Keun-Sik Hong

Cilostazol Prevents the Progression of the Symptomatic Intracranial Arterial Stenosis The Multicenter Double-Blind Placebo-Controlled Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis

Background and Purpose— Cilostazol, a phosphodiesterase inhibitor, has been reported to reduce restenosis rate after coronary angioplasty and stenting. This study was performed to investigate the effect of cilostazol on the progression of intracranial arterial stenosis (IAS). Methods— We randomized 135 patients with acute symptomatic stenosis in the M1 segment of middle cerebral artery or the basilar artery to either cilostazol 200 mg per day or placebo for 6 months. Aspirin 100 mg per day was also given to all patients. Patients with potential embolic sources in the heart or extracranial arteries were excluded. IAS was assessed by magnetic resonance angiogram (MRA) and transcranial Doppler (TCD) at the time of recruitment and 6 months later. The primary outcome was the progression of symptomatic IAS on MRA and secondary outcomes were clinical events and progression on TCD. Results— Thirty-eight patients were prematurely terminated. Dropout rates and reasons for dropouts were similar between the cilostazol and placebo groups. There was no stroke recurrence in either cilostazol or placebo group, but there was 1 death and 2 coronary events in each group. In cilostazol group, 3 (6.7%) of 45 symptomatic IAS progressed and 11 (24.4%) regressed. In placebo group, 15 (28.8%) of symptomatic IAS progressed and 8 (15.4%) regressed. Progression of symptomatic IAS in cilostazol group was significantly lower than that in placebo group (P=0.008) Conclusion— Our study suggests that symptomatic IAS is a dynamic lesion and cilostazol may prevent its progression.

Stroke Statistics in Korea: Part I. Epidemiology and Risk Factors: A Report from the Korean Stroke Society and Clinical Research Center for Stroke

The aim of the Part I of Stroke Statistics in Korea is to summarize nationally representative data of the epidemiology and risk factors of stroke in a single document. Every year, approximately 105,000 people experience a new or recurrent stroke and more than 26,000 die of stroke, which indicates that every 5 minutes stroke attacks someone and every 20 minutes stroke kills someone in Korea. Stroke accounts for roughly 1 of every 10 deaths. The estimated stroke prevalence is about 795,000 in people aged ≥30 years. The nationwide total cost for stroke care was 3,737 billion Korean won (US

Efficacy of Intra-Arterial Fibrinolysis for Acute Ischemic Stroke Meta-Analysis of Randomized Controlled Trials

3.3 billion) in 2005. Fortunately, the annual stroke mortality rate decreased substantially by 28.3% during the first decade of the 21th century (53.2/100,000 in 2010). Among OECD countries, Korea had the lowest in-hospital 30-day case-fatality rate for ischemic stroke and ranked third lowest for hemorrhagic stroke in 2009. The proportion of ischemic stroke has steadily increased and accounted for 76% of all strokes in 2009. According to hospital registry studies, the 90-day mortality rate was 3-7% for ischemic stroke and 17% for intracerebral hemorrhage. For risk factors, among Korean adults ≥30 years of age, one in 3-4 has hypertension, one in 10 diabetes, and one in 7 hypercholesterolemia. One in 3 Korean adults ≥19 years of age is obese. Over the last 10 years, the prevalence of hypertension slightly decreased, but the prevalence of diabetes, hypercholesterolemia, and obesity increased. Smoking prevalence in men has decreased, but is still as high as 48%. This report could be a valuable resource for establishing health care policy and guiding future research directions.

Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design

Background and Purpose— Although intra-arterial (IA) fibrinolysis for acute ischemic stroke has been clinically available for many years, it is not a therapy approved by the US Food and Drug Administration. Single, randomized, clinical trials (RCTs) have suggested beneficial effects, but no single RCT has demonstrated that IA fibrinolysis yields increases in both good (modified Rankin Scale score 0 to 2) and excellent (modified Rankin Scale score 0 to 1) outcomes when compared with the control group. Relatively few participants and inadequate statistical power in single RCTs may have contributed to this difficulty. Method— We performed a systematic literature search to identified RCTs of IA fibrinolysis in acute ischemic stroke. Multiple outcomes were analyzed, with emphasis on good and excellent outcomes at 90 days or at trial end point. Results— The systematic search identified 5 RCTs with 395 participants comparing IA fibrinolysis and control. IA fibrinolysis was associated with increased good (odds ratio=2.05; 95% CI, 1.33 to 3.14; P=0.001) and excellent (odds ratio=2.14; 95% CI, 1.31 to 3.51; P=0.003) outcomes. For additional end points, IA fibrinolysis was associated with increased frequencies of minimal neurologic deficit (National Institutes of Health Stroke Scale score 0 to 1), minimal impairment of activities of daily living (Barthel Index 90 to 100 or 95 to 100), and recanalization. IA fibrinolysis was associated with increased radiological and symptomatic intracerebral hemorrhage. However, there was no difference in mortality between groups. Conclusions— Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke. Increased hemorrhage frequencies are not associated with any increase in mortality.

Efficacy of homocysteine lowering therapy with folic acid in stroke prevention: a meta-analysis

Background— It is widely supposed, but not well-demonstrated, that cumulative advances in standard care have reduced recurrent stroke and cardiovascular events in secondary prevention trials. Methods and Results— Systematic search identified all randomized, controlled trials of medical secondary stroke prevention therapies published from 1960 to 2009. Randomized, controlled trials narrowly focused on single stroke mechanisms, including atrial fibrillation, cervical carotid stenosis, and intracranial stenosis, were excluded. From control arms of individual trials, we extracted data for baseline characteristics and annual event rates for recurrent stroke, fatal stroke, and major vascular events and analyzed trends over time. Fifty-nine randomized controlled trials were identified, enrolling 66 157 patients in control arms. Over the 5 decade periods, annual event rates declined, per decade, for recurrent stroke by 0.996% (P=0.001), fatal stroke by 0.282% (P=0.003), and major vascular events by 1.331% (P=0.001). Multiple regression analyses identified increasing antithrombotic use and lower blood pressures as major contributors to the decline in recurrent stroke. For recurrent stroke, annual rates fell from 8.71% in trials launched in the 1960s to 6.10% in the 1970s, 5.41% in the 1980s, 4.04% in the 1990s, and 4.98% in the 2000s. The sample size required for a trial to have adequate power to detect a 20% reduction in recurrent stroke increased 2.2-fold during this period. Conclusions— Recurrent stroke and vascular event rates have declined substantially over the last 5 decades, with improved blood pressure control and more frequent use of antiplatelet therapy as the leading causes. Considerably larger sample sizes are now needed to demonstrate incremental improvements in medical secondary prevention.

Prognostic Factors for the Surgery for Mesial Temporal Lobe Epilepsy: Longitudinal Analysis

Background and Purpose— Although a lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized, controlled trials have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of randomized, controlled trials to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods— Salient trials were identified by formal literature search. Relative risk (RR) with 95% CI was used as a measure of the association between folic acid supplementation and risk of stroke, after pooling data across trials in a fixed-effects model. Results— The search identified 13 randomized, controlled trials that had enrolled 39 005 participants for folic acid therapy to reduce homocysteine in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR=0.93; 95% CI, 0.85–1.03; P=0.16). The RR for nonsecondary prevention trials was 0.89 (95% CI, 0.79–0.99; P=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR=0.83; 95% CI, 0.71–0.97; P=0.02) and in the trials that disproportionately enrolled male patients (men:women >2; RR=0.84; 95% CI, 0.74–0.94; P=0.003). Conclusions— Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation.

Impact of neurological and medical complications on 3‐month outcomes in acute ischaemic stroke

Summary:  Purpose: Determining long‐term prognostic factors of surgery for mesial temporal lobe epilepsy (MTLE) is important for identifying ideal candidates and predicting the prognosis for individual patients. We tried to identify the prognostic factors of anterior temporal lobectomy (ATL) for MTLE with longitudinal multivariate analysis.

Effect of pre-diabetes on future risk of stroke: meta-analysis.

Objective:  To evaluate the impact of neurological and medical complications on 3‐month outcomes in acute ischaemic stroke patients.

Quantifying the Value of Stroke Disability Outcomes: WHO Global Burden of Disease Project Disability Weights for Each Level of the Modified Rankin Scale

Objectives To assess the association between pre-diabetes and risk of stroke, and to evaluate whether this relation varies by diagnostic criteria for pre-diabetes. Design Systematic review and meta-analysis of prospective studies. Data sources A search of Medline, Embase, and the Cochrane Library (1947 to 16 July 2011) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. Selection criteria Prospective cohort studies that reported multivariate adjusted relative risks and corresponding 95% confidence intervals for stroke with respect to baseline pre-diabetes were included. Data extraction Two independent reviewers extracted data on pre-diabetes status at baseline, risk estimates of stroke, study quality, and methods used to assess pre-diabetes and stroke. Relative risks were pooled using random effects models when appropriate. Associations were tested in subgroups representing different characteristics of participants and studies. Publication bias was evaluated with funnel plots. Results The search yielded 15 prospective cohort studies including 760 925 participants. In 8 studies analysing pre-diabetes defined as fasting glucose 100-125 mg/dL (5.6-6.9 mmol/L), the random effects summary estimate did not show an increased risk of stroke after adjustment for established cardiovascular risk factors (1.08, 95% confidence interval 0.94 to 1.23; P=0.26). In 5 studies analysing pre-diabetes defined as fasting glucose 110-125 mg/dL (6.1-6.9 mmol/L), the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.21, 1.02 to 1.44; P=0.03). In 8 studies with information about impaired glucose tolerance or combined impaired glucose tolerance and impaired fasting glucose, the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.26, 1.10 to 1.43; P<0.001). When studies that might have enrolled patients with undiagnosed diabetes were excluded, only impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance independently raised the future risk of stroke (1.20, 1.07 to 1.35; P=0.002). Conclusion Pre-diabetes, defined as impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance, may be associated with a higher future risk of stroke, but the relative risks are modest and may reflect underlying confounding.

Pre-surgical evaluation and surgical outcome of 41 patients with non-lesional neocortical epilepsy

Background and Purpose— The modified Rankin Scale (mRS) categorizes poststroke disability among 7 broad, ordinal grades, but the interval distances between these levels are spaced along the disability spectrum have not been previously investigated. Methods— We used the person trade-off procedure developed by the World Health Organization Global Burden of Disease Project (WHO-GBDP) to generate disability weights (DWs) ranging from 0 (normal) to 1 (dead) for each of 7 mRS grades. The ratings of an international, 9-member panel of stroke experts were combined by a modified Delphi process. Results— DWs (95% CI) were 0 for mRS 0, 0.046 (0.004 to 0.088) for mRS 1, 0.212 (0.175 to 0.250) for mRS 2, 0.331 (0.292 to 0.371) for mRS 3, 0.652 (0.625 to 0.678) for mRS 4, 0.944 (0.873 to 1.015) for mRS 5, and 1.0 for mRS 6. DWs of adjacent mRS levels were significantly different (P<0.001 for all). Coefficients of variation showed a high degree of consensus for DWs among panel members. DWs placed each of the 5 intermediate mRS states in different disability class levels of the WHO-GBDP anchor conditions and identified natural clusters to use when reducing the mRS to fewer categories. Conclusions— Formal DW assignment confirms that the mRS is an ordered but unequally spaced scale. The availability of DWs for each mRS level now permits direct comparison of each poststroke outcome state with the outcomes of hundreds of other diseases in the WHO-GBDP and the expression of stroke burden in different populations by using the uniform metric of disability-adjusted life-years lost.