Eung-Gyu Kim

Risk Factors and Stroke Mechanisms in Atherosclerotic Stroke Intracranial Compared With Extracranial and Anterior Compared With Posterior Circulation Disease

Background and Purpose— The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis. Methods— A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment. Results— Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018–1.049), male gender (OR, 3.399; 95% CI, 2.335–4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117–2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274–2.618; P=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105–2.010; P=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005–5.890; P=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (P<0.001). Conclusions— The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15-0444).

This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase‐4 (DPP‐4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end‐stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66‐fold (1.10, 1.49, 1.22 and 1.21‐fold) increase of mean area under the time‐plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non‐HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure–response relationship. Impact of HD on the removal of gemigliptin was negligible.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation–Related Mild Ischemic Stroke: A Randomized Clinical Trial

Importance In atrial fibrillation (AF)–related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration clinicaltrials.gov Identifier: NCT02042534

Two‐year direct medical costs of stroke in Korea: a multi‐centre incidence‐based study from hospital perspectives

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

Teaching NeuroImages: Isolated peripheral facial palsy due to ipsilateral pontine infarction

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.

Low- versus Standard-Dose Intravenous Alteplase in the Context of Bridging Therapy for Acute Ischemic Stroke: A Korean ENCHANTED Study.

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

IMPACT OF OBSTRUCTIVE SLEEP APNOEA AND TREATMENT RESPONSE ON IMMUNOSENESCENCE PARAMETERS IN HYPERTENSION

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.

Medication Adherence of Statin Users after Acute Ischemic Stroke

Objective: Inflammation and immunosenescence (IS) have been considered to be associated with hypertension. (HTN) Obstructive sleep apnea (OSA) was also associated with chronic inflammation by repetitive oxidative stress. However, the relationship between immunosenecenece parameters and treatment of HTN with or without OSA is unclear. We evaluate to demonstrate the association of chronic inflammation and IS parameters with OSA in hypertensive patients and the changes according to BP treatment. Design and method: Multicenter longitudinal observational study from April 2013 to October 2015. A total of 131 Hypertensive patients (SBP>140 mm Hg or DBP>90 mm Hg) were devided into OSA low risk and OSA high risk according to Berlin sleep apnea questionnaire. CD28 null and CD58 (+) fraction of CD8 T-cells were sampled at baseline in both groups. 87 patients among them were analyzed for baseline and 6 months follow-up immunosenescence parameters with treatment of HTN. Results: Among 131 subjects, 88 patients (67.2%) were OSA high risk, and 43 patients (32.8%) were OSA low risk. CD28 null fraction of CD8 T cells in OSA high risk group was 35.1 ± 18.3% vs 43.9 ± 19.9% in low risk group with a p-value 0.014. CD58+ fraction of CD8 T-cells in OSA high risk group was 37.0 ± 16.9% vs 44.7 ± 20.0% in OSA low risk group with a p-value 0.023. HTN was controlled in 56 patients (64.4%). CD28nullCD8+ T cell was significantly decreased from 41.1 ± 17.9% to 37.5 ± 18.8% (p-value=0.01) but CD57+CD8+ T cell was not correlated with HTN treatment. (42.2 ± 17.5% vs 42.7 ± 18.4%, p-value = 0.596). In multivariate analysis, only age was associated with change in CD28nullCD8+ T cell with greater reduction in CD28nullCD8+ T cell. (beta: 0.373, t = 2.412, p-value = 0.019). Conclusions: CD28 null and CD58 (+) fraction of CD8 T-cell in hypertensive patients with OSA were paradoxically higher in patients without OSA. IS parameter, CD28nullCD8+ T cell was significantly decreased with HTN treatment, especially in younger patients.

Prediction of hemorrhagic transformation in patients with mild atrial fibrillation-associated stroke treated with early anticoagulation: post hoc analysis of the Triple AXEL Trial

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.

P2-095: The differences of behavioral and psychological symptoms in the patients of Alzheimer’s disease and vascular dementia

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.