Stroke outcomes are worse with larger leukoaraiosis volumes.

Leukoaraiosis or white matter hyperintensities are frequently observed on magnetic resonance imaging of stroke patients. We investigated how white matter hyperintensity volumes affect stroke outcomes, generally and by subtype. In total, 5035 acute ischaemic stroke patients were enrolled. Strokes were classified as large artery atherosclerosis, small vessel occlusion, or cardioembolism. White matter hyperintensity volumes were stratified into quintiles. Mean age (± standard deviation) was 66.3 ± 12.8, 59.6% male. Median (interquartile range) modified Rankin Scale score was 2 (1-3) at discharge and 1 (0-3) at 3 months; 16.5% experienced early neurological deterioration, and 3.3% recurrent stroke. The Cochran-Mantel-Haenszel test with adjustment for age, stroke severity, sex, and thrombolysis status showed that the distributions of 3-month modified Rankin Scale scores differed across white matter hyperintensity quintiles (P < 0.001). Multiple ordinal logistic regression analysis showed that higher white matter hyperintensity quintiles were independently associated with worse 3-month modified Rankin Scale scores; adjusted odds ratios (95% confidence interval) for the second to fifth quintiles versus the first quintile were 1.29 (1.10-1.52), 1.40 (1.18-1.66), 1.69 (1.42-2.02) and 2.03 (1.69-2.43), respectively. For large artery atherosclerosis (39.0%), outcomes varied by white matter hyperintensity volume (P = 0.01, Cochran-Mantel-Haenszel test), and the upper three white matter hyperintensity quintiles (versus the first quintile) had worse 3-month modified Rankin Scale scores; adjusted odds ratios were 1.45 (1.10-1.90), 1.86 (1.41-2.47), and 1.89 (1.41-2.54), respectively. Patients with large artery atherosclerosis were vulnerable to early neurological deterioration (19.4%), and the top two white matter hyperintensity quintiles were more vulnerable still: 23.5% and 22.3%. Moreover, higher white matter hyperintensities were associated with poor modified Rankin Scale improvement: adjusted odds ratios for the upper two quintiles versus the first quintile were 0.66 (0.47-0.94) and 0.62 (0.43-0.89), respectively. For small vessel occlusion (17.8%), outcomes tended to vary by white matter hyperintensitiy volume (P = 0.10, Cochran-Mantel-Haenszel test), and the highest quintile was associated with worse 3-month modified Rankin Scale scores: adjusted odds ratio for the fifth quintile versus first quintile, 1.98 (1.23-3.18). In this subtype, worse white matter hyperintensities were associated with worse National Institute of Health Stroke Scale scores at presentation. For cardioembolism (20.6%), outcomes did not vary significantly by white matter hyperintensity volume (P = 0.19, Cochran-Mantel-Haenszel test); however, the adjusted odds ratio for the highest versus lowest quintiles was 1.62 (1.09-2.40). Regardless of stroke subtype, white matter hyperintensities were not associated with stroke recurrence within 3 months of follow-up. In conclusion, white matter hyperintensity volume independently correlates with stroke outcomes in acute ischaemic stroke. There are some suggestions that stroke outcomes may be affected by leukoaraiosis differentially depending on stroke subtypes, to be confirmed in future investigations.

Air Pollution Is Associated With Ischemic Stroke via Cardiogenic Embolism.

BACKGROUND AND PURPOSE: The aim of the study was to assessed the impact of short-term exposure to air pollution on ischemic stroke subtype, while focusing on stroke caused via cardioembolism. METHODS: From a nationwide, multicenter, prospective, stroke registry database, 13 535 patients with acute ischemic stroke hospitalized to 12 participating centers were enrolled in this study. Data on the hourly concentrations of particulate matter <10 µm, nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) were collected from 181 nationwide air pollution surveillance stations. The average values of these air pollutants over the 7 days before stroke onset from nearest air quality monitoring station in each patient were used to determine association with stroke subtype. The primary outcome was stroke subtype, including large artery atherosclerosis, small-vessel occlusion, cardioembolism, and stroke of other or undetermined cause. RESULTS: Particulate matter <10 µm and SO2 concentrations were independently associated with an increased risk of cardioembolic stroke, as compared with large artery atherosclerosis and noncardioembolic stroke. In stratified analyses, the proportion of cases of cardioembolic stroke was positively correlated with the particulate matter <10 µm, NO2, and SO2 quintiles. Moreover, seasonal and geographic factors were related to an increased proportion of cardioembolic stroke, which may be attributed to the high levels of air pollution. CONCLUSIONS: Our findings suggest that the short-term exposure to air pollutants is associated with cardioembolic stroke, and greater care should be taken for those susceptible to cerebral embolism during peak pollution periods. Public and environmental health policies to reduce air pollution could help slow down global increasing trends of cardioembolic stroke.

Clinical Outcomes of Posterior Versus Anterior Circulation Infarction With Low National Institutes of Health Stroke Scale Scores.

BACKGROUND AND PURPOSE: We compared baseline characteristics and outcomes at 3 months between patients with minor anterior circulation infarction (ACI) versus minor posterior circulation infarction (PCI), including the influence of large vessel disease on outcomes. METHODS: This study is an analysis of a prospective multicenter registry database in South Korea. Eligibility criteria were patients with ischemic stroke admitted within 7 days of stroke onset, lesions in either anterior or posterior circulation, and National Institutes of Health Stroke Scale score of ≤4 at baseline. Patients were divided into 4 groups for further analysis: minor ACI with and without internal carotid artery/middle cerebral artery large vessel disease and minor PCI with and without vertebrobasilar large vessel disease. RESULTS: A total of 7178 patients (65.2±12.6 years) were analyzed in this study, and 2233 patients (31.1%) had disability (modified Rankin Scale score 2-6) at 3 months. Disability was 32.3% in minor PCI and 30.3% in minor ACI (P=0.07), and death was 1.3% and 1.5%, respectively (P=0.82). In a multivariable logistic regression analysis, minor PCI was significantly associated with disability at 3 months when compared with minor ACI (odds ratio, 1.23; 95% confidence interval, 1.09-1.37; P<0.001). In pairwise comparisons, minor PCI with vertebrobasilar large vessel disease was independently associated with disability at 3 months, compared with the other 3 groups. CONCLUSIONS: Our study showed that minor PCI exhibited more frequent disability at 3 months than minor ACI. Especially, the presence of vertebrobasilar large vessel disease in minor PCI had a substantially higher risk of disability. Our results suggest that minor PCI with vertebrobasilar large vessel disease could require more meticulous care and are important targets for further study.

Comparative Effectiveness of Prestroke Aspirin on Stroke Severity and Outcome.

OBJECTIVE: The effect of prestroke aspirin use on initial severity, hemorrhagic transformation, and functional outcome of ischemic stroke is uncertain. METHODS: Using a multicenter stroke registry database, patients with acute ischemic stroke of three subtypes (large artery atherosclerosis [LAA], small vessel occlusion [SVO], or cardioembolism [CE]) were identified. NIH stroke scale (NIHSS) and hemorrhagic transformation at presentation and discharge modified Rankin Scale (mRS) were compared between prestroke aspirin users and nonusers. RESULTS: Among the 10,433 patients, 1,914 (18.3%) reported prestroke aspirin use. On crude analysis, initial NIHSS scores of aspirin users were higher than nonusers (mean difference: 0.35; 95% confidence interval [CI]: 0.04-0.66). However, a multivariable analysis with an application of inverse probability of treatment weighting based on a propensity score of prestroke aspirin, having an interaction effect of prestroke aspirin use and stroke subtype in the model, showed less stroke severity for aspirin users in LAA, but not in SVO and CE than for nonusers; mean difference in NIHSS scores in LAA was -0.97 (95% CI: -1.45 to -0.49). With respect to hemorrhagic transformation and mRS, no significant interaction effects were found. Prestroke aspirin use increased the risk of hemorrhagic transformation (adjusted odd ratio: 1.34; 95% CI: 1.05-1.73), but decreased the odds of the higher discharge mRS (0.86; 0.76-0.96). INTERPRETATION: Prestroke aspirin use may reduce initial stroke severity in atherothrombotic stroke and can improve functional outcome at discharge despite an increase of hemorrhagic transformation irrespective of stroke subtype.

Preceding Intravenous Thrombolysis in Patients Receiving Endovascular Therapy.

BACKGROUND: The beneficial effects of endovascular therapy (EVT) in acute ischemic stroke have been demonstrated in recent clinical trials using new-generation thrombectomy devices. However, the comparative effectiveness and safety of preceding intravenous thrombolysis (IVT) in this population has rarely been evaluated. METHODS: From a prospective multicenter stroke registry database in Korea, we identified patients with acute ischemic stroke who were treated with EVT within 8 h of onset and admitted to 14 participating centers during 2008-2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months. Major secondary outcomes were successful recanalization defined as a modified Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score 0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT) during hospitalization. Multivariable logistic regression analyses using generalized linear mixed models were performed to estimate the adjusted odds ratios (ORs) of preceding IVT. RESULTS: Of the 639 patients (male, 61%; age 69 ± 12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the eligibility criteria, 458 received preceding IVT. These patients showed lower mRS scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). CONCLUSION: In patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT may enhance survival and successful recanalization without additional risk of SHT, and mitigate disability at 3 months.

Family History and Risk of Recurrent Stroke.

BACKGROUND AND PURPOSE: The association between family history of stroke and stroke recurrence remains unclear. METHODS: Using a web-based multicenter stroke registry database, information on history of stroke in first-degree relatives was collected prospectively for acute ischemic stroke patients who were hospitalized within 7 days of onset. The collected information was categorized as follows: type of the affected relative(s) with stroke (paternal, maternal, sibling, or 2 or more) and age of the relative's stroke onset (<50, 50-59, 60-69, and ≥70 years). Stroke recurrence was captured prospectively using a predetermined protocol. Subgroup analyses were performed according to the patient's age at the index stroke. RESULTS: Among 7642 patients, 937 (12.3%) had a history of stroke in their first-degree relatives and 475 (6.2%: 201 within and 274 after 3 weeks from index stroke) experienced stroke recurrence (median follow-up, 365 days). In multivariable Cox proportional hazard models, overall family history was not associated with stroke recurrence (hazard ratio, 1.08; 95% confidence interval, 0.81-1.43). However, the details of their family histories, including relative's age at stroke onset (<50 years: hazard ratio, 2.14; 95% confidence interval, 1.004-4.54) and stroke history in a sibling (hazard ratio, 1.67; 95% confidence interval, 1.09-2.58), were independently associated with stroke recurrence after adjusting for potential confounders. The associations appeared to be stronger in young adults with stroke (age, <55 years) than in older stroke patients. CONCLUSIONS: This study suggests that elevated risks of recurrent stroke are associated with having relatives with early-onset stroke and siblings with stroke histories, implying that additional precautions may be needed in such populations.

Different Antiplatelet Strategies in Patients With New Ischemic Stroke While Taking Aspirin.

BACKGROUND AND PURPOSE: Selecting among different antiplatelet strategies when patients experience a new ischemic stroke while taking aspirin is a common clinical challenge, currently addressed by a paucity of data. METHODS: This study is an analysis of a prospective multicenter stroke registry database from 14 hospitals in South Korea. Patients with acute noncardioembolic stroke, who were taking aspirin for prevention of ischemic events at the time of onset of stroke, were enrolled. Study subjects were divided into 3 groups according to the subsequent antiplatelet therapy strategy pursued; maintaining aspirin monotherapy (MA group), switching aspirin to nonaspirin antiplatelet agents (SA group), and adding another antiplatelet agent to aspirin (AA group). The primary study end point was the composite of stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death up to 1 year after stroke onset. RESULTS: A total of 1172 patients were analyzed for this study. Antiplatelet strategies pursued in study patients were MA group in 212 (18.1%), SA group in 246 (21.0%), and AA group in 714 (60.9%). The Cox proportional hazards regression analysis showed that, compared with the MA group, there was a reduction in the composite vascular event primary end point in the SA group (hazard ratio, 0.50; 95% confidence interval, 0.27-0.92; P=0.03) and in the AA group (hazard ratio, 0.40; 95% confidence interval, 0.24-0.66; P<0.001). CONCLUSIONS: This study showed that, compared with maintaining aspirin, switching to or adding alternative antiplatelet agents may be better in preventing subsequent vascular events in patients who experienced a new ischemic stroke while taking aspirin.

Impact of Guidelines on Clinical Practice: Intravenous Heparin Use for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Since its introduction, controversy has existed about the administration of intravenous heparin for the treatment of acute ischemic stroke. We studied trends in the intravenous heparin use during a 6-year time period and the potential influence of clinical guidelines in national language on intravenous heparin administration in Korea. METHODS: On the basis of a prospective nationwide multicenter stroke registry, we collected data on patients with acute ischemic stroke who arrived within 7 days of symptom onset during the time period 2008 to 2013. We studied patient demographics, prestroke medical history, stroke characteristics, and stroke treatment. Data from a total of 23 425 patients from 12 university hospitals or regional stroke centers were analyzed. RESULTS: The administration of intravenous heparin steadily decreased throughout the study period: 9.7% in 2008, 10.9% in 2009, 9.4% in 2010, 6.0% in 2011, 4.7% in 2012, and 4.3% in 2013 (P for trend <0.001). The reduced intravenous heparin use was associated with moderate stroke severity, atrial fibrillation, and stroke of cardioembolic, other-, and undetermined etiology. In a multivariable logistic model, increase of 1 calendar year (odds ratio, 0.89; 95% confidence interval, 0.84-0.95; P<0.001) and release of clinical practice guidelines in Korean (odd ratio, 0.74; 95% confidence interval, 0.59-0.91; P<0.01) were independent factors associated with reduction in the frequency of intravenous heparin use. CONCLUSIONS: Use of intravenous heparin for acute ischemic stroke treatment has decreased in Korea, and this change may be attributable to the spread and successful implementation of regional clinical practice guidelines.

Endovascular Treatment in Patients with Persistent Internal Carotid Artery Occlusion after Intravenous Tissue Plasminogen Activator: A Clinical Effectiveness Study.

BACKGROUND: There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. METHODS: Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. RESULTS: Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS ≤2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37-2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade ≥2b) in the add-on EVT group was 69.2%. CONCLUSIONS: Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage.

Recurrent Stroke, Myocardial Infarction, and Major Vascular Events during the First Year after Acute Ischemic Stroke: The Multicenter Prospective Observational Study about Recurrence and Its Determinants after Acute Ischemic Stroke I.

BACKGROUND: Patients with acute ischemic stroke (AIS) are at high risk of subsequent vascular events. The aim of this study was to estimate rates of recurrent stroke, myocardial infarction (MI), and major vascular events during the first year after AIS in Korea. METHODS: Through a multicenter stroke registry in Korea, 12,227 consecutive cases of AIS were identified between November 2010 and May 2013 and were followed up for recurrent stroke, MI, and major vascular events up to 1 year after stroke. RESULTS: Cumulative 30-day, 90-day and 1-year rates were 2.7%, 3.9%, and 5.7% for recurrent stroke; .1%, .3%, and .5% for MI; and 8.1%, 10.6%, and 13.7% for major vascular events, indicating that the early period is at high risk of recurrent stroke and major vascular events. The risk of recurrent stroke was substantially higher than the risk of MI: 13.0 times at 90 days and 11.4 times at 1 year. Compared to those with small-vessel occlusion (SVO), those with ischemic stroke subtypes other than SVO had a higher risk of recurrent stroke as well as major vascular events. Other common independent predictors for recurrent stroke and major vascular events were diabetes and prior stroke history. CONCLUSIONS: During the first year after AIS, one in 18 had recurrent stroke and one in 7 major vascular events. More than two thirds of recurrent stroke and three quarters of major vascular events developed within 90 days in a Korean cohort of stroke patients. Better prevention strategies are required for high-risk patients during this high-risk period.

Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study.

BACKGROUND AND PURPOSE: The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment. Our aim was to investigate the comparative effectiveness and safety of the low-dose versus standard-dose intravenous alteplase strategy. METHODS: A total of 1526 acute ischemic stroke patients who qualified for intravenous alteplase and treated within 4.5 hours were identified from a prospective, multicenter, and nationwide stroke registry database. Primary outcomes were a modified Rankin scale score of 0 to 1 at 3 months after stroke and occurrence of symptomatic hemorrhagic transformation. Inverse probability of low-dose alteplase weighting by propensity scores was used to remove baseline imbalances between the 2 groups, and variation among centers were also accounted using generalized linear mixed models with a random intercept. RESULTS: Low-dose intravenous alteplase was given to 450 patients (29.5%) and standard-dose intravenous alteplase to 1076 patients (70.5%). Low-dose alteplase treatment was comparable to standard-dose therapy according to the following adjusted outcomes and odds ratios (95% confidence intervals): modified Rankin scale score 0 to 1 at 3 months and 0.95 (0.68-1.32); modified Rankin scale 0 to 2 at 3 months and 0.84 (0.62-1.15); symptomatic hemorrhagic transformation and 1.05 (0.65-1.70); and 3-month mortality and 0.54 (0.35-0.83). The associations were unchanged when the analysis was limited to those without endovascular recanalization. CONCLUSIONS: The low-dose alteplase strategy was comparable to the standard-dose treatment in terms of the effectiveness and safety.

Effect of pre-stroke statin use on stroke severity and early functional recovery: a retrospective cohort study.

BACKGROUND: Experimental studies suggest that pre-stroke statin treatment has a dual effect of neuroprotection during ischemia and neurorestoration after ischemic injury. The aim of this study was to evaluate the effect of pre-stroke statin use on initial stroke severity and early clinical outcome. METHODS: We used a prospective database enrolling patients with acute ischemic stroke from 12 hospitals in Korea between April 2008 and January 2012. Primary endpoint was the initial stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score. Secondary endpoints were good outcome (modified Rankin Scale [mRS], 0-2) and overall mRS distribution at discharge. Multivariable regression model and propensity score (PS) matching were used for statistical analyses. RESULTS: Among the 8340 patients included in this study, 964 patients (11.6%) were pre-stroke statin users. The initial NIHSS score (mean [95% CI]) was lower among pre-stroke statin users vs. non-users in multivariable analysis (5.7 [5.2-6.3] versus 6.4 [5.9-6.9], p = 0.002) and PS analysis (5.2 [4.7-5.7] versus 5.7 [5.4-6.0], p = 0.043). Pre-stroke statin use was associated with increased achievement of mRS 0-2 outcome (multivariable analysis: OR [95% CI], 1.55 [1.25-1.92], p < 0.001; PS matching: OR [95% CI], 1.47 [1.16-1.88]; p = 0.002) and favorable shift on the overall mRS distribution (multivariable analysis: OR [95% CI], 1.29 [1.12-1.51], p = 0.001; PS matching: OR [95% CI], 1.31 [1.11-1.54]; p = 0.001). CONCLUSIONS: Pre-stroke statin use was independently associated with lesser stroke severity at presentation and better early functional recovery in patients with acute ischemic stroke.

Trends in the effectiveness of endovascular recanalization for acute stroke: is a change taking place?

BACKGROUND: Despite recent technical advances in endovascular recanalization, there is skepticism regarding its clinical effectiveness compared with intravenous thrombolysis for treating acute ischemic stroke. We aimed to delineate its effectiveness and safety and their change over time. METHODS: Using a prospective, multicenter stroke registry database, we identified 872 patients with ischemic stroke who underwent recanalization therapy with intravenous thrombolysis alone (IVT; n = 533) or endovascular recanalization with or without intravenous thrombolysis (EVT; n = 339) between April 2008 and January 2012. All subjects had National Institute of Health Stroke Scale score of 10 or more and arrived at the hospital within 4.5 hours of onset. Propensity score was used to address baseline imbalances between treatment groups, but balance adjustment was not performed for subgroup analyses. RESULTS: The primary outcome was modified Rankin Scale score of 0-2 at discharge. The year-by-year effectiveness and safety of EVT and IVT were compared. Before 2010, the primary outcome was not associated with the recanalization method. However, in 2011, EVT increased the odds of having a primary outcome compared with IVT (adjusted odds ratio [OR], 1.87; 95% confidence interval [CI], 1.08-3.23). In 2011, EVT was superior to IVT regarding the achievement of a favorable outcome at 3 months after stroke (OR, 1.99; 95% CI, 1.10-3.59). The odds of in-hospital mortality and 3-month mortality were not different over 4 years. CONCLUSIONS: There might have been a change in the effectiveness of endovascular recanalization compared with intravenous thrombolysis, but the results remain tentative until prospectively evaluated.

Grading and interpretation of white matter hyperintensities using statistical maps.

BACKGROUND AND PURPOSE: We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. METHODS: We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. RESULTS: We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0-9.4%, median=0.6%, of the measured brain volume). For younger (≤69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. CONCLUSIONS: We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.

Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

BACKGROUND: This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. METHODS: From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. RESULTS: In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. CONCLUSIONS: The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants.

Symptomatic steno-occlusion of cerebral arteries and subsequent ischemic events in patients with acute ischemic stroke.

BACKGROUND: We aimed to assess the impact of symptomatic steno-occlusion (SYSO) of cerebral arteries and its characteristics on subsequent ischemic event (SIE) in patients with acute ischemic stroke. METHODS: Using a prospective stroke registry database, we identified consecutive patients with ischemic stroke who were hospitalized within 48 hours of symptom onset. SYSO denoted significant stenosis or occlusion of major cerebral arteries with ischemic lesions at the corresponding arterial territories and was characterized by its location and severity. Primary outcome was SIE that was defined as ischemic progression or recurrence within 1 year. RESULTS: In total, 1546 patients (age, 67.4 ± 13.0 years; median National Institutes of Health Stroke Scale score, 4) were enrolled in this study. The cumulative risk of SIE was 14.5% at 7 days, 14.9% at 14 days, 15.5% at 90 days, and 16.9% at 1 year. Patients with SYSO had significantly higher SIE rates compared with those without SYSO (23.0% versus 11.6%). Of the characteristics of SYSO, the location, not the severity, was significantly associated with SIE (P < .001 and P = .186, respectively). Multiple (adjusted hazard ratio, 5.85; 95% confidence interval, 1.81-18.85), intracranial internal carotid artery (ICA) (3.54; 1.21-8.21), and extracranial ICA SYSO (2.88; 1.01-8.21) raised the risk of SIE. CONCLUSIONS: Subsequent cerebral ischemic events (progression or recurrence) after an acute ischemic stroke occur mostly within several days of stroke onset and is associated with the location, but not the severity, of symptomatic steno-occlusion of cerebral arteries.

Current status of recanalization therapy in acute ischemic stroke with symptomatic intracranial arterial occlusion in Korea.

BACKGROUND: Recent methodological advances in recanalization therapy may alter recanalization strategies and clinical outcomes in patients with symptomatic occlusion of intracranial cerebral arteries. However, few studies have analyzed these changes at a national level, with none conducted in Korea. METHODS: On the basis of a prospective multicenter stroke registry database in Korea, 642 consecutive patients hospitalized within 12 hours of the onset with symptomatic occlusion of intracranial major cerebral arteries between March 2010 and November 2011 were identified. Recanalization therapy was used in 48% (n = 307) of patients; intravenous thrombolysis only (IVT) in 46%, intra-arterial thrombolysis only (IAT) in 16%, and combined thrombolysis (CMT) in 38%. Of the 166 patients treated by IAT or CMT, the Penumbra system or the Solitaire was used in 58% of patients. RESULTS: Early neurologic improvement (ENI), 3-month modified Rankin scale (mRS) score of 2 or less, and symptomatic hemorrhagic transformation (SHT) were observed in 43%, 39%, and 9% of the patients in the IVT group; 52%, 27%, and 12% of the patients in the IAT group; and 54%, 39%, and 12% of the patients in the CMT group, respectively. Compared with no treatment, adjusted odd ratios (95% confidence intervals) of recanalization therapy were 1.59 (1.04-2.42) for ENI, 1.37 (.81-2.30) for 3-month mRS score of 2 or less, and 2.58 (1.12-5.91) for SHT. CONCLUSIONS: The variety and active use of endovascular approaches were quite noticeable. As a whole, recanalization therapy tended to contribute to favorable outcomes despite a significant increase of symptomatic hemorrhage.

The iScore predicts clinical response to tissue plasminogen activator in Korean stroke patients.

BACKGROUND: Despite substantial differences in clinical features between Asian and Western stroke patients, there are no published prognostic tools validated in an Asiatic population for thrombolytic therapy. We assessed the ability of the iScore to predict the clinical response after intravenous thrombolysis with tissue plasminogen activator (tPA) in a Korean stroke population. METHODS: We applied the iScore to eligible participants in the nationwide multicenter stroke registry in Korea. Main outcome measures were poor functional outcome defined as having a modified Rankin Scale score 3-6 and death at 3 months. Symptomatic intracranial hemorrhage (sICH) was evaluated as a safety outcome. C statistic was calculated to assess performance of iScore. RESULTS: Among 4760 patients with an acute ischemic stroke, 622 (13.1%) received tPA, 548 patients had complete information for the analysis. C statistics for poor functional outcome and death at 3 months were .813 (95% confidence interval [CI]: .778-.848) and .820 (95% CI: .769-.872), respectively. Overall, there was a high correlation between observed and expected outcome for poor functional outcome (Pearson correlation coefficient, r = .982) and for death at 3 months (r = .950) at the risk score level. An iScore of 180 or more was associated with a more than 2 times risk of poor functional outcome and about 6 times risk of death at 3 months. There was an interaction between the iScore and tPA for a poor functional outcome (P value for the interaction < .001). We found a gradient effect in the incident risk of sICH with the iScore. CONCLUSION: The iScore reliably predicts stroke outcomes after tPA in Asiatic population.

Safety and efficacy of intravenous recombinant tissue plasminogen activator administered in the 3- to 4.5-hour window in Korea.

BACKGROUND: The safety and efficacy of intravenous tissue plasminogen activator (IV-TPA) in the 3- to 4.5-hour window were largely driven from Western populations, but have not been systematically explored in Korean population. METHODS: We compared outcomes of acute ischemic stroke patients treated in the 3- to 4.5-hour window versus those in the 0- to 3-hour window, using a prospective multicenter registry database. Safety outcomes included symptomatic intracranial hemorrhage (SICH) and 3-month mortality and efficacy outcomes were the proportions of modified Rankin Scale (mRS) 0-1 and mRS 0-2 and the overall mRS distribution at 3 months. RESULTS: Among 723 patients consecutively treated with IV-TPA alone, 616 were treated within 3 hours and 107 treated between 3 and 4.5 hours. The median onset-to-treatment time was 115 minutes for 0- to 3-hour group and 217 minutes for 3- to 4.5-hour group. The SICH rate was higher in the 3- to 4.5-hour group than in the 0- to 3-hour group (4.7% vs. 3.1%), but the difference was not significant (adjusted odds ratio [OR] [95% confidence interval {CI}], .81 [.20-3.35]). There were no significant differences between the 3- to 4.5-hour and 0- to 3-hour groups in the 3-month mortality (19.6% vs. 12.0%), mRS 0-1 (39.3% vs. 42.9%), mRS 0-2 (48.6% vs. 55.7%), and the overall mRS distribution (adjusted proportional OR [95% CI], .94 [.63-1.41]) after adjusting for covariates. CONCLUSIONS: IV-TPA treatment can be safely and efficaciously administered to eligible Korean patients up to the extended time window of 4.5 hours. However, efforts to expedite the treatment should not be neglected.

Recanalization therapy for internal carotid artery occlusion presenting as acute ischemic stroke.

BACKGROUND: We aimed to describe the current status and clinical outcomes of recanalization therapy for internal carotid artery occlusion (ICAO) presenting as acute ischemic stroke. METHODS: Using a nationwide stroke registry database in Korea, we identified consecutive ischemic stroke patients with ICAO hospitalized within 12 hours of onset between March 2010 and November 2011. RESULTS: ICAO accounted for 10.6% (322 of 3028) of acute ischemic strokes within 12 hours of onset. Among the 322 ICAO patients, 53% underwent recanalization therapy, 41% intravenous thrombolysis (IVT) alone, and 59% endovascular treatment (EVT). Twenty-two percent of those with mild deficits (National Institutes of Health Stroke Scale <4) and 50% of those 80 years of age or more received recanalization therapy. Compared with no treatment, recanalization therapy was not significantly associated with a favorable outcome (3-month modified Rankin scale, 0-2) (adjusted odds ratio [OR], 1.77; 95% confidence interval [CI], .80-3.91; P = .16). However, compared with IVT, EVT significantly improved the odds of favorable outcome (OR, 2.86; 95% CI, 1.19-6.88; P = .02) without significant increase of symptomatic intracranial hemorrhage (OR, 2.18; 95% CI, .42-11.43; P = .36) and 3-month mortality (OR, .53; 95% CI, .23-1.18; P = .12). Successful recanalization rate (Thrombolysis in Cerebral Infarction ≥2a) by EVT was 76%. CONCLUSIONS: In Korea, one tenth of acute ischemic stroke was caused by ICAO, and about 50% were treated by recanalization therapy. EVT was widely used as a recanalization modality (about 60% of cases) despite lack of evidence. However, its effectiveness and safety were acceptable.