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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.

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.

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.

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.

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.

Background There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF. Methods AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine–Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset. Results The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA). Conclusions Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.

BACKGROUND AND PURPOSE Previous observational studies have reported that patients with migraine have an increased risk of stroke. We explored whether migraine has a causal effect on stroke using a two-sample Mendelian randomization approach. METHODS Genetic instruments were selected from large genome-wide association studies of migraine and stroke. A two-sample Mendelian randomization analysis was performed, along with sensitivity analysis. We used migraine subtypes (any migraine, migraine with aura, migraine without aura) as risk factors and stroke, ischemic stroke, and hemorrhagic stroke as outcomes for this analysis. Ischemic stroke subtypes were also included to explore the underlying pathogenesis linking migraine to stroke. RESULTS Migraine did not show any association with stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.87-1.03), ischemic stroke (OR, 0.93; 95% CI, 0.85-1.02), or hemorrhagic stroke (OR, 1.26; 95% CI, 0.84-1.91), suggesting that the observed association may not be causal. Neither migraine with aura nor without aura showed causal relationship with outcomes. The sensitivity analysis supported the results of the primary analysis. Regarding ischemic stroke subtypes, migraine seemed to have a negative association with large-artery atherosclerosis (OR, 0.81; 95% CI, 0.68-0.95), whereas associations with small-vessel occlusion or cardioembolism were not evident. CONCLUSIONS Contrary to previous observational studies, we were unable to find any causal relationship between migraine and stroke. However, the suggested negative association of migraine in large-artery atherosclerosis warrants further research.

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

OBJECTIVE To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intra-arterial thrombectomy (IAT). RESEARCH DESIGN AND METHODS From the Clinical Research Center for Stroke–Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed. RESULTS A total of 1,351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA1c at admission (P = 0.02 according to HbA1c quintiles, P = 0.003 according to an HbA1c cutoff value of 7.0%) than in those with lower HbA1c levels. Higher HbA1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0–7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period. CONCLUSIONS Prestroke glucose control with a target HbA1c of ≤7.0% may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period.

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

We investigated whether intraoperative systolic blood pressure (ISBP) is associated with the risk of transient neurologic deficits (TND) following superficial temporal-to-middle cerebral artery (STA-MCA) anastomosis in adult patients with moyamoya disease (MMD). In this retrospective observational study, data from adult patients with MMD who had undergone STA-MCA anastomosis at a single tertiary academic hospital during May 2003–April 2014 were examined. Data on patient characteristics were obtained from electronic medical records, including the details of comorbidities and laboratory findings. TND was the primary outcome of interest. Out of 192 patients (228 hemispheres), 66 (29%) hemispheres had TND after surgery. There were significant differences in ISBP between patients with and without TND. The lowest ISBP quartile was independently associated with TND (odds ratio: 5.50, 95% confidence interval: 1.96–15.46). Low ISBP might lead to TND after STA-MCA anastomosis in adult patients with MMD. In patients with poor perfusion status, low ISBP was associated with an increased risk of TND. Our findings suggest that strict ISBP control might be required to prevent TND after anastomosis in patients with MMD, in particular, in patients with poor perfusion status. Given limitations due to the retrospective design, further studies are needed to clarify these findings.

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.

We aimed to investigate whether blood pressure (BP) in the subacute stage of ischemic stroke affects subsequent vascular events after acute ischemic stroke.From a prospective stroke registry database, consecutive ischemic stroke patients arriving within 48 h of onset were identified. The mean and SD of SBP per patient (SBPmean and SBPSD) in the subacute stage (from 72 h of onset to discharge), were calculated. Primary outcome was a composite of stroke, myocardial infarction and vascular death that occurred within 1 year after hospital discharge. A Cox proportional hazards model was applied to elucidate whether the increase of SBPmean and SBPSD would increase the hazards of the primary outcome.Of 4415 patients (age, 66.7 ± 13.2 years; men, 69.5%), mean ± SD of SBPmean and SBPSD in the subacute stage was 137.3 ± 15.4 and 13.3 ± 3.9 mmHg, respectively. Primary outcome events occurred in 6.9% during the first year after stroke. There was a significant dose-response relationship between the SBPSD and the risk of the primary outcome (P = 0.004), but not between SBPmean and the risk (P = 0.78). Interpolating the change of adjusted hazard ratio using restricted cubic spine function suggested an existence of a threshold effect of SBPSD and a U-shaped relationship of SBPmean for the composite event.This study shows that BP variability but not mean BP in the subacute stage of ischemic stroke may increase 1-year risk of major vascular events in patients surviving its acute stage.

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.

Purpose Although endovascular treatment is currently thought to only be suitable for patients who have pial arterial filling scores >3 as determined by multiphase computed tomography angiography (mpCTA), a cut-off score of 3 was determined by a study, including patients within 12 hours after symptom onset. We aimed to investigate whether a cut-off score of 3 for endovascular treatment within 6 hours of symptom onset is an appropriate predictor of good functional outcome at 3 months. Materials and Methods From April 2015 to January 2016, acute ischemic stroke patients treated with mechanical thrombectomy within 6 hours of symptom onset were enrolled into this study. Pial arterial filling scores were semi-quantitatively assessed using mpCTA, and clinical and radiological parameters were compared between patients with favorable and unfavorable outcomes. Multivariate logistic regression analysis was then performed to investigate the independent association between clinical outcome and pial collateral score, with the predictive power of the latter assessed using C-statistics. Results Of the 38 patients enrolled, 20 (52.6%) had a favorable outcome and 18 had an unfavorable outcome, with the latter group showing a lower mean pial arterial filling score (3.6±0.8 vs. 2.4±1.2, P=0.002). After adjusting for variables with a P-value of 2 vs. ≤2. Conclusion A pial arterial filling cut-off score of 2 as determined by mpCTA appears to be more suitable for predicting clinical outcomes following endovascular treatment within 6 hours of symptom onset than the cut-off of 3 that had been previously suggested.

Endovascular recanalization therapy (ERT) has been a standard of care for patients with acute ischemic stroke due to large artery occlusion (LAO) within 6 hours after onset since the five landmark ERT trials up to 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window up to 16 hours or 24 hours after last known normal time, improved the outcome of patients who had a target mismatch defined as either clinical-core mismatch or perfusion-core mismatch, which prompted the update of national guidelines in several countries. Accordingly, to provide evidence-based and up-to-date recommendations for ERT in patients with acute LAO in Korea, the Clinical Practice Guidelines Committee of the Korean Stroke Society decided to revise the previous Korean Clinical Practice Guidelines of Stroke for ERT. For this update, the members of the writing group were appointed by the Korean Stroke Society and the Korean Society of Interventional Neuroradiology. After thorough reviewing the updated evidence from two recent trials and relevant literature, the writing members revised recommendations, for which formal consensus was achieved by convening an expert panel composed of 45 experts from the participating academic societies. The current guidelines are intended to help healthcare providers, patients, and their caregivers make their well-informed decisions and to improve the quality of care regarding ERT. The ultimate decision for ERT in a particular patient must be made in light of circumstances specific to that patient.

Background This study explored the associations of blood pressure (BP) with various stroke outcomes and investigated their changes by the elapsed time after stroke onset. Methods Patients who arrived within 48 hours of stroke onset between April 2008 and September 2014 were consecutively enrolled. For 10 days of hospitalization, all measured systolic BP (SBP) was summarized into mean at acute (first 3 days) and subacute stage (afterward to 7 days) for each patient. Coprimary outcomes were unfavorable outcome (modified Rankin Scale >2) at discharge and time to composite cardiovascular event of stroke, myocardial infarction, and vascular death for 1-year follow-up. Adjusted odds ratios (AOR) through SBP mean in both acute and subacute stages were interpolated using restricted cubic spline technique and adopted logistic regression models with predetermined covariates. The adjusted hazard ratios for cardiovascular event by SBP mean in both stages were interpolated. Results The study enrolled 3723 subjects (mean age, 66.7 ± 13.2 years old and median baseline National Institute of Health Stroke Scale score, 3). SBP mean in both stages showed linear trends for risks of unfavorable outcome, while the increase of AOR was observed explicitly in acute stage rather than subacute stage, especially in higher values. In contrast, SBP mean demonstrated the U-shaped associations with cardiovascular event in subacute stage rather than acute stage. Conclusions In ischemic stroke, association patterns of BP would be different depending on stroke outcomes. The risky interval of BP would be changed by the elapsed time after stroke onset.

Background and purpose To investigate the number and characteristics of patients eligible for endovascular treatment (EVT) determined using three different selection methods clinical-core mismatch, target mismatch, and collateral status. Methods Using the data of consecutive patients from two prospectively maintained registries of university medical centers, the number and characteristics of patients according to the three selection methods were investigated and their correlation was analyzed. Patients with anterior circulation stroke due to occlusion of the middle cerebral and/or internal carotid artery and a National Institute of Health Stroke Scale (NIHSS) score of ≥6 points, who arrived within 8 hours or between 6 and 12 hours of symptom onset and underwent magnetic resonance imaging prior to EVT, were included. Collateral status was assessed using magnetic resonance perfusion-derived collateral flow maps. Results Three hundred thirty-five patients were investigated; the proportions of patients who were eligible and ineligible for EVT in all three selection methods were both small (n=85, 25.4%; n=54, 16.1%, respectively). The intercorrelation among the three selection methods was low (κ=0.235). The baseline NIHSS score and onset-to-selection time interval were associated with the presence of clinical-core mismatch, while the penumbra/core volume ratio and onset-to-selection time interval were related to target mismatch; none of these variables were associated with collateral status. The infarct core volume was associated with favorable profiles in all three selection methods. Conclusion s Although the application of individual selection methods resulted in favorable outcomes after EVT in clinical trials, there is a significant discrepancy in EVT eligibility depending on the selection method used.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background This study aimed to examine the association between preadmission statin use and 90-day mortality in critically ill patients and to investigate whether this association differed according to statin type and dose. We hypothesized that preadmission statin use was associated with lower 90-day mortality. Methods This retrospective cohort study analyzed the medical records of all adult patients admitted to the intensive care unit in a single tertiary academic hospital between January 2012 and December 2017. Data including preadmission statin use, statin subtype, and daily dosage were collected, and the associations between these variables and 90-day mortality after intensive care unit admission were examined. The primary endpoint was 90-day mortality. Results A total of 24,928 patients (7,396 statin users and 17,532 non–statin users) were included. After propensity score matching, 5,354 statin users and 7,758 non–statin users were finally included. The 90-day mortality rate was significantly higher in non–statin users (918 of 7,758; 11.8%) than in statin users (455 of 5,354; 8.5%; P < 0.001). In Cox regression analysis, the 90-day mortality rate was lower among statin users than among non–statin users (hazard ratio: 0.70, 95% CI: 0.63 to 0.79; P < 0.001). Rosuvastatin use was associated with 42% lower 90-day mortality (hazard ratio: 0.58, 95% CI: 0.47 to 0.72; P < 0.001). There were no specific significant differences in the association between daily statin dose and 90-day mortality. In competing risk analysis, the risk of noncardiovascular 90-day mortality in statin users was 32% lower than that in non–statin users (hazard ratio: 0.68, 95% CI: 0.60 to 0.78; P < 0.001). Meanwhile, cardiovascular 90-day mortality was not significantly associated with statin use. Conclusions Preadmission statin use was associated with a lower 90-day mortality. This association was more evident in the rosuvastatin group and with noncardiovascular 90-day mortality; no differences were seen according to daily dosage intensity.

The etiology or rate of recurrent ischemic stroke according to dosing methods including drug adherence in patients taking non-vitamin K antagonist oral anticoagulants (NOACs) remain uncertain. We investigated the association between dosing methods including drug adherence achieved with NOACs and the presence of major vessel occlusion (MVO) in patients with ischemic stroke with non-valvular atrial fibrillation (NVAF). From July 2013 through December 2016, 120 patients with recurrent ischemic stroke with NVAF on NOACs were retrospectively analyzed. Patients taking non-standard doses of NOACs were divided into the missed dose group that discontinued NOACs for ≥48 h prior to arrival, and the under-dose group that used lower doses of NOACs. A logistic regression analysis was performed to determine the association between MVO and dosing methods including drug adherence. There were 60 (50.0%), 39 (32.5%), and 21 (17.5%) patients, respectively, in the standard dose, under-dose, and missed dose groups. Twelve patients (20.0%) in the standard dose group, 15 (38.5%) in the under-dose group, and 13 (61.9%) in the missed dose group had MVO. MVO was significantly higher in the missed dose group than in the standard dose and under-dose groups (P = 0.002). In patients with ischemic stroke with NVAF, who are on NOACs, anticoagulation caused by missed or lowered doses of NOACs was significantly associated with MVO in patients with recurrent cardioembolic stroke.

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

BACKGROUND: There is limited information about non-selective and contemporary data on quality of stroke care and its variation among hospitals at a national level. PATIENTS AND METHODS: We analysed data of the patients admitted to 258 acute stroke care hospitals covering the entire country from the Acute Stroke Quality Assessment Program, which was performed by the Health Insurance Review and Assessment Service from 2008 to 2014 in South Korea. The primary outcome measure was defect-free stroke care (all-or-none), based on six get with the guidelines-stroke performance measures (except venous thromboembolism prophylaxis). RESULTS: Among 43,793 acute stroke patients (mean age, 67 ± 14 years; male, 55%), 31,915 (72.9%) were hospitalised due to ischaemic stroke. At a patient level, defect-free stroke care steadily increased throughout the study period (2008, 80.2% vs. 2014, 92.1%), but there were large disparities among hospitals (mean = 50.7%, SD = 21.7%). Defect-free stroke care was given more frequently in patients being treated in hospitals with 25 or more stroke cases per month (odds ratio [OR] 2.83; 95% confidence interval [CI] 1.69–4.72), delivery of intravenous thrombolysis one or more times per month (OR 2.37; 95% CI 1.44–3.92), or provision of stroke unit care (OR 1.75; 95% CI 1.22–2.52). DISCUSSION: This study shows that the quality of stroke care in Korea is improving over time and is higher in centres with a larger volume of stroke or intravenous thrombolysis cases and providing stroke unit care but hospital disparities exist. CONCLUSION: Reducing large differences in defect-free stroke care among acute stroke care hospitals should be continuously pursued.

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.

Non-valvular atrial fibrillation patients receiving non-vitamin K antagonist oral anticoagulants (NOACs) have half the incidence of intracerebral hemorrhage (ICH) compared to those receiving warfarin. However, the differences in outcomes of NOAC-associated ICH (NICH) and warfarin-associated ICH (WICH) remain controversial. In this study, we investigated the clinical outcome and radiologic findings of ICH in Asian patients receiving NOACs or warfarin. We retrospectively reviewed the medical records of 544 ICH patients admitted to our hospital from January 2013 through December 2017, and compared the baseline demographics, clinical characteristics, ICH-related radiologic findings, and clinical outcome between the WICH and NICH groups. WICH and NICH were diagnosed in 46 and 13 patients, respectively. Lesions were located more frequently in the supratentorial deep area (45.7% and 46.2%) than the lobar area (30.4% and 30.8%) or brainstem and cerebellum (23.9% and 23.1%) in the WICH and NICH groups, respectively. The hematoma expansion and concomitant intraventricular hemorrhage (IVH) rate was significantly higher in the WICH group than in the NICH group (58.7% versus 7.7%, P = 0.001 and 50.0% versus 15.4%, P = 0.030, respectively). Hematoma expansion (odds ratio [OR]: 50.546; 95% confidence interval [CI]: 2.763–924.748; P = 0.008) and concomitant IVH (OR: 9.240; 95% CI: 1.450–58.892; P = 0.019) were independently associated with mortality at three months, after adjustment for confounding variables. Our results indicate that the radiological findings and clinical outcome at three months in patients with ICH are more favorable in those receiving NOAC therapy than in those receiving warfarin treatment.

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

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

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

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

BackgroundDepression is the most common neuropsychiatric complication after stroke. Infarct location is associated with post-stroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations, and white matter disconnections, associated with PSDS.MethodsWe included 553 patients (age 69±11 years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale (GDS-30). Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (SVR-VLSM) and predefined regions of interest (SVR-ROI) to relate infarct location to PSDS. We externally validated our findings in an independent stroke cohort (N=459). Finally, disconnectome-based analyses were performed using SVR-VLSM, in which white matter fibers disconnected by the infarct were analyzed instead of the infarct itself. Results: Infarcts in the right amygdala, right hippocampus and right pallidum were consistently associated with PSDS (permutation-based pConclusionsInfarcts in the right amygdala and pallidum, and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits, are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS, and shed new light on pathophysiological mechanisms of depression after stroke.