Myung Suk Jang

Is asymptomatic hemorrhagic transformation really innocuous

Objectives: Asymptomatic hemorrhagic transformation (HT) is not associated with immediate deterioration of patients with acute ischemic stroke. However, it is unclear whether it is clinically innocuous with respect to long-term outcome. The aim of this study was to determine the impact of asymptomatic HT on 3-month outcome. Methods: A consecutive series of 1,618 patients, hospitalized between January 2004 and August 2007 for ischemic stroke within 7 days from symptom onset were identified in a prospective stroke registry database. Those who had no evidence of acute cerebral ischemia on diffusion-weighted MRI, who did not undergo T2-weighted gradient echo MRI, whose modified Rankin Scale (mRS) score at 3 months after stroke onset was not available, or who had symptomatic HT were excluded. The odds ratio (OR) of asymptomatic HT was calculated for the full distribution of mRS score and adjusted for variables with p < 0.25 with respect to their associations with asymptomatic HT or functional outcome. Results: Of 1,412 patients eligible for the study, 100 (7.1%) had asymptomatic HT. Patients who experienced asymptomatic HT were more likely to have cardioembolic stroke, to receive thrombolytic therapy, to receive anticoagulation with heparin, and to have a higher initial NIH Stroke Scale score. The crude and adjusted ORs of asymptomatic HT for an increment of mRS score at 3 months were 2.94 (95% confidence interval 2.05–4.24) and 1.90 (1.27–2.82), respectively. Conclusions: Our study shows that the odds of a worse outcome are increased by a factor of 2 in patients with asymptomatic HT compared with those without HT after acute ischemic stroke.

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.

Effect of blood pressure on 3-month functional outcome in the subacute stage of ischemic stroke

ABSTRACT Objective: We aimed to study various measures of blood pressure (BP) in the subacute phase of ischemic stroke to determine whether any of them predicted clinical outcome. Methods: In this retrospective observational study, a consecutive series of patients hospitalized for ischemic stroke within 48 hours of onset were enrolled. The subacute stage of stroke was defined as the time period from 72 hours of symptom onset to discharge or transfer. During this period, mean, maximum, maximum − minimum, SD, and coefficient of variation of systolic BP (SBP) and diastolic BP (DBP) were determined. A baseline severity-adjusted analysis was performed using each patient’s 3-month modified Rankin Scale score as the primary outcome. Results: Among a total of 2,271 patients, the median number of BP measurements was 34 per person and the median interval from onset to discharge was 8.7 days. Measures of variability of BP were associated with poor outcome. One SD increase of maximum − minimum (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42), SD (OR, 1.20; 95% CI, 1.07–1.34), or coefficient of variation (OR, 1.21; 95% CI, 1.09–1.35) for SBP, but not mean level of SBP (OR, 0.92; 95% CI, 0.79–1.07), was independently associated with poor outcome. Results were similar for DBP. Conclusion: This study shows that variability of BP, but not average BP in the subacute stage of ischemic stroke, is associated with functional outcome at 3 months after stroke onset.

Blood pressure variability and the development of early neurological deterioration following acute ischemic stroke

Objectives: Early neurological deterioration (END) is a common condition associated with poor outcome after acute ischemic stroke. We studied association between blood pressure (BP) variability and development of END. Methods: In this retrospective observational study, we studied a consecutive series of patients hospitalized for acute ischemic stroke within 24 h of onset. The primary outcome of interest was the development of END according to predefined criteria within the first 72 h of stroke onset. During this period, the mean, maximum (max), and minimum (min) values for the SBP and DBP were measured. The following parameters of BP variability were calculated for the SBP and DBP: the difference between the maximum and minimum (max−min), the SD, and the coefficient of variation. Results: Of the 1161 patients enrolled in the study (mean age, 67.5 ± 13.3 years; 59.6% men), 210 (18.1%) developed END. All of the BP variability parameters were linearly associated with END independent of mean BP and potential clinical variables (P values < 0.05 on likelihood ratio tests for trend), except for SBPmax−min. Among the other BP parameters, SBPmean, SBPmax, DBPmax, and DBPmin were independently associated with END. After adjustments for potential confounders, the odds for END increased 14–21% with each increase of one standard deviation in the BP variability parameter. Conclusion: BP variability is independently and linearly associated with the development of neurologic deterioration in acute stage of ischemic stroke.

Burden of Ischemic Stroke in Korea: Analysis of Disability-Adjusted Life Years Lost

Background and Purpose Disability-adjusted life years (DALY), incorporating both disability and mortality, has been widely employed to measure regional and global burdens of stroke. Thus far, the DALY lost to stroke in a population has been estimated using only the crude population-level data; no previous study has incorporated refined data from stroke registries. The aim of this study was to integrate the stroke registry data and the population-level incidence data to project the nationwide DALY lost to ischemic stroke. Methods From the data of two large ischemic stroke registries, we derived an average DALY lost due to ischemic stroke for each of the following age groups: <45, 45-54, 55-64, 65-74, 75-84, and ≥85 years. The nationwide ischemic stroke incidence for each age group was extracted from a cardiovascular and cerebrovascular surveillance study that analyzed the 2004 Korean Health Insurance database. Results The average DALY lost due to ischemic stroke for the age groups <45, 45-54, 55-64, 65-74, 75-84, and ≥85 years was 5.07, 4.63, 4.35, 3.88, 2.88, and 1.73, respectively. By multiplying the incidence and the average DALY lost, the nationwide DALY lost was determined to be 9,952 for those <45 years, 24,608 for 45-54 years, 50,682 for 55-64 years, 88,875 for 65-74 years, 52,089 for 75-84 years, and 8,192 for ≥85 years, respectively. The projected nationwide DALY lost due to 64,688 ischemic strokes in 2004 was 234,399 (121,482 for men and 113,244 for women), and the DALY lost per 100,000 person-years was 483 (500 for men and 469 for women). Conclusions Incidence data from a population study and DALY values derived from stroke registries can be integrated to provide a more refined projection of the nationwide burden of ischemic stroke. In Korea, more than 230,000 years of healthy life are being lost annually due to ischemic stroke, and hence prompt action is imperative.

Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Classification and Vascular Territory of Ischemic Stroke Lesions Diagnosed by Diffusion-Weighted Imaging

Background The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion‐weighted imaging study may help resolve this lack of clarity. Methods and Results We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion‐weighted imaging and who underwent a thorough etiological investigation. The vascular territory in which an ischemic lesion was situated was identified using standard anatomic maps of the dominant arterial territories. Stroke subtype was based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST, classification. Large‐artery atherosclerosis (37.3%) was the most common stroke subtype, and middle cerebral artery (49.6%) was the most frequently involved territory. Large‐artery atherosclerosis was the most common subtype for anterior cerebral, middle cerebral, vertebral, and anterior and posterior inferior cerebellar artery territory infarctions. Small vessel occlusion was the leading subtype in basilar and posterior cerebral artery territories. Cardioembolism was the leading cause in superior cerebellar artery territory. Compared with carotid territory stroke, vertebrobasilar territory stroke was more likely to be caused by small vessel occlusion (21.4% versus 30.1%, P<0.001) and less likely to be caused by cardioembolism (23.2% versus 13.8%, P<0.001). Multiple‐vascular‐territory infarction was frequently caused by cardioembolism (44.2%) in carotid territory and by large‐artery atherosclerosis (52.1%) in vertebrobasilar territory. Conclusions Information on vascular territory of a stroke lesion may be helpful in timely investigation and accurate diagnosis of stroke etiology.

Cortical Hubs and Subcortical Cholinergic Pathways as Neural Substrates of Poststroke Dementia

Background and Purpose— A role of neural networks in the development of poststroke dementia has not been clearly established. We hypothesized that stroke-mediated disruption of subcortical cholinergic pathway or large-scale neural networks contributes to poststroke dementia. Methods— A matched case–control study was conducted in a predetermined cohort with acute ischemic stroke. Cases were defined as newly developed dementia diagnosed >3 months after stroke using the Korean Vascular Cognitive Impairment Harmonization Standards. Each case was matched to 2 controls for age, education, and initial stroke severity. The Cholinergic Pathways HyperIntensities Scale was applied with some modifications to characterize disruption of cholinergic pathways by acute stroke lesions. Involvement of major cortical hub locations of the default mode network, central executive network, and salience network was also investigated. Results— After matching, 38 cases and 66 matched controls were included. Cholinergic Pathways HyperIntensities Scale scores were significantly higher in cases than in controls (2.2±2.9 versus 0.9±1.4). Acute ischemic lesions affecting the default mode and central executive networks were more frequently observed in cases compared with controls (36.8% versus 7.6% and 26.3% versus 6.1%, respectively). These findings remained significant in the multiple logistic regression models adjusted for various sets of potential confounders. Lesion location analysis revealed that cases were more likely to have acute lesions in the left corona radiata, hippocampal formation, and posterior parietal cortex. Conclusions— Disruption of cholinergic pathways and major hubs of large-scale neural networks might contribute to newly developed dementia after acute ischemic stroke.

Symptomatic steno-occlusion in patients with acute cerebral infarction: prevalence, distribution, and functional outcome.

Background and Purpose Symptomatic steno-occlusion (SYSO) in acute ischemic stroke has a significant impact on treatment options and prognosis. However, the prevalence, distribution, clinical characteristics, and outcome of SYSO are not well known. Methods We retrospectively identified 3,451 patients hospitalized because of ischemic stroke within 24 hours of symptom onset at 9 stroke centers in South Korea. Patients who did not undergo magnetic resonance imaging were excluded. SYSO was defined as stenosis or occlusion of cerebral arteries with relevant ischemic lesions in the corresponding arterial territory. The number, location, and severity of SYSOs and their effects on functional outcome were analyzed. Results In total, 1,929 of 3,057 subjects (63.1%) had SYSO. The most frequently affected vessels were the middle cerebral artery (34.6%), extracranial internal carotid artery (14%), vertebral artery (12.4%), and basilar artery (8.7%). SYSO predicted poor outcome on the modified Rankin Scale 3-6 (odds ratio, 1.77; 95% confidence interval, 1.46-2.15) with adjustments. Involvement of 2 or more vessels was observed in 30.6% of patients with SYSO and independently increased the risk of poor outcome (odds ratio, 2.76; 95% confidence interval, 2.12-3.59). The severity of SYSO was associated with outcome and showed a significant dose-response trend (P<0.001). The effect of SYSO on outcome did not significantly differ by individual arterial location (P for contrast=0.21). Conclusions Approximately 60% of patients with acute ischemic stroke had SYSO, and the severity and number were inversely correlated with outcome. The results suggest that SYSO could predict stroke outcome.

Validation of FLAIR Hyperintense Lesions as Imaging Biomarkers to Predict the Outcome of Acute Stroke after Intra-Arterial Thrombolysis following Intravenous Tissue Plasminogen Activator

Background: Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. Methods: With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Results: Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. Conclusions: This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimers disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD. Methods Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology. Results The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA. Conclusions Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.