Mi Hwa Yang

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.

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.

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.

Neuroimaging Markers for Early Neurologic Deterioration in Single Small Subcortical Infarction

Background and Purpose— Early neurological deterioration (END) occurs in ≥20% of single small subcortical infarctions (SSSIs; axial diameter ⩽20 mm in the perforator territories) and deters functional recovery. Both microvasculopathies and atherosclerosis have been proposed to independently contribute to the occurrence of END in SSSI cases. We hypothesized that the occurrence of END in SSSIs differs according to the pathological process. Methods— We collected data from 587 patients with SSSI within 48 hours of onset from a prospective stroke registry containing 4961 case records. Independent reviewers, blinded to END information, rated neuroimaging characteristics, including relevant artery stenosis (0% to 50% stenosis of the adjacent arteries on magnetic resonance angiography), branch atheromatous lesions (≥4 consecutive axial cuts or extensions from the basal surface of the pons), white matter hyperintensities, old lacunar infarctions, and cerebral microbleeds. Results— END occurred in 79 (13.5%) cases, including 6 recurrences, 68 progressions, 1 symptomatic hemorrhagic transformation, 1 others, and 3 unknowns. END increased the National Institutes of Health Stroke Scale score by 2.3±1.4 points. Patients with END showed higher frequencies of modified Rankin Scale scores of 3 to 6 after 3 months compared with patients without END (49% versus 23%). Patients with relevant artery stenosis (adjusted odds ratio, 1.91; 95% confidence interval, 1.13–3.21) and branch atheromatous lesions (adjusted odds ratio, 2.98; 95% confidence interval, 1.80–4.93) had significantly higher odds of exhibiting END. However, such an association was not detected with small vessel disease markers. Conclusions— Our analysis indicated a potential contribution of the localized atherosclerotic process to END in SSSIs. Precautionary measures might be used for SSSIs suggestive of atherosclerotic pathologies.

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.

Differential Effect of Previous Antiplatelet Use on Stroke Severity According to Stroke Mechanism

Background and Purpose— The effect of previous antiplatelet use on stroke severity is controversial. We assume that this controversy is attributable to its difference according to the stroke mechanism. Methods— Using a prospective stroke registry, patients who were hospitalized because of ischemic stroke and had relevant lesions on MRI were selected. Patients who were using anticoagulants or whose stroke subtype was categorized as stroke of other determined etiology or undetermined etiology were excluded. Baseline stroke severity was measured using the National Institutes of Health Stroke Scale scores at presentation and was compared between no previous antiplatelet users and previous antiplatelet users with stratification by stroke subtypes. Results— Among the 1622 patients, a total of 490 (30.2%) patients reported use of an antiplatelet within 1 week of stroke onset. The baseline National Institutes of Health Stroke Scale score showed no difference between the nonantiplatelet and antiplatelet groups by crude comparison. However, the interaction between previous antiplatelet use and stroke subtype was significant (P=0.023) in a multivariable analysis; when the study subjects were stratified by stroke subtype, the difference in baseline National Institutes of Health Stroke Scale between the nonantiplatelet and platelet groups was significant in the large artery atherothrombosis group but not in those with cardioembolism and small-vessel occlusion before and after adjustments. Conclusions— Our study suggests that the reduction of initial stroke severity in the previous antiplatelet users may differ by stroke mechanism.

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.

Can Early Ischemic Lesion Recurrence on Diffusion-Weighted MRI Affect Functional Outcome after Acute Ischemic Stroke?

Background and Purpose Ischemic lesion recurrence on diffusion-weighted imaging (DWI-LR) is a frequently observed phenomenon after acute ischemic stroke. However, no study has elucidated the impact of DWI-LR on functional outcome. Methods Among a consecutive series of patients who presented with focal symptoms or signs compatible with stroke within 48 hours from the onset over a 50-month period, those who had relevant ischemic lesions on initial DWI and underwent follow-up DWI within 14 days after the onset were enrolled in this study. As outcome variables, the scores on the modified Rankin Disability Scale (mRDS) at 3 months and 1 year were measured prospectively and dichotomized into good (0-2) vs. poor (3-6). When calculating odds ratios (ORs), adjustment was performed for age, previous stroke, initial score on the NIH Stroke Scale, stroke subtype, and IV thrombolysis. Results Among those 786 patients finally enrolled in this study, 221 (28.1%) had DWI-LR. For a poor outcome at 3 months, the crude ORs of any, symptomatic, and asymptomatic DWI-LR were 2.70 [95% confidence interval (CI), 1.96 to 3.72], 10.03 (95% CI, 4.39 to 22.96), and 2.04 (95% CI, 1.44 to 2.88), respectively. With adjustment, the OR of symptomatic DWI-LR was 6.44 (95% CI, 2.50 to 16.57), whereas those of any and asymptomatic DWI-LR lost their statistical significance: 1.44 (95% CI, 0.94 to 2.20) and 1.04 (95% CI, 0.65 to 1.65), respectively. Analyzing with the 1-year outcome produced similar results. Conclusions This study shows that symptomatic early lesion recurrence can affect functional outcome after acute ischemic stroke, whereas an asymptomatic one may not.

Impact of Both Ends of the Hemoglobin Range on Clinical Outcomes in Acute Ischemic Stroke

Background and Purpose— Although both ends of the hemoglobin range may negatively influence clinical outcomes in acute ischemic stroke, most studies have examined the linear relationship or focused on the lower end of the range. Furthermore, it is unclear whether hemoglobin concentrations at different time points during hospitalization correlate with clinical outcomes in the same manner. Methods— We identified 2681 consecutive patients with acute ischemic stroke from a prospective stroke registry database and grouped them into hemoglobin concentration quintiles using the following 5 indices: initial, nadir, time-averaged, discharge hemoglobin, and hemoglobin drop. To examine the effect of both ends of hemoglobin range, the third quintile was selected as a reference category except for hemoglobin drop, for which the first quintile was used. As outcome variables, 3-month modified Rankin Scale as an ordinal scale and 3-month mortality were used. Results— With respect to higher modified Rankin Scale scores, the adjusted odds ratios and 95% confidence intervals of the first quintiles of initial, nadir, time-averaged, and discharge hemoglobin were 1.74 (1.31−2.31), 2.64 (2.09−3.33), 1.81 (1.42−2.30), and 1.65 (1.29−2.13), respectively. The opposite ends of these hemoglobin indices were not significantly associated. The adjusted odds ratio of the fifth quintile of hemoglobin drop (greatest hemoglobin drop) was 2.09 (1.51−2.89). The mortality analysis showed similar results except for initial hemoglobin. Conclusions— In acute ischemic stroke, poor outcome was related to the lower but not the higher end of the hemoglobin range, regardless of when and how hemoglobin concentrations were measured.