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ObjectiveTo improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS).MethodsIn 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.ResultsND 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).ConclusionsND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke.

ObjectiveStroke 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.MethodsWe 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.ResultsBetween 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.ConclusionsWe 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.

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 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.

Introduction: Although the heritability of stroke might be higher in young-age stroke population, it is even uncertain how many of them has monogenic causes of stroke. We aimed to estimate the prevalence and clinical characteristics of 15 monogenic disorders associated with stroke in a large, unselected young-age stroke population Methods: From a prospective, nationwide, multicenter, acute stroke registry of consecutive patients admitted to 15 academic or regional stroke centers in Korea, we enrolled all patients aged 55 years or younger except those who refuse to participate in this study. We performed genetic analysis using a customized targeted next-generation sequencing panel ( GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP ) to find clinically relevant genetic variants, and reviewed clinical information of the patients. Results: Genetic analysis was performed in 1,033 patients (male 70.7%, mean age 45.8±7.9). Twenty-eight clinically relevant genetic variants were identified in 131 (12.7%) patients, and were found most frequently in RNF213 (59, 5.7%) followed by ABCC6 (53, 5.1%) and NOTCH3 (15, 1.5%). Genetic variants were more commonly observed in younger group than older group (17.1% vs. 9.3%, p=0.021), but were not different according to vascular risk factor burden. Patients with premature ( Conclusion: Clinically relevant genetic variants were not uncommon than expected. We might have opportunities to improve our daily practice by genetic counseling patients and their families to reduce the future stroke.

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.

Background: Incidence of gastrointestinal (GI) bleeding after acute ischemic stroke (AIS) was reported as 1.5% during hospitalization, one-thirds of which required blood transfusion. However, it is not known about the long-term incidence and the incidence rates by period after AIS. Methods: AIS patients who were admitted to the 14 participating hospitals between 2011 and 2013 were identified using a nationwide multicenter prospective stroke registry database. GI bleeding was captured with related diagnosis codes by International Classification of Diseases-10th Revision through the linkage between the registry database and the claims data. Bleeding requiring at least 2 packs of blood transfusion was defined as major GI bleeding. Incidence rates were calculated for each period as follow; 0-30 days, 31-90 days, 91-180 days, 181-365 days, 1-2 years, 2-3years, after 3 years. Results: Of 10,818 AIS patients, 59.0% were male and mean age was 67.5 ± 12.9 years. The median follow-up duration was 3.1 (interquartile range 2.3 to 4.0) years. During 31,208 person-years, 947 patients (8.8%) had 1,224 episodes of major GI bleeding. Annual incidence rate was 3.92 per 100 person-years. The incidence rates by periods were the highest at 19.21 per 100 person-years in the first month of AIS, gradually decreased to 9.02 in one to three months, 6.18 in three to six months, and 3.48 in six to twelve months. After three years, it remained at about 2.62 events per 100 person-years. During the observation period, only one major GI bleeding occurred without recurrence in about 80% of patients, about 13% recurred twice, and about 6% of patients had three or more recurrences. In the multivariable recurrent event analysis, anemia at admission, lower eGFR below 60, and mRS at 3 months ≥4 were independently associated with higher risk of major GI bleeding during the most of the observation period above 3 years. Conclusions: Major GI bleeding, requiring transfusion, seems to occur frequently after AIS, and the risk was gradually decreased after stroke. The efforts are needed to prevent it, especially in stroke patients with anemia and decreased renal function.

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.

Clinical implications of elevated fasting triglycerides (FTGs) and non-fasting triglycerides (NFTGs) in acute ischemic stroke (AIS) remain unknown. We aimed to elucidate the correlation and clinical significance of FTG and NFTG levels in AIS patients.Using a multicenter prospective stroke registry, we identified AIS patients hospitalized within 24 hours of onset with available NFTG results. The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause mortality up to one year.This study analyzed 2,176 patients. The prevalence of fasting and non-fasting hypertriglyceridemia was 11.5% and 24.6%, respectively. Multivariate analysis revealed that younger age, diabetes, higher body mass index and initial systolic blood pressure were independently associated with both fasting and non-fasting hypertriglyceridemia (allThe fasting and non-fasting hypertriglyceridemia were prevalent in AIS patients and showed similar clinical characteristics and outcomes. High FTG and NFTG levels were not associated with occurrence of subsequent clinical events up to one year.

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 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.

Introduction: Clinical implications of elevated fasting triglycerides (FTG) and non-fasting triglycerides (NFTG) in acute ischemic stroke (AIS) remain unknown. We aimed to elucidate the correlation and clinical significance of FTG and NFTG levels in AIS patients. Methods Using a multicenter prospective stroke registry, we identified AIS patients hospitalized within 24h of onset with available NFTG results. The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause mortality up to one year. Results This study analyzed 2,176 patients. The prevalence of fasting and non-fasting hypertriglyceridemia was 11.5% and 24.6%, respectively. Multivariate analysis revealed that younger age, diabetes, higher body mass index and initial systolic blood pressure were independently associated with both fasting and non-fasting hypertriglyceridemia (all p p

Background: Although chest radiographs have not been utilised well for classifying stroke subtypes, they could provide a plethora of information on cardioembolic stroke. This study aimed to develop a deep convolutional neural network that could diagnose cardioembolic stroke based on chest radiographs. Methods: Overall, 4,064 chest radiographs of consecutive patients with acute ischaemic stroke were collected from a prospectively maintained stroke registry. Chest radiographs were randomly partitioned into training/validation (n = 3,255) and internal test (n = 809) datasets in an 8:2 ratio. A densely connected convolutional network (ASTRO-X) was trained to diagnose cardioembolic stroke based on chest radiographs. The performance of ASTRO-X was evaluated using the area under the receiver operating characteristic curve. Gradient-weighted class activation mapping was used to evaluate the region of focus of ASTRO-X. External testing was performed with 750 chest radiographs of patients with acute ischaemic stroke from 7 hospitals. Findings: The areas under the receiver operating characteristic curve of ASTRO-X were 0.86 (95% confidence interval [CI], 0.83–0.89) and 0.82 (95% CI, 0.79–0.85) during the internal and multicentre external testing, respectively. The gradient-weighted class activation map demonstrated that ASTRO-X was focused on the area where the left atrium was located. Compared with cases predicted as non-cardioembolism by ASTRO-X, cases predicted as cardioembolism by ASTRO-X had higher left atrial volume index and lower left ventricular ejection fraction in echocardiography. Interpretation: ASTRO-X, a deep neural network developed to diagnose cardioembolic stroke based on chest radiographs, demonstrated good classification performance and biological plausibility. Funding Grant No. 14–2020–046 and 08–2016–051 from the Seoul National University Bundang Research Fund and NRF-2020M3E5D9079768 from the National Research Foundation of Korea.

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.

Intravenous tissue-plasminogen activator (IV-TPA) treatment in acute ischemic stroke (AIS) patients due to small vessel occlusion (SVO) has been debated because of its small expected benefit and symptomatic intracranial hemorrhage (SICH) risk. Furthermore, data on subgroups of SVO patients are limited. From a prospective multicenter stroke registry database, AIS patients due to SVO within 24 h from onset were selected. Efficacy outcomes were 3-month modified Rankin Scale (mRS) score 0-1 proportion and mRS score distribution. Additionally, subgroup analyses were conducted by age, sex, initial National Institute Health Stroke Scale (NIHSS) score, and presenting limb paresis. This study included 2482 patients: 193 in the IV-TPA group and 2289 in the control group. After adjusting covariates, IV-TPA treatment was associated with an increased mRS 0-1 outcome (adjusted OR [95% CI], 1.56 [1.06-2.29]; P = 0.0249), but was not significantly associated with a favorable mRS shift (1.33 [0.98-1.81]; P = 0.0709). SICH and 3-month death occurred in three (1.6%) and none in the IV-TPA group versus one (0.04%) and 16 (0.7%) in the control group. In subgroup analyses, the IV-TPA effect appeared significantly greater in patients aged ≥80 versus80 for mRS score distribution (P

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.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Background and Purpose— This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods— CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results— Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67–0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63–0.92]) and all stroke events (hazard ratio, 0.74 [0.61–0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use ( P interaction =0.01) and younger age (P interaction =0.07), and absence of benefit associated with small vessel occlusion subtype ( P interaction =0.08). Conclusions— Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

Background and Purpose Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. Methods We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. Results The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis –15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes (90%). Conclusions We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.

Although the effect of blood pressure on post-stroke outcome is well-recognized, the long-term trajectory of blood pressure after acute ischemic stroke and its influence on outcomes have not yet been fully elucidated. From a multicenter prospective registry of acute ischemic stroke patients, 5,514 patients with measurements of systolic blood pressure (SBP) at more than 2 of 7 prespecified time-points, up to 1-year after stroke onset, were analyzed. Outcome measures, a composite of stroke recurrence, myocardial infarction and mortality, and each stroke recurrence and mortality, were prospectively collected up to 1-year after stroke onset. The study subjects were categorized into 4 groups according to their SBP trajectories: Low (27.0%), Moderate (59.5%), Persistently high (1.2%), and Slowly dropping (12.4%). After adjustments for pre-determined covariates, the Slowly dropping SBP Group was at higher risk of the composite outcome (hazard ratio, 1.32; 95% confidence interval, 1.05‒1.65), and mortality (1.35; 1.03‒1.78) compared to the Moderate SBP Group. Four main 1-year longitudinal SBP trajectories were identified after acute ischemic stroke. One trajectory, slowly dropping SBP, was particularly prone to adverse outcomes after stroke. These findings provide possible leads for future investigations of SBP control targets after stroke.

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.

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.

We investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21–8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93–35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06–1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (Pint = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.

Background The long‐term incidence of acute myocardial infarction (AMI) in patients with acute ischemic stroke (AIS) has not been well defined in large cohort studies of various race‐ethnic groups. Methods and Results A prospective cohort of patients with AIS who were registered in a multicenter nationwide stroke registry (CRCS‐K [Clinical Research Collaboration for Stroke in Korea] registry) was followed up for the occurrence of AMI through a linkage with the National Health Insurance Service claims database. The 5‐year cumulative incidence and annual risk were estimated according to predefined demographic subgroups, stroke subtypes, a history of coronary heart disease (CHD), and known risk factors of CHD. A total of 11 720 patients with AIS were studied. The 5‐year cumulative incidence of AMI was 2.0%. The annual risk was highest in the first year after the index event (1.1%), followed by a much lower annual risk in the second to fifth years (between 0.16% and 0.27%). Among subgroups, annual risk in the first year was highest in those with a history of CHD (4.1%) compared with those without a history of CHD (0.8%). The small‐vessel occlusion subtype had a much lower incidence (0.8%) compared with large‐vessel occlusion (2.2%) or cardioembolism (2.4%) subtypes. In the multivariable analysis, history of CHD (hazard ratio, 2.84; 95% CI, 2.01–3.93) was the strongest independent predictor of AMI after AIS. Conclusions The incidence of AMI after AIS in South Korea was relatively low and unexpectedly highest during the first year after stroke. CHD was the most substantial risk factor for AMI after stroke and conferred an approximate 5‐fold greater risk.

Background We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke. Methods We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society. Results Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes. Conclusion The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time., Graphical Abstract

Background: This study compared the effectiveness of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin with that of aspirin monotherapy (AM) in mild-to-moderate acute ischemic stroke considering the risk of recurrent stroke using the Stroke Prognosis Instrument II (SPI-II) score. Methods: This study is a retrospective analysis of data from a prospective, nationwide, multicenter stroke registry database between January 2011 and July 2018. We included patients with mild-to-moderate (National Institutes of Health Stroke Scale score ≤10), acute (within 24 hours of onset), noncardioembolic ischemic stroke. The primary outcome was a 3-month composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality. Propensity scores using the inverse probability of treatment weighting method were used to mitigate baseline imbalances between the DAPT and AM groups and within each subgroup considering SPI-II scores. Results: Among the 15 430 patients (age, 66±13 years; men, 62.0%), 45.1% (n=6960) received DAPT and 54.9% (n=8470) received AM. Primary outcome events were significantly more frequent in the AM group (16.7%) than in the DAPT group (15.5%; P =0.03). Weighted Cox proportional hazards models showed a reduced risk of 3-month primary vascular events in the DAPT group versus the AM group (hazard ratio, 0.84 [0.78–0.92]; P P interaction =0.44). However, among the high-risk patients with SPI-II scores >7, a substantially larger absolute benefit was observed for 3-month composite vascular events in the DAPT group (weighted absolute risk differences, 5.4%), whereas smaller absolute benefits were observed among patients in the low- or medium-risk SPI-II subgroups (1.7% and 2.4%, respectively). Conclusions: Treatment with clopidogrel-aspirin was associated with a reduction in 3-month vascular events compared with AM in mild-to-moderate acute noncardioembolic ischemic stroke patients. Larger magnitudes of the effects of DAPT with clopidogrel-aspirin were observed in the high-risk subgroup by SPI-II risk scores.

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 (Ptrend interaction

Introduction: Although the effect of blood pressure in post-stroke outcome is well recognized, the long-term time course of BP following acute ischemic stroke and it’s influence to outcomes have not been well elucidated. Method: From a multicenter prospective registry of acute ischemic stroke patients, a total of 5,514 patients with measurement of systolic blood pressure (SBP) in more than 2 of 7 prespecified time points up to 1 year after symptom onset were analyzed. The patients were grouped according to longitudinal SBPs of each patient using a group-based trajectory model, and number of groups were determined by the optimal delta-Bayesian Information Criterion. Outcome measures, which were stroke recurrence, mortality and composite of each events along with myocardial infarction were prospectively collected up to 1 year after symptom onset. Results: Patients were categorized into four groups according to their SBP trajectories: low (27.0%), moderate (59.5%), persistently high (1.2%), and slowly dropping (12.4%). After adjustment for pre-determined covariates, there were higher risk of stroke recurrence in persistently high SBP group (hazard ratio (HR), 2.28 [95% confidence interval (CI), 1.01-5.12]). Mortality was higher only in the slowly dropping SBP group (HR, 1.50 [95% CI, 1.09-2.05]). Composite events were higher in both persistently high (HR, 1.96 [95% CI, 1.02-3.75]) and slowing dropping (HR, 1.54 [95% CI, 1.18-2.00]) SBP groups. Conclusion: There were a group of patterns in long-term longitudinal SBP changes after acute ischemic stroke. Especially, slow BP droppers might have a distinct nature with higher mortality and would be a target for future investigations.

We investigated the effectiveness of adding antiplatelet (AP) to oral anticoagulant (OAC) treatment versus OAC treatment alone in patients with AIS with atrial fibrillation (AF) and significant large artery steno-occlusion (LASO). This study is a retrospective analysis of a nationwide, prospective, multicenter stroke registry between April 2008 and November 2017. Patients with acute (within 48 h of onset) and mild-to-moderate (NIHSS score ≤ 15) stroke with AF and concomitant LASO were identified. Antithrombotic regimens at discharge were categorized into OAC alone or OAC + AP. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 3 months of stroke. Among the 2553 patients (age, 73 ± 10 years; men, 50.4%), 78.8% were treated with OAC alone, and 21.2% were treated with OAC + AP. The primary outcome events were significantly more common in the OAC + AP group (6.7%) than the OAC alone group (4.3%) (p = 0.02). Weighted Cox proportional hazard analysis showed that OAC + AP increased the risk of 3-month primary outcome events compared with OAC alone (HR, 1.62 [1.06 to 2.46]). A potential interaction between the type of LASO and discharge antithrombotics was suggested (Pinteraction = 0.04); unlike in patients with complete occlusion (OAC + AP; HR, 2.00 [1.27–3.15]), OAC + AP was comparable with OAC alone for 3-month primary outcome in patients with moderate-to-severe stenosis (HR, 0.54 [0.17–1.70]). In conclusion, OAC + AP might increase the risk of 3-month outcome events compared with OAC alone in patients with AIS with AF and concomitant LASO. However, the effect of additional AP to OAC might differ according to LASO type.

Predicting outcomes of acute stroke patients initially presenting with mild neurologic deficits is crucial in decision making regarding thrombolytic therapy. We examined the utility of individual National Institutes of Health Stroke Scale (NIHSS) score items or clusters of items as predictors of functional outcomes at 3 months after mild stroke.Using a multicenter stroke registry database, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had baseline NIHSS scores less than or equal to 5. Functional outcomes at 3 months were dichotomized as favorable (modified RankinScale [mRS] score 0 or 1) or unfavorable (mRS 2-6). Individual NIHSS items, clusters of items, and the total score were tested for their ability to predict outcomes in multivariable models. Area under the receiver operating characteristic curve (AUC) was used to assess model performance.Of the 2209 patients who met eligibility criteria, 588 (26.6%) exhibited unfavorable functional outcomes at 3 months. Of the 15 items of the NIHSS, all except item 8 (sensory) and item 11 (extinction) were significantly associated with unfavorable functional outcomes in bivariate analysis (P's .05). Among the multivariable models, the model with the total NIHSS score exhibited an AUC similar to that of the model with all NIHSS items in predicting functional outcomes (.758 [95% confidence interval .739-.775] versus .759 [.740-.776]; P = .75 for pairwise comparison).Simply using the total NIHSS score was as effective as using all individual items in predicting outcomes of mild stroke patients.

Background and purpose Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. Methods We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. Results Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barre syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2-3 weeks. Conclusions Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

Background and Purpose— We compared baseline characteristics and outcomes at 3 months between patients with minor anterior circulation infarction (ACI) versus minor posterior circulation infarction (PCI), including the influence of large vessel disease on outcomes. Methods— This study is an analysis of a prospective multicenter registry database in South Korea. Eligibility criteria were patients with ischemic stroke admitted within 7 days of stroke onset, lesions in either anterior or posterior circulation, and National Institutes of Health Stroke Scale score of ≤4 at baseline. Patients were divided into 4 groups for further analysis: minor ACI with and without internal carotid artery/middle cerebral artery large vessel disease and minor PCI with and without vertebrobasilar large vessel disease. Results— A total of 7178 patients (65.2±12.6 years) were analyzed in this study, and 2233 patients (31.1%) had disability (modified Rankin Scale score 2–6) at 3 months. Disability was 32.3% in minor PCI and 30.3% in minor ACI ( P =0.07), and death was 1.3% and 1.5%, respectively ( P =0.82). In a multivariable logistic regression analysis, minor PCI was significantly associated with disability at 3 months when compared with minor ACI (odds ratio, 1.23; 95% confidence interval, 1.09–1.37; P Conclusions— Our study showed that minor PCI exhibited more frequent disability at 3 months than minor ACI. Especially, the presence of vertebrobasilar large vessel disease in minor PCI had a substantially higher risk of disability. Our results suggest that minor PCI with vertebrobasilar large vessel disease could require more meticulous care and are important targets for further study.

Stroke severity of 1 hospital is a crucial information when assessing hospital performance. We aimed to determine the effect of stroke severity in the association between hospital patient volume and outcome after acute ischemic stroke.Data from National Acute Stroke Quality Assessment in 2013 and 2014 were analyzed. Hospital patient volume was defined as the annual number of acute ischemic stroke patients who admitted to each hospital. Comparisons among hospital patient volume quartiles before and after adjusting age, sex, onset to arrival and stroke severity were made to determine the associations between hospital patient volume and mortality at 30 days, 90 days and 1 year. Assessments for the nonlinear associations, with treating hospital patient volume as a continuous variable, and the associations between hospital patient volume and quality of care were also made.A total of 14,666 acute ischemic stroke patients admitted to 202 hospitals were analyzed. In the crude analysis, patients admitted to hospitals with lower patient volume showed higher mortality with a non-linear inverse association with a cut-off value of 227 patients/year. While the associations remained significant after adjusting age, sex and onset to arrival time (P's.05), they disappeared when stroke severity was further adjusted (P's.05). In contrary, hospital patient volume showed a nonlinear positive association with a plateau for summary measures of quality indicators even after adjustments for covariates including stroke severity (P.001).Our study implicates that stroke severity should be considered when assessing hospital performance regarding outcomes of acute stroke care.

ObjectiveIt 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.MethodsUsing 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.ResultsOf 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.ConclusionStarting 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.

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., Graphical Abstract

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.

BACKGROUND High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS). METHODS This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs. RESULTS Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005–1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013–1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874–0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086–1.526); P = 0.004] were independently associated with NILs at follow-up. CONCLUSIONS High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful.

Background and Purpose: Stroke is one of the most devastating and costly health problems of today. However, there is lack of knowledge about how costly it is in a long-term perspective and how much the long-term cost differs according to 3-month functional outcome, a major primary outcome variable of acute stroke intervention trials. Methods: Acute ischemic stroke patients who were registered into the multi-center stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) in South Korea between 2011 and 2013 were matched to the National Health Insurance Service claim database. All the healthcare expenditure was extracted from the claim database and converted into daily cost of each individual. Yearly expenditures and cumulative expenditure up to 5 yeas were obtained and expressed in US dollars and were compared according to 3-month functional outcome (modified Rankin disability scale, mRS).Results: A total of 11,136 acute ischemic stroke patients (mean age, 68 years; men 58%) were analyzed. The median follow-up period was 1,418 days. The mean cumulative healthcare expenditure over 5 years was $74,295 (SD, $91,049) and showed a dramatic increment during the first month followed by a constant increase without a considerable change. The mean 5-year cumulative expenditure differed significantly according to 3-month functional outcome; $32,261 in those with 3-month mRS 0 and $163,244 in those with 3-month mRS 5. After adjusting for the selected potential confounders, the yearly expenditures and the cumulative one at each time point differed significantly according to 3-month mRS scores. Figure given below is showing the median 5-year cumulative daily expenditure by 3-month mRS. Conclusions: This study shows that the impact of 3-month functional outcome on the long-term healthcare expenditure following acute ischemic stroke may be more than expected. The efforts for improving functional outcomes are urgent.

Background: Strict blood pressure (BP) control among acute ischemic stroke (AIS) survivors would improve prognosis and decrease recurrent vascular events, which, however, has not been investigated in detail. Methods: AIS survivors at discharge who was admitted between 2010 and 2011 were included in the analysis dataset. Baseline characteristics were gathered through a multicenter prospective stroke registry (CRCS-K). BP measurements, clinic visit and prescription of BP-lowering medications after discharge were collected through medical records until 1 year (± 2 months of grace period). Recurrent vascular events until 1 year after stroke including stroke, myocardial infarction and death were gathered through a structured telephone interview by trained research registrars or medical records review. Individual treatment intensification (TI) scores were calculated by the following equation; (observed medication change - predicted medication change by a standard guideline) / number of clinic visit. TI scores were categorized into quintile groups and their associations with recurrent events were assessed by Cox proportional hazard models. Results: Of the 3482 AIS survivors, 2675 (77%) were diagnosed of hypertension and 1977 (57%) had BP-lowering medication prescription at discharge. Median NIHSS score at admission was 3 [1 - 6] points and 1573 (45.3%) had mRS score 0f 0 - 1 at discharge. TI score over 1-year after discharge was mean - 0.24 ± 0.30 and median - 0.15 [- 0.42, 0]. Compared to Q3 (third quintile; group TI score, - 0.15 ± 0.05), Q5 (group TI score, 0.04 ± 0.08) had higher proportion of cardioembolic stroke (32% vs 20%) and higher median NIHSS score (4 vs 3). Extreme groups of TI scores, Q1 or Q5, showed increased hazard for having mortality or composite events (see Table). Conclusions: Physicians’ attitudes toward elevated BP, represented by the TI score, was significantly associated with long-term vascular outcomes.

Background: Stroke unit care is recommended as a standard care for acute stroke. We sought to determine whether morbidity and mortality of patients who admitted for acute ischemic stroke have been improved after implementation of stroke unit care in a regional public hospital. Methods: Seoul Medical Center is a regional public hospital in Seoul, the capital of Korea. Stroke unit has been established at June, 2011. Information of all consecutive stroke patients admitted to our hospital including functional outcome has been collected prospectively from April, 2008 as a part of a nationwide multicenter stroke registry. We compared outcomes of pre and post commencement of stroke unit, obtained from April, 2008 to December, 2010 and from January 2012 to November 2017, respectively. Primary outcome was a good functional outcome defined as a modified Rankin scale score of 2 or less at 3 months. A secondary outcome was death at 3 months. Results: Of all acute ischemic stroke, 366 and 1540 patients were identified as pre and post commencement of stroke unit. There were no significant differences in mean age (69.5±13.1 years versus 69.2±12.2 years; p =.684), sex distribution (male, 59.8% versus 59.4%, p =.906) and mean National Institutes of Health Stroke Scale score at admission (5.7±5.4 versus 5.6±5.9, p =.759) between two epochs. Good functional outcome was increased from 46.4% to 53.6% ( p =.015) while mortality at 3 months dropped from 11.7 % to 5.4% ( p Conclusions: Our study shows the improvement of outcomes in patients with acute ischemic stroke after commencement of stroke unit care. Stroke unit care service needs to be expanded in other regional public hospitals in Korea.

Background and Objectives: The aim of this study was to evaluate the clinical characteristics and outcomes of acute ischemic stroke according to the patients’ arrival time at hospital. Methods: In this prospective stroke registry, all consecutive patients, who admitted via emergency room of 12 participating centers nationwide from 2009/12 to 2017/11, were identified. All patients were presented with first-ever stroke within 7 days from symptom onset, and had relevant ischemic lesions on brain imaging. We categorized hospital arrival time into 4 groups, such as early morning (EM, 0 to 6), late morning (LM, 6 to 12), afternoon (AF, 12 to 18), and evening (EV, 18 to 24 o’clock). Results: Total of 31992 patients were included. In patients arriving in EM, the number was 2034 (6.4%) [vs. 9400 (29.4%), 13277 (41.5%), 7281 (22.8%)], age (mean) was 64.9 years (vs. 68.2, 67.4, and 67.0, p Conclusion: Though the number of patients arriving at hospital in EM was lowest, that group required highest rate of thrombolysis, showed younger age, higher cardioembolism, higher stroke severity, and poor functional outcome at 3 months. Adequate management needs to be considered for the patients arriving in EM.

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 20. Conclusions EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity. Electronic supplementary material The online version of this article (10.1186/s12883-019-1237-2) contains supplementary material, which is available to authorized users.

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., Graphical Abstract

Data on the drip-and-ship paradigm in Korea are limited. The present study aimed to evaluate the use of the drip-and-ship paradigm and the time delays and outcomes associated with the paradigm in Korea.We used data from the Clinical Research Center for Stroke-5 registry between January 2011 and March 2014. Among patients treated with tissue-type plasminogen activator (tPA), the use of the drip-and-ship paradigm was evaluated, and time delays and functional outcomes at 3 months were compared between patients treated with the paradigm and those treated directly at visits.Among 1843 patients who met the eligibility criteria, 244 patients (13.2%) were treated with the drip-and-ship paradigm. Subsequent endovascular recanalization therapy was used in 509 patients (27.6%). The median time from symptom onset to groin puncture was greater in patients treated with the paradigm than in those treated directly at visits (305 versus 200 minutes, P .001). In multivariate analysis, the risks of unfavorable functional outcomes and symptomatic intracranial hemorrhage were higher inpatients treated with the paradigm than in those directly treated at visits (odds ratio [OR] 2.15; 95% confidence interval [CI], 1.50-3.08; P .001 and OR 1.78; 95% CI, 1.02-3.12; P = .041, respectively).In Korea, the drip-and-ship paradigm was used in less than 15% of all patients treated with tPA. The use of the paradigm might cause an increase in the onset-to-groin puncture time. Additionally, clinical outcomes might be worse in patients treated with the paradigm than in those treated directly at visits.

BackgroundCurrent guidelines have contraindicated history of intracerebral hemorrhage for intravenous recombinant tissue plasminogen activator.AimThis study aimed to investigate the safety and effectiveness of intravenous recombinant tissue plasminogen activator for patients who had previous intracerebral hemorrhage on history or initial brain magnetic resonance imaging.MethodsUsing a prospective multicenter stroke registry database, we identified acute ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator within 4.5 h of onset. Previous intracerebral hemorrhage was defined as having a clinical history or evidence of old intracerebral hemorrhage on initial brain magnetic resonance imaging. Associations of previous intracerebral hemorrhage with symptomatic hemorrhagic transformation during hospitalization and functional outcome and mortality at discharge and three months were analyzed.ResultsAmong 1495 patients who were treated with intravenous recombinant tissue plasminogen activator, 73 (4.9%) had previous intracerebral hemorrhage; 9 on history only, 61 on magnetic resonance imaging only and 3 on both. Of those 1495 patients, 71 (4.7%) experienced symptomatic hemorrhagic transformation; 6.8% in patients with previous intracerebral hemorrhage and 4.6% in those without previous intracerebral hemorrhage. Multivariable logistic regression analysis showed that previous intracerebral hemorrhage did not significantly increase the risk of symptomatic hemorrhagic transformation (odds ratio 1.08, 95% confidence interval 0.39–2.96) mortality, and most of functional outcome measuresConclusionsPrevious intracerebral hemorrhage may neither increase the risk of symptomatic hemorrhagic transformation nor alter major clinical outcomes in acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator. This study suggests reconsideration of prior history of intracerebral hemorrhage as an exclusion criterion for intravenous recombinant tissue plasminogen activator administration in acute ischemic stroke.

Background and Purpose— Since its introduction, controversy has existed about the administration of intravenous heparin for the treatment of acute ischemic stroke. We studied trends in the intravenous heparin use during a 6-year time period and the potential influence of clinical guidelines in national language on intravenous heparin administration in Korea. Methods— On the basis of a prospective nationwide multicenter stroke registry, we collected data on patients with acute ischemic stroke who arrived within 7 days of symptom onset during the time period 2008 to 2013. We studied patient demographics, prestroke medical history, stroke characteristics, and stroke treatment. Data from a total of 23 425 patients from 12 university hospitals or regional stroke centers were analyzed. Results— The administration of intravenous heparin steadily decreased throughout the study period: 9.7% in 2008, 10.9% in 2009, 9.4% in 2010, 6.0% in 2011, 4.7% in 2012, and 4.3% in 2013 ( P for trend P P Conclusions— Use of intravenous heparin for acute ischemic stroke treatment has decreased in Korea, and this change may be attributable to the spread and successful implementation of regional clinical practice guidelines.

Limited information is known regarding acute ischemic stroke (AIS) and heart failure (HF). The aim of the study was to evaluate clinical characteristics, predisposing factors, and outcomes in AIS with HF.We included AIS patients admitted to the institutions participating in the Registry of the Canadian Stroke Network. HF was defined as history of pre-existing HF or pulmonary edema present at the time of arrival. The primary outcome was death or disability at discharge (modified Rankin Scale score3). Secondary outcomes included disposition, death at 3 months and at 1 year, and 30-day hospital readmissions.Among 12,396 patients, HF was found in 1124 (9.1%) patients. HF was associated with higher risk of death at 30 days (24.5% versus 11.2%, P .0001), at 1 year (44.3% versus 20.6, P .0001), and disability at discharge (70.4% versus 56%, P .0001). In the multivariable analysis, HF was an independent predictor of death and disability (odds ratio 1.18, 95% confidence interval [CI] 1.01-1.37), death at 30 days (hazard ratio [HR] 1.22, 95% CI 1.05-1.41), and hospital readmissions (HR 1.32, 95% CI 1.05-1.65) at 30 days. The results were unaltered when adjusting for pneumonia with the exception of death or disability at discharge.In this large cohort study, HF was observed in 9.1% of AIS patients. HF is an independent predictor of death and disability and hospital readmissions after stroke at 30 days.

Objective The effect of prestroke aspirin use on initial severity, hemorrhagic transformation, and functional outcome of ischemic stroke is uncertain. Methods Using a multicenter stroke registry database, patients with acute ischemic stroke of three subtypes (large artery atherosclerosis [LAA], small vessel occlusion [SVO], or cardioembolism [CE]) were identified. NIH stroke scale (NIHSS) and hemorrhagic transformation at presentation and discharge modified Rankin Scale (mRS) were compared between prestroke aspirin users and nonusers. Results Among the 10,433 patients, 1,914 (18.3%) reported prestroke aspirin use. On crude analysis, initial NIHSS scores of aspirin users were higher than nonusers (mean difference: 0.35; 95% confidence interval [CI]: 0.04–0.66). However, a multivariable analysis with an application of inverse probability of treatment weighting based on a propensity score of prestroke aspirin, having an interaction effect of prestroke aspirin use and stroke subtype in the model, showed less stroke severity for aspirin users in LAA, but not in SVO and CE than for nonusers; mean difference in NIHSS scores in LAA was –0.97 (95% CI: –1.45 to –0.49). With respect to hemorrhagic transformation and mRS, no significant interaction effects were found. Prestroke aspirin use increased the risk of hemorrhagic transformation (adjusted odd ratio: 1.34; 95% CI: 1.05–1.73), but decreased the odds of the higher discharge mRS (0.86; 0.76–0.96). Interpretation Prestroke aspirin use may reduce initial stroke severity in atherothrombotic stroke and can improve functional outcome at discharge despite an increase of hemorrhagic transformation irrespective of stroke subtype. Ann Neurol 2016