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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm ( P =0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm ( P =0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43]; P =0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003]; P =0.50; Table 3). Conclusions: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01359202.

Cumulative evidence regarding the use of brain magnetic resonance imaging (MRI) for predicting prognosis of unconscious out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM) is available. Theoretically, these patients are at a high risk of developing cerebral infarction. However, there is a paucity of reports regarding the characteristics of cerebral infarction in this population. Thus, we performed a pilot study to identify the characteristics and risk factors of cerebral infarction and to evaluate whether this infarction is associated with clinical outcomes.A single-center, retrospective, registry-based cohort study was conducted at Severance Hospital, a tertiary center. Unconscious OHCA survivors were registered and treated with TTM between September 2011 and December 2015. We included patients who underwent brain MRI in the first week after the return of spontaneous circulation. We excluded patients who underwent any endovascular interventions to focus on "procedure-unrelated" cerebral infarctions. We assessed hypoxic-ischemic encephalopathy (HIE) and procedure-unrelated cerebral infarction separately on MRI. Patients were categorized into the following groups based on MRI findings: HIE (-)/infarction (-), infarction-only, and HIE (+) groups. Conventional vascular risk factors showing p 0.05 in univariate analyses were entered into multivariate logistic regression. We also evaluated if the presence of this procedure-unrelated cerebral infarction lesion or HIE was associated with a poor clinical outcome at discharge, defined as a cerebral performance category of 3-5.Among 71 unconscious OHCA survivors who completed TTM, underwent MRI, and who did not undergo endovascular interventions, 14 (19.7%) patients had procedure-unrelated cerebral infarction based on MRI. Advancing age [odds ratio (OR) 1.11] and atrial fibrillation (OR 5.78) were independently associated with the occurrence of procedure-unrelated cerebral infarction (both p 0.05). There were more patients with poor clinical outcomes at discharge in the HIE (+) group (88.1%) than in the infarction-only (30.0%) or HIE (-)/infarction (-) group (15.8%) (p 0.001). HIE (+) (OR 38.69, p 0.001) was independently associated with poor clinical outcomes at discharge, whereas infarction-only was not (p 0.05), compared to HIE (-)/infarction (-).In this pilot study, procedure-unrelated cerebral infarction was noted in approximately one-fifth of unconscious OHCA survivors who were treated with TTM and underwent MRI. Older age and atrial fibrillation might be associated with the occurrence of procedure-unrelated cerebral infarction, and cerebral infarction was not considered to be associated with clinical outcomes at discharge. Considering that the strict exclusion criteria in this pilot study resulted in a highly selected sample with a relatively small size, further work is needed to verify our findings.

Background and Purpose— We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods— This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results— In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm 3 ; P P 3 . In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm 3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions— Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Aortic atheroma is a known cause of ischemic stroke. However, it is unclear whether ischemic stroke is caused by emboli from aortic atheroma or by accompanying atherosclerosis. In this study, we evaluated lesion patterns of patients with complex aortic plaque (CAP) to assume the underlying pathophysiology. Acute ischemic stroke patients who underwent transesophageal echocardiography were included. CAP was defined as a plaque in the proximal aorta ≥ 4 mm thick or with a mobile component. The diffusion-weighted imaging lesion patterns of patients with CAP were compared to those with large arterial atherosclerosis (LAA) or cardioembolism (CE). A total of 64 CAP patients, 127 LAA patients, and 80 CE patients were included. Small cortical pattern was more common in the CAP group (45.3%) than in the LAA (7.9%, p < 0.001) or the CE group (23.8%, p = 0.018). A large cortical pattern was more common in the CE group than in the CAP group (p < 0.001), whereas subcortical only pattern tended to be more common in the CAP group than in the CE group (p = 0.057). In multinominal analysis, the CAP group was more likely to have a small cortical lesion than the LAA group [odds ratio (OR) 14.63; 95% confidence interval (CI) 4.67–45.85] or the CE (OR 3.69, 95% CI 1.19–11.39) group. In conclusion, patients with CAP frequently had small cortical lesions or subcortical single lesion. These findings imply that ischemic stroke in aortic atheroma patients is associated with either small emboli or small artery disease.

Background and Purpose— The presence of intracranial artery calcification is associated with an increased risk for stroke. However, calcified atherosclerotic plaques are also known to be less vulnerable to rupture. Given this discrepancy, we investigated whether the vulnerability of intracranial arterial atherosclerosis differed based on the presence or absence of calcification. Methods— We considered consecutive patients with acute stroke in the unilateral middle cerebral artery (MCA) territory. Patients with any stenotic MCAs were included in this study. Symptomatic MCA was defined as the occurrence of infarctions relevant to the stenotic MCA. The presence of calcification in the MCA was evaluated on noncontrast thin-section computed tomography images using a 3dimensional software package. Generalized estimating equations were used to compare the frequency of calcification between symptomatic and asymptomatic stenosis. Results— Of the 1066 MCAs examined in 533 patients, 645 MCAs were stenotic and were included in the study. Among the 645 stenotic MCAs, 406 MCAs (62.9%) were symptomatic. Calcification was observed in 36 MCAs (5.6%). Calcification in the MCA was more frequently observed in the asymptomatic group (7.9% versus 4.2%; P =0.032). On multivariable analysis, the presence of calcification in MCA atherosclerosis was less frequent in the symptomatic group (odds ratio, 0.46; 95% confidence interval, 0.23–0.92; P =0.027). Conclusions— This study showed that calcified atherosclerosis in the MCA was less frequently symptomatic.

The relationship between liver fibrosis and the occurrence of ischemic stroke is unknown. We investigated the correlation between liver fibrosis assessed with transient elastography (TE) and the risk of ischemic stroke.Between April 2013 and August 2014, patients with acute ischemic stroke and subjects who underwent a health check-up were included in the study. Liver fibrotic burden was assessed with TE in all participants. The degree of liver fibrosis was compared between groups by using various multiple logistic regression models and propensity-score matched analyses.Two hundred ninety-five patients with ischemic stroke (stroke group) and 1942 subjects with health check-up (control group) were included. The mean liver stiffness (LS) on TE (5.6 vs. 4.1 kPa) and the proportion of significant fibrosis (8 kPa) (9.2% vs. 1.8%) were significantly higher in the stroke than in the control group (all p0.05). These trends were observed regardless of body mass index, the degree of hepatic steatosis, and metabolic syndrome (all p0.05). The adjusted odds ratio (OR) for ischemic stroke was 1.268 (95% confidence intervals [CI] 1.183-1.358) per 1 kPa increase and 12.033 (95% CI 5.180-27.948) for significant fibrosis, compared with no fibrosis (all p 0.05). Propensity-score matched analysis also confirmed that liver fibrosis was independently associated with the risk of ischemic stroke (OR 1.804 [95% CI 1.461-2.230] per 1 kPa increase, 13.184 [95% CI 3.127-55.645] for significant fibrosis, compared with no fibrosis; all p0.001).The degree of liver fibrosis, assessed with TE, was significantly associated with the risk of ischemic stroke.

Purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). However, it remains unclear which stroke patients should undergo evaluation for asymptomatic CAD, and which screening tools are appropriate. We investigated the role of coronary artery calcium (CAC) score as a screening tool for asymptomatic but severe CAD in acute stroke patients. We determined the selection criteria for CAC screening based on risk factors and cerebral atherosclerosis.Materials and Methods: The present study included consecutive patients with acute stroke who had undergone cerebral angiography and multi-detector computed tomography coronary angiography. Severe CAD was defined as left main artery disease or three-vessel disease. Enrolled patients were randomly assigned to two sets; a set for developing selection criteria and a set for validation. To develop selection criteria, we identified associated factors with severe CAD regarding clinical factors and cerebral atherosclerosis. CAD predictability of selection criteria with the CAC score was calculated.Results: Overall, 2,658 patients were included. Severe CAD was present in 360 patients (13.5%). CAC score was associated with CAD severity (P < 0.001). In the development set (N = 1,860), severe CAD was associated with age >65 years [odds ratio (95% confidence interval), 2.62 (1.93–3.55)], male sex (1.81 [1.33–2.46]), dyslipidemia (1.77 [1.25–2.61]), peripheral artery disease (2.64 [1.37–5.06]) and stenosis in the cervicocephalic branches, including the internal carotid (2.79 [2.06–3.78]) and vertebrobasilar arteries (2.08 [1.57–2.76]). We determined the combination of clinical and arterial factors as the selection criteria for CAC evaluation. The cut-off criterion was two or more elements of the selection criteria. The area under the curve (AUC) of the selection criteria was 0.701. The AUC significantly improved to 0.836 when the CAC score was added (P < 0.001). In the validation set (N = 798), the AUC of the selection criteria only was 0.661, and that of the CAC score was 0.833. The AUC of the selection criteria + CAC score significantly improved to 0.861(P < 0.001).Conclusion: The necessity for CAC evaluation could be determined based on the presence of risk factors and significant stenosis of the cervicocephalic arteries. CAC evaluation may be useful for screening for severe CAD in stroke patients.

Although early neurological deterioration (END) during the acute stroke period is known to be directly associated with poor short- and long-term outcomes, few studies have investigated the ability to predict END. The aim of this study was to investigate whether there are differences in the occurrence of END according to the ischemic stroke predictive risk score (iScore), which was developed to predict short- and long-term mortality.We collected data from 2150 consecutive ischemic stroke patients who were admitted to 3 study hospitals between January 2012 and June 2014. END was defined as an increase (≥4) in the National Institutes of Health Stroke Scale score within the first 72 hours of stroke onset. We calculated the 30-day iScore for each patient to determine the relationship between the iScore and occurrence of END.Among 2150 patients, END was observed in 146 patients (6.8%). There was a positive correlation between the iScore and occurrence of END. After adjusting for potential confounders, the iScore was independently associated with END (odds ratio: 1.217 per 20-point increase in iScore, 95% confidence interval: 1.121-1.321, P .001). There was good correlation between observed and expected outcomes predicted by the iScore (Pearson correlation coefficient: r = .950, P .001).The iScore can predict the risk of END development within the acute stroke stage.

Background and Purpose— We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. Methods— In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl 3 -induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. Results— Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by P =0.006) and the frequency of final recanalization decreased ( P for trends=0.006). Conclusions— Early administration of tPA after stroke onset is associated with better thrombus resolution.

Background and Purpose— Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes. Methods— Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC. Results— Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2–12] versus 3 [1–8]; P =0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P Conclusions— In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome.

Dear Sir: Shortening the interval between hospital arrival and thrombolytic treatment is critical to improve the efficacy of the treatment because of its time-sensitive effect [1]. Decision-making by patients or their families is an essential step during the process of thrombolytic treatment. In an emergency situation, decision-making by patients or their families relies mostly on the physician’s explanation concerning the benefits and risks of thrombolytic treatment. In this regard, a physician’s concise, standardized, and easily understandable explanation of the thrombolytic treatment is important for the process of decision-making and for obtaining informed consent from patients or their family. We investigated how a protocol using decision-making support (DMS) for patients and their families could reduce door-to-needle time in acute stroke. We have previously shown that quality improvement activity using a computerized physician order entry could reduce time from hospital arrival to evaluations and intravenous (IV) tissue plasminogen activator (tPA) [2-4]. While performing continuous quality improvement activity to further improve the process, we have found that the most common reason of treatment delay was waiting informed consent [5]. Therefore, we developed a protocol for DMS using standardized scrip and visual decision aid. The standardized script was developed for physicians who are responsible for providing explanations regarding thrombolysis treatment and then obtaining informed consent from patients or their families. The visual decision aid (http://stroke.ucla.edu/workfiles/VDA-for-TPA.pdf) was used by physicians to help explain the benefits and risks of IV tPA treatment to candidates for this treatment. This protocol was implemented from January 2010. All consecutive patients who visited the emergency department and were treated with IV tPA within the 3-hour time window were included in this study. The effect of DMS was investigated by comparing the door-to-needle time before (the pre-DMS group, January 2007–December 2009) and after (post-DMS group, January 2010–December 2012) the implementation of the DMS protocol. Demographic factors and time intervals were compared using the Mann–Whitney U test and the chi-square test. The possible reasons for delay were identified if the door-to-needle time was longer than 40 minutes. To determine factors associated with a door-to-needle time >40 minutes, multivariable logistic regression analysis was performed. Age, sex, and variables with P

Background and purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). Coronary screening is recommended in patients with high risks for CAD. It remains uncertain which group of stroke patients need evaluation for asymptomatic CAD, and which evaluation tool is appropriate for stroke patients. We investigated whether the coronary artery calcium (CAC) scores could predict significant CAD in patients with acute stroke and which stroke patients need a screening test for significant CAD. Methods: Among consecutive stroke patients between September 2011 and August 2013, a total of 1143 patients who underwent multiple detector CT coronary angiography and cerebral angiography were included. Atherosclerotic stenosis ≥ 50% or obstruction was classified as significant stenosis in coronary and cerebral arteries. Patients were grouped into four subgroups on the basis of CAC score: 0, 0.1-99.9, 100-399.9, and ≥ 400. Presence of hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking were considered as risk factors. Results: Of 1143 patients, significant stenosis was detected in 164 patients (14.3%) in the internal carotid artery (ICA), 279 (24.4%) in the vertebrobasilar artery (VBA), and 81 (7.1%) in the both ICA and VBA. Significant coronary artery stenosis in at least one coronary artery was detected in the 398 patients (34.8%). Two or more risk factors and one or more significant stenosis in the ICA or VBA were considered as screening criteria for choosing potential CAD patients according to AUC analysis. As the CAC score increased, odd ratio for significant CAD remarkably increased (2.1678, CI 1.0152 to 4.6290 for CAC score 0, 5.7193 ,CI 2.9192 to 11.2051 for 0 Conclusion: Two or more risk factors and one or more significant stenosis in the ICA or VBA can be used to choose patients with stroke who need to perform a screening test predicting significant CAD. CAC score also can be used as a screening to perform coronary artery evaluation even in the patients without documented cerebral atherosclerosis.

SummaryPatent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648–17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.

This retrospective study investigated whether the volume or density of the thrombus is predictive of recanalization in stent retriever (SR) treatment. Consecutive patients treated with SR thrombectomy as the first endovascular modality were enrolled. The thrombus volume and density were measured on thin-section noncontrast computed tomography using 3-dimensional software. The patients were grouped by recanalization status and the number of SR passes. Among 165 patients, recanalization was achieved with the first pass in 68 (50.0%), 2–3 passes in 43 (31.6%), and ≥4 passes in 25 (18.4%) patients. The thrombus volume was smaller in patients with (107.5 mm3) than without (173.7 mm3, p = 0.025) recanalization, and tended to be larger with increasing number of passes (p for trend = 0.001). The thrombus volume was an independent predictor of first-pass recanalization (odds ratio 0.93 per 10 mm3, 95% confidence interval 0.89–0.97). However, the thrombus density was not associated with recanalization success. Recanalization within 3 passes was associated with a favorable outcome. In conclusion, the thrombus volume was significantly related to recanalization in SR thrombectomy. Measuring the thrombus volume was particularly predictive of first-pass recanalization, which was associated with a higher likelihood of a favorable outcome.

Objectives: We investigated the association of cerebral microbleeds (CMBs) with long-term mortality in patients with nonvalvular atrial fibrillation (NVAF) according to burden and distribution of CMBs. Methods: This was a retrospective, hospital-based, observational study. In total, 504 consecutive ischemic stroke patients with NVAF who underwent brain T2-weighted, gradient-recalled echo MRI were included. Data for the date and causes of death were based on the death certificates from the Korean National Statistical Office. We determined the association of the presence, burden, and distribution of CMBs with mortality from all-cause, ischemic heart disease, ischemic stroke, and hemorrhagic stroke. Results: CMBs were found in 30.7% of patients (155/504). During a median follow-up of 2.5 years, 176 patients (34.9%) died (ischemic stroke, 81; hemorrhagic stroke, 12; ischemic heart disease, 32). Patients with CMBs died more frequently than those without (41.9% vs 31.8%, p = 0.028). After adjusting for age, sex, and other significant variables, the presence of multiple (≥5) CMBs was as an independent predictor for all-cause (hazard ratio [HR]: 1.99) and ischemic stroke (HR: 3.39) mortality. Patients with strictly lobar CMBs had an increased risk of hemorrhagic stroke mortality (HR: 5.91). Conclusions: The presence and burden of CMBs were associated with increased mortality in stroke patients with NVAF. Patients with lobar CMBs were at increased risk of death due to hemorrhagic stroke. The diagnosis of CMBs is of value in predicting long-term prognosis in stroke patients with NVAF.

Brachial-ankle pulse wave velocity (baPWV) has been proposed as a simple, noninvasive method for estimating arterial stiffness. Although high baPWV was predictive of cardiovascular mortality and morbidity among general population, its predictive value for mortality in patients with acute stroke is unknown. We evaluated the prognostic value of baPWV in 1765 patients who had been admitted for acute ischemic stroke and had completed measurement of baPWV during admission. Primary outcomes were all-cause mortality and vascular mortality (death because of heart diseases, cerebrovascular diseases, or diseases of arteries, arterioles, and capillaries, determined according to the International Classification of Diseases ) after stroke. During a mean follow-up period of 3.33±1.57 years, there were 228 all-cause deaths, including 143 vascular deaths. In multivariate Cox hazard regression, patients in the highest tertile of baPWV (>22.63 m/s) were at an increased risk for both all-cause death (adjusted hazard ratio, 1.97; 95% confidence interval, 1.25–3.08) and vascular death (adjusted hazard ratio, 2.39; 95% confidence interval, 1.33–4.29) compared with the lowest tertile (

Background and Purpose— Identifying occult coronary artery stenosis may improve secondary prevention of stroke patients. The aim of this study was to derive and validate a simple score to predict severe occult coronary artery stenosis in stroke patients. Methods— We derived a score from a French hospital–based cohort of consecutive patients (n=300) who had an ischemic stroke or a transient ischemic attack and no previous history of coronary heart disease (Predicting Asymptomatic Coronary Artery Disease in Patients With Ischemic Stroke and Transient Ischemic Attack [PRECORIS] score) and validated the score in a similar Korean cohort (n=1602). In both cohorts, severe coronary artery stenosis was defined by the presence of at least 1 ≥50% coronary artery stenosis as detected by 64-section CT coronary angiography. Results— A 5-point score (Framingham Risk Score–predicted 10-year coronary heart disease risk [≥20%=3; 10–19%=1; Conclusions— The PRECORIS score can identify a population of stroke or transient ischemic attack patients with a high prevalence of occult severe coronary artery stenosis.

Introduction: The prediction of non-recanalization after IV thrombolysis (IVT) may be helpful to avoid unnecessary treatment and determine the strategy of recanalization treatment. Thrombus volume and density can be measured using software, which may provide accurate and reliable information on thrombus characteristics. Hypothesis: We hypothesized that the thrombus volume and/or density could predict non-recanalization after IVT. Methods: This was a post-hoc analysis of prospective cohort who underwent thin-section noncontrast CT (1 or 1.25 mm) and recanalization therapy. Among them, this study considered patients who received IVT due to anterior circulation stroke from Nov. 2006 to Dec. 2015. The volume and density of thrombus were measured semi-automatically using 3-dimensional software. Recanalization was assessed on CT angiography at the end of IVT or conventional angiography in cases further treated with intra-arterial treatment. Successful recanalization was defined as arterial occlusive lesion grade 2 or 3. Results: Among 345 patients considered, 218 with visible thrombus in the intracranial arteries were included for this study. Successful recanalization was achieved in 79 patients (36.2%). Thrombus volume was significantly larger in patients with non-recanalization than those with successful recanalization (median [interquartile range]: 117.8mm 3 [60.0 - 216.8 mm 3 ] vs. 56.9 mm 3 [31.1 - 105.0 mm 3 ]. p 300 mm 3 , and in 41 of 44 cases (93.2%) with thrombus > 200 mm 3 . Thrombus density did not differ between the groups (non-recanalization vs. successful recanalization: 54.0 ± 9.1 vs. 52.6 ± 8.5, p=0.263). Conclusions: Thrombus volume was predictive of non-recanalization after IVT. Measurements of thrombus volume may be helpful to determine the strategy of recanalization treatment.

BACKGROUND AND PURPOSE The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. METHODS In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. RESULTS CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p

Background and aims Proteinuria is a marker of kidney disease and a strong risk factor for cardiovascular diseases including stroke. This study was aimed at investigating the prognostic value of proteinuria measured by urine dipstick in patients with acute ischemic stroke. Methods This post-hoc analysis of a prospective cohort study included 3404 consecutive patients who had been admitted for acute ischemic stroke between November 2005 and June 2013. Proteinuria was defined as a trace or more of protein on a urine dipstick test routinely performed at admission. Date and cause of death until December 31, 2013 were collected. We investigated the association of proteinuria with all-cause mortality, cardiovascular mortality (defined as ICD-10 codes I00–I99), and non-cardiovascular mortality. Results Proteinuria was present in 12.8% of the 3404 patients. During the mean follow-up period of 3.56 ± 2.22 years, there were 681 cases of all-cause mortality (460 cardiovascular deaths and 221 non-cardiovascular deaths). Multivariate Cox regression analysis showed that the presence of proteinuria was an independent risk factor for all-cause mortality (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.40–2.04), cardiovascular mortality (adjusted HR 1.65, 95% CI 1.31–2.08), and non-cardiovascular mortality (adjusted HR 1.59, 95% CI 1.13–2.23). Adding proteinuria to the multivariate Cox models moderately improved the model performance for all-cause mortality (integrated area under curve [95% CI]: from 0.800 [0.784–0.816] to 0.803 [0.788–0.818], p = 0.026). Conclusions Proteinuria, which was detected on a urine dipstick test, was a significant predictor of mortality after acute ischemic stroke.

BACKGROUND AND PURPOSE Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. METHODS We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. RESULTS AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). CONCLUSIONS In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

Background and Purpose: Cerebral microbleeds (CMBs) are frequently observed in patients with lacunar infarction. CMBs are associated with an increased risk of mortality in stroke patients with nonvalvular atrial fibrillation and in the elderly population. We investigated the association of CMBs with long-term mortality in patients with lacunar infarction according to characteristics of CMBs. Methods: This was a retrospective hospital-based observational study. This study included 315 patients with first-ever lacunar infarction who underwent brain gradient-recalled echo imaging. The mortality data were obtained from the Korean National Statistical Office. By using a Cox regression analysis, we investigated the relationship between CMB characteristics and all-cause, ischemic stroke, and hemorrhagic stroke mortality. Results: CMBs were noted in 17.5% of patients (55/315). During a follow-up of 4.8 median years (interquartile range, 3.4-6.2 years), 43 patients (13.7%) died (ischemic stroke, 8; hemorrhagic stroke, 3). In multivariate analysis (age, sex p < 0.1 in univariate), the presence of multiple (≥4) CMBs was an independent predictor for all-cause (hazard ratio [HR], 6.02), ischemic stroke (HR, 15.44), and hemorrhagic stroke (HR, 16.56) mortality. Considering CMB location, strictly lobar CMBs were independently related to hemorrhagic stroke mortality (HR, 101.22)(Tables and Figures). Conclusions: The presence, multiplicity, and distribution of CMBs were predictive of long-term mortality in acute lacunar infarction. The detection and evaluation of CMBs are of value in predicting long-term prognosis in patients with lacunar infarction.

Objective: To investigate whether angiographically defined occlusion type could predict of the etiology of acute intracranial large artery occlusion and the stentriever response. Methods: We reviewed consecutive patients with acute intracranial large artery occlusion who underwent endovascular treatment and examined their workups for embolic sources. Patient demographics, laboratory findings, hyperdense artery sign, and angiographic occlusion type (truncal-type or branching-site occlusion) were compared between embolic sources (+) and (−) groups. These variables were also compared between stentriever failure and success groups. Details of endovascular procedures were also compared according to occlusion type. Results: A total of 259 patients (mean age 70.3 years; M:F = 132:127) were finally included. Of these patients, 216 (83.4%) were assigned to the embolic sources (+) group after thorough evaluation. Young age, no coronary artery disease, and truncal-type occlusion (odds ratio [OR] 9.07; 95% confidence interval [CI] 3.74–22.0) were independently associated with the embolic source (−) group. Of the overall group, 224 patients (86.5%) underwent stentriever-based endovascular treatment. Hypertension, diabetes, high C-reactive protein level, and truncal-type occlusion (OR 32.2; 95% CI 7.78–133.0) were independent predictors of stentriever failure. Truncal-type occlusion was associated with more reocclusion (77.3% vs 5.0%), resulting in recanalization failure by the stentriever (81.8% vs 20.3%), a longer puncture-to-recanalization time (118.0 vs 49.5 minutes), and more rescue treatment for final successful recanalization (78.9% vs 7.0%). Conclusions: Angiographic occlusion type is an independent predictor of stentriever refractoriness and of the underlying stroke mechanism.

Background Stroke may occur during hospital admission (in-hospital stroke). Although patients with in-hospital stroke are potentially good candidates for reperfusion therapy, they often do not receive treatment as rapidly as expected. Aims We investigated the effect of a code stroke program for in-hospital stroke, which included the use of computerized physician order entry, specific evaluation and treatment protocols for in-hospital stroke patients, and regular education of medical staffs. Methods We implemented the program in the cardiology and cardiovascular surgery departments/wards (target-ward group) in November 2008. We compared time intervals from symptom onset to evaluation and reperfusion treatment before and after program implementation between the target-ward and other departments/wards (other-ward group). Results Among 70 consecutive in-hospital stroke patients who received reperfusion therapy between July 2002 and February 2015, 28 and 42 were treated before and after program implementation, respectively. After program implementation, time intervals from symptom onset to neurology notification (50 min vs. 28 min; P = 0.033), symptom onset to brain imaging (91 min vs. 41 min; P Conclusions The comprehensive program for in-hospital stroke that included the use of computerized physician order entry was effective in reducing time intervals to evaluation and reperfusion therapy.

The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350–97.547); P =0.025]. The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. • Early arterial phase CTA may underestimate thrombus length. • Thrombus length discrepancy grade reflects collateral status or presence of antegrade flow. • Outcome prediction may be better with thrombus length grade than collateral score.

Background and Purpose— Higher serum alkaline phosphatase (ALP) and phosphate levels are associated with atherosclerotic disease and an increased risk of cardiovascular events. However, the association of ALP/phosphate with cerebral atherosclerosis and prognosis in patients with acute stroke is not well known. Methods— In 1034 patients with first-ever acute cerebral infarction, levels of ALP and phosphate were compared with (1) cerebral atherosclerosis and (2) poor long-term functional outcomes as defined by the modified Rankin Scale >2 at 3 months after stroke onset. Results— ALP levels were not associated with cerebral atherosclerosis. However, higher levels of ALP were associated with a poor functional outcome (adjusted odds ratio per 1 SD, 1.25; 95% confidence interval, 1.04–1.50). Phosphate was associated with neither cerebral atherosclerosis nor functional outcome. Conclusions— A higher level of ALP was not associated with cerebral atherosclerosis but was an independent prognostic factor for long-term functional outcome after acute cerebral infarction.

PURPOSE In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA₂DS₂-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS₂ score or ≥3 points of other components of CHA₂DS₂-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION NVAF patients with high CHADS₂/CHA₂DS₂-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.

Introduction: Stroke may occur while patients are being admitted (in-hospital stroke [IHS]). Although patients with IHS are potentially good candidates for fast reperfusion therapy, many patients are often not treated rapidly as are expected. Hypothesis: A code stroke program using computerized physician order entry (CPOE) will be effective in reducing time delay to reperfusion therapy in patients with IHS. Methods: We developed a code stroke program for IHS, based on CPOE. The program included protocols for stroke recognition, activation and notification, imaging, preparation of tissue-type plasminogen activator (tPA), and regular education of medical staffs. We implemented this program for cardiology and cardiovascular surgery wards because in our previous study, about one-half of all IHS occurred in them. We compared time intervals from symptom onset to evaluations and reperfusion treatment before and after the program implementation in patients with IHS that developed inside or outside the program. Results: The program launched at November 2008. All consecutive patients who received reperfusion therapy due to IHS that developed outside the neurology department from July 2002 to June 2014 were included for this study. Among total 59 IHS patients enrolled, 20 patients were treated before and 39 patients after implementation of the program (24 patients inside the program [cardiology/cardiovascular surgery wards], 15 patients outside the program). In cases treated inside the program, time intervals from symptom onset to brain image (98.5 min vs 37 min; P Conclusions: The computerized in-hospital alert system, which was developed for IHS, was effective to reduce time delay to evaluation and reperfusion treatment. More widespread implementation of the program for patients with IHS is warranted.

Background and Purpose— Little is known about high-signal lesions in magnetic resonance diffusion-weighted imaging (DWI [+]) after stenting for intracranial atherosclerotic stenosis. This study aimed to evaluate the incidence, distribution, risk factors, and clinical implications of DWI (+) after intracranial stenting. Methods— A total of 123 patients (male:female=88:35, mean age, 64.1 years) with symptomatic intracranial atherosclerotic stenosis (mean stenosis, 76.1±7.7%) underwent both stenting and poststenting DWI. The incidence, distribution (embolic-alone versus stenosis-associated perforator/mixed), and risk factors of DWI (+) and its relationship with symptomatic ischemic complications (SIC, including stroke or transient ischemic attack) were retrospectively evaluated. Results— Forty-three patients (35.0%) had DWI (+). Middle cerebral artery, smaller distal parent artery, and treatment-related dissection were independent risk factors for DWI (+) ( P 3 (range, 76–883.5 mm 3 ) versus 119.5 mm 3 (range, 32.5–873.0 mm 3 ). However, SIC occurred more frequently in the stenosis-associated perforator/mixed type (3/11, 27.3%) than in the embolic-alone type (1/32, 3.1%; P Conclusions— The incidence of DWI (+) after intracranial stenting for intracranial atherosclerotic stenosis was 35.0%. Middle cerebral artery, smaller distal parent artery, and treatment-related dissection were independent risk factors for DWI (+). SIC occurred more frequently in the stenosis-associated perforator/mixed type than in the embolic-alone type.

Background Alberta Stroke Program Early CT Score (ASPECTS) represents the extent of irreversibly damaged tissue; while CT angiography collateral score (CTA-CS) denotes the degree of collaterals. Aims We investigated whether there is cumulative value in using both ASPECTS and CTA-CS for outcome prediction and attempted to determine the specific subgroup of patients who could benefit from successful reperfusion using these scores. Methods This is a retrospective observational study of stroke patients treated with intra-arterial reperfusion therapy for unilateral arterial occlusion in the anterior circulation. A favorable outcome was defined as modified Rankin Scale ≤ 2 at three-months. Receiver operating characteristic comparison analysis was performed to decide whether outcome predictability increases when ASPECTS and CTA-CS are used together. Classification and regression tree (CART) analysis was done to identify the variables that best predict outcome and define the specific subgroup of patients who could benefit from successful reperfusion. Results A total of 91 consecutive patients were included. Outcome predictability of ASPECTS with CTA-CS was better than that of ASPECTS ( P = 0·088) or that of CTA-CS ( P = 0·049). CART analysis revealed that ASPECTS > 5 was the primary determinant of favorable outcome, followed by CTA-CS > 1. Among 19 patients with ASPECTS ≤ 5, none had a favorable outcome. Successful reperfusion was associated significantly with favorable outcome in the 51 patients with ASPECTS > 5 and CTA-CS > 1, but not in the 21 patients with ASPECTS > 5 and CTA-CS ≤ 1. Conclusions Outcome predictability improves when using ASPECTS and CTA-CS together.

Background and Purpose— We investigated whether the brachial-ankle pulse wave velocity (baPWV) has prognostic value for predicting functional outcome after acute cerebral infarction and whether the prognostic value differs between stroke subtypes. Methods— We included 1091 consecutive patients with first-ever acute cerebral infarction who underwent baPWV measurements. Stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale score >2 at 3 months after stroke onset. Results— We noted that 181 (16.59%) patients had a poor functional outcome. In multivariate logistic regression, patients in the highest tertile of baPWV (>22.25 m/s) were found to be at increased risk for poor functional outcome (adjusted odds ratio, 1.88; 95% confidence interval, 1.06–3.40) compared with those in the lowest tertile ( Conclusions— baPWV has an independent prognostic value for predicting functional outcome after acute cerebral infarction. The prognostic value did not differ according to the stroke subtype.

SummaryThere has been little information regarding the impact of unrecognised brain infarctions (UBIs) on stroke outcome in patients with nonvalvular atrial fibrillation (NVAF). By using volumetric analysis of ischaemic lesions, we evaluated the potential impact of UBIs on clinical outcome according to their presence and categorised type. This study enrolled 631 patients with NVAF having no clinical stroke history. UBIs were categorised into three types as territorial, lacunar, or subcortical. We collected stroke severity, functional outcome at three months, and the total volume of UBIs and acute infarction lesions. We investigated the association between clinical outcome and the type or volume of UBI, using a linear mixed model and logistic regression analysis. UBIs were detected in 285 (45.2 %) patients; territorial UBIs were observed in 24.4 % of patients (154/631), lacunar UBIs in 25 % (158/631), and subcortical UBIs in 15.7 % (99/631). Although initial stroke severity was not different between patients with UBIs and those without, those with UBIs had less improvement during hospitalisation, leading to poorer outcome at three months. Among the three types of UBIs, only territorial UBIs were associated with poor outcome, especially in patients with relatively smaller acute infarction volume. UBIs, in particular, territorial UBIs, may be considered as predictors for poor outcome after ischaemic stroke in patients with NVAF. Our results suggest that the impact of UBIs on clinical outcome differs according to the type of UBIs and the acute stroke severity.

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.

Introduction: Arterial stiffness increases with aging, but is also suggested as a surrogate marker of atherosclerosis and a predictor of cardiovascular events. Brachial-ankle pulse wave velosity (baPWV) is a simple and non-invasive tool for measurement of arterial stiffness. Hypothesis: Measurement of baPWV in acute phase of stroke may have a prognostic value to predict all-cause and cardiovascular death. Methods: This was a hospital-based, retrospective observational study. We included patients who had admitted for acute ischemic stroke and undergone baPWV measurement. Date and causes of death were obtained from the database of the Korean National Statistical Office. All-cause and cardiovascular mortality after stroke onset was compared across to the tertile groups of baPWV. Results: Of included 1696 patients, mean age was 64.5 ± 12.5 years and male was 60.7 %. Mean value of baPWV was 21.04 ± 6.31 m/sec. During mean follow-up period of 1.91 ± 1.27 years, there were 126 all-cause deaths including 85 cardiovascular deaths. Kaplan-Meier survival analysis demonstrated an increased risk for all-cause and cardiovascular mortality in patients with higher baPWV (Figure). In multivariate Cox regression, patients in the highest tertile of baPWV (T3; >22.54 m/sec) were at increased risks for all-cause death [HR 1.95, 95% CI 1.13-3.36, p=0.017] and cardiovascular death [HR 2.18, 95% CI 1.11-4.25, p=0.023] compared to the lowest tertile (T1; Conclusions: This study suggested that measurement of baPWV during acute phase of stroke might be used to identify patients at a higher risk for long-term mortality.

Background: Rapid administration of intravenous recombinant tissue plasminogen (rt-PA) is an effective way to enhance thrombolytic efficacy in stroke patients. We had already shown that a stroke code program based on the computerized physician order entry system could reduce time interval from hospital arrival to IV thrombolysis. We investigated that process improvement, which is an activity to improve existing process by making changes, could further reduce in-hospital time delay in thrombolytic therapy. Methods: During the first period (Jan. 2007 - Dec. 2009), we set the target time from emergency department (ED) arrival to IV thrombolysis at 40 minutes, monitored time intervals to evaluations and treatment at weekly stroke conference and determined the possible factors that were associated with time delay in cases who did not receive IV thrombolysis within 40 minutes. During the second period (Jan. 2010 - Dec. 2012), after review of factors of time delay during the first period, we implemented a tool for explanation to patients and their families, which included a standardized script and a Visual Decision Aid for tPA treatment (developed by UCLA stroke center). Results: After setting the target time and continuous monitoring of the process, median time from ED arrival to IV thrombolysis was reduced from 63 min to 45 min (p Conclusion: Continuous process improvement activity was effective in reduction of time intervals from ED arrival to IV thrombolysis in acute stroke patients. Setting target time with continuous monitoring of the performance and a standardized explanation for patients and their families using a script and a Visual Decision Aid were helpful to improve stroke team performance and reduction of time delays.

Background and purpose Although the stent retriever (SR) has shown a better reperfusion rate and clinical outcome than the older generation mechanical clot retrieval device, it is uncertain whether the SR is superior to intra-arterial fibrinolysis (IAF). Methods Ischaemic stroke patients who were treated with SR or IAF as initial endovascular treatment modality for unilateral arterial occlusion in the anterior circulation were included. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction grade ≥2b. A favourable clinical outcome was defined as a modified Rankin Score ≤2 at 3 months. Results Between January 2009 and May 2012, 55 patients were treated with SR and 50 patients were treated with IAF. The baseline characteristics were similar between the two groups except for the occlusion site and rescue treatment. In binary logistic regression analysis adjusted for the occlusion site and rescue treatment, SR was independently associated with increased successful reperfusion [82.0% vs. 47.3%; odds ratio (OR) 5.21; 95% confidence interval (CI) 1.92–14.14) and a more favourable clinical outcome at 3 months (54.0% vs. 43.6%; OR 3.40; 95% CI 1.31–8.84). The frequency of symptomatic intracranial haemorrhage and mortality at 3 months was not different between the two groups. Conclusions Stent retriever was as safe as and more effective than IAF. Our findings suggest that SR may be considered as an initial modality rather than IAF in acute stroke patients who undergo endovascular treatment.

Background and Purpose— We investigated whether the presence of nonrelevant cerebral atherosclerosis (NRCA) had prognostic value in patients with acute stroke. Methods— We compared prognosis in 780 consecutive patients with first-ever acute cerebral infarction who underwent cerebral angiography and diffusion-weighted MRI. Results— NRCA was present in 267 patients (34.2%). Multivariate analysis demonstrated that the presence of NRCA was independently associated with less improvement in National Institute of Health Stroke Scale score during the first 7 days ( P =0.004), and a poor functional outcome (modified Rankin Scale score >2) after 3 months (odds ratio, 2.51; 95% confidence interval, 1.55–4.07). An increase in burden count of NRCA was also associated with poor outcomes. Conclusions— The presence and burden count of NRCA were associated with poor neurological outcomes in patients with acute cerebral infarction.

Objective: The objective of this study was to assess the prognostic value of interarm difference of blood pressure (IAD) measured in acute ischemic stroke and to investigate its association with systemic atherosclerosis. Methods: This was a hospital-based retrospective observational study. Survival data and systolic/diastolic IAD were collected in patients with acute ischemic stroke. Systemic atherosclerosis was determined based on coronary CT angiography, transesophageal echocardiography, ankle-brachial index examination, and cerebral angiography covering both intracranial and extracranial cerebral arteries. Results: Of 834 patients, 10.3% had a systolic IAD ≥10 mm Hg, and 6.0% had a diastolic IAD ≥10 mm Hg. During a mean follow-up period of 2.96 ± 0.95 years, 92 patients died (including 68 cardiovascular deaths). In multivariate Cox regression adjusted for cardiovascular risk factors and initial stroke severity, the presence of systolic IAD ≥10 mm Hg was associated with increased risk of all-cause mortality (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.16–3.35) and cardiovascular mortality (HR 2.49, 95% CI 1.39–4.46). Patients with diastolic IAD ≥10 mm Hg also had increased risk of all-cause mortality (HR 3.43, 95% CI 1.94–6.08) and cardiovascular mortality (HR 3.51, 95% CI 1.83–6.74). The presence of systolic or diastolic IAD ≥10 mm Hg was associated with peripheral artery disease in the lower limbs, but not with atherosclerosis in the cerebral artery, coronary artery, or the aorta. Conclusions: The presence of interarm systolic or diastolic blood pressure difference ≥10 mm Hg is a strong independent prognostic marker in acute ischemic stroke.

Purpose Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. Materials and methods This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (-) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. Results During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (-) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (-) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172-8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (-) group seemed to also have a higher risk of recurrent stroke. Conclusion Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.

Purpose Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. Materials and Methods Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. Results Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p

Background: Patients with unilateral neglect after the right hemispheric lesion fail to respond normally to stimuli on the left side. Several paper-based tests for detecting neglect had been widely used. Here, we developed an application that runs on a tablet device to evaluate unilateral spatial neglect and investigated its feasibility in stroke patients. Methods: We enrolled acute ischemic stroke patients with neglect (n = 20) who had at least one of visual, auditory or tactile extinction. By comparison, stroke patients who had cortical lesions without neglect (n = 10), and healthy controls (n = 10) were recruited. The iNeglect application running on the iPad device was developed. In the table setting test of the iNeglect, the subjects were requested to drag the 12 food items on the table, and the deviation of each item from the midline was measured automatically. Line bisection tests using paper or iPad were also performed and compared. Results: Among neglect patients, mean deviation to the right side were 2.03 ± 2.11 mm of line bisection on paper, 18.47 ± 20.89 mm of line bisection on iPad, and 15.79 ± 18.17 mm of the table setting test. Patients with neglect showed larger deviation to the right side; in line bisection on paper (compared without neglect, p = 0.016 and control, p Conclusions: The iNeglect application was feasible in discriminating the patients with neglect and recognizing the right side deviation. The iNeglect application might be helpful to evaluate neglect patients and to objectify neurological deficit.

Backgrounds: Large inter-arm difference of blood pressure (IAD) is associated with development of cardiovascular events and increased mortality in the general population and in patients with cardiovascular risk factors. However, it is unknown whether the presence of large IAD has prognostic value in acute stroke patients and whether it is associated with atherosclerosis on other vascular beds (cerebral, coronary, and peripheral arteries, and aorta). We evaluated the prognostic value of large IAD measured in acute ischemic stroke, and the association between large IAD and atherosclerosis on multiple arterial beds (cerebral, coronary, and peripheral arteries, and aorta). Methods: We included 836 consecutive patients with acute ischemic stroke. Large IAD was defined by more than 10 mmHg absolute difference of systolic blood pressure between the arms. The presence of systemic atherosclerosis was determined based on cerebral angiography, coronary CT angiography, transesophageal echocardiograpghy and ankle-brachial index examination. Results: Large IAD was observed in 7.4 % of patients. During a mean study period of 419.4 ± 250.2 days, 48 patients (5.7 %) died (including 34 cardiovascular deaths). The Kaplan-Meier survival curves showed significantly higher mortality in the group with large IAD than those without (Figure, a log-rank test, (A) p Conclusions: The presence of large IAD is a strong independent prognostic marker in acute ischemic stroke.

Background: Several studies reported that repeated thrombolysis in patients with myocardial infarction or pulmonary embolism is safe. There are scant reports about repeated thrombolysis in patients with acute stroke. Recently, mechanical thrombectomy showed promising results in recanalization of occluded cerebral artery. However, no studies so far have evaluated the safety and feasibility of repeated thrombolytic therapy in the era of multimodal thrombolytic treatments. Methods: We investigated the patients with acute ischemic stroke who received thrombolytic therapy from Yonsei Stroke Registry for 10 years. The patients were divided into the repeated thrombolytic therapy group and the group who received thrombolysis once. Using propensity score to adjust for basic demographic, clinical, and treatment characteristics, we analyzed the rates of recanalization (Thrombolysis in Cerebral Infarction >=2), good outcome (modified Rankin Scale 0-2), and symptomatic intracranial hemorrhage. Results: Of the 437 patients who received thrombolytic treatments (IV in 41.4%, intra-arterial in 19.7%, and multimodal treatments in 38.9%), repeated thrombolysis was undergone in 7 patients (1.6%). Median age of repeated thrombolytic therapy group was 67.5 years old (range 50 to 78) and three of them were males. The median time interval between first and repeated treatment was 1.3 years (range 6 days to 6 years). Median NIHSS score was 15 (IQR 10-20). Six patients (85.7%) of 7 repeated treatment group had atrial fibrillation. After propensity matching there was no significant difference between repeated thrombolytic treatment and single treatment groups in the recanalization rates (100% vs. 85.7%, p = 0.28), and good outcome at 3 months (71.43% vs. 57.14%, p = 0.655). No symptomatic intracranial hemorrhage was occurred in the repeated thrombolytic treatment group. Conclusion: Repeated thrombolysis for chronologically separate acute ischemic stroke was rarely performed by the stroke team. Our data showed that repeated thrombolysis was safe and feasible.

Background Patients with unilateral neglect fail to respond normally to stimuli on the left side. To facilitate the evaluation of unilateral spatial neglect, we developed a new application that runs on a tablet device and investigated its feasibility in stroke patients. Methods We made the computerized table setting test (CTST) to run on the tablet computer. Forty acute ischemic stroke patients (20 patients with right hemispheric infarction with neglect, 10 patients with right hemispheric infarction without neglect, and 10 patients with left hemispheric infarction) and 10 healthy controls were prospectively enrolled to validate the CTST. The test requires subjects to set a table by dragging 12 dishes located below the table on the tablet screen. The horizontal deviation of the 12 dishes from the midline of the table, the selection tendency measured by the sequence of the dish selection, and the elapsed time for table setting were calculated automatically. Results Parameters measured by the CTST were correlated with the results of conventional neglect tests. The horizontal deviation was significantly higher in patients with right hemispheric infarction with neglect compared with the other groups. The selection tendency and elapsed time also were significantly different in patients with right hemispheric infarction with neglect compared with the left hemispheric infarction and control groups, but were similar to those with right hemispheric infarction without neglect. Conclusions The CTST is feasible to administer and comparable with conventional neglect tests. This new application may be useful for the initial diagnosis and follow-up of neglect patients.

Background & Aims Liver fibrosis is a multifactorial disease that can affect the development of cerebral small vessel diseases (SVDs) including cerebral microbleeds (CMBs), leukoaraiosis, and silent infarctions. Transient elastography can accurately assess the degree of liver fibrosis by measuring liver stiffness (LS). In the present study, we investigated the association between SVDs and LS values. Methods We recruited 300 participants (mean age 56 years, 170 men) who underwent a comprehensive medical health check-up between January 2011 and December 2012. Transient elastography was taken on the right lobe of the liver through intercostal space with patients lying in the dorsal decubitus position with the right arm in maximal abduction. Mild and significant fibrosis were defined as LS values >5.6 and >8.0 kPa, respectively. The presence of each SVD was determined using the FLAIR, GRE MR imaging as well as T1-, T2-weighted MR images. We tested whether the presence and burden of each type of SVD were different by LS values. Results Of the different types of SVDs, only the presence (p = 0.001) and number of CMBs (p8.0 kPa) was an independent predictor of CMBs (odds ratio 6.079, 95% confidence interval 1.489–24.819, p = 0.012). However, leukoaraiosis and silent infarctions were not associated with LS values (all p>0.05). Conclusions The degree of liver fibrosis, as assessed using transient elastography, was independently associated with the presence and burden of CMBs in healthy, asymptomatic participants. Understanding the link between the brain and liver may advance future research on the pathomechanisms of CMBs.

Purpose: Although early neurological deterioration (END) during the acute stroke period is known to be associated with poor functional outcomes, there is little data regarding the impact of END on long-term outcomes according to the characteristics of END. The aim of this study was to investigate whether there are differences in long-term mortality according to the characteristics of END among acute ischemic stroke or transient ischemic attack patients. Materials and Methods: END was defined as any increase (≥1) in National Institute of Health Stroke Scale score within 7 days after admission. We assessed the characteristics of END, such as the etiology and severity of END, as well as recovery after END. The relationship between 30-day or long-term mortality and each characteristic of END was investigated using multiple logistic analysis or Cox regression model. Results: Among 2820 patients, END was observed in 344 patients (12.2%). After adjustment for age, sex, underlying cardiovascular diseases, stroke severity, and stroke subtypes, END was associated with long-term mortality, whether it was mild or severe and whether or not it was followed by recovery. However, 30-day mortality was strongly related to the severity of END or the absence of recovery after END. Among the causes of END, recurrent stroke and medical illness were related to 30-day mortality, as well as long-term mortality, while brain herniation and intracranial hemorrhagic complications were only associated with 30-day mortality. Conclusion: The results of the present study demonstrated that END is associated with higher mortality and the effects of END on short-term and long-term mortality depend on END characteristics.