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Background: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke., Methods: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile., Results: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups., Conclusions: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban., (© 2024. The Author(s).)

Background: Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT., Methods: We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles., Results: Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p  = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p  = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time., Conclusion: Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Hong, Yoon, Bae, Rha and Park.)

The present study aimed to investigate mother-teacher discrepancies in reports of preschoolers' behavior problems and to examine whether maternal attribution to behavior problems, perception of parenting, and behavior management strategies predicted the discrepancies. The mothers and teachers of 384 preschoolers aged 3-6 years from 16 preschools of Seoul, South Korea, completed the Child Behavior Checklist and the Caregiver-Teacher Report Form. Based on their ratings, they were classified into three groups: (a) mother-teacher Agreement Group, (b) Disagreement Group with Mother only reporting at Risk (Disagreement Group-MR), and (c) Disagreement Group with Mother only reporting No Risk (Disagreement Group-MNR). The results showed marginal similarities between mothers' and teachers' reports of behavior problems, indicating both low correlations and differences in percentages of at-risk children. Multinomial logistic regressions revealed that maternal attribution and maternal perception of parenting difficulties predicted group membership regarding mother-teacher discrepancies. For both internalizing and externalizing problems, mothers who attributed environmental factors as primary causes of children's behavior problems were more likely to be in the Agreement Group than the Disagreement Group-MNR. With regard to externalizing problems, the more the mothers perceived parenting difficulties, the more likely they were to belong to either of the Disagreement Groups. The outcomes suggest the importance of considering that mothers' reports of children's behavior and mother-teacher discrepancies partly mirror mothers' beliefs and perceptions regarding children's behavior and parenting. Professionals need to be aware that information from mother-teacher discrepancies can be of help in understanding mothers as well as children in practice.

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown., Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes., Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores., Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups., Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Background: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis., Methods: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022., Conclusion: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs., Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women., Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 ( P = 0.028) for total CMBs, 0.037 ( P = 0.047) for deep CMBs, and 0.047 ( P = 0.009) for lobar CMBs]., Conclusion: The progression of CMB over 2 years was significantly greater in women than in men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoon, Rha, Park, Park, Kwon, Kim, Youn, Jeong, Han and Choi.)

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI., Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed., Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI., Conclusions: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background Prehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI. Methods and Results We identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed-effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1-person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off-hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI. Conclusions The effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.

Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial., Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics., Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P <0.001), modified Rankin Scale score >0 ( P <0.001), and current tobacco use ( P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS., Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Purpose: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA)., Methods: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache., Results: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different., Conclusion: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache., (© 2022 S. Karger AG, Basel.)

Background: In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect., Aims: We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage)., Methods: In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death., Results: Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01-0.60]; p  = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52-4.90]; p  = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant ( p interaction  = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41-1.01]; p  = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63-1.67]; p  = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction ( p interaction  = 0.165)., Conclusions: Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed., Clinical Trial Registration: URL:http://www.clinicaltrials.gov. NCT01013532.

Background/aims: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting., Methods: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries., Results: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively., Conclusion: This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

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., Competing Interests: All the investigators received research grant based on the study contracts for the number of subjects enrolled and/or for the conduct of the study from Boryung Pharmaceutical Co., Ltd., Seoul, Korea., (Copyright © 2021 Korean Neurological Association.)

Blood pressure variability (BPV) is associated with higher cardiovascular morbidity risks; however, its association with cognitive decline remains unclear. We investigated whether higher BPV is associated with faster declines in cognitive function in ischemic stroke (IS) patients. Cognitive function was evaluated between April 2010 and August 2015 using the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment in 1,240 Korean PICASSO participants. Patients for whom baseline and follow-up cognitive test results and at least five valid BP readings were available were included. A restricted maximum likelihood-based Mixed Model for Repeated Measures was used to compare changes in cognitive function over time. Among a total of 746 participants (64.6 ± 10.8 years; 35.9% female). Baseline mean-MMSE score was 24.9 ± 4.7. The median number of BP readings was 11. During a mean follow-up of 2.6 years, mean baseline and last follow-up MMSE scores were 25.4 ± 4.8 vs. 27.8 ± 4.4 (the lowest BPV group) and 23.9 ± 5.2 vs. 23.2 ± 5.9 (the highest BPV group). After adjusting for multiple variables, higher BPV was independently associated with faster cognitive decline over time. However, no significant intergroup difference in cognitive changes associated with mean systolic BP was observed. Further research is needed to elucidate how BPV might affect cognitive function.

No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without NOTCH3 variant [ NOTCH3 (+) svMCI vs. NOTCH3 (-) svMCI]. We prospectively recruited patients with svMCI and screened for NOTCH3 variants by sequence analysis for mutational hotspots in the NOTCH3 gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the NOTCH3 (+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the NOTCH3 (-) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yoon, Kim, Kim, Ki, Lee, Rha, Na and Seo.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

No previous study has reported endovascular treatment (EVT) in a patient with hemophilia who had an acute ischemic stroke (AIS). Herein, we report the case of a patient with hemophilia A who presented with hyperacute stroke due to a near occlusion of the proximal internal carotid artery (ICA). A 54-year-old man was admitted to our emergency department with a sudden onset of left-sided weakness that occurred 4 hours prior to admission. He had been diagnosed with congenital hemophilia A during his childhood. Although brain computed tomography revealed no evidence of hemorrhage, we did not consider intravenous thrombolysis because of his bleeding-prone condition. Diffusion-weighted imaging revealed a restricted diffusion in the right anterior and middle cerebral artery territories. Magnetic resonance angiography revealed that the right proximal ICA was nearly occluded and had a residual stump. Digital subtraction angiography revealed a near occlusion of the right proximal ICA with a thread-like lumen. Balloon angioplasty was performed in the proximal ICA, and distal flow was restored, but residual stenosis was observed. Stepwise revascularization by carotid endarterectomy (CEA) was planned instead of immediate carotid stenting. He underwent CEA with preoperative and postoperative coverage of factor VIII and recovered without any bleeding complication., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke., Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018., Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups., Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo., Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke ( P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P =0.01). A marginal interaction between treatment group and white matter change on any stroke ( P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P =0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P =0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Background and Purpose: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients., Methods: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission., Results: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI ≥ 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI ≥ 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024; 95% confidence interval 1.006 to 1.042; P = .008)., Conclusions: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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 five landmark ERT trials conducted by 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window of 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 thoroughly 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 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: High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS)., Methods: This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs., Results: Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005-1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013-1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874-0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086-1.526); P = 0.004] were independently associated with NILs at follow-up., Conclusions: High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Although blood pressure (BP) variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT., Methods: A total of 211 patients with acute ischemic stroke and successful recanalization (thrombolysis in cerebral infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP. sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale., Results: Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio = 1.71, 95% confidence interval = 1.013-2.886)., Interpretation: Time-related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP levels. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT. Ann Neurol 2019;85:574-581., (© 2019 American Neurological Association.)

Even though stroke presents as a variety of clinical syndromes, neuroimaging is the most important biomarker to help differentiate between stroke subtypes and assess treatment eligibility. Therapeutic advances have led to intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation being standard care for acute ischaemic stroke. Providing access to this care has implications for existing systems of care for stroke and their organisation and has reintroduced the possibility of adjuvant and neuroprotective treatment strategies in acute ischaemic stroke. The use of neuroimaging for patient selection and speed of diagnosis and delivery of treatment are the dominant themes of modern ischaemic stroke care., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recent clinical trials demonstrated the clinical benefit of endovascular treatment (EVT) in patients with acute ischemic stroke due to large vessel occlusion. These trials confirmed that good outcome after EVT depends on the time interval from symptom onset to reperfusion and that in-hospital delay leads to poor clinical outcome. However, there has been no universally accepted in-hospital workflow and performance benchmark for rapid reperfusion. Additionally, wide variety in workflow for EVT is present between each stroke centers. In this consensus statement, Korean Society of Interventional Neuroradiology and Korean Stroke Society Joint Task Force Team propose a standard workflow to reduce door-to-reperfusion time for stroke patients eligible for EVT. This includes early stroke identification and pre-hospital notification to stroke team of receiving hospital in pre-hospital phase, the transfer of stroke patients from door of the emergency department to computed tomography (CT) room, warming call to neurointervention (NI) team for EVT candidate prior to imaging, NI team preparation in parallel with thrombolysis, direct transportation from CT room to angiography suite following immediate decision of EVT and standardized procedure for rapid reperfusion. Implementation of optimized workflow will improve stroke time process metrics and clinical outcome of the patient treated with EVT.

Objective: Current guideline recommends intensive blood pressure (BP) control in hypertensive patients, but the appropriate target BP level after ischemic stroke due to intracranial atherosclerotic stenosis remains uncertain., Methods: In this randomized, single-blinded trial, patients with symptomatic internal carotid or middle cerebral artery steno-occlusion (>50%) within 7-42 days after index stroke received intensive (target SBP < 120 mmHg) or modest (target SBP < 140 mmHg) BP control from April 2010 to December 2012. The primary outcome was the change in ischemic lesion volume in white matter lesions at the whole forebrain between baseline and 24 weeks as measured from fluid attenuation inversion recovery (FLAIR) images, which was tested in noninferiority test (noninferiority margin of 3 cm)., Results: Among 132 patients, follow-up FLAIR images were available in 111 (59 in the intensive and 52 in the moderate BP control groups). After 24 weeks, the SBP in the intensive group was significantly lower (124.6 ± 10.5 mmHg) than in the modest group (132.3 ± 10.6 mmHg). The ischemic lesion volume increased more in the intensive group (4.9 ± 18.3 cm) than the modest group (2.2 ± 8.2 cm), which failed to prove noninferiority. The frequency of new ischemic lesions on 24-week FLAIR images was nonsignificantly higher in the intensive group than the modest group [10 (16.9%) vs. 5 (9.6%), respectively; P = 0.26)]. Only one recurrent stroke developed during the study period in each group., Conclusion: Intensive BP control in intracranial atherosclerotic stenosis patients failed to prove noninferiority compared with modest BP control, and may increase ischemic lesion volume in the subacute stage.

Background: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients., Methods: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532., Findings: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation., Interpretation: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events., Funding: Korea Otsuka Pharmaceutical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown., Methods: In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616)., Results: Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; P =0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, P =0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; P =0.149)., Conclusions: There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.

Systemic vasculitis, which can involve the brain, may be one of the causes of stroke in young adults; therefore, a test panel for systemic vasculitis is considered for some young stroke patients. However, little is known about this test's yield as a screening test in young adults with ischemic stroke. We evaluated the yield of a panel for systemic vasculitis as a screening test in young patients with ischemic stroke. Consecutive patients aged 18-45 years with ischemic stroke between January 2010 and December 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, lupus anticoagulant, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies. Among 3,593 consecutive patients with acute ischemic stroke during the study period, 198 (5.5%) were aged 18-45 years. Only 4 patients (2.0%) were diagnosed with systemic vasculitis; 2 had systemic lupus erythematosus, 1 had Sjogren's syndrome, and 1 had Churg-Strauss syndrome. Vasculitis panel screening in every young ischemic stroke patient is not of high yield unless a vasculitic process is highly suspected based on other systemic symptoms or signs of vasculitis. Screening should be targeted toward persons with clinical suspicion., (© 2019 S. Karger AG, Basel.)

Objective: To survey AOAN member countries regarding their organizational structure, postgraduate neurology training program, and resources for neurological care provision., Methodology: A cross-sectional survey using a 36-item questionnaire was conducted among country representatives to AOAN from August 2015 to August 2016., Results: A total of 18/20 AOAN member countries participated in the survey. All the countries have organized association with regular meetings, election of officers and neurology training program. In 9/18 countries, professionals other than neurologists were eligible for affiliation. In 11/18 countries, prior Internal medicine training (or equivalent postgraduate housemanship) is prerequisite to neurology program. Recertification examination is not a practice, but submission of CME is required in 7/18 countries to maintain membership. 12/18 countries publish peer-reviewed journals with at least 1 issue per year. Subspecialty training is offered in 14/18 countries. The ratio of neurologist to population ranges from 1:14,000 to as low as 1:32 million with 9/18 having <1 neurologist per 100,000 population. 6/18 countries have at least 1 specialized center solely for neurological diseases. In government-funded hospitals, the lag time to be seen by a neurologist and/or obtain neuroimaging scan ranges from 1day to 3months. All except one country have several medical- and lay- advocacy or support groups for different neurological conditions., Implications: The data generated can be used for benchmarking to improve neurological care, training, collaborative work and research in the field of neurosciences among the AOAN member countries. The paper presented several strategies used by the different organizations to increase their number of neurologists and improve the quality of training. Sharing of best practices, academic networking, exchange programs and use of telemedicine have been suggested., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: The quality of anticoagulation is critical for ensuring the benefit of warfarin, but this has been less well studied in Korean ischemic stroke patients with atrial fibrillation (AF)., Methods: This study retrospectively analyzed the data of patients who had an AF-related ischemic stroke and were treated with long-term warfarin therapy in 16 Korean centers. The quality of warfarin therapy was primarily assessed by the time in therapeutic range [TTR; international normalized ratio (INR), 2.0-3.0] and additionally by the proportion of INR values within the therapeutic range., Results: The long-term warfarin-treated cohort comprised 1,230 patients. They were aged 70.1±9.7 years (mean±SD), 42.5% were female, and their CHA₂DS₂-VASc score was 4.75±1.41. The TTR analysis included 33,941 INR measurements for 27,487 months: per patients, 27.6 (SD, 22.4) INR measurements for 22.4 (SD, 12.9) months. The mean TTR of individual patients was 49.1% (95% confidence interval, 47.9-50.3%), and the TTR quartiles were <34.5, 34.5-49.1, 49.1-64.5%, and >64.5%. None of the 16 centers achieved a mean TTR of >60%. Of all INR measurements, 44.6% were within the therapeutic range, 41.7% were <2.0, and 13.7% were >3.0., Conclusions: In Korean ischemic stroke patients who had AF, the quality of warfarin therapy was low and might be inadequate to effectively prevent recurrent stroke or systemic embolism., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2017 Korean Neurological Association)

Objective: We performed this study to assess the effect of an antiplatelet agent on the progression of white matter hyperintensities (WMH)., Methods: From August 2003 to May 2005, we consecutively enrolled patients who underwent brain magnetic resonance imaging (MRI) for health check-up purposes and showed no significant findings other than WMH of any degree. Patients were divided into two groups based on whether or not they received antiplatelet therapy. All patients had a follow-up brain MRI after 5 years and WMH volume change was measured using imaging analysis software. To minimize selection bias potentially arising from antiplatelet treatment assignment, analyses were inverse probability weighted., Results: Among the 93 patients who met the inclusion criteria, 54 patients (58.1%) were grouped as the antiplatelet group (AG), and the remaining 39 patients (41.9%) as the non-antiplatelet group (NAG). After inverse propensity weighting, all baseline characteristics were similar between the two groups, and antiplatelet treatment did not show any significant effect on the total WMH volume change (p = 0.957)., Conclusion: Antiplatelet medication may not alter the progression of WMH.

Background and Purpose: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence., Methods: In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding., Results: Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group., Conclusions: Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268., (© 2016 American Heart Association, Inc.)

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.

Purpose: Snakebite is an emergency which causes local symptoms such as pain and edema around the bite. Systemic symptoms may also develop, such as dizziness or renal failure, and may even cause death. The purpose of this research was to assess the validity and safety of snakebite protocol for surgery when treating snakebite patients., Materials and Methods: Retrospective research was performed on patients who were admitted after being treated at the emergency center from January 2008 to December 2012. When necessary, debridement was also performed, and 46 of 111 patients (41.4%) underwent debridement. Those who had received debridement without antivenom administration due to a positive skin reaction test were classified as group A, and group B received antivenom and delayed debridement. We reviewed the emergency and admission charts of the patients in each group and recorded and compared their age, sex, bite site, severity of local and general symptoms, time to receive antivenin, and complications., Results: Of the ten patients (21.7%) in group A, two (66.6%) developed cellulites, and one of them experienced skin necrosis, resulting in a skin graft. In group B, there were 36 patients (78.2%), 19 (52.7%) of whom developed cellulitis. Skin necrosis occurred in two patients, and one of these patients received a skin graft. Compartment syndrome was found in one patient, and fasciotomy and a skin graft were performed., Conclusion: The treatment protocol implemented to treat snakebite patients admitted to the emergency center during this research was safely and properly followed during surgical treatment.

Background and Purpose: Recent randomized clinical trials (RCTs) have demonstrated benefits of endovascular recanalization therapy (ERT) contrary to earlier trials. We aimed to estimate the benefits of ERT added to standard therapy in acute ischemic stroke., Methods: From a literature search of RCTs testing ERT, we performed a meta-analysis to estimate an overall efficacy and safety of ERT for all trials, stent-retriever trials, and RCTs comparing ERT and intravenous tissue plasminogen activator (IV-TPA)., Results: We identified 15 relevant RCTs including 2,899 patients. For all trials, ERT was associated with increased good outcomes (odds ratio [OR] 1.79; 95% confidence interval [CI] 1.34, 2.40; P<0.001) compared to the control. ERT also increased no or minimal disability outcomes, good neurological recovery, good activity of daily living, and recanalization. ERT did not significantly increase symptomatic intracranial hemorrhage (SICH) (OR 1.19; 95% CI 0.83, 1.69; P=0.345) or death (OR 0.87; 95% CI 0.71, 1.05; P=0.151). In contrast, ERT significantly reduced extreme disability or death (OR 0.77; 95% CI 0.61, 0.97; P=0.025). Restricting to five stent-retriever trials comparing ERT plus IV-TPA vs. IV-TPA alone, the benefit was even greater for good outcome (OR 2.39; 95% CI 1.88, 3.04; P<0.001) and extreme disability or death (OR 0.57; 95% CI 0.41, 0.78; P=0.001). Restricting to eight RCTs comparing ERT (plus IV-TPA in six trials) with IV-TPA alone showed similar efficacy and safety., Conclusions: This updated meta-analysis shows that ERT substantially improves clinical outcomes and reduces extreme disability or death without significantly increasing SICH compared to standard therapy.