Search

The objective of this study was to apply and test the effects of cognitive training on community-dwelling, elderly Koreans. The cognitive training was applied for 24 weeks to 129 elderly participants. The participants were divided into two groups to receive either cognitive training followed by observational period, or observational period followed by cognitive training. The primary outcome measures were the geriatric depression scale (Geriatric Depression Scale Short Form-Korean, GDS-SF-K) and minimental status examination (Mini-Mental State Examination in the Korean version, MMSE-KC) scores. There were no differences between the average GDS-SF-K and MMSE-KC scores of the two groups. However, the participants with cognitive dysfunction (defined as baseline MMSE below the 16th percentile according to age, sex and educational level) who received cognitive training initially had significantly improved MMSE-KC score on weeks 8 and 16, compared with the participants with cognitive dysfunction who were observed first. However, the participants who received cognitive training later did in fact catch up with the other group in terms of MMSE-KC score. Cognitive training by visiting nursing services was more effective in the elderly with cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men., Aim: This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea., Methods: A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality., Results: A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years., Conclusion: Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.K.S. received honoraria for lectures from Otsuka Korea, Dong-A Pharmaceutical Co., Ltd., study grants from Dong-A ST.

Background: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS)., Methods: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days., Results: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 μg/mL vs 16.9 ± 16.9 μg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P  = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P  = 0.06) and 90-day mortality (40.0% vs 25.0%, P  = 0.31) were noted in the edoxaban group., Conclusion: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS., Trial Registration: clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Endovascular treatment for vertebral artery dissecting aneurysms (VADAs) includes overlapping stents and flow diverters. This study compared the safety and effectiveness of overlapping stents and flow diverters for unruptured VADAs., Methods: We retrospectively enrolled patients with unruptured VADAs who underwent overlapping stents or flow diverters at two tertiary hospitals in South Korea. The primary clinical outcome was the occurrence of stroke. The primary angiographic outcomes (>12 months) were categorized as regression, no decrease in size, recanalization, or stent occlusion, of which only regression was defined as a favorable angiographic outcomes., Results: Of the 146 patients with VADAs, 25 (17.1%) had flow diverters and 121 (82.9%) had overlapping stents. For the primary angiographic outcomes over 12 months, the rate of favorable angiographic outcomes for flow diverters was 81.8% and for overlapping stents (triple stents) was 98.8% (P=0.006). In the multivariale analysis, after adjusting for partially thrombosed aneurysms, aneurysm shape, non-dominant vessel, posterior inferior cerebellar artery involvement, and procedure type, overlapping stents (triple stents) was not associated with favorable angiographic outcomes compared with flow diverters (OR 7.040, 95% CI 0.549 to 90.294; P=0.134), but partially thrombosed aneurysms was inversely associated with favorable angiographic outcomes (OR 0.056, 95% CI 0.005 to 0.589; P=0.016). The primary clinical outcome followed up to the last angiography did not occur in all patients., Conclusion: There was no difference in safety and effectiveness between overlapping stents and flow diverters in unruptured VADAs. Further endovascular treatment studies are needed regarding the association of partially thrombosed aneurysms with unfavorable angiographic outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Aging manifests as many phenotypes, among which age-related changes in brain vessels are important, but underexplored. Thus, in the present study, we constructed a model to predict age using cerebrovascular morphological features, further assessing their clinical relevance using a novel pipeline. Age prediction models were first developed using data from a normal cohort (n = 1181), after which their relevance was tested in two stroke cohorts (n = 564 and n = 455). Our novel pipeline adapted an existing framework to compute generic vessel features for brain vessels, resulting in 126 morphological features. We further built various machine learning models to predict age using only clinical factors, only brain vessel features, and a combination of both. We further assessed deviation from healthy aging using the age gap and explored its clinical relevance by correlating the predicted age and age gap with various risk factors. The models constructed using only brain vessel features and those combining clinical factors with vessel features were better predictors of age than the clinical factor-only model (r = 0.37, 0.48, and 0.26, respectively). Predicted age was associated with many known clinical factors, and the associations were stronger for the age gap in the normal cohort. The age gap was also associated with important factors in the pooled cohort atherosclerotic cardiovascular disease risk score and white matter hyperintensity measurements. Cerebrovascular age, computed using the morphological features of brain vessels, could serve as a potential individualized marker for the early detection of various cerebrovascular diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: To validate the accuracy of high-risk criteria for carotid endarterectomy (CEA) and analyze the correlation between age and outcome of CEA and carotid artery stenting (CAS) in risk groups., Methods: We reviewed a prospectively managed vascular surgery database in a single tertiary referral center, and 2482 internal carotid arteries (ICAs) had undergone carotid revascularization from November 1994 to December 2021. To validate high-risk criteria for CEA, patients were classified as high risk (Hr) and normal risk (Nr). Subgroup analysis was performed with patients older or younger than 75 years to investigate the relationship between age and outcome in each group. Primary endpoints were 30-day outcomes including stroke, death, stroke/death, myocardial infraction (MI), and major adverse cardiovascular events (MACEs)., Results: A total of 2345 ICAs in 2256 patients were enrolled. The number of patients in the Hr group was 543 (24%) and the number in the Nr group was 1713 (76%). CEA and CAS were performed on 1384 (61%) and 872 (39%) patients, respectively. The 30-day stroke/death rate was higher with CAS than CEA in both the Hr (1.1% vs. 3.9%, p = 0.032) and Nr (1.2% vs. 6.9%, p < 0.001) groups. In unmatched logistic regression analysis of the Nr group ( n = 1778), the rate of 30-day stroke/death (OR, 5.575; 95% CI, 2.922-10.636; p < 0.001) was higher for CAS than CEA. In propensity score matching of the Nr group, the rate of 30-day stroke/death (OR, 5.165; 95% CI, 2.391-11.155; p < 0.001) was also higher for CAS than CEA. In the age <75 subgroup of the Hr group ( n = 428), CAS was associated with higher 30-day stroke/death (OR, 14.089; 95% CI, 1.314-151.036; p = 0.029). In the age ≥75 subgroup of the Hr ( n = 139), there was no difference in 30-day stroke/death between CEA and CAS. In the age <75 subgroup of the Nr group ( n = 1318), 30-day stroke/death (OR, 6.300; 95% CI, 2.797-14.193; p < 0.001) was higher in CAS. In the age ≥75 subgroup of the Nr group ( n = 460), 30-day stroke/death (OR, 6.468; 95% CI, 1.862-22.471; p = 0.003) was higher in CAS., Conclusions: In patients older than 75 years in the Hr group, there were relatively poor 30-day treatment outcomes in both CEA and CAS. Alternative treatment is needed that can expect better outcomes in older high-risk patients. In the Nr group, CEA has a significant benefit compared with CAS, and CEA should be recommended more to these patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS., (© 2024. The Author(s).)

Background: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment., Methods: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis., Results: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups., Conclusion: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data., Methods: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data., Results: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018., Conclusion: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Objectives: The incidence and risk of ischemic stroke (IS) and hemorrhagic stroke (HS) in Korean patients with CHD have not been reported, therefore, we aimed to investigate this., Materials and Methods: Participants were selected from the Korean National Health Insurance Service benefit records from 2006-2017. Cases were extracted using diagnosis codes related to CHD. Controls without CHD were selected through age- and sex-matched random sampling at a 1:10 ratio., Results: The case and control groups included 232,203 and 3,024,633 participants, respectively. The median (interquartile range) follow-up period was 7.28 (3.59-8.73) years. The incidence rates of IS and HS per 100,000 person-years were much higher in cases than in controls (IS: 135 vs. 47; HS: 41.7 vs. 24.9). After adjusting for confounders, CHD was a risk factor for IS and HS (subdistribution HR; 1.96 and 1.71, respectively). In patients with CHD, the following risk factors were identified: diabetes, heart failure, and atrial fibrillation for any stroke; hypertension, atrial septal defects, and use of antiplatelet agents for IS only; and coronary artery bypass graft surgery for HS only., Conclusions: Korean patients with CHD have a high risk of stroke. A personalized preventive approach is needed to reduce the incidence of stroke in this population., Competing Interests: Declaration of Competing Interest The authors declare no competing interests related to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Prognostic prediction and the identification of prognostic factors are critical during the early period of atrial-fibrillation (AF)-related strokes as AF is associated with poor outcomes in stroke patients., Methods: Two independent datasets, namely, the Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke Patients (K-ATTENTION) and the Korea University Stroke Registry (KUSR), were used for internal and external validation, respectively. These datasets include common variables such as demographic, laboratory, and imaging findings during early hospitalization. Outcomes were unfavorable functional status with modified Rankin scores of 3 or higher and mortality at 3 months. We developed two machine learning models, namely, a tree-based model and a multi-layer perceptron (MLP), along with a baseline logistic regression model. The area under the receiver operating characteristic curve (AUROC) was used as the outcome metric. The Shapley additive explanation (SHAP) method was used to evaluate the contributions of variables., Results: Machine learning models outperformed logistic regression in predicting both outcomes. For 3-month unfavorable outcomes, MLP exhibited significantly higher AUROC values of 0.890 and 0.859 in internal and external validation sets, respectively, than those of logistic regression. For 3-month mortality, both machine learning models exhibited significantly higher AUROC values than the logistic regression for internal validation but not for external validation. The most significant predictor for both outcomes was the initial National Institute of Health and Stroke Scale., Conclusion: The explainable machine learning model can reliably predict short-term outcomes and identify high-risk patients with AF-related strokes., Competing Interests: J-MJ has received lecture honoraria from Pfizer, Sanofi-Aventis, Ostuka, Dong-A, and Hanmi Pharmaceutical Co., Ltd. and consulting fees from Daewoong Pharmaceutical Co., Ltd. W-KS received honoraria for lectures from Pfizer, Sanofi-Aventis, Otsuka Korea, and Dong-A Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeon, Jung, Yeo, Seo and Jung.)

Purpose: To propose standardized and feasible imaging protocols for constructing artificial intelligence (AI) database in acute stroke by assessing the current practice at tertiary hospitals in South Korea and reviewing evolving AI models., Materials and Methods: A nationwide survey on acute stroke imaging protocols was conducted using an electronic questionnaire sent to 43 registered tertiary hospitals between April and May 2021. Imaging protocols for endovascular thrombectomy (EVT) in the early and late time windows and during follow-up were assessed. Clinical applications of AI techniques in stroke imaging and required sequences for developing AI models were reviewed. Standardized and feasible imaging protocols for data curation in acute stroke were proposed., Results: There was considerable heterogeneity in the imaging protocols for EVT candidates in the early and late time windows and posterior circulation stroke. Computed tomography (CT)-based protocols were adopted by 70% (30/43), and acquisition of noncontrast CT, CT angiography and CT perfusion in a single session was most commonly performed (47%, 14/30) with the preference of multiphase (70%, 21/30) over single phase CT angiography. More hospitals performed magnetic resonance imaging (MRI)-based protocols or additional MRI sequences in a late time window and posterior circulation stroke. Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) were most commonly performed MRI sequences with considerable variation in performing other MRI sequences. AI models for diagnostic purposes required noncontrast CT, CT angiography and DWI while FLAIR, dynamic susceptibility contrast perfusion, and T1-weighted imaging (T1WI) were additionally required for prognostic AI models., Conclusion: Given considerable heterogeneity in acute stroke imaging protocols at tertiary hospitals in South Korea, standardized and feasible imaging protocols are required for constructing AI database in acute stroke. The essential sequences may be noncontrast CT, DWI, CT/MR angiography and CT/MR perfusion while FLAIR and T1WI may be additionally required.

Background: Constipation symptoms are highly prevalent in acute ischemic stroke, but the clinical and neuroimaging predictors are unknown. This study aimed to identify lesions and clinical features associated with acute constipation., Methods: Data from patients with acute ischemic stroke registered in a hospital-based stroke registry between January 2018 and December 2019 were analyzed. Clinical, laboratory, and imaging features were examined for associations with acute constipation. Using the topographic lesion on diffusion-weighted images, multivariate support vector regression-based lesion-symptom mapping (SVR-LSM) was conducted and compared between the non-constipation and acute constipation groups., Results: A total of 256 patients (mean age 67 years, men: 64%) were included. Acute constipation was noted in 81 patients (32%). Initial stroke severity, represented by initial National Institutes of Health and Stroke Scale (NIHSS) scores, was associated with acute constipation. Laboratory parameters, including fibrin degradation products (FDP), fibrinogen, D-dimer, lipoprotein (a), and free fatty acid levels, also showed statistically significant differences between the non-constipation and constipation groups. FDP, D-dimer, and free fatty acid levels were independently associated with acute constipation in the logistic regression model after adjusting for initial NIHSS scores and potassium levels. SVR-LSM revealed that bilateral lesions in the precentral gyrus, insula, opercular part of the inferior frontal gyrus, the inferior parietal lobule, and lesions in the right middle frontal gyrus were significantly associated with acute constipation. The results were consistent after controlling for the initial NIHSS scores and poststroke potassium levels. When cardioembolic stroke subjects were excluded, the right insular and prefrontal cortex lesions lost their association with acute constipation., Conclusion: Acute constipation symptoms after acute ischemic stroke are mainly related to bilateral lesions in the insula, precentral gyrus, postcentral gyrus, and inferior parietal lobule. Clinically important predictors of acute constipation include initial neurological severity and thromboembolic markers of stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Han, Lee, Song, Baek, Choi, Chung, Bang, Kim and Seo.)

Introduction: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF., Methods: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100., Results: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score., Conclusions: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Purpose: The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA 2 DS 2 -VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs)., Methods: Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival., Results: Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p =0.006), hypertension (HR 3.18, p =0.030), persistent AF type (HR 2.51, p =0.016), and initial hemoglobin level (HR 0.74, p =0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p =0.050)., Conclusions: This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications., Competing Interests: Woo-Keun Seo received honoraria for lectures from Sanofi-Aventis, Otsuka Korea, Dong-A Pharmaceutical Co, Ltd; study grants from Daiichi Sankyo Korea Co, Ltd; a consulting fee from OBELAB, Inc; and a stock option from JLK Inspection. The other authors report no conflicts., (Copyright © 2023 Korean Neurological Association.)

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Background and Purpose: This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke., Methods: This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort., Results: This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692-0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077-0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels., Conclusion: Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.

Background and Purpose: Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke., Methods: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events., Results: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups., Conclusion: Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

Background and Aims: Pleiotropic effects of statins result in the stabilization of symptomatic intracranial arterial plaque. However, little is known about the effect of statins in non-symptomatic cerebral arteries. We hypothesized that intensive statin therapy could produce a change in the non-symptomatic cerebral arteries., Methods: This is a sub-study of a prospective observational study under the title of "Intensive Statin Treatment in Acute Ischemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging (HR-MRI) study." Patients with statin-naive acute ischemic stroke who had symptomatic intracranial artery stenosis (above 50%) were recruited for this study. HR-MRI was performed to assess the patients' cerebral arterial status before and 6 months after the statin therapy. To demonstrate the effect of statins in the non-symptomatic segment of intracranial cerebral arteries, we excluded symptomatic segments from the data to be analyzed. We compared the morphological changes using cerebrovascular morphometry., Results: A total of 54 patients (mean age: 62.9 ± 14.4 years, 59.3% women) were included in this study. Intensive statin therapy produced significant morphological changes of overall cerebral arteries. Among the morphological features, the arterial luminal area showed the highest number of significant changes with a range from 5.7 and 6.7%. Systolic blood pressure (SBP) was an independent factor associated with relative changes in posterior circulation bed maximal diameter percentage change (beta -0.21, 95% confidence interval -0.36 to -0.07, p  = 0.005)., Conclusion: Intensive statin therapy produced a favorable morphological change in cerebral arteries of not only the target arterial segment but also non-symptomatic arterial segments. The change in cerebral arterial luminal diameter was influenced by the baseline SBP and was dependent on the topographic distribution of the cerebral arteries. Clinical Trial Registration : ClinicalTrials.gov, identifier NCT02458755., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sim, Song, Choi, Lee, Baek, Cho, Kim, Chung, Kim, Park, Bang and Seo.)

Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the 'segmentation-stacking' method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image's 90-99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99-1.00 [0.97-1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91-100%; middle cerebral arteries, 82-98%; anterior cerebral arteries, 88-100%; posterior cerebral arteries, 87-100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90-99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease., (© 2023. The Author(s).)

This study aimed to develop a supervised deep learning (DL) model for grading collateral status from dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) images from patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) and compare its performance against experts' manual grading. Among consecutive LVO-AIS at three medical center sites, DSC-MRP data were processed to generate collateral flow maps consisting of arterial, capillary, and venous phases. With the use of expert readings as a reference, a DL model was developed to analyze collateral status with output classified into good and poor grades. The resulting model was externally validated in a later-collected population from one medical center site. The model was trained on 255 patients and externally validated on 72 patients. In the all-site internal validation population, DL grading of good collateral probability yielded a c statistic of 0.91; in the external validation population, the c statistic was 0.85. In the external validation population, there was moderate agreement between the experts' grades and DL grades (kappa = 0.53, 95% CI = 0.32-0.73, p < 0.0001). Day 7 infarct growth volume was higher in DL-graded poor collateral group than good collateral group patients (median volume [26 mL vs. 6 mL], p = 0.01) in patients with successful reperfusion (modified treatment in cerebral infarction (mTICI) = 2b-3). In all patients with a 90-day modified Rankin Scale (mRS) score, there was a shift to more favorable outcomes in the good collateral group, with a common odds ratio of 2.99 (95% CI = 1.89-4.76, p < 0.0001). The DL-based collateral grading was in good agreement with expert manual grading in both development and validation populations. After exclusion of patients with large infarct volume, early reperfusion is more likely to benefit patients with the poor collateral flow, and the DL method has the potential to aid the assessment of collateral status., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy., Methods: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR., Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P <0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics., Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Purpose: Congenital heart disease (CHD) is a known risk factor for acquired cardiovascular and cerebrovascular diseases. However, available evidence on CHD is limited mostly to Western populations. This study aimed to evaluate the prevalence of vascular events and all-cause mortality in Korean patients with CHD and to further corroborate CHD as a predictor of vascular events and all-cause mortality., Materials and Methods: The claims data of the Korean National Health Insurance Service (NHIS) were retrospectively reviewed. Information regarding diagnostic codes, comorbidities, medical services, income level, and residential area was also collected. Outcomes of interest included stroke, myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE)., Results: We included 232203 patients with CHD and 3024633 individuals without CHD as a control group through age- and sex-matched 1:10 random sampling. The prevalences of hypertension, congestive heart failure, ischemic heart disease, hyperlipidemia, and atrial fibrillation were significantly higher in the CHD group, which had a more than two-fold higher incidence of vascular events and all-cause mortality, than in the group without CHD. Multivariable models demonstrated that CHD was a significant risk factor for stroke, MI, all-cause mortality, and MACE., Conclusion: In conclusion, this nationwide study demonstrates that Korean patients with CHD have a high incidence of comorbidities, vascular events, and mortality. CHD has been established as an important predictor of cardiovascular events. Further studies are warranted to identify high-risk patients with CHD and related factors to prevent vascular events., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Background and Purpose: The natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process., Methods: Serial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant., Results: The progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups ( p =0.005 and p =0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10-0.84, p =0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively)., Conclusions: Adult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted., Trial Registration: ClinicalTrials.gov identifier NCT02074111., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Korean Neurological Association.)

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

Objective: Liver fibrosis (LF) is associated with a poor prognosis in patients with ischemic stroke (IS). We aimed to assess whether LF affects long-term outcomes in patients with atrial fibrillation-related stroke or such effects vary according to sex., Methods: We conducted a multicenter prospective cohort study of Korean patients with atrial fibrillation-related IS. We calculated the fibrosis-4 (FIB-4) index, and LF degree was categorized into two groups (non-advanced vs. advanced) based on the FIB-4 index. Recurrent IS, major adverse cardiac events (MACEs), and all-cause mortality were evaluated using Cox proportional hazard model., Results: A total of 2897 patients were included; the median age was 75 (interquartile range 68-80) years, and 51.8% were men. The median follow-up period was 16.3 months. Of these patients, 23% had advanced LF indicated by FIB-4 index. Multivariable analysis in all populations demonstrated that the FIB-4 index and advanced LF were significantly associated with MACEs and all-cause mortality but not with recurrent IS. Furthermore, a sex disparity was observed in the outcomes of the patients. A high FIB-4 index in men was a significant predictor of recurrent IS [subdistribution hazard ratio (95% confidence interval): 1.08 (1.02-1.14)]. However, the significance of advanced LF disappeared in MACEs in women and in all-cause mortality in men., Conclusion: The FIB-4 index and advanced LF indicated by FIB-4 index are independent prognostic factors for long-term outcomes in Asian patients with atrial fibrillation-related IS. However, these predictors may contribute differently to patient outcomes depending on the sex., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: Collateral flow in acute ischemic stroke is known as a predictor of treatment outcome and long-term prognosis. However, factors determining the initial collateral flow remain unclear. We investigated factors related to collateral flow in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and further analyzed the results according to stroke etiology., Methods: This was a retrospective study using prospective stroke registry data from a single university hospital from October 2014 to May 2021. AIS-LVO with middle cerebral artery M1 occlusion identified by pre-treatment multiphasic computed tomography angiography was included. Collateral flow score was graded on a 6-point ordinal scale according to pial arterial filling., Results: A total of 74 patients [cardioembolism (CE): 57; large artery atherosclerosis (LAA): 17] was included. The mean age of all patients was 72.2 ± 11.7 years, and 37.8 % ( n = 28) were men. Multivariate regression analysis showed that initial SBP [odds ratio (OR): 0.994; 95% confidence interval ( CI ): 0.990-0.998; p = 0.002] and stroke etiology ( OR : 0.718; 95% CI : 0.548-0.940; p = 0.019) were independent factors of the collateral flow grade. Collateral flow grade was independently associated with initial SBP in the CE group ( OR : 0.993; 95% CI : 0.989-0.998; p = 0.004) but not in the LAA group ( OR : 0.992; 95% CI : 0.980-1.004; p = 0.218). Initial SBP was significantly correlated with NIHSS score in the CE group but not in the LAA group ( r 2 = 0.091, p = 0.023; r 2 = 0.043, p = 0.426, respectively)., Conclusions: Elevated initial SBP was associated with poor cerebral collateral flow and more severe symptoms in the CE group, but not in the LAA group in patients with AIS-LVO. These findings suggest differential effects of initial SBP elevation on collateral flow by stroke subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sim, Chung, Seo, Bang and Kim.)

Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF-related stroke. Methods and Results We included consecutive patients with AF-related stroke between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. A 3-month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF-related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01-1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60-6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF-related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF-related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

Background: This study aimed to investigate clinical outcome predictors of acute stroke patients with large vessel occlusion and active cancer and validate the significance of D-dimer levels for endovascular thrombectomy decisions., Methods: We analyzed a prospectively collected hospital-based stroke registry to determine clinical EVT outcomes of acute stroke patients within 24 h with following criteria: age ≥18 years, NIHSS ≥6, and internal carotid artery or middle cerebral artery lesion. All patients were classified into EVT and non-EVT groups. Patients were divided into two groups by initial D-dimer level. We explored variables potentially associated with successful recanalization as well as 3-month functional outcomes and mortality rates., Results: Among 68 patients, 36 were treated with EVT, with successful recanalization in 55.6%. The low D-dimer group showed a higher rate of successful recanalization and favorable outcome than the high D-dimer group. The mortality rate was higher in the high D-dimer group. No EVT and high D-dimer level were independent predictors of mortality, whereas lesion volume and low D-dimer level were independently associated with favorable outcomes., Conclusions: D-dimer level is a prognostic factor in acute LVO stroke patients with active cancer, and its high value for EVT decisions provisionally supports its testing in this patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pan, Kim, Chung, Kim, Bang, Jeon, Kim and Seo.)

Background: The CHADS 2 , CHA 2 DS 2 -VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT)., Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient., Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS 2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198-2.009, p = 0.001; CHA 2 DS 2 VASc score: OR 1.269, 95% CI 1.080-1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011-1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167-1.849, p = 0.001). The CHADS 2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS 2 score; 0.618, 95% CI 0.554-0.681)., Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Background: The optimal strategy for stroke prevention in cancer patients is unknown. We compared the underlying mechanisms of coagulopathy and the effects of anticoagulants in patients with active cancer and atrial fibrillation (AF)., Methods: We retrospectively enrolled 46 consecutive patients with embolic stroke of unknown source and active cancer (cancer stroke). We consecutively screened patients with cancer patients without stroke ( n = 29), AF stroke ( n = 52), and healthy subjects ( n = 28), which served as controls. Patients with cancer stroke were treated with either enoxaparin (a low-molecular-weight heparin) or a factor Xa inhibitor, and those with AF stroke were treated with factor Xa inhibitors. D-dimer, factor Xa, and circulating cell-free DNA (cfDNA), a marker of neutrophil extracellular traposis, were measured at both before and after anticoagulation., Results: In AF stroke, factor Xa activity and cfDNA and D-dimer levels were decreased by treatment with factor Xa inhibitors. In contrast, in cancer stroke, factor Xa activity was decreased, D-dimer levels were unchanged, and cfDNA levels were increased by treatment with factor Xa inhibitors. In cancer stroke patients treated with enoxaparin, D-dimer levels were decreased ( p = 0.011) and cfDNA levels were unchanged., Conclusion: The anticoagulation effects of factor Xa inhibitors differed between cancer stroke and AF stroke.

Background: In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect., Aims: We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage)., Methods: In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death., Results: Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01-0.60]; p  = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52-4.90]; p  = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant ( p interaction  = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41-1.01]; p  = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63-1.67]; p  = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction ( p interaction  = 0.165)., Conclusions: Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed., Clinical Trial Registration: URL:http://www.clinicaltrials.gov. NCT01013532.

Objective: The efficacy of antidepressants in post-stroke depressive symptoms (PSD) varies. We aimed to examine whether the effect of escitalopram on PSD differs according to individual depressive symptoms and stroke lesion location., Methods: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram on depression in acute stroke patients (237 with placebo, 241 with escitalopram). Depressive symptoms were evaluated with the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Changes in MADRS and individual item scores at 12 weeks were compared between the treatment groups and among the stroke lesion location groups. Stroke lesion locations were grouped according to the anatomical distribution of serotonin fibers that originate from the midbrain/pons and spread to the forebrain via subcortical structures: "Midbrain-Pons," "Frontal-Subcortical," and "Others." Least-squares means were calculated to demonstrate the independent effect of lesion location., Results: Total MADRS scores decreased more significantly in the escitalopram than in the placebo group, while a significant effect of escitalopram was observed in only 3 items: apparent sadness, reported sadness, pessimistic thoughts. In the lesion location analyses, escitalopram users in the Frontal-Subcortical group showed significant improvement in total MADRS scores (placebo [n = 130] vs. escitalopram [n = 148], least-square mean [95% CI]: -2.3 [-3.5 to -0.2] vs. -4.5 [-5.5 to -3.4], p = .005), while those in the Midbrain-Pons and Others groups did not., Conclusions: The effect of escitalopram on PSD may be more prominent in patients with particular depressive symptoms and stroke lesion locations, suggesting the need for tailored treatment strategies.

Background: Ischemic stroke with atrial fibrillation (AF) may recur despite appropriate treatment. It may be AF-related or AF-unrelated. We compared the factors associated with AF-related and AF-unrelated recurrences among ischemic stroke patients with AF. Methods: Patients with ischemic stroke and AF were enrolled from 11 centers in Korea. Ischemic stroke recurrence was classified as AF-related if the lesion pattern was compatible with cardioembolism without significant stenosis or as AF-unrelated if the lesion was more likely due to small vessel disease or arterial stenosis. Factors associated with stroke recurrence (AF-related and AF-unrelated) were investigated. Results: Among the 2,239 patients, 115 (5.1%) experienced recurrence (75 AF-related and 40 AF-unrelated). Factors independently associated with any stroke recurrence included AF diagnosed before stroke, small subcortical infarctions, and small scattered lesions in a single vascular territory. Type of AF was associated with the type of stroke recurrence, with persistent AF being associated with AF-related stroke [hazard ratio (HR) = 2.94, 95% confidence interval (CI) 1.69-5.26; p < 0.001]. By contrast, paroxysmal AF (HR = 3.76, 95% CI 1.56-9.04; p = 0.003), AF diagnosed before stroke (HR = 2.38, 95% CI 1.19-4.55; p = 0.014), small scattered lesions in a single vascular territory (reference: corticosubcortical lesion, HR = 3.19, 95% CI 1.18-8.63; p = 0.022), and the use of antiplatelet agents (HR = 2.11, 95% CI 1.11-4.03; p = 0.024) were independently associated with AF-unrelated stroke. Conclusion: Persistent AF was more associated with AF-related stroke recurrence, whereas paroxysmal AF was more associated with AF-unrelated stroke recurrence. A scattered lesion in a single vascular territory may predict AF-unrelated stroke recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Hwang, Park, Kim, Choi, Jung, Yu, Kim, Oh, Song, Kim, Park, Kim, Park, Choi, Chung, Bang, Kim, Heo and Seo.)

We aimed to develop a novel prediction model for early neurological deterioration (END) based on an interpretable machine learning (ML) algorithm for atrial fibrillation (AF)-related stroke and to evaluate the prediction accuracy and feature importance of ML models. Data from multicenter prospective stroke registries in South Korea were collected. After stepwise data preprocessing, we utilized logistic regression, support vector machine, extreme gradient boosting, light gradient boosting machine (LightGBM), and multilayer perceptron models. We used the Shapley additive explanation (SHAP) method to evaluate feature importance. Of the 3,213 stroke patients, the 2,363 who had arrived at the hospital within 24 h of symptom onset and had available information regarding END were included. Of these, 318 (13.5%) had END. The LightGBM model showed the highest area under the receiver operating characteristic curve (0.772; 95% confidence interval, 0.715-0.829). The feature importance analysis revealed that fasting glucose level and the National Institute of Health Stroke Scale score were the most influential factors. Among ML algorithms, the LightGBM model was particularly useful for predicting END, as it revealed new and diverse predictors. Additionally, the effects of the features on the predictive power of the model were individualized using the SHAP method., (© 2021. The Author(s).)

Background and Purpose: Successful reperfusion therapy is supposed to be comprehensive and validated beyond the grade of recanalization. This study aimed to develop a novel scoring system for defining the successful recanalization after endovascular thrombectomy. Methods: We analyzed the data of consecutive acute stroke patients who were eligible to undergo reperfusion therapy within 24 h of onset and who underwent mechanical thrombectomy using a nationwide multicenter stroke registry. A new score was produced using the predictors which were directly linked to the procedure to evaluate the performance of the thrombectomy procedure. Results: In total, 446 patients in the training population and 222 patients in the validation population were analyzed. From the potential components of the score, four items were selected: Emergency Room-to-puncture time (T), adjuvant devices used (A), procedural intracranial bleeding (B), and post-thrombectomy reperfusion status [Thrombolysis in Cerebral Infarction (TICI)]. Using these items, the TAB-TICI score was developed, which showed good performance in terms of discriminating early neurological aggravation [AUC 0.73, 95% confidence interval (CI) 0.67-0.78, P < 0.01] and favorable outcomes (AUC 0.69, 95% CI 0.64-0.75, P < 0.01) in the training population. The stability of the TAB-TICI score was confirmed by external validation and sensitivity analyses. The TAB-TICI score and its derived grade of successful recanalization were significantly associated with the volume of thrombectomy cases at each site and in each admission year. Conclusion: The TAB-TICI score is a valid and easy-to-use tool to more comprehensively define successful recanalization after endovascular thrombectomy in acute stroke patients with large vessel occlusion., Competing Interests: W-KS received honoraria for lectures from Pfizer, Sanofi-Aventis, Otsuka Korea, Dong-A Pharmaceutical Co, Ltd, Beyer, Daewoong Pharmaceutical Co, Ltd, Daiichi Sankyo Korea Co, Ltd, and Boryung Pharmaceutical; a study grant from Daiichi Sankyo Korea Co, Ltd; consulting fees from OBELAB Inc.; and a stock option from JLK INSPECTION. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Seo, Nam, Chung, Kim, Kim, Bang, Kim, Kim, Jeon and Heo.)

Rationale: Very early stage blood pressure (BP) levels may affect outcome in stroke patients who have successfully undergone recanalization following intra-arterial treatment, but the optimal target of BP management remains uncertain., Aim: We hypothesized that the clinical outcome after intensive BP-lowering is superior to conventional BP control after successful recanalization by intra-arterial treatment., Sample-Size Estimates: We aim to randomize 668 patients (334 per arm), 1:1., Methods and Design: We initiated a multicenter, prospective, randomized, open-label trial with a blinded end-point assessment (PROBE) design. After successful recanalization (thrombolysis in cerebral infarction score ≥ 2 b), patients with elevated systolic BP level, defined as the mean of two readings ≥ 140 mmHg, will be randomly assigned to the intensive BP-lowering (systolic BP < 140 mm Hg) group or the conventional BP-lowering (systolic BP, 140-180 mm Hg) group., Study Outcomes: The primary efficacy outcomes are from dichotomized analysis of modified Rankin Scale (mRS) scores at three months (mRS scores: 0-2 vs. 3-6). The primary safety outcomes are symptomatic intracerebral hemorrhage and death within three months., Discussion: The OPTIMAL-BP trial will provide evidence for the effectiveness of active BP control to achieve systolic BP < 140 mmHg during 24 h in patients with successful recanalization after intra-arterial treatment., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Introduction: The aim of this study is to investigate the influence of white matter hyperintensity (WMH) on stroke severity and prognosis in patients with symptomatic carotid artery stenosis., Methods: Patients with symptomatic carotid artery stenosis were retrieved from the Samsung Medical Center stroke registry from January 2011 to December 2016. Stroke severity was categorized into three levels according to National Institutes of Health Stroke Scale (NIHSS): transient ischemic attack (TIA) or transient symptoms with infarction (TSI), mild stroke, and moderate to severe stroke. WMH volume was measured with medical image processing and visualization. The clinical outcome was assessed using the modified Rankin scale on the 90th day from which the latest onset of the neurological symptom. Logistic regression was used to predict stroke severity, and ordinal regression was used to compare the clinical outcome., Results: Among 158 patients, the numbers of patients with TIA or TSI, mild stroke, and moderate to severe stroke were 48 (30.4%), 59 (37.3%), and 51 (32.3%), respectively. The larger WMH volume was associated with moderate to severe strokes (TIA/TSI vs. moderate to severe strokes, odds ratio (OR) 2.318, 95% confidence interval (CI) 1.194-4.502, p = 0.007; mild vs. moderate to severe strokes, OR 1.972, 95% CI 1.118-3.479, p = 0.013). Patients with larger volume of WMH showed poorer clinical outcome (cutoff value: 9.71 cm 3 , OR 2.099, 95% CI 1.030-4.311, p = 0.042)., Conclusion: Our study showed that larger WMH volume is associated with more severe stroke and poorer prognosis in patients with symptomatic carotid artery stenosis., (© 2021. Fondazione Società Italiana di Neurologia.)

Aims: Lowering the low-density lipoprotein cholesterol level reduces the risk of stroke, but it has not been clear whether the stroke risk would continuously decrease by lowering low-density lipoprotein cholesterol to a very low level. The purpose of this study was to evaluate the association between achieved low-density lipoprotein cholesterol levels and stroke risk., Methods and Results: A systematic search of MEDLINE, EMBASE and Cochrane Library databases was conducted to identify randomised controlled trials that tested cholesterol-lowering pharmacological therapies and reported both achieved low-density lipoprotein cholesterol levels and stroke outcomes. A meta-regression analysis was conducted to assess the linear association between the achieved low-density lipoprotein cholesterol levels and stroke risk. In addition, we evaluated pooled estimates of low-density lipoprotein cholesterol-lowering effect stratified by achieved low-density lipoprotein cholesterol levels of active arms. A total of 222,149 participants in 23 trials (52 arms of 26 studies) were included. The meta-regression analysis showed that each 1 mmol/L decrease in the achieved low-density lipoprotein cholesterol level (down to 0.78 mmol/L) was associated with a significant reduction of 23.5% (slope 0.235, 95% confidence interval 0.007-0.464, P = 0.044) in stroke risk. Irrespective of achieved low-density lipoprotein cholesterol levels in the active arms, the effects of lowering the low-density lipoprotein cholesterol level on stroke risk were significant and consistent (test for subgroup difference, P = 0.23, I2 = 31%). However, there was no significant increase in haemorrhagic stroke risk with lower achieved low-density lipoprotein cholesterol levels., Conclusion: In this meta-analysis of randomised controlled trials, the stroke risk monotonically reduced with lowering of low-density lipoprotein cholesterol to very low levels., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The annual incidence of venous thromboembolism (VTE) is increasing, and the treatment pattern of oral anticoagulants (OACs) has changed with introduction of new oral anticoagulants (NOACs). The aims of this study were to assess the annual incidence of VTE in a Korean population and the change of treatment pattern with availability of NOACs using a population-based database., Methods: Using the Korean National Health Insurance Services database, we identified patients diagnosed with VTE between 2009 and 2016. The annual prevalence of VTE and clinical characteristics and treatment pattern were investigated. The annual incidence of VTE was calculated using direct and indirect methods using the estimated Korean population in 2009 as the reference., Results: The annual incidence of VTE in Korean has increased yearly from 23.9 per 100,000 in 2009 to 42.2 in 2016. The overall rate of OAC prescription for VTE treatment increased from 55.9% to 68% in the same time period. The rate of initiation of NOAC treatment greatly increased, particularly from 2013 onwards, with a 20-fold increase from 2009 to 2016 (2.1% vs. 54.3%)., Conclusions: The annual incidence of VTE in Korea increased by almost two-fold from 2009 to 2016. The rate of initiation of NOAC treatment has increased substantially since 2013, and these agents have surpassed VKAs as the anticoagulant of choice for VTE. This temporal pattern of OAC prescription is consistent with the current clinical guidelines, which indicate NOACs over the warfarin in patients with VTE., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2021 Korean Society of Echocardiography.)

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke., Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy., Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245])., Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events., Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3–4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed., Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00–1.56) for ASVD 1, 1.34 (95% CI, 1.02–1.76) for ASVD 2, and 1.93 (95% CI, 1.24–2.99) for ASVD 3–4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01–1.74), 1.47 (1.06–2.03), and 2.39 (1.47–3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05–1.54]) and all-cause death (1.45 [1.17–1.81])., Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.

Background and Purpose: Previous studies have assessed the relationship between cerebral vessel tortuosity and intracranial aneurysm (IA) based on two-dimensional brain image analysis. We evaluated the relationship between cerebral vessel tortuosity and IA according to the hemodynamic location using three-dimensional (3D) analysis and studied the effect of tortuosity on the recurrence of treated IA., Methods: We collected clinical and imaging data from patients with IA and disease-free controls. IAs were categorized into outer curvature and bifurcation types. Computerized analysis of the images provided information on the length of the arterial segment and tortuosity of the cerebral arteries in 3D space., Results: Data from 95 patients with IA and 95 controls were analyzed. Regarding parent vessel tortuosity index (TI; P<0.01), average TI (P<0.01), basilar artery (BA; P=0.02), left posterior cerebral artery (P=0.03), both vertebral arteries (VAs; P<0.01), and right internal carotid artery (P<0.01), there was a significant difference only in the outer curvature type compared with the control group. The outer curvature type was analyzed, and the occurrence of an IA was associated with increased TI of the parent vessel, average, BA, right middle cerebral artery, and both VAs in the logistic regression analysis. However, in all aneurysm cases, recanalization of the treated aneurysm was inversely associated with increased TI of the parent vessels., Conclusions: TIs of intracranial arteries are associated with the occurrence of IA, especially in the outer curvature type. IAs with a high TI in the parent vessel showed good outcomes with endovascular treatment.

Background and Purpose: We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion., Methods: Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization., Results: Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032)., Conclusions: The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.