minutes had superior outcomes (85.1%, p = 0.047). In contrast, EVT with PT > 35 minutes resulted in worse outcomes than BMM (mRS scores 0-2: 59.8%, p = 0.008). The number needed to treat for PT ≤ 35 minutes was 10, whereas PT > 35 minutes yielded a number needed to harm of 6. CONCLUSIONS:PT critically modulates the benefit of EVT in minor stroke. While efficient EVT yields better outcomes than BMM, prolonged procedures are associated with harm. These findings may explain prior inconsistent evidence on EVT in patients with low NIHSS scores and underscore the need to individualize procedural thresholds in this population.

Background Current stroke guidelines lack subtype‐specific recommendations for optimal low‐density lipoprotein cholesterol targets. Indeed, most lipid‐lowering trials have not differentiated between stroke subtypes or focused primarily on large artery atherosclerosis, leaving a gap in evidence for other stroke subtypes, such as small vessel occlusion stroke. This study is designed to evaluate whether intensive lipid‐lowering therapy is superior to standard therapy in reducing major adverse cardiovascular events among patients with small vessel occlusion stroke. Methods SVO70 (Optimal Target Low‐Density Lipoprotein Cholesterol Level for Small Vessel Occlusion Stroke) is a multicenter, prospective, randomized, open, blinded‐end point clinical trial in which adult patients with neuroimaging‐confirmed small vessel occlusion stroke within 180 days of randomization will be enrolled. Key exclusion criteria include predefined low‐density lipoprotein cholesterol targets for other comorbidities, contraindications to statin, and pregnancy or lactation. Eligible participants will be randomized 1:1 to achieve low‐density lipoprotein cholesterol <70 mg/dL (intensive group) or 90 to 110 mg/dL (standard group). The trial aims to enroll 4016 participants over a 2‐year recruitment period, with a minimum follow‐up of 4 years. The primary end point is the occurrence of major adverse cardiovascular events, defined as cardiovascular death, stroke, and acute coronary syndrome, during the follow‐up period. Secondary end points include (1) any stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, (4) cardiovascular death, (5) myocardial infarction, (6) all‐cause death, and (7) acute coronary syndrome. Conclusions This study will provide valuable information for determining optimal low‐density lipoprotein cholesterol targets for patients with small vessel occlusion stroke. Registration URL: https://ClinicalTrials.gov; Unique Identifier: NCT06649240, Clinical Research Information Service (KCT0009043).

OBJECTIVE:This study investigated whether educational attainment independently predicts long-term prognosis following acute coronary syndrome (ACS) and stroke, and whether this association is modified by acute-phase suicidal ideation (SI). METHODS:Data from two prospective cohorts (1,152 ACS; 396 stroke) were analyzed. Educational attainment (low ≤10 high vs. high >10 years) and SI were assessed approximately 2 weeks post-event. Primary endpoints-major adverse cardiac events (MACE) for ACS and cerebro-cardiovascular events (CCVE) for stroke-were ascertained over a 5-14 year follow-up. Hierarchical Cox models sequentially adjusted for vascular factors (Model 1), psychosocial/disease severity (Model 2), and combined covariates (Model 3). Sensitivity analyses used a ≥12-year education cutoff. RESULTS:Educational attainment was not an independent predictor of outcomes in either cohort across all models. However, a significant education×SI interaction emerged for MACE in the ACS cohort across all models (p=0.031-0.046). Among ACS patients with SI, higher education was associated with significantly reduced MACE risk (hazard ratio [HR]=0.54, 95% confidence interval 0.34-0.86, p=0.009), while no association existed without SI (HR=1.05, p=0.690). Similar interaction patterns in the stroke cohort achieved significance in Models 1 and 3, though stratified effects were attenuated, likely reflecting limited statistical power. Sensitivity analyses demonstrated directional consistency in both cohorts with some attenuation in fully adjusted models. CONCLUSION:Educational background modifies the prognostic impact of psychological distress in post-ACS patients. Lower-educated patients experiencing SI represent a high-risk subgroup requiring targeted psychosocial intervention. These findings support integrating educational status into psychosocial risk stratification protocols for acute cardiovascular care.

BACKGROUND:This study aimed to describe the temporal evolution of antithrombotic treatment strategies and associated clinical outcomes after atrial fibrillation-related acute ischemic stroke. METHODS:This multicenter prospective cohort study enrolled patients with acute ischemic stroke and atrial fibrillation from 16 tertiary stroke centers across South Korea between February 2018 and January 2021, with follow-up completed by January 2022. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause death. Secondary outcomes included individual components of the primary outcome and major bleeding events. RESULTS:The median follow-up duration was 1.92 years. Among 2965 patients (mean±SD age, 75.3 [10.2] years; 54.1% male), antithrombotic strategies varied widely in the acute phase. Within 48 hours of admission, 50.9% received antiplatelet-only therapy (29.4% single, 21.5% dual), 23.2% received non-vitamin K antagonist oral anticoagulant monotherapy, and 10.4% received a combination of antiplatelets and anticoagulants. By discharge, non-vitamin K antagonist oral anticoagulant monotherapy had become the predominant treatment strategy (65.7%), and this pattern persisted throughout follow-up. The incidence of the primary end point was highest in the first 2 weeks (32.70 [95% CI, 29.64-36.06] per 100 person-months) and declined thereafter. Across all time periods, patients receiving non-vitamin K antagonist oral anticoagulant monotherapy consistently had lower incidence rates (3-month rate, 4.95 [95% CI, 4.37-5.61] per 100 person-months) than those receiving antiplatelet-only therapy (11.98 [95% CI, 9.57-15.01]) or no antithrombotic therapy (18.44 [95% CI, 14.26-23.86]). CONCLUSIONS:In this prospective cohort of patients with atrial fibrillation-related stroke, early antithrombotic treatment strategies were heterogeneous but evolved primarily toward use of non-vitamin K antagonist oral anticoagulant monotherapy. Treatment selection was associated with marked differences in outcomes, particularly during the early high-risk period.

BACKGROUND:This study aimed to evaluate secular trends in the control of major risk factors at the time of ischemic stroke to assess the real-world implementation of prevention guidelines and identify areas needing greater clinical attention for improved early stroke outcomes. METHODS:We retrospectively analyzed data from a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke between 2011 and 2022. For risk factor controls of interest, hypertension, diabetes, dyslipidemia, and atrial fibrillation (AF) were considered. Well-controlled risk factors were defined as follows: "well-controlled hypertension": hypertension with prior antihypertensive medication and systolic blood pressure <140 mm Hg on admission; "well-controlled diabetes": prior antidiabetic medication with glycated hemoglobin <7.0%; "well-controlled dyslipidemia": prior statin therapy with low-density lipoprotein cholesterol <100 mg/dL; and "well-controlled AF": presence of AF with prior oral anticoagulant use. Linear trends in control rates were tested via the Cochran-Armitage and linear contrast tests. RESULTS:Among 76 962 patients (68.8±13.3 years;men, 59.0%), the adjusted rate of well-controlled hypertension decreased from 35.7% (95% CI, 34.0%-37.5%) in 2011 to 25.5% (95% CI, 24.4%-26.7%) in 2022, whereas well-controlled status improved for diabetes (26.4%-29.4%), dyslipidemia (22.2%-48.6%), and AF (26.0%-55.7%) from 2011 to 2022 (Ptrend<0.001). The rates of well-controlled risk factors were relatively higher in patients with a history of stroke than in those with no history of stroke, except for hypertension. The 3-month composite of stroke, myocardial infarction, and all-cause death significantly declined from 10.0% in 2011 to 8.6% in 2022 (Ptrend<0.001). CONCLUSIONS:Our study confirmed a continuous increase in prestroke risk factor control, including diabetes, dyslipidemia, and AF, but the rate remained suboptimal at stroke onset. These findings may help inform strategies to improve risk factor management by identifying priority areas that warrant targeted intervention in clinical practice and population-level guidelines.

BACKGROUND:Endovascular thrombectomy (EVT) has transformed acute ischemic stroke (AIS) care, with onset-to-puncture (OTP) time widely recognized as a critical determinant of outcome. However, emerging evidence suggests that in-hospital procedure time (PT)-from arterial puncture to final recanalization-may have an equally or more significant impact. This study examines the relative contribution of PT versus OTP to functional outcomes in patients with AIS undergoing EVT. METHODS:A retrospective analysis was conducted of 6644 patients with AIS treated at 44 international stroke centers from the Stroke Thrombectomy and Aneurysm Registry (STAR; 2016-2023). Multivariable regression, time-equivalence analysis, and marginal effects modeling were used to assess associations between PT, OTP, and 90-day modified Rankin Scale (mRS) outcomes. Centers were stratified by procedural efficiency and compared using propensity score matching (PSM). Mediation analysis evaluated whether PT accounted for inter-center differences. RESULTS:PT and OTP were independently associated with functional outcomes; however, PT had a significantly stronger effect (adjusted OR for mRS 0-2: PT=0.56 vs OTP=0.96 per hour). Each 5 min increase in PT was equivalent to 78-100 min of additional OTP in outcome impact. Centers with faster average PT had higher rates of functional independence (number needed to treat (NNT)=10), fewer complications, and lower symptomatic intracranial hemorrhage rates. PT significantly mediated the relationship between center tier and outcomes (Sobel's P<0.001). CONCLUSION:While minimizing OTP remains important, PT exerts a greater influence on outcomes after EVT. Procedural efficiency should be emphasized in stroke systems of care and included in center performance metrics to improve patient outcomes.

BACKGROUND:Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. METHODS:In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. RESULTS:Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). CONCLUSIONS:ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.

Introduction: Cranio-cervical artery dissection (CAD) is a major cause of ischemic stroke in young and middle-aged adults. Although the overall prognosis is often favorable, a substantial proportion of patients experience recurrent ischemic events, particularly in the early period. The incidence and predictors of ischemic stroke recurrence after CAD remain poorly defined, particularly in patients presenting with acute ischemic stroke or transient ischemic attack (TIA). Methods: We conducted a multicenter, prospective cohort study using data from the Clinical Research Collaboration for Stroke in Korea–National Institute of Health (CRCS-K-NIH), a nationwide web-based stroke registry. The study included consecutive patients aged ≥18 years who were admitted with acute ischemic stroke or TIA to one of 17 participating academic centers between January 2011 and April 2021. CAD was diagnosed within 7 days of symptom onset. Recurrent ischemic stroke events were assessed over a 1-year follow-up. Analyses were stratified by dissection location (intracranial vs. extracranial), and by angiographic patterns (occlusion, stenosis without dilatation, dilatation without stenosis, and the pearl-and-string sign), and other vascular imaging features (intramural hematoma, intimal flap, and double lumen). Results: Among the 711 patients (mean [SD] age, 49.0 [12.5] years; 73.0% men), 541 (76.1%) had intracranial dissections. Recurrent ischemic stroke occurred in 243 patients (27.9%), and 74.5% of events occurred within 7 days of symptom onset. In time-specific analysis, recurrence incidence was highest on day 1 (131.8 per 1,000 person-days) and declined sharply thereafter. Dissection location was not significantly associated with recurrence risk after adjustment. In contrast, vascular morphologic features were strongly associated with recurrence timing and risk: occlusion was linked to recurrence on day 1 (adjusted IRR, 2.18; 95% CI, 1.03–4.61), double lumen to recurrence at 4–7 days (IRR, 2.83; 95% CI, 1.41–5.68), and dilatation without stenosis beyond 7 days (IRR, 2.86; 95% CI, 1.00–8.17). Conclusion: Recurrent ischemic stroke after CAD is common and occurs predominantly within the first week. Vascular morphologic features—not dissection location—are the most powerful and time-sensitive predictors of recurrence. Early identification of high-risk imaging features may facilitate individualized monitoring and secondary prevention strategies during the acute period.

Background Adults aged 80 years and older are the fastest-growing segment of the stroke population. Whether contemporary advances in stroke care have produced sustained outcome gains in this group during the past decade, including the post-pandemic era, has not been examined in nationwide longitudinal data with concurrent age-specific comparison. Methods Using the Clinical Research Collaboration for Stroke in Korea-National Institutes of Health (CRCS-K-NIH) registry, we analyzed consecutive adults with acute ischemic stroke admitted within 7 days of symptom onset between 2011 and 2022. Patients aged 80 years and older formed the primary cohort; those aged 18-79 years served as comparators. Primary outcomes were 3-month utility-weighted modified Rankin Scale (UW-mRS) and 1-year all-cause mortality. Non-linear trends and age-group-by-year interaction were modeled using restricted cubic splines adjusted for sex, age, and baseline NIHSS. Results Of 83,953 patients, 18,514 (22.1%) were aged 80 years and older; their proportion rose from 17.4% to 27.3%. Despite treatment intensification (endovascular thrombectomy 4.2% to 10.6%; oral anticoagulation for atrial fibrillation 52.5% to 76.9%), 1-year mortality in this group fell from 27.5% in 2011 to 19.4% in 2019, then rose to 23.7% by 2022; 3-month UW-mRS improved from 0.47 to 0.51 over the same period, then stagnated at 0.48. Restricted cubic splines confirmed significant nonlinearity in both outcomes after adjustment for sex, age, and NIHSS (P < 0.01 for both). Younger patients showed no comparable functional deterioration. Age-group-by-year interaction was significant for 3-month UW-mRS (P < 0.001) but not for 1-year mortality (P = 0.058), which showed a similar direction in both age groups. Conclusion In this nationwide registry, patients aged 80 years and older experienced an age-specific inflection of functional recovery gains after 2019 despite continued intensification of acute stroke care. Sustaining outcome gains in this population may require attention to post-acute care infrastructure. ### Competing Interest Statement Hee-Joon Bae reports grants from Amgen Korea Limited., Celltrion, Dong-A ST, Otsuka Korea, Samjin Pharm, and Takeda Pharmaceuticals Korea Co., Ltd., and personal fees from Amgen Korea, Bayer, Boehringer Ingelheim, Daewoong Pharmaceutical Co., Ltd., Daiichi Sankyo Korea, Eisai Korea, Inc., and Otsuka Korea, outside the submitted work. PBG reports grants from the Havey Institute for Global Health, Northwestern University and NIH Fogarty Institute Center, and support from JLK, American Telephysicians/NeuroX, and Quantal X. ### Clinical Trial Not applicable ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data collection within the CRCS-K-NIH registry was approved by the local institutional review boards (IRBs) of all participating centers. The secondary use of fully anonymized, pre-existing registry data for this analysis was approved by the IRB of Seoul National University Bundang Hospital (approval number B-2505-973-101) and other participating centers, which waived the requirement for individual informed consent given the retrospective, non-interventional nature of the analysis and the absence of identifiable patient information. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Individual deidentified participant data from the CRCS-K-NIH registry that underlie the results reported in this article, together with the data dictionary, study protocol, and statistical analysis plan, will be made available to qualified investigators on reasonable request beginning at the time of publication. Requests, including a methodologically sound research proposal and IRB documentation from the requesting institution, should be directed to the corresponding author (Hee-Joon Bae; braindoc{at}snu.ac.kr) and will be reviewed by the CRCS-K-NIH Steering Committee. A signed data use agreement is required, and approved data will be provided in a deidentified format in accordance with the Korean Personal Information Protection Act.

BACKGROUND:Dual antiplatelet therapy (DAPT) is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack. However, the optimal timing for initiating DAPT remains unclear. METHODS:From a prospective multicenter cohort involving 20 stroke centers between January 2011 and April 2023, patients with minor noncardioembolic ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack who presented within 7 days of symptom onset were included. We evaluated outcomes based on in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a composite of recurrent stroke, myocardial infarction, and death within 90 days. Patients were grouped by time from symptom onset to hospital arrival: 0 to 24 hours, 24 to 72 hours, and >72 hours. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores. The adjusted models incorporated demographic factors, baseline clinical characteristics, vascular risk factors, stroke subtype, relevant arterial status, and prior antiplatelet use. RESULTS:Among the 41 530 patients (mean age, 66.3 years; 25 771 [62%] male), 25 112 (60.5%) received DAPT. The 90-day primary outcome occurred in 2663 (10.7%) of the DAPT group versus 1900 (11.6%) in the monotherapy group (hazard ratio, 0.82 [95% CI, 0.77-0.87]). The benefit of DAPT was most pronounced when initiated within 24 hours (hazard ratio, 0.74 [95% CI, 0.69-0.79]). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (hazard ratio, 1.00 [95% CI, 0.88-1.15]), and a higher risk was suggested for initiation beyond 72 hours (hazard ratio, 1.25 [95% CI, 1.01-1.55]). Time-dependent analysis showed a benefit crossing the null at ≈42 hours. CONCLUSIONS:Early initiation of DAPT was associated with the greatest clinical benefit, consistent with current guideline recommendations. The therapeutic effect appeared to decline progressively beyond this period, with an estimated threshold around 42 hours.

Abstract Background In atrial fibrillation (AF), cerebral microbleed (CMB) burden guides anticoagulation decisions, yet AF is itself inconsistently associated with CMBs, a paradox unexplained by frameworks that treat CMBs as a unitary marker of small vessel disease. We hypothesized that the white matter hyperintensity (WMH) context in which CMBs arise modifies their vascular meaning, and that this context-dependence underlies the inconsistent AF–CMB association. Methods From a multicenter Korean stroke registry, we analyzed 5,735 first-ever ischemic stroke patients imaged at nine centers using susceptibility-weighted MRI. WMH volume and CMB count were extracted by validated deep learning pipelines. Patients were cross-classified by age-adjusted WMH residual (median split) and CMB count (≥2) into four groups. The AF–CMB association was estimated by multivariable logistic regression within each WMH stratum with formal interaction testing. Spatial CMB distribution was analyzed against the Automated Anatomical Labeling atlas. Results In the full cohort (mean age 69.5 years; 57.7% male), AF was not associated with CMBs (OR 1.04; 95% CI 0.87–1.25). Stratification yielded divergent estimates: the adjusted AF OR was 1.46 (1.11–1.93; P = 0.007) in the WMH-low stratum and 0.95 (0.73–1.22; P = 0.665) in the WMH-high stratum, with significant interaction (OR 0.56; P < 0.001). The discordant phenotype (low WMH, high CMB; 8.9%) was enriched for AF (28.0%) and showed fronto-temporal cortical predominance with deep structure sparing. AF independently reduced the proportion of deep CMBs (IRR 0.80; P = 0.040). The interaction was preserved across prespecified sensitivity analyses. Conclusions The AF–CMB association is confined to patients with low WMH burden relative to age and is accompanied by a topographically distinct CMB distribution. Clinical assessment of small vessel disease based on WMH alone may overlook a CMB phenotype linked to AF.

Background Hemorrhagic transformation (HT) after endovascular thrombectomy (EVT) is a principal determinant of clinical outcome. Artificial intelligence (AI) algorithms for spontaneous hemorrhage detection exist, but none has been validated for post-procedural HT across multiple imaging modalities. Methods We conducted a multicenter diagnostic accuracy study within the Clinical Research Collaboration for Stroke in Korea registry (18 centers, 2022 to 2023). Patients who underwent EVT and received follow-up NCCT, GRE, or SWI within 168 hours were included. AI-derived hemorrhage volumes were compared against expert determined ECASS classification. Three-month modified Rankin Scale (mRS) scores were evaluated for volume outcome association. Results Among 1,490 patients (median age 73; 57.4% male), HT was present in 41.4% and parenchymal hemorrhage (PH) in 11.1%. PH detection sensitivity exceeded 94% across all modalities (NCCT 95.4%, GRE 94.4%, SWI 98.3%), with AUCs of 0.900, 0.943, and 0.953, respectively. AI-derived volume correlated with 3-month mRS (Spearman ρ = 0.353, P < 0.001); good outcome (mRS 0 to 2) declined from 61.8% to 6.7% across increasing volume categories. Among ECASS 0 cases, AI-positive patients had significantly worse outcomes than true-negatives (good outcome 48.2% vs 67.2%, mortality 10.7% vs 4.6%, P < 0.001). Conclusions AI based hemorrhage quantification provides high detection of clinically significant PH after EVT and demonstrates a dose response association with functional outcome. AI derived volume may serve as a continuous prognostic biomarker that identifies at-risk subgroups beyond categorical ECASS grading. ### Competing Interest Statement Wi-Sun Ryu, Dongmin Kim, and Myungjae Lee are employees of JLK Inc., Republic of Korea. Hee-Joon Bae reports grants from Amgen Korea Limited, Bayer Korea, Bristol Myers Squibb Korea, Celltrion, Dong-A ST, Otsuka Korea, Samjin Pharm, and Takeda Pharmaceuticals Korea Co., Ltd.; and personal fees from Amgen Korea, Bayer, Daewoong Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Korea, Inc., JW Pharmaceutical, SK Chemicals, and Otsuka Korea, outside the submitted work. In addition, Hee-Joon Bae and Dong-Eog Kim hold stock in JLK Inc., the developer of the software evaluated in this study. Authors affiliated with JLK Inc. were excluded from data analysis and reference standard adjudication. Other authors reported no conflict of interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the institutional review boards of all participating centers (lead site: Seoul National University Bundang Hospital IRB [IRB No. B-2308-845-302]). Written informed consent was obtained from all participants or their legal representatives. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymized data supporting the findings of this study are available from the corresponding author upon reasonable request, subject to institutional data-sharing agreements and privacy regulations.