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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.

Background: Pathophysiology of intracranial atherosclerotic stenosis (ICAS) development and subsequent stroke occurrence is diverse, including cholesterol deposition, arterial dissection, and intrinsic vasculopathies. To differentiate these specific etiologies, performing high-resolution MRI (HR-MRI) has increased. However, the information on serial change of ICAS on HR-MRI was limited. Methods: Patients hospitalized at a tertiary university hospital for AIS and who took HR-MRI more than twice between 2015 and 2019 were collected. Two specialists manually segmented the contour of the culprit and reference vessel's inner lumen, outer wall, and plaque. The stenotic degree, remodeling index, and enhancement signal were measured for the culprit lesion at each examination. Results: A total of 202 HR-MRI examinations from 93 patients were analyzed. The Median follow-up was 270 days (118-390). The ranges of the serial change in stenotic degree (-86% to 41%), remodeling index (-83% to 266%), and enhancement signal (-85% to 71%) were very diverse. Changes in stenotic degree and enhancement according to the initial stenotic degree were insignificant. On the other hand, the change in enhancement signal was greater in the initially more enhanced lesions (0.1±23.0; mild vs. -23.1±22.6; moderate vs. -35.5±28; severe, p difference difference =.005). Conclusions: ICAS showed very dynamic changes in the follow-up HR-MRIs. To identify the underlying etiology, such as arterial dissection and Moyamoya disease, serial HR-MRI will be helpful.

Introduction: Intracranial arterial disease (ICAD) may have dynamic temporal changes which high-resolution MR (HR-MR) images can visualize. Until now, there is only limited evidence on the risk factor for the evolution of ICAD after ischemic stroke. Method: We have collected acute ischemic stroke patients admitted to a single referral stroke center between 01/2015 and 06/2019 with baseline and follow-up HR-MR images on their ICAD lesions. A total of 246 patients were identified, and for the current pilot study, HR-MR images from 93 patients were used. Degree of stenosis on T1/gadolinium-enhanced (Gd) T1 sequences, remodeling index on proton-density sequence, and enhancement signal on Gd-T1 sequence were measured. Temporal changes were defined as (1-([parameters at the initial]/[parameters at the follow-up])*100. The temporal changes of image parameters were compared by bivariate baseline blood risk factors, such as LDLC ( ≥ 100 vs. ≥ 6.5 vs. Result: A total of 93 patients were analyzed for the pilot study. Temporal changes in the degree of stenosis, remodeling index, and enhancement signal of ICAD lesion were -19.6 ± 50.3%, 2.9 ± 45.6%, and -15.0 ± 31.6%, respectively. ICAD parameters were further mitigated in lower levels of selected markers, such as the degree of stenosis (-24.9±37.6% from lower vs. -16.0±57.5% from higher LDLC, P =0.37; -23.0±54.9% from lower Hb A1c vs. -9.3±32.3% from higher Hb A1c, P =0.16) and the enhancement signal (-18.0±29.1% from lower vs. -12.9±33.2% from higher LDLC, P=0.45; -17.1±32.2% from lower Hb A1c vs. -6.5±28.4% from higher Hb A1c, P=0.17). Linear associations between change in the enhancement signal and LDLC in higher LDLC (B=0.38, P=0.01) and degree of stenosis and Hb A1c in higher Hb A1c (B=0.49, P=0.02) were observed. Conclusion: ICAD lesions in acute ischemic stroke patients may have temporal appearance changes. Baseline LDLC and Hb A1c levels may be used as a marker for the evolution of ICAD.

Introduction: Stress hyperglycemia is an essential survival response. However, it is associated with poor prognosis after ischemic stroke, and its contribution to collateral failure is not well defined. We investigated whether stress hyperglycemia would be associated with early neurological deterioration (END) in acute large vessel occlusion (LVO) patients who present with mild neurological deficit. Methods: From a multicenter stroke registry, ischemic stroke patients with acute anterior circulation LVO and mild symptoms (NIHSS Results: Among a total of 731 mild LVO patients (mean age 68.0±12.9 years; 62.7% male), 172 (23.5%) had a history of diabetes, and 73 (10.0%) were newly diagnosed with diabetes during admission. The SHR was higher in known diabetic patients compared to no-DM / newly diagnosed diabetic patients (24.3±8.5 vs. 21.8±5.6, p-value Conclusions: Stress hyperglycemia was associated with END in acute LVO patients with low NIHSS, especially in the subgroup of patients without or newly diagnosed diabetes. In patients without a history of diabetes, where the physiologic response to hyperglycemia may currently be preserved, intensive glycemic control may benefit in maintaining leptomeningeal collaterals.

Background: Medical care disparities are wide, and stroke in no exception. Reperfusion therapy is the standard treatment for acute ischemic stroke, but its use may vary across hospitals. Methods: Data from 75,870 patients admitted to 247 acute stroke hospitals nationwide were obtained through the 2013-2018 acute stroke quality evaluation program conducted by the Health Insurance Review and Assessment Service. The primary outcome was the hospital reperfusion therapy rate (RTR), defined as the proportion of intravenous tissue plasminogen activator (IVT) and/or endovascular thrombectomy (EVT) cases in patients potentially eligible for reperfusion therapy (onset-to-arrival time ≤ 6 hours and initial NIHSS score ≥ 4). Hospital RTRs, adjusted for age, sex, onset-to-arrival time, and initial stroke severity, were analyzed with hospital characteristics. Results: During the study period, 10,513 stroke patients were potentially eligible for reperfusion treatment and were admitted to 247 acute care hospitals. The RTR of the study population was 52.9%. The mean hospital RTR was 34.8% [median (IQR) 37.5% (9.8 - 56.2)]. A higher number of beds and average monthly stroke admissions were associated with a higher hospital RTR. Multivariable analysis revealed the average stroke admission per month, presence of stroke unit, the average IVT per month, and the average EVT per month were the independent determinants for hospital RTR. Hospital RTR was inversely correlated with 1-year mortality regardless of hospital stroke volume. Conclusions: RTRs vary widely across hospitals. The higher the hospital stroke volume, the higher the hospital RTRs. High hospital RTRs correlates with low 1-year mortality regardless of hospital stroke volume.

The expected growth of stroke burden in Korea in early 2000s led to the initiation of a government-funded clinical research project with the goal of development and implementation of national stroke guidelines. The CRCS-K (Clinical Research Collaboration for Stroke in Korea) began as a part of this project. For stroke epidemiology and quality of care research, the CRCS-K developed a multicenter, prospective, stroke registry and began collection of data in 2008. Now, about 100 000 cases have been registered at 17 university hospitals or regional stroke centers and about 200 articles have been published based on the registry experience. The analysis of the 10-year secular trends showed overall improvement of stroke care and outcomes and areas for improvement. This large-scale, high-quality dataset provides opportunities to explore and compare treatment disparities using the comparative effectiveness research methods, design and conduct a registry-based randomized clinical trial, connect the registry data with other data sources including the national claims data and neuroimaging or genetic data, and collaborate with other international researchers. An international stroke registry consortium may be a viable future direction.

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

Background and Purpose— Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods— Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1–6.9 mmol/L), and normal (FGL Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results— Patients with T2D had significantly poorer performance in global cognition (SD, −0.59 [95% CI, −0.82 to −0.36]; P P =0.55) or in any cognitive domain. Conclusions— Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.

Background and Purpose— Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation. Methods— This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event. Results— Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69–81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335–365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02–2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups. Conclusions— The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502.

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.

Objectives: The blood viscosity would quantify the physiological state of abnormal blood flow and hypercoagulability, which are crucial predisposing factors of ischemic stroke. It investigated whether the viscosity increase in the stroke. Methods: It enrolled a series of patients who visited the hospital with any neurologic symptom or sign within 24 h of last well-being. Blood was immediately sampled at the time of hospital arrival as a routine clinical practice along the acute stroke clinical pathway. The viscosity was investigated in a point-of-care test manner using ARS M-200, Rheology Solutions, Korea. It placed the whole blood between the two plates and measured the viscosity by applying a torque of 10 Hz within 5 minutes of taking the blood sample. The primary outcome was an ischemic stroke and other diseases, and the difference in blood viscosity between the two groups was compared. Results: In 2021, it enrolled 47 subjects (age, 69.5 ± 12.9 years-old, male, 51.0%) of whose were diagnosed as ischemic stroke (n = 18) and other diseases (n = 29) consisted of hemorrhagic stroke, metabolic encephalopathy, vertigo, seizure, drug intoxication, and peripheral neuropathy. The viscosity of ischemic stroke with 10 Hz torque was significantly higher than those of non-stroke (22.7 ± 7.4 vs. 18.4 ± 7.0 Ps, P = 0.02). In stroke, the viscosity was significantly different between direct visits (25.5 ± 6.6 Ps) and transferred subjects with intravenous fluids (14.3 ± 1.4) (P = 0.003). In the case of hemorrhagic stroke, traumatic hemorrhage presented the highest values (27.1 ± 5.8), which was different from intracerebral hemorrhage (22.1 ± 7.3 Ps, Figure). Conclusion: The blood viscosity increased in acute ischemic stroke, which would be used as an auxiliary factor in the emergency setting. Also, it may be warranted the following studies for investigating their prognostic roles.

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.

Purpose: Acute stroke care systems have been shifted to clusters of hospitals for cooperatively applying advanced treatment. It developed various forms of network care systems, of which measurement and evaluation are requested. Methods: Using cross-sectional national data for acute stroke care in Korea, hospital usage information after a medical contact was surveyed and transformed into node (hospital) and edge (transfer) format. Of them, dense-linked hospital groups were partitioned as a stroke community using the Louvain algorithm. It investigated the concentration, strength of connection, and functions of derived communities. Results: For six months, a total of 19113 subjects with ischemic stroke headed primarily to 1009 hospitals. They merged into 246 ASHs (acute stroke care hospitals) via 3114 (16.3%) secondary interhospital transfers. Those connections were partitioned for the 93 stroke communities (Figure A) comprising median of 9 hospitals (IQR, 5 - 14) and managed a median of 31.3 subjects per month (IQR, 18.2 - 48). They presented highly centralized structure (median group centralization degree [GDC], 1.00), which used to classify the communities (Figure B). One- or two-hospital centered communities showed similar performances of endovascular treatment (EVT) compared to lower volume or poor formatted communities. Conclusions: The network analysis method effectively contoured the high centralizing stroke communities and helped the functions on the EVT accessibility.

Introduction: Leptomeningeal collaterals help maintain cerebral perfusion after the large vessel occlusion (LVO), potentially regulated by systemic blood pressure (BP). We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by the baseline perfusions status and before and after recanalization. Method: From a prospective registry, we identified anterior circulation LVO patients who received EVT ≤24 hours after their onset, had baseline perfusion, and achieved post-EVT mTICI ≥2b. BPs were measured from arrival at 5-minute intervals in the ER and during the procedure. Systolic BPs (SBP) up to 24 hours after EVT were summarized as dropmax (the maximal decrement over two consecutive measurements), incmax (the maximal increment), mean, coefficient of variation, and standard deviation. Baseline perfusion images were quantified using Olea Sphere. Infarct proportion was defined as the volume of final infarct on DWI within the volume of Tmax>6 sec. Significant hemorrhage included PH2 or HBC class 3. 3-month mRS was prospectively collected. Result: A total of 388 LVO patients were included. Mean SBP at arrival was 153 ± 42 mm Hg; the average count of BP measurements was 47 ± 17 per patient.In the adequate baseline perfusion group, i.e., hypoperfusion intensity ratio (HIR) Conclusion: Association between BP and patient outcomes differs by baseline perfusion status and before and after recanalization. BP management during the peri-EVT period may therefore need to be individualized.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has changed the medical use of stroke patients. This study evaluated the health-seeking behavior of stroke patients and changes in stroke care services at the time of three domestic COVID-19 outbreaks in Korea using the Korean Stroke Registry (KSR) data. Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) from Jan 2019 to May 2021. There were three domestic COVID-19 outbreaks (1st: Feb to Mar 2020, 2nd Aug to Sep 2020, 3rd Nov 2020 to Jan 2021). Outcomes included patient characteristics, times from stroke onset to hospital arrival, and in-hospital stroke pathways. Results: The study included 34,271 patients who visited hospitals that contribute to the KSR. In the first outbreak, in Daegu city (the main epicenter), the number of patients decreased by two-thirds compared to the pre-COVID period, and the number of TIA patients was particularly decreased (9.97% to 2.91%). Unlike other regions, the median onset-to-door time increased significantly in the epicenter (361 min vs. 526.5 min, p=0.016), and longer times were common for patients with mild symptoms and who were in their 60s or 70s. The median onset-to-door time increased in the epicenter during the second outbreak, but it was not statistically significant. At the third outbreak, the median onset-to-door time was reduced even in the epicenter compared to the previous one. The number of patients decreased with each outbreak compared to the previous one, but the decrease gradually became smaller. Conclusions: Korean stroke patients in a COVID-19 outbreak region showed clear changes in health-seeking behaviors and showed a pattern of adaptation to the COVID-19 environment. There is a need for continued attention to an appropriate triage system and public education on the importance of early treatment during the COVID-19 pandemic.

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.

Background: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. Methods: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. Results: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033]; P P Conclusions: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

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.

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— 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 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: In-hospital and 30-day mortality, 3-month functional outcome were reported as associated with endovascular treatment (EVT) case volume per hospital, but one-year mortality was unknown. Furthermore, the hospital EVT volume threshold based on one-year mortality was not reported. We aimed to investigate whether there was a correlation between annual EVT case volume per hospital and one-year mortality and suggest volume threshold. Methods: Data from Korean national survey for assessing quality of acute stroke care were used. The survey was conducted since 2005 and the subject was patients with acute stroke who were admitted via emergency rooms within 7 days of onset at hospitals treating 10 or more stroke cases during the three (2013, 2014) or six (2016) month survey period. Ischemic stroke cases treated with EVT during the last available three assessments (2013, 2014, and 2016) were selected for the analysis. Results: A total of 1,746 ischemic stroke cases (age, 69.2 ± 12.4years; male, 56.6%) treated in 120 hospitals with EVT were analyzed. The median annual EVT case volume was 12.0 cases per hospital (interquartile range, 6.0-22.9) and the mortality at one-month, three-month, and one-year were 12.7%, 16.6%, and 23.3%, respectively. When divided into quartiles according to the annual EVT case volume, the lowest quartile group was found to have the highest one-year mortality (odds ratio [95% confidence intervals], 1.49 [1.04-2.13]), adjusted for age, sex, NIHSS, onset to arrival time. Restricted cubic splines performed on the annual EVT case volume per hospital revealed that cut-off value for the probability of one-year mortality was 15 cases per year ( p Conclusions: There was an association between annual EVT case volume and one-year mortality, and the volume threshold per hospital based on the one-year mortality was found to be 15 EVT cases per year.

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.

Background and purpose: With the wide spread of coronavirus disease 2019 (COVID-19) around the world, not only patients with COVID-19, but also patients with other disease such as stroke have undergone many changes in their health-seeking behavior. Between late February and March 2020, COVID-19 was epidemic in the community of Daegu city and Gyeongsangbuk-do region (D-G region) in Korea. We aimed to clarify the changes in the health-seeking behaviors of stroke patients and stroke care services by region in Korea through analysis of data from Korean Stroke Registry (KSR). Methods: We retrospectively reviewed the data with acute stroke and transient ischemic attack (TIA) patients between 2019 and 2020. We compared the stroke onset to hospital arrival (onset-to-door) time of these patients in the D-G region and other regions in Korea during the epidemic period in 2020 (post-COVID-19: February 18-March 31, 2020) and the same period in 2019 (Pre-COVID-19). In addition, we investigated the in-hospital stroke pathways with the patients. Results: 1,792 patients in pre-COVID-19 and 1,555 patients in post-COVID-19 who visited KSR-registered hospitals were analyzed. Compared to pre-COVID-19, the number of patients registered in KSR decreased in most regions in post-COVID-19. In the D-G region, the number of registered patients decreased by two thirds, and the proportion of patients with TIA decreased significantly. (9.97% to 2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 versus 526.5 minutes, p=0.0084). The proportion of patients with onset-to-door time within 3 hours also decreased significantly (36.45% versus 28.16%, p=0.0485). Patients in their 60s and 70s and mild symptoms (NIHSS score 0 to 3) came to the hospital later. As a result, the patients who underwent thrombectomy also decreased, but the treatment time did not differ between the two periods. Conclusion: During the epidemic of COVID-19, the patients residing in the epicenter showed distinct changes in health-seeking behavior. Appropriate public education about stroke is needed during the COVID-19 pandemic.

Purpose: Stroke patients generally transport stroke patients either to nearest stroke hospital with secondary transfers or to hub hospitals in selective cases. This study aimed to determine the stroke community of close networks and to evaluate their role for the access the endovascular treatment (EVT). Methods: Using the nationwide acute stroke hospital (ASH) surveillance data assessed the major quality indicators of all stroke patients of South Korea, triage information both initial visit and secondary interhospital transfers were extracted according to the hospitals. Based on them, stroke community with dense linkages were partitioned using the network-based Louvain algorithm. The hierarchical model estimated the function of stroke community for the EVT. Results: For 6-month surveying period, 19113 subjects admitted to the 246 ASHs. Of them, 1831 (9.6%) were transferred from 763 adjacent facilities not ASH, while 1283 (6.7%) from the other ASHs. The algorithm determined the 113 stroke communities where composed median 7 hospitals (2 ASHs and 5 adjacent facilities) and treated about 30 subjects per month. Most of communities formed the spindle shape with higher centralization index and located within 150 Km (Figure). Stroke communities significantly affected 11% of EVT after adjustments. Conclusions: Network analysis method effectively contoured the high centralizing stroke communities and helped the functions on the EVT accessibility.

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

Background: There is evidence that smoking increases stroke risk. However, the impact of smoking status on age at onset of ischemic stroke has not been studied. The aim of this study is to explore the effect of smoking status on the age at onset of first-ever ischemic stroke using the Korean Stroke Registry(KSR), the nation-wide, multicenter, hospital-based stroke registry in Republic of Korea. Methods: This study used individual data of first-ever ischemic stroke patients from the KSR, between 2014 and 2018. We divided the patients into four groups according to their smoking status; current smokers, past-smokers - quit in recent 5 years, past smokers - quit over than 5 years, and never-smokers. Results: A total of 27,942 patients were included in the analysis. The mean age at onset of the first-ever stroke were 60.0±11.9 in current smokers, 65.9±11.9 past-smokers - quit in recent 5 years, 70.1±10.8 in past smoker - quit over than 5 years, and 70.5±12.8 in never-smokers (p Conclusions: The smoking status of patients was associated with an earlier onset age of the first-ever stroke. The onset age tends to be delayed with the longer duration of cessation period.

Background: Recent endovascular treatment (EVT) trials suggest the presence of target mismatch profiles up until 24 hours after stroke symptom onset. We aim to a) demonstrate the presence of target mismatch in patients presenting beyond these recent time thresholds and b) potential benefit with EVT in these patients. Methods: Between 01/2012 and 12/2018, patients with AIS with ICA or MCA occlusion and baseline NIHSS score ≥6 arriving ≥16 hours from last known well were identified. CT or MR perfusion images at presentation were evaluated using RAPID software; ischemic core was defined as rCBF Results: Of 154 patients [55% male, mean age 70 ± 13 years, median baseline NIHSS 13 [IQR 8 - 18], 76 (49%) had unwitnessed onset. Median last known well to arrival in hospital time was 42.2 [22.8 - 76.9]. CTP or MR perfusion were obtained in 115 (75%). Median ischemic core volume i.e., 11.0 ml [iqr 0 - 40 ml], and penumbra volume (Tmax >6 s) i.e., 57 ml [16 - 133 ml] and a median mismatch ratio 4.0 [iqr 0.9 - 18.0] were noted. When inclusion criteria of the following trials, namely, ESCAPE, DAWN and DEFUSE3 trial were applied, DAWN-eligible patients were n=45 (29%), DEFUSE3 n= 61 (40%) and ESCAPE n=59 (43%). Figure 1a shows trial eligibility by time from last known well. 24 (16%) patients had EVT. EVT was associated with better functional recovery at 3 months (Figure 1b) for 90-day mRS 0-2 (adjusted OR [95% CI], 8.11 [2.49 - 30.44]) and 90-day mRS shift (common adjusted OR 5.50 [2.33 - 13.29]). Treatment effect with EVT was seen from 16 to 240 hours since last known well (Figure 1c). Parenchymal Hemorrhage type 2 was seen in 13 % offered EVT vs. 3% (adjusted OR 4.11 [0.73 - 21.72]). Conclusions: Patients with anterior circulation LVO presenting very late, even days from last known well, may potentially benefit from EVT.

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.

Background: Women, compared with men, tend to have worse functional outcome after stroke. The gender effect is not fully explained by age, pre-stroke dependency, and stroke severity. We hypothesized that it might be due to different prognostic impacts of stroke-related brain lesions in women vs. men. Objective: To investigate if the effects of acute infarct volume and white matter hyperintensity (WMH) volume on initial stroke severity and 3-month functional outcome are modified by gender. Methods: This prospective study included 6748 patients with acute ischemic stroke ( Results: Women, compared with men, were older (mean 72 vs. 65, p2: adjusted OR [95%], 1.36 [1.09-1.69]). The association of WMH volume with 3-month mRS score was significantly modified by gender (p-for-interaction=0.049), with the WMH effect being greater in women (adjusted ORs of the highest vs. lowest quartile for the worse outcome: 2.47 in women vs. 1.51 in men). Conclusion: Women, compared with men, are probably more susceptible to the adverse effects of infarct volume and WMH volume on stroke severity and functional outcome.

Introduction: There have been few reports on status of acute stroke management at a national level worldwide, and none in Korea. This study is aimed to describe the current status and disparities of acute stroke management in Korea. Methods: Data from 5th (2013) and 6th (2014) national surveys for assessing quality of acute stroke care were used. Patients with principal diagnosis codes indicating subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), ischemic stroke (IS), who were admitted via emergency rooms within 7 days of onset at hospitals treating 10 or more stroke cases during the each 3-month survey period were selected. Results: A total of 19,608 stroke cases (age, 67.7±13.5years; female, 45%; IS, 76%; ICH, 15%; SAH, 9%) treated in 216 hospitals were analyzed. Thirty-one percent of hospitals had stroke units and 41% of stroke cases were treated at hospitals without stroke units. In IS, IV thrombolysis (IVT) and endovascular treatment (EVT) rates were 10.7% and 3.6%, respectively. Thirty-nine percent of IVT and fifty-two percent of EVT cases were performed in hospitals with annual volume of Conclusions: This study is the first report on the status of acute stroke care in Korea on a national level. Large number of recanalization therapies were performed in low-volume-hospitals. Expansion of stroke unit service, stroke center certification or accreditation, and connections between stroke centers and EMS are highly recommended.

Introduction: Even high blood pressure (BP) is regarded as an important target for the secondary prevention of ischemic stroke, there is limited information how it is controlled and what effect is on the prognosis. Methods: This study was a nation-wide, multicenter, prospective study to observe 3-month BP and long-term outcomes in patients with acute ischemic stroke. For all enrolled subjects, 3-month BP after index stroke event were collected and classified into good and poor controlled hypertension (SBP < 130 mmHg versus ≤ 130 mmHg) and normotensive state. The association of 3-month BP with a composite outcome of stroke recurrence, myocardial infarction and vascular death was investigated using Cox proportional hazard model with predetermined adjusting variables. Results: Of enrolled 17976 subjects (age; 67.8 ± 13.1 years-old, male proportion: 57.9%), hypertension was estimated in 64.1% (n = 10459) at index event. After 3-month, SBP was mean 130.1 ± 1.3 mmHg in patients with hypertension, of which 67.8% showed poor controlled hypertension. In the Kaplan-Meier survival curve, a hypertension-controlled state showed significant association with the composite outcome (Figure). As referenced with normotensive state, poor controlled hypertension independently increased the hazards for composite event (adjusted odds ratio, 1.32; 95% confidence interval, 1.04 - 1.66), but not good controlled hypertension (1.20; 0.91 - 1.59) with adjustments for age, sex, diabetes mellitus, dyslipidemia, atrial fibrillation, stroke severity and stroke subtypes. Conclusion: This study clarified the clinical impact to monitor and control the BP after ischemic stroke.

Introduction: Atrial fibrillation (AF) and large artery diseases (LAD) share several risk factors and often coexist in the same patient. Optimal treatments for acute ischemic stroke (AIS) patients with concomitant AF and LAD have not been extensively studied so far. Objective: This study aimed to compare the effectiveness of the addition of antiplatelet (AP) to oral anticoagulant (OAC) with that of OAC alone in AIS with AF according to the LAD. Methods: Using a multicenter stroke registry, acute (within 48h of onset) and mild-to-moderate (NIHSS score ≤15) stroke patients with AF were identified. Propensity scores using IPTW were used to adjust baseline imbalances between the OAC+AP group and the OAC alone group in all patients and in each subgroup by LAD. The primary outcome was major vascular events, defined as the composite of recurrent stroke, MI, and all-cause mortality at up to 3 months after index stroke. Results: Among the 5469 patients (age, 72±10yrs; male, 54.9%; initial NIHSS score, 4 [2-9]), 79.0% (n=4323) received OAC alone, and 21.0% (n=1146) received OAC+AP. By weighted Cox proportional hazards analysis, a tendency of increasing the risk of 3-months primary composite events in the OAC+AP group vs the OAC alone (HR 1.36 [0.99-1.87], p=0.06), with significant interaction with treatments and LAD (Pint=0.048). Briefly, among patients with moderate-to-severe large artery stenosis, tendency of decrease in 3-months primary composite events of the OAC+AP group, compared with OAC alone group, was observed (HR 0.54 [0.17-1.70]), whereas among patients with complete occlusion, the OAC+AP group markedly increased the risk of 3-months composite events (HR 2.00 [1.27-3.15]), compared with the OAC alone group. No interaction between direct oral anticoagulant and warfarin on outcome was observed (Pint=0.35). Conclusion: In conclusion, treatment with addition of AP to OAC had a tendency to increase the risk of 3-months vascular events, compared with OAC alone in AIS with AF. However, the effects of antithrombotic treatment could be modified according to the LAD, with substantial benefits of OAC alone in subgroup of large artery occlusion. Our results address the need for the further study to tailor the optimal treatment in AIS with concomitant AF and LAD.

Introduction: Our aim was to determine the prevalence and factors associated with delayed appearance of DWI lesion among initially DWI-negative clinically suspected stroke patients in the follow-up DWIs during in-hospital care. Method: Among 5271 patients admitted to stroke unit as clinically suspected stroke/TIA within 7 days from symptom onset in our hospital via ER for 2010~2017, we selected subjects based on the following criteria 1) initial negative DWI (n=827), 2) follow-up DWI within 14 days (n=751). Then, we excluded 57 cases (hemorrhagic cases (n=4), cerebral angiography studies between MRIs (n=53)). Finally-included 694 cases were divided into two cohorts for temporal external validation (2010~2015 (n=488) as derivation; 2016~2017 (n=206) as validation). Results: Of 5271 cases, 827 cases (15.7%) showed initial negative DWI. In 694 finally-included cases, 22.5% (n=156) showed delayed appearance of DWI lesion. In derivation cohort, factors showing significant relationship with positive conversion comprised: medical histories such as atrial fibrillation (aOR 6.17, 3.23-12.01); symptoms including objective hemiparesis (aOR 4.39, 1.90-10.32) (Table 1). These factors were used to construct DWI-CONVERSION score (Table 2a). Its c-statistic was 0.813 in derivation cohort and 0.808 in validation cohort, which is significantly higher than that of ABCD2 score in validation cohort (c-statistic=0.678; P Conclusion: We identified prevalence and clinical factors significantly associated with delayed appearance of DWI lesions in clinically suspicious stroke patients. DWI-CONVERSION score is a simple tool to predict it.

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.

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.

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.

Backgrounds: Irrespective of the indication for statin, statin adherence after ischemic stroke was associated with better clinical outcome. We studied the association between statin adherence and recurrent cardiovascular (CV) events among the patients with acute ischemic stroke and statin benefit. Methods: Using Comprehensive Registry Collaboration for Stroke in Korea (CRCS-K), patients with acute ischemic stroke were identified. Statin benefit was defined using the secondary prevention guidelines of American Stroke Association in 2014. The data for statin prescription after discharge were obtained from National Health Insurance Services (NHIS) claim data by matching with CRCS-K. Statin adherence was measured by the medication possession ratio (MPR), which was dichotomized, setting a threshold of MPR ( Results: Among 11,768 patients in NHIS-CRCS-K matching database, 5,504 patients were the statin benefit group and prescribed with statin on discharge. Overall MPR for 1 year after discharge was 73.1%. Overall CV events for 1 year were 569, which was more prevalent in low adherence group. (MPR Conclusion: Adequate statin adherence in the patients with acute ischemic stroke and statin benefit was significantly associated with recurrent CV events.

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.

Purpose: This study aimed to investigate the initial and subsequent interhospital transfer routes for endovascular treatment in patients with ischemic stroke and to estimate their effects on recanalization therapy and outcome. Methods: From the nationwide acute stroke quality assessment program database, patients diagnosed with ischemic stroke were identified through all kinds of acute stroke care hospitals in South Korea for 6 months survey period. Among them, we defined thrombectomy-eligible patients who had NIHSS score of 7 or more and arrived at the hospital within 6 hours from last well-being time. After determining the in- and outflow routes per person, patients were dichotomized into initially anchored in thrombectomy capable hospital (TCH) and initially anchored in non-TCH according to the initial visiting hospital. In each group, they were subclassified into stay-on and transfer-out according to outflow routes. Implementation of intravenous thrombolysis (IVT) and endovascular treatment (EVT), and clinical outcomes were compared by initial visiting hospitals and sub-groups. Results: Of 14902 patients with ischemic stroke, thrombectomy-eligible patients were 2180 (male, 51.9% and age, 72.9 ± 12.5 years old). Initial routes were TCH (35.5%) and non-TCH (64.5%), which were associated with IVT (53.8% for patients anchored in TCH versus 35.5% for patients initially anchored in non-TCH, P < 0.001) and EVT (33.3% versus 8.1%, P < 0.001). Initial visiting hospital showed a significant difference in 1 y mortality (29.3% versus 36.0%, P = 0.002). Transfer-out to TCH in patients initially anchored in non-TCH (n = 1406) was rated 17.4%, which was significantly associated with higher EVT (34.8% versus 7.5%) compare to stay-on, not with IVT (35.7% versus 34.9%). Conclusion: In acute stroke, the initial route and interhospital transfer affected the implementation of recanalization therapy and would be the key step toward renovating the stroke care system.

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.

Introduction: We present a descriptive epidemiology data of ischemic stroke patients with atrial fibrillation from South Korea and Japan. Methods: Based on prospective registries from South Korea (CRCS-K registry) and Japan (SAMURAI-NVAF study), we collected acute ischemic stroke or transient ischemic attack (TIA) patients with documented atrial fibrillation between 2011 and 2014. Data elements, data fields, and their definitions were harmonized to generate a single dataset. A total of 6036 patients were includedin the analysis (4844 from CRCS-K and 1192 from SAMURAI-NVAF). Results: Regarding baseline characteristics, noticeable differences were found in the following variables between South Korea and Japan; mean age at onset (73.7 ± 10.1 vs 77.7 ± 9.9), TIA as an index event (2.3% vs 4.3%), diabetes (28.6% vs 20.1%), dyslipidemia (28.1% vs 32.9%), smoking (28.3% vs 36.9%), antiplatelets before stroke (39.5% vs 24.3%), anticoagulants before stroke (16.9% vs 31.8%), and recanalization treatment (31.6% vs 22.3%). Median [interquartile range] NIHSS score at admission was comparable (9 [3 - 16] vs 8 [2 - 18]). Functional recovery and event outcomes were different between two countries; mRS score 0 - 1 at 3 months (31.9% vs 36.9%), mortality at 3 months(16.8% vs 6.3%) and at 1 year (22.8% vs 15.4%) and recurrent stroke until 1 year (6.2% vs 10.6%). Conclusions: In spite of common ethnic and cultural background, ischemic stroke patients with atrial fibrillation in South Korea and Japan differ in the following points; 1) favorable recovery and event outcomes of Japanese patients in spite of older age at onset, 2) lower pre-morbid anticoagulants in South Korea, and 3) lower rate of acute recanalization treatment in Japan.

Background: Current territorial maps are difficult to interpret because of highly variable territorial boundaries noted, thus complicating the assessment of stroke mechanism . Objective: To offer further knowledge on the variable anatomy of cerebral artery territory by providing terriorial maps of the anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA, respectively). Methods and Results: Digital maps of supratentorial infarcts were generated using diffusion-weighted MRIs of 1160 acute ( Conclusion: The new topographic brain atlas can be used in clinical care and research to objectively define the supratentorial arterial territories and their borders.

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 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.