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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.

Introduction: Post-stroke statin therapy is known to reduce subsequent major vascular events in patients with ischemic stroke. However, the efficacy of statin therapy in acute ischemic stroke patients with low low-density lipoprotein cholesterol (LDL-C) at baseline is not well defined. This study aimed to determine whether statin therapy would be beneficial in stroke patients with low or well-controlled LDL-C at baseline. Methods: We assessed ischemic stroke patients with baseline LDL-C Results: A total of 3,350 patients (mean age 68.6 ± 13.9 years; 62.9% male; 21.5% with previous statin therapy; 37.0% with atherosclerotic stroke) were included. The mean baseline LDL-C of the patients was 73.6 ± 17.6mg/dL, which did not differ between patients with or without post-stroke statin therapy (74.0 ± 17.7mg/dL in statin users; 73.4 ± 17.6mg/dL in statin non-users). Statins were prescribed in 2,638 (78.8%) after stroke and LDL-C was significantly reduced in patients who received statin therapy (65.9 ± 21.7mg/dL in statin users; 80.2 ± 26.7mg/dL in statin non-users). Statin therapy was significantly associated with a lower risk of major vascular events (adjusted hazard ratios (aHR) 0.37 [95% confidence interval (CI) 0.31 - 0.46]). However, post-stroke LDL-C reduction (aHR 1.00 [95% CI 0.995 - 1.01]), percent LDL-C reduction (aHR 0.999 [95% CI 0.996 - 1.003]) and achieved LDL-C Conclusions: Post-stroke statin therapy was associated with a reduction in major vascular events after acute ischemic stroke, even in patients with low or well-controlled LDL-C. However, achieved LDL-C levels were not associated with post-stroke major vascular events in this population.

Purpose: The usefulness of the existing risk stratification tools for atrial fibrillation (AF) is limited in predicting stroke recurrence in patients with acute ischemic stroke (AIS). Neuroimaging parameters obtained from diagnostic work-up of AIS could offer more elaborate prediction. Methods: A multicenter prospective cohort of AIS patients with AF recruited from 14 university hospitals or regional stroke centers were followed up for recurrent ischemic stroke (RIS) and a composite of all stroke and TIA. Neuroimaging features were derived from acute and chronic infarction patterns, and SVD markers such as lacunes, CMBs, and WMH. Cumulative incidences according to each neuroimaging parameter were estimated and compared using the Kaplan-Meier method with log-rank test and multivariable cause-specific hazard models with death as a competing risk. Results: A total of 2,270 patients were followed up for 431 days (IQR, 365-735), during which 111 RISs and 130 composite outcomes occurred. In unadjusted analysis, lesion multiplicity among acute infarction patterns, the presence of chronic non-lacunar infarction, and the presence of lacunes among SVD markers increased the risk of RIS significantly (Table). Other neuroimaging features such as territory multiplicity and location, confluency, topography, and size of acute lesions, lesion multiplicity, territory multiplicity, confluency, topography, and size of chronic infarction, number of lacunes, presence of CMBs, and WMH did not affect the incidence of RIS. The adjusted hazard ratios of lesion multiplicity of acute infarction, chronic infarction and lacunes were 1.45 (95% CI, 0.99-2.11), 1.57 (1.06-2.34) and 1.97 (1.30-2.98) for RIS, respectively. Similar findings were obtained for the composite outcome. Conclusions: Several neuroimaging markers were associated with recurrent ischemic stroke in AIS with AF. This could pave the way to a new stratification scheme for AF including neuroimaging parameters.

Introduction: Tricuspid regurgitation (TR) is a common valvular heart disease and traditionally known to develop secondary to cardiopulmonary comorbidities. Since isolated TR without structural heart disease are known to be related with poor outcome, clinical course of TR itself has been focused recently. However, relationship between TR and ischemic stroke had not been investigated. In this study, we aimed to explore the association between characteristics of TR and subtypes of ischemic stroke. Methods: Patients with ischemic stroke who were admitted to a single tertiary hospital from 2011 to 2020 were screened. Subtypes of stroke were divided into two groups (cardioembolic (CE) and non-CE). Echocardiographic indices including E/e’ ratio, left ventricular (LV) ejection fraction, left atrial volume index (LAVI), right ventricular systolic pressure, severity of valvular heart diseases (no/trivial, mild, moderate/severe) were assessed. Logistic regression models were constructed to determine the association of severity, subtypes of TR and CE stroke. Modifying effects of demographic characteristics and echocardiographic indices were also tested. Results: Among 6,472 consecutive patients with ischemic stroke, 12.5% of patients had TR and CE stroke was diagnosed in 24.7%. Patients with CE stroke were related to impaired LV systolic and diastolic function, pulmonary hypertension, and elevated LAVI. TR was more frequently observed in CE stroke group (6.2% vs. 32.7%, p -value < 0.01). After adjustment for covariates which were selected from bivariate analysis, TR shown significant association with CE stroke (OR [95% CI], 3.24 [2.61 - 4.02]). This association persisted across models which subdivided TR according to severity (mild TR, 2.91 [2.32 - 3.64]; moderate/severe TR, 5.58 [3.62 - 8.61]) and presence of cardiopulmonary comorbidities (isolated TR 2.04 [1.59 - 2.63]; non-isolated TR 2.15 [1.57 - 2.96]). There were no significant interactions for any of the predefined potential effect modifiers. Conclusions: Our study demonstrated that TR has significant association with CE stroke. TR related hemodynamic change within cardiac chamber and accompanying atrial cardiopathy might be an underestimated risk factor for CE stroke.

Background and Purpose— The aim of this study was to explore clinical and radiological prognostic factors for long-term swallowing recovery in patients with poststroke dysphagia and to develop and validate a prognostic model using a machine learning algorithm. Methods— Consecutive patients (N=137) with acute ischemic stroke referred for swallowing examinations were retrospectively reviewed. Dysphagia was monitored in the 6 months poststroke period and then analyzed using the Kaplan-Meier method and Cox regression model for clinical and radiological factors. Bayesian network models were developed using potential prognostic factors to classify patients into those with good (no need for tube feeding or diet modification for 6 months) and poor (tube feeding or diet modification for 6 months) recovery of swallowing function. Results— Twenty-four (17.5%) patients showed persistent dysphagia for the first 6 months with a mean duration of 65.6 days. The time duration of poststroke dysphagia significantly differed by tube feeding status, clinical dysphagia scale, sex, severe white matter hyperintensities, and bilateral lesions at the corona radiata, basal ganglia, or internal capsule (CR/BG/IC). Among these factors, tube feeding status ( P P =0.001), and clinical dysphagia scale ( P =0.042) were significant prognostic factors in a multivariate analysis using Cox regression models. The tree-augmented network classifier, based on 10 factors (sex, lesions at CR, BG/IC, and insula, laterality, anterolateral territory of the brain stem, bilateral lesions at CR/BG/IC, severe white matter hyperintensities, clinical dysphagia scale, and tube feeding status), performed better than other benchmarking classifiers developed in this study. Conclusions— Initial dysphagia severity and bilateral lesions at CR/BG/IC are revealed to be significant prognostic factors for 6-month swallowing recovery. The prediction of 6-month swallowing recovery was feasible based on clinical and radiological factors using the Bayesian network model. We emphasize the importance of bilateral subcortical lesions as prognostic factors that can be utilized to develop prediction models for long-term swallowing recovery.

Background and Purpose— For patients with emergent large vessel occlusion who may not benefit from timely recanalization treatment, maintaining adequate cerebral perfusion to prevent penumbral tissue loss is a key therapeutic strategy. Cerebral perfusion should be proportional to systemic blood pressure (BP) due to the loss of autoregulation properties in ischemic brain tissue. We hypothesized that acute fluctuations in BP would lead to aggravated penumbral tissue loss in persistent large vessel occlusion. Methods— A total of 80 patients with persistent large vessel occlusion of internal carotid artery or middle cerebral artery admitted within 24 hours after onset, and with a baseline, National Institutes of Health Stroke Scale score ≥4-point were included. Baseline and follow-up (median 88 hours) magnetic resonance images were analyzed, and penumbra was defined as the T max >6 s region excluding baseline infarction. The hypoperfusion intensity ratio (T max >10 s/T max >6 s) was calculated within the penumbra. Penumbral tissue loss (%) was defined as the proportion of follow-up infarct in the penumbra. With serial BP measurements in the first 24 hours (median 29, interquartile range 26–35), BP and BP variability parameters, including BP dropmax (change from local maxima to minima), were calculated and compared. Generalized linear models were applied to examine the association between BP parameters and the penumbral tissue loss. Results— The median penumbral volume was 79.3 mL (interquartile range, 38.2–129.6) and median penumbral tissue loss was 36.7% (interquartile range, 12.0–56.1). In a multivariable analysis, systolic BP (SBP) SBP dropmax (β±SE of fourth quartile, 17.82±6.58; P value, 0.01) and diastolic BP (DBP) DBP dropmax (β±SE of fourth quartile, 14.04±6.38; P value, 0.01) were associated with increasing penumbral tissue loss, independently of age, baseline infarction and hypoperfusion intensity ratio. DBP incmax , SBP max , DBP max , SBP max-min , DBP max-min , and most of the DBP variability indices were associated with penumbral tissue loss. Conclusions— BP fluctuations, even a brief and drastic BP drop in the first 24 hours, significantly contributed to penumbral tissue loss irrespective of baseline hypoperfusion.

Background and Purpose— Automatic segmentation of cerebral infarction on diffusion-weighted imaging (DWI) is typically performed based on a fixed apparent diffusion coefficient (ADC) threshold. Fixed ADC threshold methods may not be accurate because ADC values vary over time after stroke onset. Deep learning has the potential to improve the accuracy, provided that a large set of correctly annotated lesion data is used for training. The purpose of this study was to evaluate deep learning–based methods and compare them with commercial software in terms of lesion volume measurements. Methods— U-net, an encoder-decoder convolutional neural network, was adopted to train segmentation models. Two U-net models were developed: a U-net (DWI+ADC) model, trained on DWI and ADC data, and a U-net (DWI) model, trained on DWI data only. A total of 296 subjects were used for training and 134 for external validation. An expert neurologist manually delineated the stroke lesions on DWI images, which were used as the ground-truth reference. Lesion volume measurements from the U-net methods were compared against the expert’s manual segmentation and Rapid Processing of Perfusion and Diffusion (RAPID; iSchemaView Inc) analysis. Results— In external validation, U-net (DWI+ADC) showed the highest intraclass correlation coefficient with manual segmentation (intraclass correlation coefficient, 1.0; 95% CI, 0.99–1.00) and sufficiently high correlation with the RAPID results (intraclass correlation coefficient, 0.99; 95% CI, 0.98–0.99). U-net (DWI+ADC) and manual segmentation resulted in the smallest 95% Bland-Altman limits of agreement (−5.31 to 4.93 mL) with a mean difference of −0.19 mL. Conclusions— The presented deep learning–based method is fully automatic and shows a high correlation of diffusion lesion volume measurements with manual segmentation and commercial software. The method has the potential to be used in patient selection for endovascular reperfusion therapy in the late time window of acute stroke.

Background: The significance of silent brain infarction (SBI) for stroke recurrence in acute ischemic stroke (AIS) patients with atrial fibrillation (AF) has yet to be elucidated. This study aims to evaluate SBI as an independent predictor and which characteristics of SBI are associated with stroke recurrence in AIS patients with AF. Methods: A multicenter prospective cohort recruited AIS patients with non-valvular AF from 14 centers from Oct 2017 to Dec 2018, and followed for ischemic stroke recurrence, all types of stroke and TIA, and all-cause mortality. Three patient groups; stroke patients with prior stroke history (PS), first-ever stroke with SBI [F-SBI(+)] and first-ever stroke without SBI [F-SBI(-)] were compared with Cox frailty model according to predetermined covariates. SBI subtypes; embolic-appearing pattern (EAP) and non-EAP, and SBI characteristics; size, numbers, and vascular territory involvements were assessed. Results: A total of 978 AF-AIS patients [27.5% PS, 29.1% F-SBI(+), 43.4% F-SBI(-)] were followed for 365 [348-374] days (median). Incidence of ischemic stroke recurrence in F-SBI(+) was higher than F-SBI(-), however, there was no significant difference compared to PS (p=0.860). Adjusted hazards for ischemic stroke recurrence and all kinds of stroke and TIA in F-SBI(+) were shown to be elevated [HR 3.87 (95% CI 1.53-9.16) and 2.60 (1.21-5.56)], and similar to PS [4.20 (1.73-10.24) and 2.90 (1.36-6.18)] when compared to F-SBI(-), respectively. Despite irrelevance in non-EAP SBI, a 4-fold increase of hazards in EAP SBI was observed [4.07 (1.63-10.13)]. Other SBI characteristics were not associated with outcomes. SBI and SBI features did not increase all-cause mortality. Conclusions: SBI and specifically, EAP SBI elevated stroke recurrence in AF-AIS patients as much prior stroke has increased the risk. Considering SBI to predict recurrence is suggested likewise prior stroke history is scored in AF thromboembolic risk estimation tools.

Cervical dystonia is a common issue in patients with athetoid cerebral palsy. Botulinum toxin injection to dystonic cervical muscles is a well-recognized treatment option, but it is known to be associated with dysphagia. Previously reported cases of dysphagia after botulinum toxin injection to the sternocleidomastoid muscle were related to the regional spread of toxin to the pharyngeal muscles. We report a unique case of posture-dependent dysphagia due to preactivation of the suprahyoid and infrahyoid muscles to compensate for impaired head stabilization by the weakened sternocleidomastoid muscle while swallowing. This case suggests a possible mechanism of dysphagia in patients with athetoid cerebral palsy.

OBJECTIVE The aim of this study was to investigate the association between grip strength on the unaffected side and post-stroke functional improvement. DESIGN A total of 127 patients with unilateral stroke were included in this study. Demographic data, clinical data on initial grip strength, initial National Institutes of Health Stroke Scale, admission and discharge Modified Barthel Index (MBI), and stroke profiles were retrospectively reviewed. RESULTS Univariate and multiple linear regression analyses were carried out to evaluate the predictive values of each variable. In the model for discharge MBI, age, initial National Institutes of Health Stroke Scale, grip strength on the unaffected side, lesion side, and admission MBI were shown to be independent predictors. Meanwhile, grip strength on the unaffected side, lesion side, and admission MBI had significant predictive values in the model for difference between admission and discharge MBI. CONCLUSION The current study suggests for the first time that grip strength on the unaffected side is an independent predictor for short-term functional gain and outcome after stroke. This result may change post-stroke rehabilitation strategies to emphasize exercises to prevent loss of muscle strength. In addition, this implies the possibility of a relationship between sarcopenia and post-stroke function. Further research is needed to reveal the effect of sarcopenia on stroke patients and its mechanism.

Supplemental Digital Content is available in the text., Background and Purpose— The susceptibility vessel sign (SVS) is a hypointense signal visualized because of the susceptibility effect of thrombi, sensitively detected on susceptibility-weighted magnetic resonance imaging. The relationship of SVS parameters with the stroke subtype and recanalization status after endovascular treatment remains uncertain. Methods— The data from 89 patients with acute stroke caused by anterior circulation infarcts who underwent susceptibility-weighted magnetic resonance imaging before endovascular treatment were examined. Independent reviewers, blinded to the stroke subtype and recanalization status, measured the SVS diameter, length, and estimated volume. The intra- and interrater agreements of the SVS parameters were assessed. Results— The SVS was identified in 78% of the patients. SVS was more commonly associated with cardioembolism than with noncardioembolism (P=0.01). The SVS diameter (P

To compare clinical outcomes of patients who received early initiation (24 hours) of antithrombotics with those who received standard management (antithrombotics administered ≥24 hours).A total of 712 patients who had an acute ischemic stroke and underwent IV or endovascular (intra-arterial [IA]) recanalization between July 2007 and March 2015 were selected from a prospective clinical registry. Antithrombotics were initiated by an individual clinical decision. We systemically gathered information regarding the exact timing of antithrombotic initiation from a database of the electronic barcode medication administration system.The recanalization treatment cases included in this study comprised 34% (n = 243) IV only, 32% (n = 229) IA only, and 34% (n = 240) combined IV-IA strategies. Antithrombotics were administered within 24 hours in 64% (n = 456) of the patients. Earlier initiation of antithrombotics was associated with decreased odds of having any hemorrhages (adjusted odds ratio 0.56; 95% confidence interval 0.35-0.89), but was not associated with symptomatic hemorrhages (0.85; 0.35-2.10) or modified Rankin Scale scores of 0-1 at 3 months after stroke (1.09; 0.75-1.59). Ultra-early initiation (12 hours) did not increase the odds of hemorrhagic transformation (0.26; 0.12-0.52). The effects of earlier antithrombotics on the clinical outcomes were not significantly modified by the modality of recanalization treatment.In our retrospective analysis of a prospective registry, early antithrombotic (within 24 hours after initiation) administration did not increase hemorrhages after recanalization treatment. Early antithrombotic therapy may be advantageous for a subset of stroke patients despite the current guidelines.

Background and Purpose— Wake-up stroke (WUS) represents a quarter of all ischemic strokes and may be a specific subgroup. Nocturnal desaturation secondary to sleep-disordered breathing is an independent risk factor for stroke, but the association between nocturnal desaturation and WUS remains unclear. We investigated the relationship between nocturnal desaturation using oxygen desaturation index and WUS in patients with acute stroke in the stroke unit. Methods— A total of 298 patients admitted for acute ischemic stroke to the stroke unit between July 2013 and May 2015 were enrolled. The oxygen desaturation index was calculated using pulse oximetry data sampled every 1 minute during 9 hours on the first night (10:00 pm –7:00 am ) of the stroke unit admission, and nocturnal desaturation was defined as an oxygen desaturation index of 5 at least per hour. We compared the clinical characteristics and nocturnal desaturations between patients with and without WUS. Results— Among all patients (age, 67.7±12.6 years; male, 54.4%), 26.5% patients had WUS. The proportion of nocturnal desaturation was significantly greater in patients admitted with WUS (29.1% versus 12.3%, P =0.001). The age, sex, risk factors except for hyperlipidemia, stroke severity, and stroke mechanisms were similar between the 2 groups. After adjustment for covariates, it was found that nocturnal desaturation was significantly more common in the WUS group (odds ratio, 3.25; 95% confidence interval, 1.63–6.46). Conclusions— Nocturnal desaturation was more frequently observed in patients admitted with WUS during the first night in the stroke unit. This suggests that nocturnal desaturation is a possible modifiable risk factor for the occurrence of WUS.

Backgrounds: Penumbral perfusion dynamically changes with alterations of collateral flow and systemic blood pressure. We investigated the association between acute changes of systolic blood pressures and infarct growth within penumbral area. Method: We included ischemic stroke patients 15 mL, and mismatch ratio >1.8. Perfusion quantification, 3D voxel-registration and image segmentation were done by Olea 3.0 and Analyze 12.0. Penumbra was defined as Tmax >6s lesion without infarct. Infarct growth within penumbra was defined by the infarct volume at a follow-up image. Hypoperfusion intensity ratio (HIR) was defined by the proportion of Tmax >10s within penumbra. Blood pressure change integral (BPCI) was defined by an integration of SBP initial - SBP trajectory over 24 h (Figure A). BP dropmax was defined by a maximum decrease of SBP between successive measurements. Results: Among 25 patients included (age, 71.3±13.5; male, 56%), median baseline NIHSS score was 13 (interquartile range [IQR], 8-18). Median volume of initial infarct within Tmax >6s was 16 mL (IQR, 6-58), penumbra was 80 mL (IQR, 29-138), HIR was 46% (IQR, 31-63), and infarct growth within penumbra was 26% (IQR, 11-48). Median BPCI was 157.4 mmHg·h (IQR, -76.8-566.2) and BP dropmax was 34 mmHg (IQR, 25-43). Median infarct growth was linearly associated with BPCI (β=0.022; p -value=0.03; Figure B), BP dropmax (β=0.77; p -value=0.048; Figure C), and HIR (β=0.69; p -valuedropmax increased infarct growth rate (Figure D). Conclusions: Acute decline of systemic blood pressure may aggravates penumbral perfusion and thus increase infarct growth within penumbral tissue in emergent large vessel occlusion patients without recanalization.

Background and Aims: Theranostics is an emerging concept of integrating therapy and imaging into a single platform. Intracerebral hemorrhage (ICH) causes intense inflammation by toxic effect of hematoma itself and mechanical disruption of brain tissue, which is a promising target of theranostics. We developed a novel theranostic protocells loaded with cerium oxide nanoparticles (CeNPs) for treatment and iron-oxide nanoparticles (FeNPs) for imaging. Method: We synthesized 100-nm mesoporous silica nanoparticle (MSN) as a bio-compatiable nanocarrier, incorporated FeNPs in the core and CeNPs on the surface, and encapsulated MSN with lipid bilayer. Reactive oxygen species (ROS) scavenging and cytoprotective effects of the protocells were assessed in RAW264.7 cells. Brain water content, macrophage infiltration, and behavior function (corner turn and forelimb use asymmetry) were measured in collagenase-induced rodent ICH model after injecting the protocells. Serial brain MR imaging was also performed to confirm diagnostic ability of working site of protocells. Results: The protocells were monodisperse in water and highly loaded with CeNPs, which exhibited a strong ROS scavenging (-26%, P Conclusions: As the first theranostic nanobiomaterial, our protocells successfully visualized its working site in peri-hematomal area by MR imaging, and improved inflammatory status and neurologic outcomes after ICH. Beyond its potential for ICH theranosis, protocells could be generalized to other inflammatory diseases.

Background and Aims: About 40% of patients have poor functional outcome even after modern endovascular treatment (EVT), which is strongly requiring post-EVT therapies targeting damages from ischemia-reperfusion. Futile or effective reperfusion can be a significant noise in assessing efficacy of post-EVT therapies. Thus, we investigated whether post-EVT NIHSS score better discriminates long-term outcomes after EVT. Methods: We identified 566 stroke patients who received EVT at Seoul National University Bundang Hospital between Apr 2008 and Dec 2015. We prospectively collected post-EVT NIHSS score, which was measured by on-duty physician right after completion of EVT. The prognostic values of post-EVT NIHSS score, recanalization status and other baseline profiles in discriminating favorable 3-month outcome (modified Rankin Scale 0-2) were assessed using 4 different logistic regression models (Figure). The c-statistic was used as the primary measure of model discrimination. The integrated discrimination index (IDI) and the category-free net reclassification index (NRI) were also compared. Results: The post-EVT NIHSS score was 11.8 ± 7.8 pts, which showed overall improvement of 2.3 ± 6.3 pts compared to the baseline NIHSS score (14.0 ± 7.1 pts). Any change of NIHSS score was present in 79%. Favorable 3-month outcome was achieved in 47% of patients. Based on the results of differences among the c-statistics, both model 3 and model 4 were significantly more discriminative of favorable outcome than model 1 or model 2 (Figure). Model 4 showed significant improvement of both IDI and NRI as compared to all other models, but the magnitude from model 3 to model 4 was modest (IDI, 0.021; NRI, 0.322). Conclusions: Post-EVT NIHSS score was the strongest factor in discriminating long-term outcomes after EVT, which was superior to baseline NIHSS or recanalization status. Therefore, post-EVT NIHSS score should to be considered when assessing the efficacy of post-EVT therapies.

Background and aims: Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurologic deficit. Thus, a novel therapeutic agent that directly targets brain damages after SAH is strongly required. For this purpose, we developed aminocaproic acid stabilized ceria nanoparticles (Amicar-CeNPs), which have incomparable anti-oxidative activity and biocompatibility. Methods: Uniform water-dispersed Amicar-CeNPs were prepared from short sol-gel reaction of cerium (III) ions in aqueous phase with aminocaproic acid. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of Amicar-CeNPs (0.5mg/kg) or saline control were randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade and brain water content were evaluated at 72 hours. Mortality and neurologic function were assessed for 14 days. Results: Amicar-CeNPs, 3-nm in size and with high Ce 3+ to Ce 4+ ratio, demonstrated very potent anti-oxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH model, Amicar-CeNPs significantly reduced neuronal death (1.1% vs. 90.1%; P Conclusions: Amicar-CeNPs, totally synthesized in aqueous phase, demonstrated very promising results against SAH via potent anti-oxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, Amicar-CeNPs are strongly required to be tested in SAH patients as an investigational new drug.

Background: Alcohol consumption is associated with negative consequences including liver disease, major trauma and various cancers. However, a paradoxical beneficial effect of alcohol has been documented for cardiovascular disease in a large meta-analysis. On the other hand, a similar relationship has not been consistently documented or modest for the risk of stroke due to its heterogeneity in subtypes and pathophysiology. In this context, more comprehensive approaches using a representative dataset and composite outcomes are required to clarify the differential effects of alcohol on cardio-cerebrovascular disease (CCVD). Methods: The Korean National Health Insurance Service (NHIS) is the sole provider of full-coverage health insurance for Korean citizens. NHIS-National Sample Cohort (NHIS-NSC) was a standardized cohort representative of Korean population. Based on biennial health exam at 2003 and 2004, we investigated the relationship between alcohol consumption and the incidence of CCVDs [ischemic stroke (IS), hemorrhagic stroke (HS) and myocardial infarction (MI)] and all-cause mortality until 2013, using multivariable Cox proportional hazards models. Results: Among 204,557 participants (median follow up, 9.1 years), the following events were observed: IS 3,274; HS 1,056; MI 1,065 ; and all-cause mortality 8,771 cases. The hazards for IS and MI remained below the null point for the moderate alcohol consumption, but the risk for HS increased in heavy drinkers. In composite outcome indices, moderate consumption was associated with a lower risk for CCVD and all-cause mortality; however, the risk for all-cause mortality was significantly elevated in cases of heavy drinkers. Conclusions: Alcohol consumption was associated with a decreased risk of both CCVD, specifically ischemic vascular disease, and all-cause mortality at moderate dose, but this protective relationship was offset by an increase in the risk for HS and mortality at heavy dose.

Introduction: Endovascular recanalization (EVT) for acute ischemic stroke patients with sizable penumbral tissues seems plausible even beyond 6 hours from their last seen normal (LSN), provided that there remain salvageable tissues. Methods: A total of 111 acute ischemic stroke patients were included in the analysis, who had ICA or MCA occlusion cases with baseline NIHSS score ≥6-point and arrived 6 - 12 hours after LSN. Baseline demographics, stroke information and functional outcomes were prospectively collected during routine clinical practice. Attending physicians made treatment decisions for EVT by current guidelines and institutional protocols. MR image parameters, including volume of diffusion-restrcted lesions (ADC value ≤450) and mapping of hypoperfused area (T max delay ≥6 seconds), were quantified using an automated commercial software with minimal manual operations. Binary logistic regression analysis models taking mRS score 0 - 1 at 3 months after stroke as a dependent variable were constructed. Results: Of the 111 ICA or MCA occlusion cases who arrived 6 - 12 hours after LSN, 58% had mismatch ratio of ≥1.8 at baseline and 42% had favorable imaging profiles by DEFUSE-2 study. EVT was done in 54% of cases. Three-month mRS score 0 - 1 was found in 19% and mortality in 14%. EVT was associated with significantly increased odds of having mRS score 0 - 1 at 3 months after stroke (adjusted OR, 6.15 [95% CI, 1.12 - 44.10]) after controlling for covariates. Good response to EVT was dependent upon the baseline infarct volume and time delay (Figure) Sensitivity analyses for propensity weighting, location of occlusion, preceding intravenous tPA, size of penumbral tissues showed consistent associations favoring for EVT. Conclusions: EVT is feasible and efficacious for anterior circulation occlusion with substantial neurological deficits even 6 - 12 hours after LSN. More research is warranted to target the best candidates of EVT using image parameters.

Introduction: Recent studies have consistently reported that gamma-glutamyl transferase (GGT) is correlated with higher risk of stroke independent of stroke risk factors and alcohol intake. However, it remains to be further elucidated why GGT is associated with stroke. To clarify the question, we focused on atrial fibrillation (AF), which has also been noted to have a close relationship with GGT. Hypothesis: GGT may be associated with cardioembolic stroke through AF. Methods: From a prospective stroke registry of Seoul National University Hospital, acute ischemic stroke patients who had checked GGT within 7 days from the admission were selected for analysis. The binary logistic regression was used to investigate the relationship between GGT, AF, and cardioembolic stroke. Results: Among 958 eligible patients, 134 patients (13.99%) had AF and 269 (28.08%) patients were classified as cardioembolism according to the TOAST system. GGT was significantly associated with AF in ischemic stroke patients (Adjusted OR, 2.43; 95% CI, 1.32-4.52). Patients with elevated GGT were more likely to be assigned to cardioembolism compared to other TOAST classifications, after adjustment for all potential confounders except for AF (OR, 2.14; 95% CI, 1.31-3.52). When an additional adjustment for AF was made, the increasing trend in OR according to increasing GGT quartile was lost and the association between GGT and cardioembolism was considerably attenuated, although the relationship remained significant (OR, 1.79; 95% CI, 1.01-3.2). Conclusions: GGT showed significant correlation with cardioembolic stroke, potentially owing in large part to its relationship with AF. It may be a possible answer to explain the association between GGT and stroke.

Background The current guideline recommends moderate‐ to vigorous‐intensity physical activity ( PA ) at least 40 min/day for 3 to 4 days/week. Although recent evidence has demonstrated that low‐dose PA could reduce cardiovascular mortality, the relationship between low‐dose PA and the risk of stroke remains uncertain. Methods and Results Using data from a nation‐wide sample cohort in Korea, we examined 336 326 individuals who received a general health examination between 2009 and 2010. Level of PA was assessed using a questionnaire for weekly PA frequencies regarding 3 intensity categories: light, moderate, and vigorous. Moderate‐ to vigorous‐intensity PA ( MVPA ) was classified into 4 frequency categories: none, 1 to 2, 3 to 4, or ≥5 times/week. Cox proportional hazard models were constructed to estimate the risk of stroke. During the average follow‐up of 3.6 years, 2213 stroke cases occurred. MVPA was none in 50%, 1 to 2 times/week in 20%, 3 to 4 times/week in 13%, and ≥5 times/week in 18% of the cohort. Individuals with MVPA 1 to 2 times/week had a 16% reduced risk of stroke (adjusted hazard ratio, 0.84; 95% confidence interval, 0.73–0.96) compared with those with no MVPA . The population attributable fraction of no MVPA was 12%, which was the second most important risk factor for a stroke after hypertension. Conclusions Even 1 to 2 times a week of MVPA might be beneficial to prevent a first‐ever stroke in the general population, although a quantitative validation of the questionnaire is needed. From a public health perspective, we need to encourage inactive people to start exercising with more‐achievable goals.

Introduction: Statin has the potential to be effective in the early phase of recanalization. However it is largely unknown in which group, when, and at what doses statin use is beneficial after recanalization. Methods: From a total of 7663 stroke cases of Seoul National University Bundang Hospital between July 2007 and Dec 2015, we collected eligible cases with the following inclusion criteria; (1) Lesion-documented ischemic stroke (N=6151); (2) received recanalization treatment (N=908). We excluded cases with missing in (1) the time information (N=26) and (2) modified Rankin Score (mRS) at 3 months (N=1). We gathered the exact timing, type, dose of statin use from a database of electronic bar-code medication administration system. Multivariable ordinal logistic regression was performed for mRS at 3 months (improved outcome). Results: Of the 881 analyzable cases (male, 58%; mean age, 68.9; median initial NIHSS score, 12), recanalization treatment consisted of 33% of IV-only, 33% of IA-only and 34% of combined IV-IA strategies. Stroke mechanisms were 26% of large artery atherosclerosis (LAA), 49% of cardioembolism (CE) and 25% of non-LAA/CE. Statins were administered in the acute phase (within 7 days) in 68% (n=598) patients ( Conclusions: Acute statin use after recanalization treatment may positively influence functional outcome, more in patients with IA treatment or when used within 24 hours. Low-to-moderate intensity statin may be as beneficial as high intensity statin after recanalization.

Introduction: The current stroke guideline recommends moderate- to vigorous- intensity physical activity (PA) at least 40 min/d 3 to 4d/wk. But recent evidences suggest low-level PA can also reduce cardiovascular mortality. We assessed the benefits of a range of PA to prevent incident stroke in a Korean population. Methods: From a prospective cohort data of National Health Insurance in Korea, we included 352896 individuals who received general health examination at 2009 and 2010. We excluded participants (1) with previous stroke (N=5917), (2) with incomplete data on PA (N=5155) and (3) disqualified due to death or emigration at the same year of examination (N=5498). Level of PA was assessed using questionnaire for frequencies of weekly PA in each of three intensity categories; light (≥30min/d; eg, walking), moderate (≥30min/d; eg, brisk walking) or vigorous (≥20min/d; eg, running). Moderate- to vigorous- intensity PA (MVPA) was classified into 4 categories; none, 1-2 times, 3-4 times, ≥5 times per wk. Cox proportional hazard regression was performed to assess the influence of each categories of MVPA on the risk of incident stroke. Results: In 336326 individuals (171681 men and 164645 women) with an average follow-up of 3.6 years, 2213 incident stroke cases occurred (1866 ischemic stroke and 347 intracerebral hemorrhage). MVPA was none in 50%, 1-2 times/wk in 20%, 3-4 times/wk in 13%, and ≥5 times/wk in 18% of the cohort. Multivariable analysis (adjusted for age, sex, income, alcohol, smoking, light intensity PA, hypertension, diabetes and hyperlipidemia) showed even individuals in MVPA 1-2 times/wk group had a 16% reduced risk of incident stroke (HR: 0.84, 95% CI: 0.73-0.96) compared with those in none MVPA group. MVPAs 3-4 and ≥5 times/wk were also associated with lower risk of incident stroke (0.79, 0.68-0.91 in 3-4 times/wk; 0.79, 0.70-0.89 in ≥5 times/wk). Similar results were observed in ischemic stroke, but not in intracerebral hemorrhage. Conclusions: Even 1-2 times a week of MVPA might be beneficial to prevent first-ever stroke in general population. From a public health perspective we need to encourage inactive people to do exercise with more achievable goal, considering 50% of individuals in this cohort were still physically inactive.

Introduction: Serum cystatin C has emerged as a risk factor of cardiovascular disease and death. Cystatin C is promoted a better marker of renal function compared to estimated glomerular filtration rate (GFR). However, the impact of cystatin C on the functional outcome after ischemic stroke in patients with CKD remains unclear. Hypothesis: We assessed the prognostic value of cystatin C for functional outcome after ischemic stroke in CKD patients. Methods: A consecutive 239 patients with CKD who were admitted within 7 days after ischemic stroke onset between January 2010 and February 2014 were included for analysis. An estimated GFR < 60mL/min/1.73 m 2 defined CKD. We compared the demographic information, clinical characteristics and laboratory findings including serum cystatin C level. We evaluated the short-term outcomes using a modified Rankin Scale (mRS) at three-months after onset of ischemic stroke. We divided patients into two groups with favorable outcome (mRS score ≤2) and unfavorable outcome (mRS score ≥3). Results: Among the total patients, 36.0% (n=86) patients had unfavorable outcome. These patients were mostly male (52.9%), with a mean age of 73.5 years. Older age, atrial fibrillation and history of previous stroke were significantly higher in the unfavorable outcome group. Participants with unfavorable outcome tended to have lower body mass index, higher initial NIHSS, lower estimated GFR, and higher C-reactive protein concentration. Compared to the favorable outcome group, cystatin C level was significantly higher (1.25±0.41 vs. 1.54±0.64 mg/dL, P = 0.001) in the unfavorable outcome group. After controlling for confounding factors, higher cystatin C levels were independently related to the unfavorable outcome at three-months (Odds ratio, 3.19; 95% Confidence interval, 1.02-9.96). In contrast, estimated GFR did not show any significant association with the unfavorable outcome (Odds ratio, 1.01; 95% Confidence interval, 0.96-1.06). Conclusions: In conclusion, our study showed that elevated cystatin C levels were independently associated with the unfavorable functional outcome after ischemic stroke in patients with CKD. Cystatin C may be a potent predictor of short-term functional outcome after ischemic stroke in CKD patients.