Standard Versus Intensive Blood Pressure Control in Acute Ischemic Stroke Patients Successfully Treated With Endovascular Thrombectomy: A Systemic Review and Meta-Analysis of Randomized Controlled Trials / 대한뇌졸중학회지

Background@#and Purpose The optimal blood pressure (BP) control after successful endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) with large vessel occlusion (LVO) remains debatable. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluate the efficacy and safety of standard BP control (with systolic BP ≤180 mm Hg) versus intensive BP control (systolic BP <140 mm Hg) during the 24 hours after successful EVT in AIS with LVO. @*Methods@#PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Embase were searched to identify relevant trials. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated and estimates using random-effects models were pooled. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: CRD42023450673). @*Results@#Four RCTs involving 1,559 participants were included. Regarding efficacy outcomes, intensive BP control was associated with a lower likelihood of functional independence (OR: 0.68; 95% CI: 0.51–0.91 for modified Rankin Scale [mRS] ≤2) and walking without assistance (OR: 0.65; 95% CI: 0.53–0.81 for mRS ≤3). For safety outcomes, consistent with the efficacy findings, intensive BP control was significantly associated with severe disability or death (mRS 5 or 6) (OR: 1.34; 95% CI: 1.07–1.69). However, there were no significant differences including all-cause mortality, any intracerebral hemorrhage (ICH), symptomatic ICH, parenchymal hematoma type 2, and stroke recurrence. @*Conclusion@#While all four RCTs were conducted to demonstrate the superiority of intensive BP control over standard BP control, standard BP control may be beneficial for the outcome after EVT for AIS with LVO without increasing adverse safety outcomes. Caution should be needed with the application of intensive BP control during the 24 hours following successful recanalization after EVT.

Brain Frailty and Outcomes of Acute Minor Ischemic Stroke With Large-Vessel Occlusion

Background@#and Purpose The influence of imaging features of brain frailty on outcomes were investigated in acute ischemic stroke patients with minor symptoms and large-vessel occlusion (LVO). @*Methods@#This was a retrospective analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute (within 24 h) minor (National Institutes of Health Stroke Scale score=0–5) ischemic stroke with anterior circulation LVO (acute minor LVO). Brain frailty was stratified according to the presence of an advanced white-matter hyperintensity (WMH) (Fazekas grade 2 or 3), silent/old brain infarct, or cerebral microbleeds. The primary outcome was a composite of stroke, myocardial infarction, and all-cause mortality within 1 year. @*Results@#In total, 1,067 patients (age=67.2±13.1 years [mean±SD], 61.3% males) were analyzed. The proportions of patients according to the numbers of brain frailty burdens were as follows: no burden in 49.2%, one burden in 30.0%, two burdens in 17.3%, and three burdens in 3.5%. In the Cox proportional-hazards analysis, the presence of more brain frailty burdens was associated with a higher risk of 1-year primary outcomes, but after adjusting for clinically relevant variables there were no significant associations between burdens of brain frailty and 1-year vascular outcomes. For individual components of brain frailty, an advanced WMH was independently associated with an increased risk of 1-year primary outcomes (adjusted hazard ratio [aHR]=1.33, 95% confidence interval [CI]=1.03–1.71) and stroke (aHR=1.32, 95% CI=1.00–1.75). @*Conclusions@#The baseline imaging markers of brain frailty were common in acute minor ischemic stroke patients with LVO. An advanced WMH was the only frailty marker associated with an increased risk of vascular events. Further research is needed into the association between brain frailty and prognosis in patients with acute minor LVO.

A Multimodal Ensemble Deep Learning Model for Functional Outcome Prognosis of Stroke Patients / 대한뇌졸중학회지

Background@#and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. @*Methods@#We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. @*Results@#Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). @*Conclusion@#The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke

Background@#For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. @*Methods@#Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). @*Results@#The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). @*Conclusions@#In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Emergency Cervical Carotid Artery Stenting After Intravenous Thrombolysis in Patients With Hyperacute Ischemic Stroke

Background@#Intravenous recombinant tissue plasminogen activator (IV rtPA) is the mainstay of treatment for acute ischemic stroke to recanalize thrombosed intracranial vessels within 4.5 hours. Emergency carotid artery stenting for the treatment of acute stroke due to stenoocclusion of the proximal internal carotid artery (ICA) can improve symptoms, prevent neurological deterioration, and reduce recurrent stroke risk. The feasibility and safety of the combination therapy of IV rtPA and urgent carotid artery stenting have not been established. @*Methods@#From November 2005 to October 2020, we retrospectively assessed patients who had undergone emergent carotid artery stenting after IV rtPA for hyperacute ischemic stroke due to steno-occlusive proximal ICA lesion. Hemorrhagic transformation, successful recanalization, modified Rankin Scale (mRS) score at 90 days, and stent patency at 3 and 12 months or longer were evaluated. Favorable outcome was defined as a 90-days mRS score of ≤ 2. @*Results@#Nineteen patients with hyperacute stroke had undergone emergent carotid artery stenting after IV rtPA therapy. Their median age was 70 (67.5–73.5) years (94.7% men).Among 15 patients with an additional intracranial occlusion after flow restoration in the proximal ICA, a modified TICI grade ≥ 2b was achieved in 11 patients (73.3%). Hemorrhagic transformation occurred in five patients (26.3%); mortality rate was 5.7%. Eleven patients (57.9%) had favorable outcomes at 90 days. Stent patients (94.1%) maintained stent patency for ≥ 12 months. @*Conclusion@#We showed that emergent carotid artery stenting after IV rtPA therapy for hyperacute stroke caused by atherosclerotic proximal ICA steno-occlusion was feasible and safe.

The effectiveness of systemic and endovascular intra-arterial thrombectomy protocol for decreasing door-to-recanalization time duration

Objective@#Variable treatment strategies and protocols have been applied to reduce time durations in the process of acute stroke management. The aim of this study is to investigate the effectiveness of our intra-arterial thrombectomy (IAT) protocol for decreasing door-to-recanalization time duration and improve successful recanalization. @*Methods@#A systemic and endovascular protocol included door-to-image, image-to-puncture and puncture-to-recanalization. We retrospectively analyzed the patients of pre- (Sep 2012–Apr 2014) and post-IAT protocol (May 2014–Jul 2018). Univariate analysis was used for the statistical significance according to variable factors (age, gender, the location of occluded vessel, successful recanalization TICI 2b-3). Independent t-test was used to compare the time duration. @*Results@#Among all 267 patients with acute stroke of anterior circulation, there were 50 and 217 patients with pre- and post-IAT protocol. Age, gender, and the location of occluded vessel have no statistical significance (p＞0.05). In pre- and post-IAT group, successful recanalization was 39 of 50 (78.0%) and 185/217 (85.3%), respectively (p＜0.05). Post-IAT (48.8%, 106/217) group had a higher tendency of good outcome than pre-IAT group (36.0%, 18/50) (p＞0.05). Pre- and post-IAT group showed 61.7±21.4 vs. 25±16.0 (p＜0.05), 102.0±29.8 vs. 82.7±30.4 (min) (p＜0.05), and 79.1±47.5 vs. 58.4±75.3 (p＜0.05) in three steps, respectively. @*Conclusions@#We suggest that the application of systemic and endovascular IAT protocols showed a significant time reduction for faster recanalization in patients with LVO. To build-up the well-designed IAT protocol through puncture-to-recanalization can be needed to decrease time duration and improve clinical outcome in recanalization therapy in acute stroke patients.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality / 대한뇌졸중학회지

Background@#and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. @*Methods@#We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). @*Results@#There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. @*Conclusions@#During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Factors Contributing to an Efficacious Endovascular Treatment for Acute Ischemic Stroke in Asian Population / 신경중재치료의학

Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.

Factors Contributing to an Efficacious Endovascular Treatment for Acute Ischemic Stroke in Asian Population / 신경중재치료의학

Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.

Prehospital Notification Using a Mobile Application Can Improve Regional Stroke Care System in a Metropolitan Area

Background@#Acute ischemic stroke is a time-sensitive disease. Emergency medical service (EMS) prehospital notification of potential patients with stroke could play an important role in improving the in-hospital medical response and timely treatment of patients with acute ischemic stroke. We analyzed the effects of FASTroke, a mobile app that EMS can use to notify hospitals of patients with suspected acute ischemic stroke at the prehospital stage. @*Methods@#We conducted a retrospective observational study of patients diagnosed with acute ischemic stroke at 5 major hospitals in metropolitan Daegu City, Korea, from February 2020 to January 2021. The clinical conditions and time required for managing patients were compared according to whether the EMS employed FASTroke app and further compared the factors by dividing the patients into subgroups according to the preregistration received by the hospitals when using FASTroke app. @*Results@#Of the 563 patients diagnosed with acute ischemic stroke, FASTroke was activated for 200; of these, 93 were preregistered. The FASTroke prenotification showed faster door-tocomputed-tomography times (19 minutes vs. 25 minutes, P < 0.001), faster door-to-intravenousthrombolysis times (37 minutes vs. 48 minutes, P < 0.001), and faster door-to-endovascularthrombectomy times (82 minutes vs. 119 minutes, P < 0.001). The time was further shortened when the preregistration was conducted simultaneously by the receiving hospital. @*Conclusion@#The FASTroke app is an easy and useful tool for prenotification as a regional stroke care system in the metropolitan area, leading to reduced transport and acute ischemic stroke management time and more reperfusion treatment. The effect was more significant when the preregistration was performed jointly.

Long-Term Changes in Post-Stroke Depression, Emotional Incontinence, and Anger / 대한뇌졸중학회지

Background@#and Purpose Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied. @*Methods@#This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim’s criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP. @*Results@#A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P<0.01) decreased, while the prevalence of PSD (35.6%, 44.6%; P=0.03) and mean MADRS (6.16, 8.67; P<0.01) increased at LTP. ESSI was associated with PSD and PSA, but not with PSEI. The effect of the baseline National Institutes of Health Stroke Scale score on PSD decreased over time. The effect of low social support on PSD was greater than that of mRS at LTP. @*Conclusions@#The prevalence and degree of PSD significantly increased, while those of PSEI and PSA decreased at LTP. PSD in this stage appeared to be more closely associated with a lack of social support than patients' physical disabilities.

Care Process of Recanalization Therapy for Acute Stroke during the COVID-19 Outbreak in South Korea

Background@#and Purpose We aimed to determine whether the care process and outcomes in patients with acute stroke who received recanalization therapy changed during the outbreak of coronavirus disease 2019 (COVID-19) in South Korea. @*Methods@#We used data from a prospective multicenter reperfusion therapy registry to compare the care process including the time from symptom onset to treatment, number of treated patients, and discharge disposition and treatment outcomes between before and during the COVID-19 outbreak in South Korea. @*Results@#Upon the COVID-19 outbreak in South Korea, the number of patients receiving endovascular treatment to decrease temporarily but considerably. The use of emergency medical services by stroke patients increased from 91.5% before to 100.0% during the COVID-19 outbreak (p=0.025), as did the median time from symptom onset to hospital visit [median (interquartile range), 91.0 minutes (39.8–277.0) vs. 176.0 minutes (56.0–391.5), p=0.029]. Furthermore, more functionally dependent patients with disabilities were discharged home (59.5% vs. 26.1%, p=0.020) rather than staying in a regional or rehabilitation hospital. In contrast, there were no COVID-19-related changes in the times from the hospital visit to brain imaging and treatment or in the functional outcome, successful recanalization rate, or rate of symptomatic intracerebral hemorrhage. @*Conclusions@#These findings suggest that a prehospital delay occurred during the COVID-19 outbreak, and that patients with acute stroke might have been reluctant to visit and stay in hospitals. Our findings indicate that attention should be paid to prehospital care and the behavior of patients with acute stroke during the COVID-19 outbreak.

Long-Term Changes in Post-Stroke Depression, Emotional Incontinence, and Anger / 대한뇌졸중학회지

Background@#and Purpose Long-term changes in post-stroke depression (PSD), post-stroke emotional incontinence (PSEI), and post-stroke anger (PSA) have rarely been studied. @*Methods@#This is a sub-study of EMOTION, a randomized, placebo-controlled trial, that examined the efficacy of escitalopram on PSD, PSEI, and PSA in patients with stroke. We interviewed patients at the long-term period (LTP) using predefined questionnaires: Montgomery-Åsberg depression rating scale (MADRS) for PSD, modified Kim’s criteria for PSEI, and Spielberger trait anger scale for PSA. Additionally, the ENRICHD Social Support Instrument (ESSI) for the social support state and the modified Rankin Scale (mRS) were measured. We investigated the changes in and factors behind PSD, PSEI, and PSA at LTP. @*Results@#A total of 222 patients were included, and the median follow-up duration was 59.5 months (interquartile range, 50 to 70). Compared to the data at 6 months post-stroke, the prevalence of PSEI (11.7% at 6 months, 6.3% at LTP; P=0.05) and mean anger score (21.62, 16.24; P<0.01) decreased, while the prevalence of PSD (35.6%, 44.6%; P=0.03) and mean MADRS (6.16, 8.67; P<0.01) increased at LTP. ESSI was associated with PSD and PSA, but not with PSEI. The effect of the baseline National Institutes of Health Stroke Scale score on PSD decreased over time. The effect of low social support on PSD was greater than that of mRS at LTP. @*Conclusions@#The prevalence and degree of PSD significantly increased, while those of PSEI and PSA decreased at LTP. PSD in this stage appeared to be more closely associated with a lack of social support than patients' physical disabilities.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study

Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study

Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Characteristics of Acute Stroke in Patients with Coronavirus Disease 2019 and Challenges in Stroke Management during an Epidemic

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infection associated with high morbidity and mortality. The Korean city of Daegu endured the first large COVID-19 outbreak outside of China. Since the report of the first confirmed case in Daegu on February 18, 2020, a total of 6,880 patients have been reported until May 29, 2020. We experienced five patients with ischemic stroke and COVID-19 during this period in four tertiary hospitals in Daegu. The D-dimer levels were high in all three patients in whom D-dimer blood testing was performed.Multiple embolic infarctions were observed in three patients and suspected in one. The mean time from stroke symptom onset to emergency room arrival was 22 hours. As a result, acute treatment for ischemic stroke was delayed. The present case series report raises the possibility that the coronavirus responsible for COVID-19 causes or worsens stroke, perhaps by inducing inflammation. The control of COVID-19 is very important; however, early and proper management of stroke should not be neglected during the epidemic.

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial / 대한뇌졸중학회지

Background@#and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. @*Methods@#Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. @*Results@#One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. @*Conclusions@#Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study.

The aim of the ICARO-3 study was to evaluate whether intra-arterial treatment, compared to intravenous thrombolysis, increases the rate of favourable functional outcome at 3 months in acute ischemic stroke and extracranial ICA occlusion. ICARO-3 was a non-randomized therapeutic trial that performed a non-blind assessment of outcomes using retrospective data collected prospectively from 37 centres in 7 countries. Patients treated with endovascular treatment within 6 h from stroke onset (cases) were matched with patients treated with intravenous thrombolysis within 4.5 h from symptom onset (controls). Patients receiving either intravenous or endovascular therapy were included among the cases. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale (mRS), dichotomized as favourable (score of 0-2) or unfavourable (score of 3-6). Safety outcomes were death and any intracranial bleeding. Included in the analysis were 324 cases and 324 controls: 105 cases (32.4 %) had a favourable outcome as compared with 89 controls (27.4 %) [adjusted odds ratio (OR) 1.25, 95 % confidence interval (CI) 0.88-1.79, p = 0.1]. In the adjusted analysis, treatment with intra-arterial procedures was significantly associated with a reduction of mortality (OR 0.61, 95 % CI 0.40-0.93, p = 0.022). The rates of patients with severe disability or death (mRS 5-6) were similar in cases and controls (30.5 versus 32.4 %, p = 0.67). For the ordinal analysis, adjusted for age, sex, NIHSS, presence of diabetes mellitus and atrial fibrillation, the common odds ratio was 1.15 (95 % IC 0.86-1.54), p = 0.33. There were more cases of intracranial bleeding (37.0 versus 17.3 %, p = 0.0001) in the intra-arterial procedure group than in the intravenous group. After the exclusion of the 135 cases treated with the combination of I.V. thrombolysis and I.A. procedures, 67/189 of those treated with I.A. procedures (35.3 %) had a favourable outcome, compared to 89/324 of those treated with I.V. thrombolysis (27.4 %) (adjusted OR 1.75, 95 % CI 1.00-3.03, p = 0.05). Endovascular treatment of patients with acute ICA occlusion did not result in a better functional outcome than treatment with intravenous thrombolysis, but was associated with a higher rate of intracranial bleeding. Overall mortality was significantly reduced in patients treated with endovascular treatment but the rates of patients with severe disability or death were similar. When excluding all patients treated with the combination of I.V. thrombolysis and I.A. procedures, a potential benefit of I.A. treatment alone compared to I.V. thrombolysis was observed.