Jong-Moo Park

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.

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.

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.

Reduced neurogenesis after suppressed inflammation by minocycline in transient cerebral ischemia in rat

Recently, the beneficial role of minocycline on endogenous neurogenesis after cerebral ischemia has been contradicted by many reports. We examined whether minocycline influences post-ischemic neurogenesis in the subventricular zone. Adult male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h, and divided into a minocycline-treated (90 mg/Kg on reperfusion and 45 mg/Kg daily for maintenance) and a saline-treated group. Bromodeoxyuridine was injected to determine levels of cell proliferation. Inflammation was assessed by counting polymorphonuclear cell and activated microglia and by measuring myeloperoxidase activity. Endogenous neurogenesis was quantified by immunohistochemical staining and functional outcome was measured by infarct size and behavioral tests. Minocycline treatment decreased inflammation on 1st and 4th days after ischemia. BrdU-positive cells on 7th day (saline vs. minocycline: 602.80+/-146.96 vs. 399.40+/-109.69) and the number of double labeling cells of BrdU/NeuN on 7th day (13.00+/-4.36 vs. 6.40+/-2.07) and BrdU/DCx on 4th day (17.00+/-5.00 vs. 7.50+/-1.91) were significantly decreased in minocycline-treated rats. Infarct size and behavioral tests were not different. Our results indicate that minocycline may reduce immediate post-ischemic neurogenesis despite adequately suppressed inflammation.

Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry.

There are limited data on the utilization of diagnostics and the variation of treatments at the national level in acute stroke care. Clinical Research Center for Stroke – 5th division stroke registry aimed to describe stroke statistics and quality of care in Korea and to implement quality indicators. Clinical Research Center for Stroke – 5th division registry was established in April 2008 and covers pretreatment demographics, medical and stroke severity measures, diagnostic evaluation, hyperacute revascularization, in-hospital management, discharge disposition, quality indicators, and long-term functional outcomes. Consecutive stroke cases from 12 participating centers are registered to a web-based database. Meticulous data management and auditing policy were applied. A total of 14 792 ischemic stroke cases were enrolled from April 2008 to January 2012. The median National Institutes of Health Stroke Scale score was 4 at admission, with median delay of onset to arrival of 14 h. Rate of risk factor management before stroke exceeds more than 80% for hypertension and diabetes. Revascularization procedures were performed in 1736 subjects (12%), and 34% were endovascular (n = 598). Substantial variability was noted in the preferred modality of hyperacute revascularization (range of endovascular recanalization = 6–60%), use of computed tomography (30–93%), and perfusion imaging (2–96%). The Clinical Research Center for Stroke – 5th division registry documented that the current practice of acute stroke care in South Korea largely met the standard of guidelines, but variability of practice still remains. The registry would provide an opportunity to evaluate the quality of stroke care across South Korea and compare it with that of other countries.

Cilostazol in Acute Ischemic Stroke Treatment (CAIST Trial): A Randomized Double-Blind Non-Inferiority Trial

Background: Aspirin is a proven antiplatelet agent in acute ischemic stroke, and there are no current guidelines for other antiplatelet treatments. We aimed to compare the efficacy and safety of cilostazol with aspirin in acute stroke. Methods: Patients with measurable neurological deficits (NIHSS score ≤15) within 48 h of onset were randomly assigned to cilostazol (200 mg/day) or aspirin (300 mg/day) for 90 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0–2 at 90 days. Cardiovascular events, bleeding complications, and other functional outcomes were also assessed. Statistical analysis was carried out by intention-to-treat and per-protocol bases. This trial is registered with ClinicalTrials.gov (NCT00272454). Results: In total, 458 patients were enrolled (mean age of 63 years, median NIHSS of 3), and mRS at 90 days was obtained in 447 patients. The primary endpoint was achieved in 76% (173/228) of those randomized to cilostazol and in 75% (165/219) assigned to aspirin, which supported the pre-specified non-inferiority of cilostazol to aspirin (95% CI of proportion difference: –6.15 to 7.22%, p = 0.0004). These results were also supported by per-protocol analysis (p = 0.045). Cardiovascular events occurred in 6 patients (3%) treated with cilostazol, and in 9 patients (4%) treated with aspirin (p = 0.41). Adverse events were more common in cilostazol-treated patients during the trial (91 vs. 85%, p = 0.055), while the frequencies of bleeding complications (cilostazol 11%, aspirin 13%, p = 0.43) or drug discontinuation (cilostazol 10%, aspirin 7%, p = 0.32) were not different. Conclusion: Cilostazol is feasible in acute ischemic stroke, and comparable to aspirin in its efficacy and safety.

Reperfusion Therapy in Unclear-Onset Stroke Based on MRI Evaluation (RESTORE) A Prospective Multicenter Study

Background and Purpose— Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. Methods— This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch >20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. Results— Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5 ± 10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14–4.49). Conclusions— In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification

Background and Purpose In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). Methods We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. Results The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). Conclusions Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.

Cognitive Impairment Evaluated With Vascular Cognitive Impairment Harmonization Standards in a Multicenter Prospective Stroke Cohort in Korea

Background and Purpose— Since the Vascular Cognitive Impairment Harmonization Standards (VCIHS) neuropsychological test protocol was proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network, no studies have applied this neuropsychological protocol to poststroke survivors in a large-scale, multicenter stroke cohort. We determined the frequency of vascular cognitive impairment (VCI) and investigated the feasibility of using the Korean version of the VCIHS neuropsychological protocol in a multicenter, hospital-based stroke cohort in Korea. Methods— We prospectively enrolled 620 subjects with ischemic stroke within 7 days of symptom onset among 899 patients who were consecutively admitted to 12 university hospitals in Korea. Neuropsychological assessments using the 60-minute Korean VCIHS neuropsychological protocol were administered at 3 months after stroke. Results— Of the 620 patients, 506 were followed up at 3 months after stroke. Of these, 353 (69.8%) were evaluated for cognitive function using the 60-minute Korean VCIHS neuropsychological protocol. The frequency of VCI at 3 months was 62.6%: VCI with no dementia in 49.9% and vascular dementia in 12.7%. Old age (P=0.014), poor functional outcomes at 3 months (P=0.029), and stroke subtypes other than small vessel disease (P=0.004) were independent risk factors of VCI. Conclusions— VCI, evaluated using the Korean VCIHS neuropsychological protocol, is substantial at 3 months after ischemic stroke in Korea. The use of the 60-minute Korean VCIHS neuropsychological protocol was feasible in large-scale multicenter studies.

Cerebral Microbleeds and Early Recurrent Stroke After Transient Ischemic Attack Results From the Korean Transient Ischemic Attack Expression Registry

IMPORTANCE The risk of early recurrent stroke after transient ischemic attack (TIA) may be modifiable by optimal treatment. Although ABCD2 scores, diffusion-weighted imaging lesions, and large artery stenosis are well known to predict early stroke recurrence, other neuroimaging parameters, such as cerebral microbleeds (CMBs), have not been well explored in patients with TIA. OBJECTIVE To determine the rate of early recurrent stroke after TIA and its neuroimaging predictors. DESIGN, SETTING, AND PARTICIPANTS In this hospital-based, multicenter prospective cohort study, consecutive patients with TIA were enrolled from 11 university hospitals from July 1, 2010, through December 31, 2012. Patients who were admitted within 24 hours after symptom onset and underwent diffusion-weighted imaging were included. MAIN OUTCOMES AND MEASURES The primary end point was recurrent stroke within 90 days. Baseline demographics, clinical manifestations, neuroimaging findings, and use of antithrombotics or statins also were analyzed. RESULTS A total of 500 patients (mean age, 64 years; male, 291 [58.2%]; median ABCD2 score, 4) completed 90-day follow-up with guideline-based management: antiplatelets (457 [91.4%]), anticoagulants (74 [14.8%]), and statins (345 [69.0%]). Recurrent stroke occurred in 25 patients (5.0%). Compared with patients without recurrent stroke, those with recurrent stroke were more likely to have crescendo TIA (20 [4.2%] vs 4 [16.0%], P = .03), white matter hyperintensities (146 [30.7%] vs 13 [52.0%], P = .03), and CMBs (36 [7.6%] vs 7 [28.0%], P = .003). On multivariable Cox proportional hazards analysis, CMBs remained as independent predictors for recurrent stroke (hazard ratio, 3.66; 95% CI, 1.47-9.09; P = .005). CONCLUSIONS AND RELEVANCE Immediate and optimal management seems to modify the risk of recurrent stroke after TIA. Cerebral microbleeds may be novel predictors of stroke recurrence, which needs further validation.