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Objective: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS)., Methods: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods., Results: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2., Interpretation: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799., (© 2024 American Neurological Association.)

Background: This study explored the risk factors, neuroimaging features, and prognostic implications of nonhypertensive white matter hyperintensity (WMH) in patients with acute ischemic stroke and transient ischemic attack., Methods and Results: We included 2283 patients with hypertension and 1003 without from a pool of 10 602. Associations of moderate-to-severe WMH with known risk factors, functional outcome, and a composite of recurrent stroke, myocardial infarction, and all-cause mortality were evaluated. A subset of 351 patients without hypertension and age- and sex-matched pairs with hypertension and moderate-to-severe WMH was created for a detailed topographic examination of WMH, lacunes, and microbleeds. Approximately 35% of patients without hypertension and 65% of patients with hypertensive stroke exhibited moderate-to-severe WMH. WMH was associated with age, female sex, and previous stroke, irrespective of hypertension. In patients without hypertension, WMH was associated with initial systolic blood pressure and was more common in the anterior temporal region. In patients with hypertension, WMH was associated with small vessel occlusion as a stroke mechanism and was more frequent in the periventricular region near the posterior horn of the lateral ventricle. The higher prevalence of occipital microbleeds in patients without hypertension and deep subcortical lacunes in patients with hypertension were also observed. Associations of moderate-to-severe WMH with 3-month functional outcome and 1-year cumulative incidence of the composite outcome were significant (both P <0.01), although the latter lost significance after adjustments. The associations between WMH and outcomes were consistent across hypertensive status., Conclusions: One-third of patients without hypertension with stroke have moderate-to-severe WMH. The pathogenesis of WMH may differ between patients without and with hypertension, but its impact on outcome appears similar.

Background: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population., Methods: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed., Results: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years ( P trend =0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; P <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased ( trend <0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; P trend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased ( P trend <0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; P trend =0.04), although the difference was not significant after adjusting for sex and age., Conclusions: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress., Competing Interests: Disclosures Dr Gorelick reports grants from Amerian Telephysicians, AbbVie, and Pickus Law, outside the submitted work. Dr Bae reports grants from AstraZeneca, Bayer Korea, Bristol Myers Squibb Korea, Dong-A ST, Jeil Pharmaceutical Co, Ltd, Korean Drug Co, Ltd, Samjin Pharm, Takeda Pharmaceuticals Korea Co, Ltd, and Yuhan Corporation and people fees from Amgen Korea, Bayer, Daiichi Sankyo, JW Pharmaceutical, Hanmi Pharmaceutical Co, Ltd, Otsuka Korea, SK Chemicals, and Viatris Korea, outside the submitted work. The other authors report no conflicts.

Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated., Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype., Methods and Study Design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months., Study Outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding., Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype., Trial Registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group ( P <0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). Conclusions Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.

Background: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission., Objective: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes., Patients and Methods: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored., Results: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (P non-linearity <0.001), with substantial relationships in the no pretreatment subgroup., Conclusions: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Although elevated body mass index (BMI) is a risk factor for stroke, it appears to protect against recurrent vascular events. We tried to evaluate BMI and waist circumference (WC) as predictors of recurrent stroke and vascular events in a cohort of stroke survivors who were followed for 12 months., Materials and Methods: We analyzed the stroke registry database of 6 hospitals and recruited patients with a first-ever stroke who were admitted from January 2011 to November 2019 and had their BMI and WC measured. Cox proportional hazards models were used to compare risks of recurrent stroke and major vascular events (a composite of stroke, myocardial infarction, or vascular death) between different BMI and WC quintiles. Reference categories were patients in the lowest quintiles., Results: A total of 14 781 patients were analyzed. Patients in the second quintile of BMI had the lowest risk of recurrent stroke (adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.58-0.91); patients in the highest quintile had the lowest risk or a major vascular event (adjusted HR 0.71; 95% CI 0.58-0.86). Patients in the fourth quintile of WC had the lowest risk of recurrent stroke (adjusted HR 0.73; 95% CI 0.59-0.91) and a major vascular event (adjusted HR 0.72; 95 % CI 0.60-0.86)., Conclusions: Our results show favorable effects of excess body weight and intra-abdominal fat on avoidance of vascular events after stroke and a favorable effect of intra-abdominal fat on avoidance of recurrent stroke., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown., Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes., Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores., Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups., Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Background: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke., Methods: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed., Results: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures., Conclusions: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke., Competing Interests: Disclosures None.

Background and Objectives: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location., Methods: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations., Results: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001)., Discussion: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population., Methods: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel., Results: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients., Interpretation: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782., (© 2022 American Neurological Association.)

Background: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis., Methods: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022., Conclusion: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated., Materials and Methods: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed., Results: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months., Conclusion: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Whether admission hyperglycemia is differentially associated with early vascular outcomes in acute ischemic stroke (AIS) depending on stroke subtype has been incompletely delineated., Methods: In a multicenter, prospective stroke registry, patients with AIS were categorized based on admission glucose levels into normoglycemia, moderate hyperglycemia, and severe hyperglycemia (<140mg/dl, 140-179mg/dl, and ≥180mg/dl, respectively) groups. Multivariate analysis assessed the interaction between the hyperglycemia and ischemic stroke subtypes of large artery atherothrombosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) and early vascular outcomes (3-month stroke, all-cause mortality, and composite of stroke, MI, and all-cause mortality)., Results: Among the 32,772 patients (age:69.0±12.6yrs, male:58.4%) meeting eligibility criteria, 61.9% were in the normoglycemia group, 19.5% were in the moderate hyperglycemia group, and 18.7% were in the severe hyperglycemia group. Substantial interactions between hyperglycemia groups and stroke subtypes were observed for 3-month stroke (P interaction  = 0.003) and composite of stroke, MI, and all-cause mortality (P interaction  = 0.001), with differential recurrence strongest among CE, intermediate among LAA, and least among SVO., Conclusions: Hyperglycemia was differently associated with the risk of 3-month stroke by ischemic stroke subtype. The associations of hyperglycemia with 3-month stroke were greatest in CE subtype but not in SVO subtype. These results suggest that the effect of glucose-lowering treatment after AIS may differ according to stroke subtype., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023. Published by Elsevier B.V.)

Background: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF)., Methods: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated., Results: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively ( P =0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16])., Conclusions: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Background and Purpose: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF)., Methods: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders., Results: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14)., Conclusions: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to elucidate whether low-density lipoprotein cholesterol (LDL-C) levels differentially affect functional outcomes after intravenous thrombolysis (IVT) depending on prestroke statin use. Patients with acute ischemic stroke treated with IVT were categorized into low, intermediate, and high LDL-C groups based on LDL-C levels at admission (< 100/100-130/ > 130 mg/dl, respectively). Multivariable logistic regression analyses were performed to explore the relationships between LDL-C and clinical outcomes (good outcomes at 3 months, modified Rankin Scale scores 0-2). The interaction between LDL-C levels and prestroke statin use regarding functional outcomes was investigated. Among the 4711 patients (age, 67 ± 12 years; males, 62.1%) who met the eligibility criteria, compared with the high LDL-C group, the low and intermediate LDL-C groups were not associated with good outcomes at 3 months according to the multivariable analysis. A potential interaction between the LDL-C group and prestroke statin use on good outcomes at 3 months was observed (P interaction  = 0.07). Among patients with prestroke statin use, low (aOR 1.84 [1.04-3.26]) and intermediate (aOR 2.31 [1.20-4.47]) LDL-C groups were independently associated with a greater likelihood of having a 3-month good outcome. Our study showed that LDL-C was not associated with a 3-month good outcome, but prestroke statin use could modify the influence of LDL-C levels on functional outcomes after IVT., (© 2022. The Author(s).)

This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis., Competing Interests: Authors Lesén E, Hedberg J, Tank A and Fita EG are employees of AstraZeneca. Independent of the submitted work, Bae HJ reports: grants from AstraZeneca Korea, Bayer, BMS Korea, Boehringer Ingelheim, Daichi Sankyo, Dong-A Pharmaceutical, Korean Drug Co. Ltd., Servier, Shin Poong Pharm. Co. Ltd and Yuhan Corporation; grants and personal fees from ESAI-Korea and Shire Korea Ltd; and personal fees from Amgen Asia Holding Limited, and Otsuka Korea outside the submitted work. The other authors report no conflicts., (© 2022 The Korean Academy of Medical Sciences.)

Background: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups., Methods: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups., Results: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively., Conclusions: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Background Previous literature about the effect of heart rate on poststroke outcomes is limited. We attempted to elucidate (1) whether heart rate during the acute period of ischemic stroke predicts subsequent major clinical events, (2) which heart rate parameter is best for prediction, and (3) what is the estimated heart rate cutoff point for the primary outcome. Methods and Results Eight thousand thirty-one patients with acute ischemic stroke who were hospitalized within 48 hours of onset were analyzed retrospectively. Heart rates between the 4th and 7th day after onset were collected and heart rate parameters including mean, time-weighted average, maximum, and minimum heart rate were evaluated. The primary outcome was the composite of recurrent stroke, myocardial infarction, and mortality up to 1 year after stroke onset. All heart rate parameters were associated with the primary outcome ( P 's<0.001). Maximum heart rate had the highest predictive power. The estimated cutoff point for the primary outcome was 81 beats per minute for mean heart rate and 100 beats per minute for maximum heart rate. Patients with heart rates above these cutoff points had a higher risk of the primary outcome (adjusted hazard ratio, 1.80 [95% CI, 1.57-2.06] for maximum heart rate and 1.65 [95% CI, 1.45-1.89] for mean heart rate). The associations were replicated in a separate validation dataset (N=10 000). Conclusions These findings suggest that heart rate during the acute period of ischemic stroke is a predictor of major clinical events, and optimal heart rate control might be a target for preventing subsequent cardiovascular events.

Background Although the effect of blood pressure on poststroke outcome is well recognized, the long-term trajectory of blood pressure after acute ischemic stroke and its influence on outcomes have not been studied well. Methods and Results We analyzed systolic blood pressure (SBP) measurements in 5514 patients with acute ischemic stroke at ≥2 of 7 prespecified time points during the first year after stroke among those enrolled in a multicenter prospective registry. Longitudinal SBPs were categorized using a group-based trajectory model. The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause mortality up to 1 year after stroke. The study subjects were categorized into 4 SBP trajectory groups: low (27.0%), moderate (59.5%), persistently high (1.2%), and slowly dropping (12.4%). In the first 3 groups, SBP decreased during the first 3 to 7 days and remained steady thereafter. In the slowly dropping SBP group , SBPs decreased from 182 to 135 mm Hg during the first 30 days, then paralleled the trajectory of the moderate SBP group . Compared with the reference, the moderate SBP group , the slowly dropping SBP group was at higher risk for the primary outcome (adjusted hazard ratio [HR], 1.32; 95% CI, 1.05‒1.65) and mortality (adjusted HR, 1.35; 95% CI, 1.03‒1.78). Primary outcome rates were similarly high in the persistently high SBP group . Conclusions Four 1-year longitudinal SBP trajectories were identified in patients with acute ischemic stroke. Patients in the slowly dropping SBP and persistently high SBP trajectory groups were prone to adverse cardiovascular outcomes after stroke.

Background: No study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel-aspirin) versus clopidogrel-aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke., Methods: We identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel-aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months., Results: Among 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel-aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel-aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel-aspirin group than in the other combination group (weighted HR: 0.82 (0.59-1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76-1.44)) or other combination group and the 3-month primary outcome., Conclusion: Other combined antiplatelet treatment, compared with aspirin alone or clopidogrel-aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel-aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke., Methods: This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use., Results: The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score < 3), particularly in large artery atherosclerosis stroke and cardioembolic stroke (adjusted difference = 7.2%, 95% CI = 1.8 to 12.5 and adjusted difference = 6.4%, 95% CI = 1.7 to 11.1, respectively). Pre-stroke aspirin use (vs nonuse) was associated with 85% less frequent cerebral thrombus-related susceptibility vessel sign (SVS) in large artery atherosclerosis stroke (adjusted difference = -1.4%, 95% CI = -2.1 to -0.8, p < 0.001) and was associated with ~40% lower SVS volumes, particularly in cardioembolic stroke (adjusted difference = -0.16 cm 3 , 95% CI = -0.29 to -0.02, p = 0.03). Moreover, pre-stroke aspirin use was not significantly associated with hemorrhagic transformation (adjusted difference = -1.1%, p = 0.09)., Interpretation: Pre-stroke aspirin use associates with improved functional independence in patients with first-ever ischemic large arterial stroke by reducing infarct volume and/or END, likely by decreasing thrombus burden, without increased risk of hemorrhagic transformation. ANN NEUROL 2021;90:763-776., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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 and Objectives: We evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes., Methods: Patients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models., Results: Of the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%-7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3-6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8-7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3-8.5])., Dicussion: In patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%-7.0% and differed according to the ischemic stroke subtype., (© 2021 American Academy of Neurology.)

Objective: To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intra-arterial thrombectomy (IAT)., Research Design and Methods: From the Clinical Research Center for Stroke-Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA 1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed., Results: A total of 1,351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA 1c at admission ( P = 0.02 according to HbA 1c quintiles, P = 0.003 according to an HbA 1c cutoff value of 7.0%) than in those with lower HbA 1c levels. Higher HbA 1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0-7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period., Conclusions: Prestroke glucose control with a target HbA 1c of ≤7.0% may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period., (© 2021 by the American Diabetes Association.)

Background It remains unclear whether physicians' attitudes toward timely management of elevated blood pressure affect the risk of stroke recurrence. Methods and Results From a multicenter stroke registry database, we identified 2933 patients with acute ischemic stroke who were admitted to participating centers in 2011, survived at the 1-year follow-up period, and returned to outpatient clinics ≥2 times after discharge. As a surrogate measure of physicians' attitude, individual treatment intensification (TI) scores were calculated by dividing the difference between the frequencies of observed and expected medication changes by the frequency of clinic visits and categorizing them into 5 groups. The association between TI groups and the recurrence of stroke within 1 year was analyzed using hierarchical frailty models, with adjustment for clustering within each hospital and relevant covariates. Mean±SD of the TI score was -0.13±0.28. The TI score groups were significantly associated with increased risk of recurrent stroke compared with Group 3 (TI score range, -0.25 to 0); Group 1 (range, -1 to -0.5), adjusted hazard ratio (HR) 13.43 (95% CI, 5.95-30.35); Group 2 (range, -0.5 to -0.25), adjusted HR 4.59 (95% CI, 2.01-10.46); and Group 4 (TI score 0), adjusted HR 6.60 (95% CI, 3.02-14.45); but not with Group 5 (range, 0-1), adjusted HR 1.68 (95% CI, 0.62-4.56). This elevated risk in the lowest TI score groups persisted when confining analysis to those with hypertension, history of blood pressure-lowering medication, no atrial fibrillation, and regular clinic visits and stratifying the subjects by functional capacity at discharge. Conclusions A low TI score, which implies physicians' therapeutic inertia in blood pressure management, was associated with a higher risk of recurrent stroke. The TI score may be a useful performance indicator in the outpatient clinic setting to prevent recurrent stroke.

Objective: To improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS)., Methods: In this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed., Results: ND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24-48 hours, and 0.66 within 72-96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3-6) at 3 months and 1 year were 1.75 (1.70-1.80) and 1.70 (1.65-1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45-1.74)., Conclusions: ND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke., (© 2020 American Academy of Neurology.)

Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictive risk score for future vascular events, the Essen Stroke Risk Score (ESRS). A total of 2348 patients (age, 69 ± 11 years; male, 57.7%) were analyzed, and 55.3%, 25.3% and 19.4% were treated with clopidogrel-aspirin, aspirin and clopidogrel, respectively. While the likelihood of choosing clopidogrel-aspirin increased as the ESRS increased, the likelihood of choosing aspirin decreased as the ESRS increased (P trend  < 0.001). The ESRS category (0-1/2-3/ ≥ 4) modified the effect of antiplatelet regimens for 1-year vascular events (P interaction  < 0.01). Among patients with ESRS ≥ 4, clopidogrel-aspirin (HR 0.47 [0.30-0.74]) and clopidogrel (HR 0.30 [0.15-0.60]) significantly reduced the risk of outcome events. Our study showed that more than half of the patients with aspirin failure were treated with clopidogrel-aspirin. In particular, a higher ESRS, which indicates an increased risk of recurrent stroke, was associated with the choice of clopidogrel-aspirin rather than aspirin.

Objective: It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population., Methods: Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes., Results: Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers ( p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death., Conclusion: Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin., (© 2020 American Academy of Neurology.)

Background and Purpose- We evaluated whether hemoglobin concentration at admission was associated with stroke recurrence and composite vascular events (stroke, myocardial infarction, and vascular death) in acute ischemic stroke. Methods- We collected data from patients with acute ischemic stroke or transient ischemic attack from a multicenter stroke registry database in Korea. The association of hemoglobin concentration with 1-year stroke recurrence and composite vascular events was evaluated with respect to age, presence of cerebral artery stenosis, stroke severity, and stroke subtype. Results- Hemoglobin levels were inversely associated with stroke recurrence and composite vascular events. One-year rates of stroke recurrence and composite vascular events were significantly higher in patients with anemia or moderate anemia. In multivariable analyses, moderate anemia remained an independent predictor of stroke recurrence (adjusted hazard ratio, 1.43 [95% CI, 1.16-1.75]) and composite vascular events (adjusted hazard ratio, 1.26 [95% CI, 1.07-1.48]). Moderate anemia increased the risk of composite vascular events in patients with mild-to-moderate stroke severity (National Institutes of Health Stroke Scale score <16, P =0.01 for interaction). Conclusions- Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.

Objective: Stroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials., Methods: We analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score., Results: Between January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0-5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score ( p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke., Conclusions: We show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care., (© 2020 American Academy of Neurology.)

Background: Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected., Methods: From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database., Results: Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively., Conclusions: Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality ( P <0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence ( P >0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

Background: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms., 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 for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex., Results: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009)., Conclusion: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed., (© 2020 S. Karger AG, Basel.)

Background Off-hour presentation can affect treatment delay and clinical outcomes in endovascular therapy (EVT) for acute ischemic stroke. We aimed to examine the treatment delays and clinical outcomes of EVT between on- and off-hour admission and to evaluate the effect of hospital procedure volume and the number of neurointerventionalists on off-hour EVT. Methods and Results From a multicenter registry, we identified patients who were treated with EVT within 12 hours of symptom. Annual hospital procedure volume was divided as low (<30), medium (30-60), and high (>60). The effect of the number of neurointerventionalists and annual hospital procedure volume on clinical outcome was estimated by the generalized estimation equation. Of the 31 133 stroke patients, 1564 patients met the eligibility criteria (mean age: 69±12 years; median baseline National Institutes of Health stroke scale score, 15 [interquartile range, 10-19]). Of 1564 patients, 893 (57.1%) arrived during off-hour. The off-hour patients had greater median door-to-puncture time (110  versus 95 minutes; P <0.001) compared with on-hour patients. Despite the treatment delay, the functional outcome at 3 months did not differ between off- and on-hour (odds ratio with 95% CI for 3-month modified Rankin Scale 0-2, 0.99 [0.78-1.25]; P =0.90). The presence of three neurointerventionalists was significantly associated with favorable outcomes at 3 months during on- and off-hour (2.07 [1.53-2.81]; P <0.001). The association was not observed for annual hospital procedural volume and the functional outcomes. Conclusions The number of neurointerventionalists was more crucial to effective around-the-clock EVT for acute stroke patients than hospital procedural volume.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel plus aspirin (DAPT) with that of aspirin monotherapy (AM) in patients with acute, nonminor, and noncardioembolic stroke. Methods- Using a prospective, nationwide, multicenter stroke registry database, acute (within 24 hours of onset), nonminor (baseline National Institutes of Health Stroke Scale score, 4-15), and noncardioembolic stroke patients were identified. Propensity scores using inverse probability of treatment weighting were used to adjust baseline imbalances between the DAPT and AM groups. A primary outcome measure was a composite of all types of stroke (ischemic and hemorrhagic), myocardial infarction, and all-cause mortality within 3 months of stroke onset. Results- Among the 4461 patients meeting the eligibility criteria (age, 69±13 years; men, 57.7%), 52.5% (n=2340) received AM, and 47.5% (n=2121) received DAPT. The primary outcome event was not significantly different between the DAPT group and the AM group (20.9% versus 22.6%, P =0.13). The event rates of all types of stroke were also not different between the 2 groups (19.3% versus 20.1%, P =0.35), while all-cause mortality was significantly lower in the DAPT group than in the AM group (3.4% versus 4.9%, P =0.02). In the propensity-weighted Cox proportional hazards models with robust estimation, DAPT did not reduce the risk of the primary outcome event (hazards ratio, 0.91; 95% CI, 0.79-1.04) but did reduce the risk of all-cause mortality (0.69; 0.49-0.97). There was no treatment heterogeneity among the predefined subgroups, although the potential benefits of DAPT were suggested in subpopulations of moderate-to-severe relevant arterial stenosis and relatively severe deficits (National Institutes of Health Stroke Scale score, 12-15). Conclusions- Compared to AM, clopidogrel plus aspirin did not reduce the risk of the primary outcome event during the first 3 months after a nonminor, noncardioembolic, ischemic stroke.

Noninvasive and precise stem cell tracking after transplantation in living subject is very important to monitor both stem cell destinations and their in vivo fate, which is closely related to their therapeutic efficacy. Herein, we developed bicyclo[6.1.0]nonyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-NPs) as a delivery system of dual-modal stem cell imaging probes. Near-infrared fluorescent (NIRF) dye Cy5.5 was chemically conjugated to the BCN-NPs, and then oleic acid-coated superparamagnetic iron oxide nanoparticles (OA-Fe 3 O 4 NPs) were encapsulated into BCN-NPs, resulting in Cy5.5-labeled and OA-Fe 3 O 4 NP-encapsulated BCN-NPs (BCN-dual-NPs). For bioorthogonal labeling of human adipose-derived mesenchymal stem cells (hMSCs), first, hMSCs were treated with tetra-acetylated N -azidoacetyl-d-mannosamine (Ac 4 ManNAz) for generating azide (-N 3 ) groups onto their surface via metabolic glycoengineering. Second, azide groups on the cell surface were successfully chemically labeled with BCN-dual-NPs via bioorthogonal click chemistry in vitro . This bioorthogonal labeling of hMSCs could greatly increase the cell labeling efficiency, safety, and imaging sensitivity, compared to only nanoparticle-derived labeling technology. The dual-modal imaging-guided precise tracking of bioorthogonally labeled hMSCs was tested in the photothrombotic stroke mouse model via intraparenchymal injection. Finally, BCN-dual-NPs-labeled hMSCs could be effectively tracked by their migration from the implanted site to the brain stroke lesion using NIRF/ T 2 -weighted magnetic resonance (MR) dual-modal imaging for 14 days. Our observation would provide a potential application of bioorthogonally labeled stem cell imaging in regenerative medicine by providing safety and high labeling efficiency in vitro and in vivo .

Background: Using data from a large national stroke registry, we aimed to investigate the incidence and determinants of in-hospital and post-discharge recovery after acute ischemic stroke and the independence of their occurrence., Methods: In-hospital recovery was defined as an improvement of 4 points or > 40% in the National Institutes of Health Stroke Scale (NIHSS) score from admission to discharge. Post-discharge recovery was defined as any improvement in the modified Rankin Scale (mRS) score from discharge to 3 months after stroke onset. Two analytic methods (multivariate and multivariable logistic regression) were applied to compare the effects of 18 known determinants of 3-month outcome and to verify whether in-hospital and post-discharge recovery occur independently., Results: During 54 months, 11,088 patients with acute ischemic stroke meeting the eligibility criteria were identified. In-hospital and post-discharge recovery occurred in 36% and 33% of patients, respectively. Multivariate logistic regression with an equality test for odds ratios showed that 7 determinants (age, onset-to-admission time, NIHSS score at admission, blood glucose at admission, systolic blood pressure, smoking, recanalization therapy) had a differential effect on in-hospital and post-discharge recovery in the way of the opposite direction or of the same direction with different degree (all P values < 0.05). Both in-hospital and post-discharge recovery occurred in 12% of the study population and neither of them in 43%. The incidence of post-discharge recovery in those with in-hospital recovery was similar to that in those without (33.8% vs. 32.7%, respectively), but multivariable analysis showed that these 2 types of recovery occurred independently., Conclusion: Our findings suggest that, in patients with acute ischemic stroke, in-hospital and post-discharge recovery may occur independently and largely in response to different factors., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Objective: To define the role and risks associated with white matter hyperintensity (WMH) load in a stroke population with respect to recurrent stroke and mortality after ischemic stroke., Methods: A total of 7,101 patients at a network of university hospitals presenting with ischemic strokes were followed up for 1 year. Multivariable Cox proportional hazards model and competing risk analysis were used to examine the independent association between quartiles of WMH load and stroke recurrence and mortality at 1 year., Results: Overall recurrent stroke risk at 1 year was 6.7%/y, divided between 5.6%/y for recurrent ischemic and 0.5%/y for recurrent hemorrhagic strokes. There was a stronger association between WMH volume and recurrent hemorrhagic stroke by quartile (hazard ratio [HR] 7.32, 14.12, and 33.52, respectively) than for ischemic recurrence (HR 1.03, 1.37, and 1.61, respectively), but the absolute incidence of ischemic recurrence by quartile was higher (3.8%/y, 4.5%/y, 6.3%/y, and 8.2%/y by quartiles) vs hemorrhagic recurrence (0.1%/y, 0.4%/y, 0.6%/y, and 1.3%/y). All-cause mortality (10.5%) showed a marked association with WMH volume (HR 1.06, 1.46, and 1.60), but this was attributable to nonvascular rather than vascular causes., Conclusions: There is an association between WMH volume load and stroke recurrence, and this association is stronger for hemorrhagic than for ischemic stroke, although the absolute risk of ischemic recurrence remains higher. These data should be helpful to practitioners seeking to find the optimal preventive/treatment regimen for poststroke patients and to individualize risk-benefit ratios., (© 2019 American Academy of Neurology.)

Background: Patients who survive an acute phase of stroke are at risk of falls and fractures afterwards. However, it is largely unknown how frequent fractures occur in the Asian stroke population., Methods: Patients with acute (< 7 days) ischemic stroke who were hospitalized between January 2011 and November 2013 were identified from a prospective multicenter stroke registry in Korea, and were linked to the National Health Insurance Service claim database. The incidences of fractures were investigated during the first 4 years after index stroke. The cumulative incidence functions (CIFs) were estimated by the Gray's test for competing risk data. Fine and Gray model for competing risk data was applied for exploring risk factors of post-stroke fractures., Results: Among a total of 11,522 patients, 1,616 fracture events were identified: 712 spine fractures, 397 hip fractures and 714 other fractures. The CIFs of any fractures were 2.63% at 6 months, 4.43% at 1 year, 8.09% at 2 years and 13.00% at 4 years. Those of spine/hip fractures were 1.11%/0.61%, 1.88%/1.03%, 3.28%/1.86% and 5.79%/3.15%, respectively. Age by a 10-year increment (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.17-1.30), women (HR, 1.74; 95% CI, 1.54-1.97), previous fracture (HR, 1.72; 95% CI, 1.54-1.92) and osteoporosis (HR, 1.44; 95% CI, 1.27-1.63) were independent risk factors of post-stroke fracture., Conclusion: The CIFs of fractures are about 8% at 2 years and 13% at 4 years after acute ischemic stroke in Korea. Older age, women, pre-stroke fracture and osteoporosis raised the risk of post-stroke fractures., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

Background and Purpose- Two large-scale randomized controlled trials of recurrent stroke prevention suggest that dual antiplatelet therapy with clopidogrel plus aspirin is beneficial for prevention of subsequent ischemic events. There is a paucity of data, however, on the efficacy or effectiveness of such an approach in the treatment of stroke patients with symptomatic large artery atherosclerotic occlusive disease. Methods- We used a multicenter stroke registry database (Clinical Research Collaboration for Stroke in Korea) to analyze acute ischemic stroke patients due to large artery atherosclerotic occlusive disease who were treated with aspirin alone or combination of clopidogrel and aspirin from May 2008 to May 2015. The results were analyzed by intention-to-treat, per-protocol, and as-treated methodologies. The primary end point was the 1-year composite outcome of stroke recurrence, myocardial infarction, and all-cause death. To balance the differences between groups, a frailty model using propensity scores and inverse probability of treatment weighting was used. Results- A total of 5934 patients with symptomatic large artery atherosclerotic occlusive disease were treated either with clopidogrel plus aspirin (n=2903, 49%) or aspirin (n=3031, 51%). The frequency of the primary outcome was 12% (n=353) in the clopidogrel-aspirin group and 14% (n=410) in the aspirin group. The hazards of the primary outcome with combination over aspirin only were significantly reduced in the per-protocol and as-treated analyses (hazard ratio, 0.71; 95% CI, 0.57-0.88; P=0.002 and hazard ratio, 0.81; 95% CI, 0.69-0.96; P=0.02, respectively), but there was borderline significance in the intention-to-treat analysis (hazard ratio, 0.86; 95% CI, 0.74-1.01; P=0.06). Combination therapy was beneficial for all-cause death in all analyses but did not reduce recurrent stroke. Conclusions- Compared with patients receiving aspirin monotherapy, the primary outcome seemed to occur less frequently in patients receiving dual antiplatelet therapy, which is explained mainly by the decrease of all-cause death. Since this is a nonrandomized, retrospective, observational study, our study should be cautiously interpreted.

Rationale: After a stroke, patients frequently experience altered systemic immunity resulting in peripheral immunosuppression and higher susceptibility to infections, which is at least partly attributed to lymphopenia. The mechanisms that profoundly change the systemic leukocyte repertoire after stroke are incompletely understood. Emerging evidence indicates that stroke alters hematopoietic output of the bone marrow., Objective: To explore the mechanisms that lead to defects of B lymphopoiesis after ischemic stroke., Methods and Results: We here report that ischemic stroke triggers brain-bone marrow communication via hormonal long-range signals that regulate hematopoietic B lineage decisions. Bone marrow fluorescence-activated cell sorter analyses and serial intravital microscopy indicate that transient middle cerebral artery occlusion in mice arrests B-cell development beginning at the pro-B-cell stage. This phenotype was not rescued in Myd88 -/- and TLR4 -/- mice with disrupted TLR (Toll-like receptor) signaling or after blockage of peripheral sympathetic nerves. Mechanistically, we identified stroke-induced glucocorticoid release as the main instigator of B lymphopoiesis defects. B-cell lineage-specific deletion of the GR (glucocorticoid receptor) in CD19-Cre loxP Nr3c1 mice attenuated lymphocytopenia after transient middle cerebral artery. In 20 patients with acute stroke, increased cortisol levels inversely correlated with blood lymphocyte numbers., Conclusions: Our data demonstrate that the hypothalamic-pituitary-adrenal axis mediates B lymphopoiesis defects after ischemic stroke.

Background and Purpose- Randomized trials comparing the use of multimodal magnetic resonance imaging (MRI) to multimodal computed tomography (CT)/ CT angiography (CTA) for selecting candidates for endovascular therapy (EVT) have not been reported. This study aimed to elucidate whether MRI-based selection for EVT is safe and effective within and after a 6-hour time window compared with conventional CTA-based selection. Methods- Data from a prospective, nationwide, multicenter stroke registry were analyzed. Workflow timelines were compared between patients selected for EVT based on MRI (the MRI group) and CTA (the CTA group). Multivariable ordinal and binary logistic regression analyses were performed to explore the relationships between decision imaging for EVT and clinical outcomes, including good and excellent outcomes (modified Rankin Scale scores of 0-2 and 0-1, respectively) at 3-month, modified Rankin Scale score distributions and safety outcomes (symptomatic intracranial hemorrhage [SICH] and mortality). Results- Ultimately, 1265 patients (age, 69±12 yrs; men, 55%) were enrolled in this study. The median National Institutes of Health Stroke Scale score was 15 (11-19). All workflow time metrics were significantly delayed in the MRI group compared with the CTA group. There was no difference in good 3-month outcomes in patients arriving within 6 hours of onset between the MRI and CTA groups (38.1% versus 38.5%), but SICH and mortality rates were lower in the MRI group than the CTA group (3.8% versus 7.7%, P=0.01 for SICH; 15.4% versus 20.9%, P=0.04 for mortality). In the multivariable analysis, decision imaging was not significantly associated with 3-month functional outcomes (all P>0.1) or mortality ( P=0.051); however, the MRI group was less likely to develop SICH than the CTA group ( P=0.01; odds ratio, 0.34 [95% CI, 0.17-0.77]). Conclusions- Our study found MRI-based selection for EVT was not associated with improving functional outcome compared with CT-based selection, but may be better at reducing the risk of SICH, despite the delays in all workflow time metrics.

Background: Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT., Methods: Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b-3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3-6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age., Results: Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12 h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ≤5, 34.6% in 6-10, 58.9% in 11-20, and 63.8% in > 20 (p < 0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction < 0.001): 0.1% in NIHSS ≤5, 18.6% in 6-10, 28.7% in 11-20, and 34.3% in > 20., Conclusions: EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.

Background and Purpose- Blood pressure dynamics in patients with acute ischemic stroke may serve as an important modifiable and prognostic factor. Methods- A total of 8376 patients with acute ischemic stroke were studied from a prospective multicenter registry. Patients were eligible if they had been admitted within 24 hours of symptom onset and had ≥5 systolic blood pressure (SBP) measurements during the first 24 hours of hospitalization. SBP trajectory groups in the first 24 hours were identified using the TRAJ procedure in SAS software with delta-Bayesian Information Criterion and prespecified modeling parameters. Vascular events, including recurrent stroke, myocardial infarction, and death, were prospectively collected. The risk of having vascular events was calculated using the frailty model to adjust for clustering by hospital. Results- The group-based trajectory model classified patients with acute ischemic stroke into 5 SBP trajectory groups: low (22.3%), moderate (40.8%), rapidly stabilized (11.9%), acutely elevated (18.5%), and persistently high (6.4%) SBP. The risk of having vascular events was increased in the acutely elevated (hazard ratio, 1.28 [95% confidence interval, 1.12-1.47]) and the persistently high SBP groups (hazard ratio, 1.67 [95% confidence interval, 1.37-2.04]) but not in the rapidly stabilized group (hazard ratio, 1.13 [95% confidence interval, 0.95-1.34]), when compared with the moderate SBP group. Conclusions- SBP during the first 24 hours after acute ischemic stroke may be categorized into distinct trajectory groups, which differ in relation to stroke characteristics and frequency of subsequent recurrent vascular event risks. The findings may help to recognize potential candidates for future blood pressure control trials.

Background: We investigated whether left ventricular filling pressure is associated with arterial occlusion in patients with ischemic stroke related to atrial fibrillation (AF)., Methods: Ninety-nine patients with AF-related stroke were included. Left ventricular filling pressure was assessed by E (early mitral inflow velocity)/e' (early diastolic velocity of the mitral valve annulus velocity) ratio based on tissue Doppler echocardiography. Arterial occlusion was evaluated by computed tomography or magnetic resonance angiography. In addition, the presence of a hyperdense middle cerebral artery sign (HMCAS) on noncontrast brain computed tomography, a marker of acute thrombus burden, was assessed. Multiple logistic regression was used to evaluate the association of E/e' with arterial occlusion and the HMCAS., Results: The mean age was 73.2 (±10.2), and 56% were men. Thirty-six (36.4%) patients had arterial occlusion on imaging. E/e' ratios were independently associated with arterial occlusion with an odds ratio of 1.24 (per 1 increase, 95% confidence interval 1.11-1.38). The receiver operating characteristics curve demonstrated that E/e' ratios have an excellent discriminatory capacity in predicting arterial occlusion with an area under the curve of .77 (P < .001). In addition, E/e' ratios were higher in patients with HMCAS than in those without (19.1 versus 14.0, P < .001)., Conclusion: E/e' ratios were associated with arterial occlusion in AF-related stroke and may play a role in identifying patients at high risk of severe stroke., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: Selective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery., Methods: This was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke. Patients with no/minimal disability initially (modified Rankin Scale (mRS) 0-1) were excluded. Of the participants, 301 underwent genetic studies of the STin2 (a variable number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes) and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of SERT. We explored whether neurological function (National Institutes of Health Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT polymorphisms within each treatment arm (escitalopram and placebo)., Results: Among the escitalopram users (n=159), neurological function in subjects with STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2 12/10 independently predicted a good clinical outcome (mRS 0-1) (OR 2.99, 95% CI 1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not associated with neurological recovery in any treatment group., Conclusion: STin2 VNTR polymorphisms may be associated with poststroke neurological recovery after SSRI therapy. Further studies are needed to identify the role of serotonin in neurological recovery after stroke., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Purpose: This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events., Methods: Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively., Results: Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P =0.004) and secondary ( P <0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant ( P <0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively., Conclusions: Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters., (© 2017 American Heart Association, Inc.)

Background and Purpose: Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea., Methods: Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge., Results: Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy., Conclusions: Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea., (© 2017 American Heart Association, Inc.)