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Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

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: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23–0.60, p Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Background and Purpose— The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.

Objective Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. Methods This was a phase 2, 2‐part, multicenter trial in stroke patients (19–80 years old) receiving rtPA. Intravenous otaplimastat was administered

ObjectiveTo evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke.MethodsIn this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death.ResultsIn the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25–4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32–6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups.ConclusionAmong patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence.ClinicalTrials.gov identifierNCT01600235.Classification of evidenceThis study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

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

High cholesterol and lipids, especially low-density lipoprotein cholesterol (LDL-C) in the blood are associated with a higher risk of vascular events including stroke and myocardial infarction. In addition to therapeutic lifestyle changes, treatment with an HMG coenzyme-A reductase inhibitor (statin) medication is recommended for the primary prevention of ischemic stroke in patients estimated to have a high risk for cardiovascular events. Aggressive reduction of low-density lipoprotein cholesterol is likely to yield greater benefit than more modest reductions. Epidemiological evidence has suggested that high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with stroke risk. Nevertheless, direct evidence for the clinical benefit of elevating HDL-C is scarce, because the efficacy of lipid-modifying drugs that raise HDL-C levels had not been directly assessed in large-scale clinical trials in stroke patients.

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 (

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.

Objective: The purpose of this study was to compare and analyze the kinematic variables and electromyography (EMG) findings that change with varying characteristics of crouch start and feedback provision, and to provide the fundamental data for record improvement in 400 mH. Method: Four short-distance runners participated in the experiment. The analyzed variables were elapsed time per interval, stride length, and muscle activities in three lower limb muscles. These variables were analyzed by using Kwon3d XP and Noraxon Myoresearch. The participants were subjected to three conditions, including two conditions that relate to the thrusting foot on the rear block and another condition pertinent to feedback provision. Results: In terms of a one-step interval, the elapsed time in condition A was longer than that in condition B, and the one after the feedback was the longest. The stride length of a one-step interval was the longest in condition A. The stride length of a two-step interval was the shortest in condition A. The muscle activity during a one-step interval showed differences in vastus medialis and medial gastrocnemius, with condition A being the highest. Conclusion: When the non-dominant left foot was located at the back, negative results were observed in terms of elapsed time and stride length. Moreover, an imbalance in muscle activity was observed between the left and right feet when the left foot was placed at the back. As a result, significant differences in elapsed time, stride length, and muscle activity were observed depending on the foot placed on the rear block. In conclusion, we identified the characteristics of crouch start in 400 mH, and a specialized program must be suggested.

The aim of this study was to evaluate an extremely small pseudoparamagnetic iron oxide nanoparticle (ESPIO), KEG3, as a potential blood pool agent in 3 T coronary magnetic resonance angiography (MRA) in canine models and compare its efficacy to that of a gadolinium-based contrast agent.Nine mongrel dogs were subjected to whole-heart coronary MRA in 2 separate sessions at 7-day intervals with a 3 T scanner using the FLASH sequence with either gadoterate meglumine (Gd-DOTA) or the ESPIO (KEG3). Coronary MRA was performed twice at each MR examination: the first scan during the administration of the contrast agent and the subsequent second scan at 15 minutes after contrast injection. Objective measurements of the Gd-DOTA and ESPIO images, including the signal-to-noise ratios (SNRs) for the coronary arteries and cardiac veins, contrast-to-noise ratios (CNRs) between the vessels and fat (CNRfat) and the vessels and the myocardium (CNRmyocardium), and subjective image quality scores on a 4-point scale were evaluated and compared.The mean SNRs and CNRs of all vascular regions in the ESPIO images were similar to those of the corresponding regions in the Gd-DOTA images in the first scan (98.1 ± 32.5 vs 79.1 ± 38.4 for SNR of coronary arteries, P = 0.3; 74.2 ± 30.1 vs 61.4 ± 38.5 for CNR, P = 0.7) and more than 2 times higher than the latter in the second scan (95.2 ± 31.3 vs 32.1 ± 8.1 for SNR of coronary arteries, P = 0.008; 76.1 ± 35.8 vs 17.6 ± 19.2 for CNR, P 0.008). Similarly, the mean values of the subjective measurements of the ESPIO images were similar to those of the Gd-DOTA images (3.9 ± 0.3 vs 3.3 ± 0.8 for coronary arteries, P = 0.1) in the first scan and significantly better than the latter in the second scan (3.9 ± 0.2 vs 2.1 ± 0.6 for coronary arteries, P = 0.007).The experimental blood pool agent KEG3 offers equivalent image quality for whole-heart coronary MRA at 3 T upon contrast administration and persistent better quality in the subsequent scans, compared with a traditional extracellular gadolinium-based contrast agent.

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, PP

Purpose The clinical benefit of endovascular thrombectomy (EVT) after intravenous recombinant tissue plasminogen activator (IV rt-PA) has been demonstrated in several studies. Near 10% of acute ischemic stroke (AIS) patients are accompanied with carotid artery atherosclerotic occlusion. The MR Clean study in the Netherlands reported that acute carotid artery stenting (CAS) was performed in 30 patients in the intervention group (12.9%). However, there is no evidence of the benefit for emergent CAS in AIS patients, and there are no clear guidelines for specific medications as an adjunctive therapy within 24 hours of IV rt-PA. Methods We analyzed single-center registry data retrospectively for 2006 to 2018. Emergent CAS during EVT was performed in select patients according to the operator’s decision. Most patients for emergent CAS was not used to antithrombotic medications routinely within 24 hours of IV rt-PA. Only some complicated cases were used intra-arterial or oral antithrombotics within 24 hours of IV rt-PA. Recanalization results were assessed by TICI grade immediately after the procedure. The clinical outcome was evaluated using the 3 months modified Rankin Scale. Results Among 177 consecutive patients with AIS treated with rt-PA and EVT from 2006 to 2018, twenty-three(12.9%) patients underwent CAS as an EVT. Eighteen patients (78.3%) were accompanied with tandem occlusion. Median age was 68. Median NIHSS was 13. During the emergent carotid artery stenting, pre-stent balloon angioplasty was performed in 20 patients. Carotid Wallstent (Boston Scientific, Natick, USA) was used in all patients who treated with emergency CAS. Successful installation of CAS was achieved in 22 patients (95.6%). One case of CAS was failed. Two patients were installed multiple carotid stent for carotid dissection. And embolic protection device was used in 13 patients.However, four cases of CAS experienced thromboembolic complications including in-stent thrombosis and distal migration of emboli. In those cases, IA glycoprotein IIb/IIIa infused as a rescue method, and early antiplatelet within 24 hours of rt-PA was administered in one patient.Final successful recanalization (mTICI 2b-3) was achieved in 16 patients (69.5%). Eleven patients (47.8%) had a good functional outcome (modified mRS 0–2). Intracranial hemorrhage was occurred in 4 cases. The mortality case was two. The accompanying tandem occlusion was 61%. Conclusions In this analysis, successful rate of emergency CAS and intracranial EVT after IV rt-PA was high as 95.6% and 69.5%. The good functional outcomes (mRS 0–2) were 46.7% in patients treated with emergency CAS and the overall clinical outcome would be acceptable. Disclosures J. Seo: None. E. Kim: None.

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.

Aims: Limited studies have compared the effectiveness of Solitaire and Trevo stentrievers for endovascular thrombectomy to achieve recanalization and improve functional outcomes of patients with acute ischemic stroke. Therefore, we compared the safety and efficacy of the two stents during endovascular thrombectomy for patients with acute ischemic stroke. Materials and Methods: This study included 130 patients who underwent endovascular thrombectomy using either the Trevo (n = 51) or the Solitaire (n = 79) stent for anterior circulation acute ischemic stroke. Recanalization was classified using thrombolysis in cerebral infarction (TICI) grading. Efficacy and safety of the devices during endovascular thrombectomy were analyzed by evaluating the rate of good recanalization after the first pass, clot retrieval rate, final recanalization grade, use of rescue treatment, recanalization time, and hemorrhagic and thromboembolic complications. Results: Overall, good recanalization (TICI grades 2b and 3) was achieved (Solitaire: n = 57, 72.2%; Trevo: n = 46, 90.2%) (P = 0.01). The rate of good recanalization after the first pass and clot retrieval rate were similar between groups; however, the use of rescue treatment was more frequent in the Solitaire group. Recanalization time was shorter in the Trevo group. The good clinical outcome rate was higher in the Trevo group but not statistically significantly. The rates of symptomatic hemorrhage and thromboembolism were not significantly different between groups. Conclusion: The Trevo stent achieved more successful recanalization with less need for rescue treatment and less time for recanalization than the Solitaire stent. There was no statistically significant difference in the clinical outcomes.

Meralgia paresthetica (MP) is a sensory mononeuropathy of the lateral femoral cutaneous nerve (LFCN). MP has rarely been reported after a femoral intervention approach. We report a case of bilateral meralgia paresthetica following bilateral femoral cannulation. A 64-year-old male received cardiac catheterization and treatment via a bilateral femoral vein. After cardiac catheterization, the patient presented with paresthesia in the anterolateral aspect of the bilateral thigh. After performing nerve conduction studies and electromyography, he was diagnosed as MP. Although a bilateral LFCN lesion following a femoral approach is very rare, MP might require caution regarding potential variations in LFCN when performing the femoral approach.

Objectives To investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study. Patients and methods The Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging. Results We analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33–3.91, P = 0.003). Conclusion PCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation.

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.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).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.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.

Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients’ awareness of hyperlipidemia (OR 1.62; 95% CI 1.07–2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19–2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06–2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40–0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88–0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.

Background: In this multicentre, randomised controlled trial, we evaluated the safety and efficacy of induced hypertension in patients with acute ischaemic stroke. Methods: Patients with acute non-cardioembolic ischaemic stroke within 24 hours of onset who were ineligible for revascularisation therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was intravenously administered to increase systolic blood pressure (SBP) up to 200 mmHg. The primary efficacy endpoint was early neurological improvement (reduction in NIHSS score ≥ 2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin scale score of 0-2 at 90 days. Safety outcomes included symptomatic intracranial haemorrhage/oedema, myocardial infarction, and death. Findings: Totals of 76 and 77 patients were included in the intervention and control groups, respectively. Relative to the control group, patients in the intervention group were younger, exhibited higher baseline NIHSS values, and were more likely to experience progressive stroke and large vessel occlusion. Sixty-seven (88·2%) patients of the intervention group exhibited improvements in NIHSS scores ≥2 during induced hypertension (mean SBP: 179·7±19·1 mmHg). After adjusting for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio: 2·49; 95% CI: 1·25-4·96; P=0·010) and secondary efficacy endpoints (odds ratio: 2·97; 95% CI: 1·32-6·68; P=0·009). The numbers needed to treat were 3·7 and 8·4 for the primary and secondary endpoints, respectively. Safety outcomes did not significantly differ between groups. Interpretation: Among patients with non-cardioembolic stroke who were ineligible for revascularisation therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurological improvement and long-term functional independence (class IB evidence). Clinical Trial Number: This trial is registered with ClinicalTrials.gov (NCT01600235). Funding: Samsung Medical Center and IlDong Pharma, Inc. Seoul, South Korea. Declaration of Interests: All authors declare no competing interests. Ethic Approval Statement: Patients from eight sites in South Korea were enrolled between June 2012 and December 2017. The trial was approved by the appropriate national regulatory authorities and relevant ethnics committee at each participating site. All participants provided written informed consent.

Extrapyramidal signs are neurological dysfunction commonly associated with Wilson's disease (WD). In addition, cognitive dysfunction has been reported in the early stages of WD. In this report, we describe a 49-year-old woman presenting with memory impairments and without Parkinsonian or extrapyramidal signs. She was diagnosed with WD based on the presence of Kayser-Fleischer rings around the irises of her eyes and two ATP7B gene mutations, R778L at exon 8 and A874V at exdyon 11. Serial magnetic resonance imaging analysis and neuropsychological tests showed improvements following treatment with trientine.

Summary 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.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

BACKGROUND AND PURPOSE: Absence of the MCA susceptibility vessel sign (negative MCA susceptibility vessel sign) on gradient recalled-echo MR imaging in acute stroke is commonly associated with in situ stenosis and thrombotic occlusion. We evaluated the effectiveness and safety of the Solitaire stent as the first-line device for the recanalization of MCA occlusion with a negative MCA susceptibility vessel sign. MATERIALS AND METHODS: Thirty-eight consecutive patients presenting with acute ischemic stroke due to MCA occlusion were treated by using the Solitaire AB stent alone or combined with thrombolytic drugs. Among these patients, 11 (7 men and 4 women; median age, 70 years; range, 49–89 years) who underwent multimodal stroke MR imaging before the endovascular procedure and had no MCA susceptibility vessel sign on the initial gradient recalled-echo MR imaging were included in this study. The primary end point was the recanalization of the occluded artery evaluated by the arterial occlusive lesion score. Clinical outcome was assessed at discharge and 90 days, as was the degree of residual MCA stenosis or reocclusion. RESULTS: Successful recanalization (arterial occlusive lesion score ≥ II) without balloon angioplasty was obtained in 9 patients (81.8%). Six patients (54.5%) had an mRS score of ≤2 at 90 days. After a median of 147 days, no patient showed reocclusion on follow-up imaging. There were no symptomatic intracerebral hemorrhages. CONCLUSIONS: The Solitaire stent is a feasible tool as the first-line device for multimodal endovascular recanalization therapy in acute ischemic stroke with a negative MCA susceptibility vessel sign. It has a good rate of successful and complete recanalization and is a fast yet safe procedure.

Background Despite increasing socio-economic burden of stroke, few studies have investigated the costs associated with the stroke care in Korea. We estimated the two-year direct medical costs associated with stroke. Methods This was a multi-centre, incidence-based, retrospective observational study. We examined the records of all adult patients who were admitted in eight large hospitals throughout Korea due to acute stroke [I60: sub-arachnoid haemorrhage; I61: intracerebral haemorrhage; I62: other nontraumatic haemorrhage; I63: cerebral infarction, by The International Statistical Classification of Diseases and Related Health Problems (ICD)-10] between 1 November and 31 December 2006. Direct medical inpatient and outpatient cost of each patient was extracted from the medical record and the reimbursement claim data of the hospital. Results Out of 908 studied patients (14% diagnosed as I60, 18% as I61, 3% as I62, and 65% as I63), 460 (50·7%) were assessed for more than one-year. The annual average direct medical costs were Korean ₩ 8 114 471 US$8732) for the first year, and Korean ₩ 431 527 for the second year. The first year costs for haemorrhagic stroke (I60–I62) (Korean ₩ 13 090 179) were significantly higher than those associated with cerebral infarction (I63) (Korean ₩ 5 460 459), whereas the second year costs were not different. Factors independently associated with high cost were female gender, young age, and first stroke. Conclusions Direct medical costs for stroke in Korea were determined, which seem to be lower than those of other developed countries. Female gender, young age, and first stroke were factors related to higher stroke cost.

Parkinson's disease (PD) can be divided into the akinetic-rigid (ART), mixed (MT), and tremor-dominant (TDT) subtypes according to the clinically dominant symptoms. We analyzed the correlations between (123)I-meta-iodobenzylguanidine (MIBG) uptake and the clinical features of patients with various PD subtypes. In addition, we evaluated the relationship between MIBG uptake and the severity of the cardinal motor symptoms among patients with PD subtypes. The mean Unified Parkinson's Disease Rating Scale motor scores differed significantly among patients with different PD subtypes (± standard deviation [SD]) (ART, 34.6 ± 18.28; MT, 24.63 ± 7.78; TDT, 16.22 ± 4.15, p=0.002), especially between the ART and TDT subtypes (p=0.022). The mean MIBG uptake (± SD) was decreased in the TDT (1.69 ± 0.39), MT (1.35 ± 0.32), and ART (1.35 ± 0.22) subtypes (p=0.049). The MIBG uptake values differed significantly between the ART and TDT subtypes (p=0.02). The MIBG uptake was inversely correlated with the severity of hypokinesia in the ART subtype (r=-0.75; p=0.01) and the MT subtype (r=-0.8; p=0.02), but it was not correlated with the severity of any of the parkinsonian motor symptoms in the TDT subtype. These results imply that hypokinesia is strongly associated with sympathetic myocardial degeneration and that sympathetic myocardial degeneration can reflect the progression of the disease in patients with the ART and mixed MT subtypes of PD.

Background and PurposezzFrovatriptan is a selective 5-HT1B/1D agonist with a long duration of action and a low incidence of side effects. Although several placebo-controlled trials have documented the clinical efficacy and safety of frovatriptan in adults with migraine, this drug has not previously been studied in Asian including Korean patients. MethodszzIn this double-blind multicenter trial, 229 patients with migraine were randomized to receive frovatriptan 2.5 mg or placebo upon the occurrence of a moderate-to-severe migraine. The primary outcome was the 2-hour headache response rate. ResultszzFrovatriptan significantly increased the 2-hour headache response rate compared with placebo (52.9% vs. 34.0%, p=0.004). The headache response rates at 4, 6, and 12 hours were significantly higher in the frovatriptan group than in the placebo group, as was the pain-free rate at 2 hours (19.0% vs. 5.7%, p=0.004), 4 hours (40.7% vs. 23.0%, p=0.006), and 6 hours (56.1% vs. 34.0%, p=0.002). The median time to a headache response was significantly shorter in the frovatriptan group than in the placebo group (2.00 hours vs. 3.50 hours, p

Background and Purpose: Several studies have reported that diffusion-weighted imaging (DWI) is able to help discriminate a Parkinson variant of multiple system atrophy (MSA-p) from Parkinson’s disease (PD) on the basis of the increased regional apparent diffusion coefficient (rADC). We analyzed the usefulness of DWI by using the rADC for differential diagnosis between MSA-p and PD and investigated the correlation between the rADC value and clinical features of MSA-p and PD. Methods: Twelve patients with PD and 10 with MSA-p were studied. The rADC value was determined in different brain regions, including the dorsal putamen (DP) and middle cerebellar peduncles (MCP). Results: The rADC values of the DP showed a greater increase in MSA-p patients than in PD patients (p=0.03). MSA-p patients also presented increased rADC values of the MCP compared with PD patients (p=0.0001). In particular, the sensitivity, specificity and positive predictive values of the MCP rADC were higher than those of the DP rADC. However, DP and MCP rADC values were not correlated with clinical features in either MSA or PD patients. Conclusions: DWI discriminated between PD and MSA-p based on rADC values in DP and MCP. The MCP rADC value, in particular, could better discriminate MSA-p from PD. Journal of Movement Disorders 2009;2:64-68

Purpose Patterns of prescriptions are markedly influenced by regional disease entities, medical education, culture, economic status, and available pharmaceutical companies. Features of adverse drug reactions (ADRs) may vary in different countries. In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea. Methods Six Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%). Results Based upon the World Health Organization (WHO)-Uppsala Monitoring Center criteria (certain—13.7%, probable—46.1%, possible—32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.1%), anti-psychotics (5.4%), anti-convulsants (5.2%), cardiovascular agents (4.8%), anti-neoplastics (4.6%), and opiates and non-opiate pain killers (3.5%). Among the antibiotics, cephalosporins (8.1%) were the most common, followed by anti-tuberculosis agents (5.7%), quinolones (4.0%), vancomycin (3.1%), and penicillin (2.8%). The most common side effect was skin manifestations, which were seen in 42% of the patients, followed by neurologic manifestations (14%), gastrointestinal involvements (12.9%), generalized reactions (9.4%), and respiratory involvements (4.5%). Conclusion Antibiotics, contrast dyes, and NSAIDs were the most common causative drugs for ADRs, which reflects the prescription pattern and the prevalence of diseases in Korea. These data may be useful in establishing a Korean pharmacovigilance system. Copyright © 2009 John Wiley & Sons, Ltd.

Uniform-sized semiconducting nanocrystals of binary metal sulfides are synthesized from the thermolysis of metal-oleate complexes in alkanethiol. The size ofthe Cu 2 S nanocrystals can be tuned from 7 to 20 nm by varying the reaction conditions. Various shaped nanocrystals of CdS, ZnS, MnS, and PbS are synthesized from the thermal reaction of metal-oleate complex in alkanethiol.

Objectives: To evaluate the efficacy and tolerability of donepezil in patients with Binswanger type subcortical vascular dementia. Methods: Patients (n = 34, mean age = 71.8 + 7.12) with Binswanger type subcortical vascular dementia from 8 multicenter, according to clinical and neuroradiological working criteria, were selected to receive donepezil 5 mg/day (n = 2) or donepezil 10 mg/day (n = 32, after 5 mg/day) for 24 weeks. Our primary endpoints were change from baseline to weeks 12 and 24 in the Seoul Neuropsychological Screening Battery-Dementia version (SNSB-D) and the Korean version of neuropsychiatric inventory (K-NPI). Results: A total of 24 patients received donepezil completed the study (mean age = 72.0 + 7.5 K-Mini-Mental State Examination [MMSE] = 21.0 + 5.1). After 12 weeks and 24 weeks, patients showed improvements in cognitive function on the SNSB-D compared baseline of 16.29 points at 12 weeks (P < .05) and 12.44 points at 24 weeks (P < .05). Significant improvements were shown in only memory domain, immediate verbal recall and delayed recall tests. Subgroup with better cognitive function (SNSB-D > 100) were more effective in frontal and memory domains than the other subgroup (SNSB-D < 100). Withdrawal rates due to adverse events were very low (4.16%). Conclusions: Donepezil-treated patients with Binswanger type subcortical vascular dementia demonstrated significant improvement in cognition compared with baseline, and donepezil was well tolerated.

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.

A 72-year-old woman presented left peripheral facial palsy for 1 day. Neurologic examination revealed isolated left peripheral facial palsy (figure 1). She did not have additional pontomedullary symptoms or signs, such as diplopia, abduction weakness, facial sensory loss, vertigo, nystagmus, or dysarthria. A brain diffusion-weighted MRI scan showed a hyperintense signal in the left dorsal pons (figure 2) in the region of the seventh nerve nucleus. Infranuclear facial palsy with isolated facial weakness has been reported rarely, and may be misdiagnosed as Bell palsy.1,2