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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.

OBJECTIVE We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score

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

Background Noncontrast computed tomography (NCCT) markers for hematoma expansion (HE) in intracerebral hemorrhage (ICH) are difficult to be found in small ICHs, of which can also expand. We aimed to investigate whether there were size-related differences in the prevalence of NCCT markers and their association with HE. Methods This retrospective analysis of prospectively collected stroke registry included 267 consecutive patients with ICH who underwent baseline NCCT within 12 h of onset. Qualitative NCCT markers, including heterogeneous density and irregular shape, were assessed. Hematoma density, defined as mean Hounsfield unit of hematoma, and hematoma volume were measured by semiautomated planimetry. Hematoma volume was categorized as small (≤ 10 ml) and large (> 10 ml). Associations of NCCT markers with HE were analyzed using multivariable logistic regression analyses. The model performances of NCCT markers and hematoma density were compared using receiver operating characteristic curves. Results Hematoma expansion occurred in 29.9% of small ICHs and 35.5% of large ICHs. Qualitative NCCT markers were less frequently observed in small ICHs. Heterogeneous density, irregular shape, and hematoma density were associated with HE in small ICH (adjusted odds ratios [95% confidence interval] 3.94 [1.50-10.81], 4.23 [1.73-10.81], and 0.72 [0.60-0.84], respectively), and hematoma density was also related to HE in large ICH (0.84 [0.73-0.97). The model performance was significantly improved in small ICHs when hematoma density was added to the baseline model (DeLong's test, p = 0.02). Conclusions The prevalence of NCCT markers and their association with HE differed according to hematoma volume. Quantitative hematoma density was associated with HE, regardless of hematoma size.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients’ healthcare use. This study evaluated changes in Korean stroke patients’ health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). Results: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO­VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%–2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. Discussion/Conclusion: Korean stroke patients in a CO­VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Low hemoglobin levels are known to be associated with hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). However, it is not yet known whether low hemoglobin itself causes HE directly or is merely a confounder. Thus, we investigated the mediation effect of the mean Hounsfield unit (HU) of hematoma on the relationship between low hemoglobin and expansion of ICH. Overall, 232 consecutive patients with ICH who underwent non-contrast computed tomography (NCCT) within 12 h since onset were included. The mean HU and hematoma volume on NCCT were investigated using semi-automated planimetry. HE was defined as an increase in hematoma volume > 33% or 6 mL. The respective associations among the hemoglobin level, mean HU, and HE were analyzed using multivariable regression analysis, adjusting for age, sex, and known HE predictors. Mediation analysis was performed to examine the potential causal association among the three. HE occurred in 34.5% of patients; hemoglobin levels were inversely associated with HE occurrence (adjusted odds ratio, 0.90; p = 0.03). The mean HU of the hematoma was lower in patients with HE than in patients without HE (58.5 ± 3.3 vs. 56.8 ± 3.0; p p p = 0.04). The proportion of indirect effect through the mean HU among the total effect was 19% (p = 0.05). The mediation effect became nonsignificant in the when the multivariable model was adjusted with additional covariates (baseline systolic blood pressure and hematoma location). The mean HU of the hematoma mediated the association between hemoglobin levels and HE occurrence. Therefore, the mean HU of the hematoma may be a potential marker of impaired hemostasis in patients with ICH.

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Background Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model. Methods In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was done by three clinicians, and accuracy, inter-rater reliability, and intra-rater reliability were assessed with Cohen's weighted kappa. Findings In our sample of 2950 patients (mean age 66 & middot;8 years [SD 11 & middot;6]; 1157 [39 & middot;2%] women), 1286 (43 & middot;6%) had PSCI. We achieved high lesion coverage of the brain in our analyses (86 & middot;9%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (after false discovery rate correction, q20). On cross-validation, the location impact score showed good correspondence, based on visual assessment of goodness of fit, between predicted and observed risk of PSCI across cohorts after adjusting for cohort specific PSCI occurrence. Cross-validations showed that the location impact score by itself had similar performance to the combined model with other PSCI predictors, while allowing for easy visual assessment. Therefore the univariable model with only the location impact score was selected as the final model. Correspondence between visual ratings and actual location impact score (Cohen's weighted kappa: range 0 & middot;88-0 & middot;92), inter-rater agreement (0 & middot;85-0 & middot;87), and intra-rater agreement (for a single rater, 0 & middot;95) were all high. Interpretation To the best of our knowledge, this study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI.A location impact score was derived from this map that robustly predicted PSCI across cohorts.Furthermore, we developed a quick and reliable visual rating scale that might in the future be applied by clinicians to identify individual patients at risk of PSCI.

The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated.In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed.Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months.END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

The temporal characteristics of stroke risks were evaluated in emergency department patients who had a diagnosis of peripheral vertigo. It was also attempted to reveal the stroke risk factor amongst those with peripheral vertigo.This is a parallel-group cohort study in a tertiary referral hospital. After assigning each of 4367 matched patients to the comparative set of peripheral vertigo and appendicitis-ureterolithiasis groups and each of 4911 matched patients to the comparative set of peripheral vertigo and ischaemic stroke groups, the relative stroke risk was evaluated. In addition, to predict the individual stroke risk in patients with peripheral vertigo, any association between the demographic factors and stroke events was evaluated in the peripheral vertigo group.The peripheral vertigo group had a higher stroke risk than the appendicitis-ureterolithiasis group (hazard ratio 1.73, 95% confidence interval 1.18-2.55) but a lower risk than the ischaemic stroke group (hazard ratio 0.30, 95% confidence interval 0.24-0.37). The stroke risk of the peripheral vertigo group was just below that of small vessel stroke. The stroke risk of the peripheral vertigo group differed markedly by time: higher within 7 days, moderate between 7 days and 1 year, and diminished thereafter. Old age (65 years), male gender and diabetes mellitus were the risk factors for stroke in the peripheral vertigo group.Patients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk and so a stroke preventive strategy tailored to the timing of symptom onset and individual risk is required.

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 and aims This study explores the relationship between systolic blood pressure during the acute period of stroke and poor functional outcome in patients with lacunar stroke, emphasizing a possible time-dependent nature of the relationship. Methods Based on multicenter stroke registry data, patients with acute lacunar stroke were identified, and systolic blood pressure levels at eight time points (1, 2, 4, 8, 16, 24, 48, and 72 h) after stroke onset were extracted at the 15 participating centers in South Korea. Poor functional outcome was defined as a three-month modified Rankin Scale score of 2–6. Non-linear restricted cubic spline and linear models were used for assessing the relationship at each time point. Results A total of 97,349 systolic blood pressure measurements of 3,042 patients were analyzed. At 1 h and 4 h after stroke onset, the relationship between systolic blood pressure and poor outcome showed a non-linear association. The nadir was 155 mmHg at 1 h and 124 mmHg at 4 h. After this time period, a higher systolic blood pressure was associated with a poorer outcome. This linear relationship weakened over time after 12 h (coefficient values of the adjusted linear models: 0.0081 at 8 h, 0.0105 at 12 h, 0.0102 at 24 h, 0.0082 at 48 h, 0.0054 at 72 h). Conclusions Based on our cohort of large number of lacunar stroke patients, our findings suggest that systolic blood pressure levels may follow a time-dependent course in relation to prediction of outcome at three months. The findings may be valuable for hypothesis generation in association with clinical trial development for blood pressure control in acute stroke patients.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

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

Background and Purpose Lesions on diffusion-weighted imaging (DWI) occasionally appear on follow-up magnetic resonance imaging (MRI) among initially DWI-negative but clinically suspicious stroke patients. We established the prevalence of positive conversion in DWI-negative stroke and determined the clinical factors associated with it.Methods This retrospective, observational, single-center study included 5,271 patients hospitalized due to stroke/transient ischemic attack (TIA) in a single university hospital during 2010 to 2017. Patients without initial DWI lesions underwent follow-up DWI imaging as a routine practice. Adjusted hazard ratios (aHRs) for recurrent stroke risk according to positive conversion were determined using Cox proportional hazard regression. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for positive conversion among initially DWI-negative patients were estimated.Results In total, 694 (13.2%) patients (mean±standard deviation age, 62.9±13.7 years; male, 404 [58.2%]) were initially DWI-negative. Among them, 22.5% had positive-conversion on follow-up DWI. Positive conversion was associated with a higher risk of recurrent stroke (aHR, 3.12; 95% CI, 1.56 to 6.26). Early neurologic deterioration (aOR, 15.1; 95% CI, 5.71 to 47.66), atrial fibrillation (aOR, 6.17; 95% CI, 3.23 to 12.01), smoking (aOR, 3.76; 95% CI, 2.19 to 6.63), pre-stroke dependency (aOR, 1.62; 95% CI, 1.15 to 2.27), objective hemiparesis (aOR, 4.39; 95% CI, 1.90 to 10.32), longer symptom duration (aOR, 2.17; 95% CI, 1.57 to 3.08), high cholesterol (aOR, 4.70; 95% CI, 1.78 to 12.77), National Institutes of Health Stroke Scale score (aOR, 1.44; 95% CI, 1.08 to 1.91), and high systolic blood pressure (aOR, 1.01; 95% CI, 1.00 to 1.02) were associated with a higher incidence of lesions with delayed appearance. Regarding the location of lesions on follow-up DWI, 34.6% and 21.2% were in the cortex and brainstem, respectively.Conclusions In DWI-negative stroke/TIA, positive conversion is associated with a higher risk of recurrent stroke. DWI-negative stroke with factors related to positive conversion may require follow-up MRI for a definitive diagnosis.

Background Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods We examined associations between impairment on the MMSE (Results Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p 15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.

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.

The association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context.National audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data.We analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (Annual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.

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.

Background and purpose To examine sex differences in disease profiles and short-term outcomes after acute ischemic stroke treated with recombinant tissue plasminogen activator. Methods Eight national and regional stroke registries contributed individual participant data from mainland China, Japan, Philippines, Singapore, South Korea and Taiwan in 2005–2018. The primary outcome was ordinal-modified Rankin scale at 90 days. Key safety outcome was symptomatic intracerebral hemorrhage (sICH). Results Of 4453 patients included in the analyses, 1692 (36.3%) were women who were older, more likely to have a more severe neurological deficit, history of hypertension and atrial fibrillation, and a cardioembolic stroke compared to men. Women were more likely than men to have unfavorable shift of modified Rankin scale (fully adjusted odds ratio) (women vs. men) 1.14, 95% confidence interval 1.02–1.28). There was no significant sex difference for death 1.05 (0.84–1.31) or sICH (1.17, 0.89–1.54). Women were more likely to have unfavorable functional outcome with increasing age (P = 0.022 for interaction). In the age groups 70–80 and ≥80 years, women had a worse functional outcome compared to men (1.22, 1.02–1.47 and 1.43, and 1.06–1.92, respectively). Conclusion In this pooled data from Asian acute stroke registries, women had poorer prognosis than men after receiving recombinant tissue plasminogen activator for acute ischemic stroke, which worsened with age. Women older than 70 appear to have a worse outcome than men which could be explained by greater stroke severity, more AF, and cardioembolic stroke.

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.

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 Clot contraction reinforces hemostasis by providing an impermeable barrier and contractile force. Since computed tomography attenuation of intracerebral hemorrhage is largely determined by the density of red blood cells, clot contraction can be reflected in an increase of Hounsfield unit (HU) of hematoma. Aims We hypothesized that hematoma expansion is inversely associated with mean HU of intracerebral hemorrhage at presentation. Methods Eighty-nine consecutive spontaneous intracerebral hemorrhage patients with onset to first computed tomography within 24 h were included. Hematomas were segmented using semiautomated planimetry to measure the volume and mean HU. Hematoma expansion was defined as an increase in hematoma volume by over 33% or 6 mL. Multivariable logistic regression was performed for hematoma expansion. The discrimination power of mean HU for hematoma expansion was assessed using C-statistic. Results The computed tomography attenuation of hematoma at presentation was 57.5 ± 3.3 HU and the volume was 16.9 ± 23.2 mL. Hematoma expansion occurred in 37.1% of patients. The computed tomography attenuation of hematoma was lower in patients with hematoma expansion than with no expansion (55.7 ± 2.9 HU vs. 58.6 ± 3.1 HU, p-value Conclusions Intracerebral hemorrhage with lower mean HU of hematoma at presentation is more likely to undergo hematoma expansion. This finding suggests the potential presence of clot contraction process that reinforces hemostasis in intracerebral hemorrhage.

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.

There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI.Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed.Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMIAIS; for EMS use, AMIAIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI.Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

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.

The serum lactate level is a useful predictor of mortality in critically ill patients. However, little is known about the association between the serum lactate level and mortality in patients admitted to neuro-intensive care units (NCUs). The present study aimed to investigate the association between the initial lactate level and 90-day mortality in NCU patients. This retrospective observational study was conducted by reviewing the medical records of adult (age ≥18 years) patients admitted to the NCU at a single tertiary care academic hospital during 2013–2017. The initial lactate level (mmol L−1) was defined as the serum lactate level measured within 6 h following NCU admission. The final analysis included 2737 patients, of whom 280 (10.2%) died within 90 days of NCU admission. In a receiver operating characteristic (ROC) analysis, the estimated area under the curve (AUC) for the initial lactate level in predicting overall 90-day mortality was 0.55 [95% confidence interval (CI): 0.52–0.59]. The corresponding values for neurologic and non-neurologic disease-related 90-day mortality were 0.76 (95% CI: 0.71–0.82) and 0.49 (95% CI: 0.45–0.53), respectively. In a multivariable Cox regression analysis, a 1-mmol L−1 increase in the initial lactate level was associated with 1.17- and 1.22-fold increases in overall and neurologic disease-related 90-day mortality, respectively, but not with non-neurological disease-related 90-day mortality (P = 0.422). Elevated lactate levels were related with an increase in overall 90-day mortality among NCU patients. This association was specifically attributed to neurologic disease-related 90-day mortality.

Background To clarify differences in clinical significance of intracardiac thrombi in nonvalvular atrial fibrillation‐associated stroke as identified by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). Methods and Results Using patient data on nonvalvular atrial fibrillation‐associated ischemic stroke between 2011 and 2014 from 15 South Korean stroke centers (n=4841) and 18 Japanese centers (n=1192), implementation rates of TEE/TTE, and detection rates of intracardiac thrombi at each center were correlated. The primary outcome was recurrent ischemic stroke at 1 year after the onset. A total of 5648 patients (median age, 75 years; 2650 women) were analyzed. Intracardiac thrombi were detected in 75 patients (1.3%) overall. Thrombi were detected in 7.8% of patients with TEE (either TEE alone or TEE+TTE: n=679) and in 0.6% of those with TTE alone (n=3572). Thrombus detection rates varied between 0% and 14.3% among centers. As TEE implementation rates at each center increased from 0% to 56.7%, thrombus detection rates increased linearly (detection rate [%]=0.11×TEE rate [%]+1.09 [linear regression], P P =0.53). Intracardiac thrombi were associated with risk of recurrent ischemic stroke overall (adjusted hazard ratio [aHR] 2.35, 95% CI, 1.07–5.16). Thrombus‐associated ischemic stroke risk was high in patients with TEE (aHR, 3.13; 95% CI, 1.17–8.35), but not in those with TTE alone (aHR, 0.89; 95% CI, 0.12–6.51). Conclusions Our data suggest clinical relevance of TEE for accurate detection and risk stratification of intracardiac thrombi in nonvalvular atrial fibrillation‐associated stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502.

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: Data on adjunctive intra-arterial thrombolysis during mechanical thrombectomy for refractory thrombus are sparse. The aim of this study was to evaluate the efficacy and safety of local intra-arterial urokinase as an adjunct to mechanical thrombectomy for refractory large-vessel occlusion. MATERIALS AND METHODS: We retrospectively evaluated patients with acute ischemic stroke who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion between January 2016 and December 2019. Patients were divided into 2 groups based on the use of intra-arterial urokinase as an adjunctive therapy during mechanical thrombectomy for refractory thrombus: the urokinase and nonurokinase groups. Herein, refractory thrombus was defined as the target occlusion with minimal reperfusion (TICI 0 or 1) despite >3 attempts with conventional mechanical thrombectomy. The baseline characteristics, procedural outcomes, and clinical outcome were compared between the 2 groups. RESULTS: One hundred fourteen cases of refractory thrombus were identified. A total of 45 and 69 patients were in the urokinase and the nonurokinase groups, respectively. The urokinase group compared with the nonurokinase group showed a higher rate of successful reperfusion (82.2% versus 63.8%, P = .034), with lower procedural times (54 versus 69 minutes, P = .137). The rates of good clinical outcome, distal embolism, and symptomatic intracranial hemorrhage were similar between the 2 groups. The use of intra-arterial urokinase (OR = 3.682; 95% CI, 1.156–11.730; P = .027) was an independent predictor of successful reperfusion. CONCLUSIONS: The use of local intra-arterial urokinase as an adjunct to mechanical thrombectomy may be an effective and safe method that provides better recanalization than the conventional mechanical thrombectomy for refractory thrombus in patients with embolic large-vessel occlusion.