Hee-Joon Bae

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.

Cerebral microbleeds are regionally associated with intracerebral hemorrhage

Background: Cerebral microbleeds (CMB) may be indicative of a hemorrhage-prone microangiopathy. Objective: To determine if increased numbers of these lesions are predictive of intracerebral hemorrhage (ICH), especially in terms of a distributional association. Methods: The authors examined consecutively 227 patients with acute stroke. CMB were counted using T2*-weighted gradient echo MRI data, and old lacunes and leukoaraiosis were also evaluated. The associations between the vascular risk factors and ICH were analyzed. With use of multivariate logistic regression analysis, the locations of the CMB or the old lacunes, which were categorized as being in the corticosubcortical area, the deep gray matter area, or the infratentorial area, were examined with regard to their relationships to the locations of the ICH. Results: The degrees of the CMB (r = 0.43, p < 0.01) and leukoaraiosis (r = 0.20, p < 0.01) were well correlated with the presence of ICH. Multivariate analysis revealed that the grades of the CMB were associated with the presence of ICH (p < 0.01, odds ratio [OR] = 2.67). CMB in the corticosubcortical area (p < 0.01, OR = 5.50) or deep gray matter (p < 0.01, OR = 2.55) were strongly associated with the presence of ICH in the same area, but no such association was observed in the case of CMB in the infratentorial area or in the case of old lacunes in any area. Conclusions: Cerebral microbleeds are strongly associated with the presence of intracerebral hemorrhage, and the distributional associations are also quite strong.

Low Concentration of Serum Total Cholesterol Is Associated With Multifocal Signal Loss Lesions on Gradient-Echo Magnetic Resonance Imaging Analysis of Risk Factors for Multifocal Signal Loss Lesions

Background and Purpose— Multifocal signal loss lesions (MSLLs) on T2*-weighted gradient-echo (GE) MRI are believed to be microbleeds histopathologically. Previous epidemiological studies suggested that low serum cholesterol is associated with the increased risk of intracerebral hemorrhage. We investigated risk factors of MSLLs and the relationship between lipid profiles and MSLLs on GE-MRI. Methods— We included consecutively 172 patients who underwent brain MRI. MSLLs on GE-MRI were counted by 2 neurologists separately and graded by consensus. The concentrations of lipid profiles were categorized as quartiles, and the MSLLs were graded as absent (total count, 0), mild (1 to 2), moderate (3 to 10), and severe (>10). Results— The mean concentrations of total cholesterol and low-density lipoprotein cholesterol were significantly lower in patients with a severe degree of MSLLs than in those without MSLL (P <0.05). By multivariate analysis, MSLLs were significantly correlated with hypertension (odds ratio [OR], 3.42; 95% CI, 1.17 to 9.97), leukoaraiosis (OR, 4.62; 95% CI, 2.87 to 7.41), the lowest quartile of serum total cholesterol (<4.27 mmol/L; OR, 10.91; 95% CI, 3.98 to 25.57), and the highest quartile of high-density lipoprotein (>1.47 mmol/L; OR, 3.5; 95% CI, 1.45 to 8.29). Conclusions— Our results suggest that both the lipid profile levels and the severity of hypertension may be closely associated with MSLLs on GE-MRI.

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

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

Safety and efficacy of MRI-based thrombolysis in unclear-onset stroke. A preliminary report

Background: Standard selection criteria for thrombolysis typically exclude patients with acute ischemic stroke with unclear onset. Multimodal MRI screening may be able to identify those with a favorable benefit-risk ratio for thrombolysis. We aimed to evaluate the safety and efficacy of MRI-based thrombolysis in unclear-onset stroke (UnCLOS). Methods: We reviewed the thrombolysis database registries from 3 medical centers in Korea. Subjects received thrombolysis with intravenous tissue plasminogen activator (tPA) or combined intravenous tPA and intra-arterial urokinase within 3 h, or intra-arterial urokinase within 6 h from symptom detection. For patients with UnCLOS, MRI-specific eligibility criteria (i.e. positive perfusion-diffusion mismatch and absence of well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions) were applied. Rates of immediate and 5-day recanalization, early neurological improvement and symptomatic intracranial hemorrhage (ICH) within 48 h after treatment and 3-month modified Rankin Scale (mRS) scores were compared between patients with UnCLOS and those with clear-onset stroke (CLOS). Results: 32 patients with UnCLOS and 223 patients with CLOS were included. Baseline characteristics were comparable between the two groups, except that the proportion of MRI screening was higher, and detection-to-door time and door-to-needle time were longer in the UnCLOS group (p < 0.01). Rates of recanalization (immediate, 81.3 vs. 63.1%; delayed, 80.6 vs. 69.1%), early neurological improvement (on day 1, 46.9 vs. 35.9%; on day 7, 50.0 vs. 49.3%), symptomatic ICH (6.3 vs. 5.8%) and 3-month outcome (mRS 0–1, 37.5 vs. 35.0%; mRS 0–2, 50.0 vs. 49.3%) did not differ between the UnCLOS and CLOS groups. Conclusion: These preliminary results suggest that thrombolysis based on MRI criteria may safely be applied to acute stroke patients with unclear onset.

Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

BackgroundDelayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea.MethodsA prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay.ResultsAmong the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival.ConclusionsIn Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.

Intracranial Cerebral Artery Disease as a Risk Factor for Central Nervous System Complications of Coronary Artery Bypass Graft Surgery

Background and Purpose— Although extracranial carotid artery disease (ECAD) is accepted as a risk factor for central nervous system (CNS) complications after coronary artery bypass graft (CABG) surgery, it remains to be clarified whether intracranial cerebral artery disease (ICAD) may also increase the risk. We conducted a prospective study to elucidate the relation between ICAD and CNS complications after CABG surgery. Methods— We prospectively studied 201 patients undergoing nonemergency isolated CABG surgery during a 39-month period (from March 1995 to June 1998). Each patient was evaluated before surgery with neurological examination, transcranial Doppler, and carotid duplex ultrasonography. Magnetic resonance angiography was used to determine the presence and severity of ECAD and ICAD in patients with abnormal findings on clinical examination, carotid duplex ultrasonography, or transcranial Doppler. Patients were followed after surgery and evaluated for the development of CNS complications. Association between CNS complications and their potential predictors was analyzed. Results— One hundred nine patients (54.2%) were found to have ECAD and/or ICAD. ECAD alone was found in 48 patients (23.9%), ICAD alone in 33 (16.4%), and both ECAD and ICAD in 28 (13.9%). Fifty-one patients (25.4%) had single or multiple CNS complications: 23 (11.4%) had delirium; 18 (9.0%) had hypoxic-metabolic encephalopathy; 7 (3.5%) had stroke; and 7 (3.5%) had seizure. In multivariate analysis, ICAD was found to have an independent association with the development of CNS complications (prevalence OR, 2.28; 95% CI, 1.04 to 5.01) after controlling for covariates including age, occurrence of intraoperative events, and reoperation. The joint effect of ECAD and ICAD was also statistically significant and stronger than ICAD alone (prevalence OR, 3.87; 95% CI, 1.80 to 6.52). Conclusions— Our results suggest that ICAD may be an independent risk factor for CNS complications after CABG surgery. These results support pre-CABG evaluation of the intracranial arteries for the risk assessment of CABG surgery, at least in black and Asian patients, in whom there may be a higher prevalence of intracranial arterial stenosis.

Comparative analysis of the spatial distribution and severity of cerebral microbleeds and old lacunes

Background: Cerebral microbleeds, which result from microangiopathic changes following chronic hypertension, may reflect bleeding-prone microangiopathy. However, the distribution of these lesions has not been compared with that of lacunes, which represent occlusive type microangiopathy. Objectives: To compare the cerebral distribution of microbleeds and lacunes and correlate their severity. Methods: The study population comprised 129 hypertensive patients who underwent brain magnetic resonance imaging (MRI), including gradient echo (GE) sequences. Cerebral microbleeds were counted using GE-MRI data, and lacunes were also counted by comparing T1 and T2 weighted MRI. To investigate the distributions, the number of patients with each type of lesion was compared, and the occurrence index (the total number of the specific lesions divided by the total number of patients) was examined statistically. Correlation analyses were done on the relations between the different grades of microbleeds, lacunes, and leukoaraiosis. Results: Cerebral microbleeds and lacunes were found at various foci in the brain, with a preference for the cortico-subcortical region and the deep grey matter. The occurrence index of microbleeds, but not of lacunes, was significantly higher in the cortico-subcortical region than in the deep grey matter. The severity of the microbleeds was positively correlated with the severity of lacunes, and both types of lesion were closely correlated with the degree of leukoaraiosis. Conclusions: These data suggest that microbleeds and lacunes tend to occur to a similar extent in long standing hypertension, but not necessarily in the same locations.

Efficacy and Safety of Combination Antiplatelet Therapies in Patients With Symptomatic Intracranial Atherosclerotic Stenosis

Background and Purpose— An optimal strategy for management of symptomatic intracranial atherosclerotic stenosis (ICAS) has not yet been established. We compared the efficacy of 2 combinations of antiplatelets, aspirin plus cilostazol (cilostazol group) verus aspirin plus clopidogrel (clopidogrel group), on the progression of ICAS, which is known to be associated with clinical stroke recurrence. Methods— In this investigator-initiated double-blind trial, 457 patients with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or the basilar artery were randomly allocated into either a cilostazol group or a clopidogrel group. After 7 months of treatment, follow-up MR angiogram and MRI were performed. The primary end point was the progression of ICAS in comparison with stenosis on the baseline MR angiogram. Secondary end points included the occurrence of new ischemic lesions on MRI, composite of cardiovascular events, and major bleeding complications. Results— Cardiovascular events occurred in 15 of 232 patients (6.4%) in the cilostazol group and 10 of 225 (4.4%) in the clopidogrel group (P=0.312). Cilostazol did not reduce the progression of symptomatic ICAS (20 of 202) compared to clopidogrel (32 of 207) (odds ratio, 0.61; P=0.092), although favorable changes in serum lipoproteins were observed in the cilostazol group. There were no significant differences between the 2 groups with respect to new ischemic lesions (18.7% versus 12.0%; P=0.078) and major hemorrhagic complications (0.9% versus 2.6%; P=0.163). Conclusions— This trial failed to show significant difference in preventing progression of ICAS and new ischemic lesions between the 2 combination antiplatelet therapies in the patients with symptomatic ICAS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039.

The Significance of Blood Pressure Variability for the Development of Hemorrhagic Transformation in Acute Ischemic Stroke

Background and Purpose— Elevated blood pressure (BP) is commonly observed in acute ischemic stroke and is known to be associated with hemorrhagic transformation (HT). However, the effect of BP variability on the development of HT is not known well. Methods— A consecutive series of patients with acute ischemic stroke, who were hospitalized within 24 hours of onset and showed no HT on initial gradient echo MRI, were enrolled in this study. BP measurements during the first 72 hours were obtained, and BP variability of each patient was described using various summary parameters: SD, maximum (max), minimum (min), difference between max and min (max−min), average squared difference between successive measurements (sv), and maximum sv (svmax). Results— Of 792 patients meeting the eligibility criteria, 70 (8.8%) developed HT. Among BP variability parameters categorized into quartiles, SBPmax, SBPmin, SBPmax−min, SBPsvmax, DBPSD, DBPmax, DBPmin, DBPmax−min, and DBPsvmax were significantly associated with HT independent of mean SBP, age, interval from onset to arrival, initial stroke severity, diabetes mellitus, stroke subtype, thrombolysis, initial glucose, and total cholesterol (P<0.05 on likelihood ratio test of trend). The analyses about the interaction between thrombolysis and variability parameters showed that the effects of BP variability on the development of HT did not differ by whether patients received thrombolysis or not. Conclusions— Our study suggests that we may consider not only the absolute level of BP but also its variability to prevent hemorrhagic transformation.