Search

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.

PURPOSE Infarct core can expand rapidly in acute stroke patients receiving intravenous tissue plasminogen activator (IV t-PA). We investigated changes in the extent of infarct core during IV t-PA treatment, and explored the associative factors of this infarct core expansion in patients with proximal artery occlusion. MATERIALS AND METHODS We included patients who were considered for sequential intra-arterial therapy (IAT) due to occlusion of intracranial proximal artery after IV t-PA. Patients who had a baseline Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) ≥6 and who underwent two consecutive CT scans before and shortly after IV t-PA infusion were enrolled. Patients were classified into no, moderate, and marked expansion groups based on decreases in ASPECTS (0-1, 2-3, and ≥4, respectively) on follow-up CT. Collateral status was graded using CT angiography. RESULTS Of the 104 patients, 16 (15.4%) patients showed moderate and 13 (12.5%) patients showed marked infarct core expansion on follow-up CT scans obtained at 71.1±19.1 min after baseline CT scan. Sixteen (15.4%) patients had an ASPECTS value

Background Acute superior mesenteric artery occlusion is a life-threatening disease that often has nonspecific symptoms. However, it should be suspected in those with known risk factors such as atrial fibrillation, cardiac thrombus or cardiac valvular disease. Case Report We reported two cases of acute thromboembolic occlusions of superior mesenteric artery that developed in acute cerebral infarction patients with confirmed atrial fibrillation. Conclusions Nonspecific symptoms of acute superior mesenteric artery occlusion should be closely monitored in acute cerebral infarction patients with atrial fibrillation, considering significance of early management of both vascular disease entities.

Background: Central sleep apnea is characterized by loss of automatic respiration during sleep. There are only a few reports which document that medullary infarction resulted in central sleep apnea and failure in early recognition of this condition could be catastrophic. We report a case of central sleep apnea following lateral medullary infarction. Case Report: A 49-year-old woman with an unknown past history presented with sudden onset of dizziness, loss of balance, and dysarthria for 1-hour duration. Diffusion-weighted imaging confirmed right lateral medullary infarction. She had episodes of hypercapnia and respiratory arrest due to central sleep apnea, which was confirmed by polysomnography. Tracheostomy was performed and she was put on a home ventilator. After 3 months, follow-up polysomnography showed disappearance of central sleep apnea. Conclusion: Patients with lateral medullary infarction need to be monitored closely with respect to the respiratory pattern.

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 developed a novel method named Gray-matter Volume Estimate Score (GRAVES), measuring early ischemic changes on Computed Tomography (CT) semi-automatically by computer software. This study aimed to compare GRAVES and Alberta Stroke Program Early CT Score (ASPECTS) with regards to outcome prediction and interrater agreement. Methods This was a retrospective cohort study. Among consecutive patients with ischemic stroke in the anterior circulation who received intra-arterial therapy (IAT), those with a readable pretreatment CT were included. Two stroke neurologists independently measured both the GRAVES and ASPECTS. GRAVES was defined as the percentage of estimated hypodense lesion in the gray matter of the ipsilateral hemisphere. Spearman correlation analysis, receiver operating characteristic (ROC) comparison test, and intra-class correlation coefficient (ICC) comparison tests were performed between GRAVES and ASPECTS. Results Ninety-four subjects (age: 68.7 ± 10.3; male: 54 [54.9%]) were enrolled. The mean GRAVES was 9.0 ± 8.9 and the median ASPECTS was 8 (interquartile range, 6-9). Correlation between ASPECTS and GRAVES was good (Spearman’s rank correlation coefficient, 0.642; P < 0.001). ROC comparison analysis showed that the predictive value of GRAVES for favorable outcome was not significantly different from that of ASPECTS (area under curve, 0.765 vs. 0.717; P= 0.308). ICC comparison analysis revealed that inter-rater agreement of GRAVES was significantly better than that of ASPECTS (0.978 vs. 0.895; P < 0.001). Conclusions GRAVES had a good correlation with ASPECTS. GRAVES was as good as ASPECTS in predicting a favorable clinical outcome, but was better than ASPECTS regarding inter-rater agreement. GRAVES may be used to predict the outcome of IAT.

Background and purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm(3) vs. placebo: 0.3±1.3 mm(3); P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

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 Factors associated with early arrival may vary according to the characteristics of the hospital. We investigated the factors associated with early hospital arrival in two different stroke centers located in Korea and Japan. Methods Consecutive patients with ischemic stroke arrived hospital within 48 hours of onset between January 2011 and December 2012 were identified and the clinical and time variables were retrieved from the prospective stroke registries of Severance Hospital of Yonsei University Health System (YUHS; Seoul, Korea) and National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan). Subjects were dichotomized into early (time from onset to arrival ≤4.5 hours) and late (>4.5 hours) arrival groups. Univariate and multivariate analyses were performed to evaluate factors associated with early hospital arrival. Results A total of 1,966 subjects (992 from YUHS; 974 from NCVC) were included in this study. The median time from onset to arrival was 6.1 hours [interquartile range, 1.7-17.8 hours]. In multivariate analysis, the factors associated with early arrival were atrial fibrillation (Odds ratio [OR], 1.505; 95% confidence interval [CI], [1.168-1.939]), higher initial National Institute of Health Stroke Scale scores (OR, 1.037; 95% CI [1.023-1.051]), onset during daytime (OR, 2.799; 95% CI [2.173-3.605]), and transport by an emergency medical service (OR, 2.127; 95% CI [1.700-2.661]). These factors were consistently associated with early arrival in both hospitals. Conclusions Despite differences between the hospitals, there were common factors related to early arrival. Efforts to identify and modify these factors may promote early hospital arrival and improve stroke outcome.

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.

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.

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.

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.

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.

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 & 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.