Search

Background d ‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d ‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d ‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d ‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results In the 170 patients, the median d ‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d ‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P d ‐dimer level was independently associated with poor outcome 3 months after EVT (odds ratio [OR], 4.399 [95% CI, 1.594–12.135]). Kaplan–Meier survival analysis showed that a high d ‐dimer level was independently associated with death within 6 months after EVT (OR, 5.441 [95% CI, 1.560–18.978]; log‐rank test, P d ‐dimer effect showed no heterogeneity across the subgroups for poor outcome 3 months after EVT or death within 6 months after EVT. The direction of effect was unfavorable for tertile 3 across all demographic strata. Conclusions High plasma d ‐dimer levels were predictive of early neurologic worsening, poor functional outcome 3 months after EVT, and death within 6 months after EVT. Registration URL: http://www.clinicaltrials.gov ; Unique identifier: NCT02964052.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Background The purpose of the RAFAS (Risk and Benefits of Urgent Rhythm Control of Atrial Fibrillation in Patients With Acute Stroke) trial was to explore the risks and benefits of early rhythm control in patients with newly documented atrial fibrillation (AF) during an acute ischemic stroke (IS). Method and Results An open‐label, randomized, multicenter trial design was used. If AF was diagnosed, the patients in the early rhythm control group started rhythm control within 2 months after the occurrence of an IS, unlikely the usual care. The primary end points were recurrent IS within 3 and 12 months. The secondary end points were a composite of all deaths, unplanned hospitalizations from any cause, and adverse arrhythmia events. Patients (n=300) with AF and an acute IS (63.0% men, aged 69.6±8.5 years; 51.2% with paroxysmal AF) were randomized 2:1 to early rhythm control (n=194) or usual care (n=106). A total of 273 patients excluding those lost to follow‐up (n=27) were analyzed. The IS recurrences did not differ between the groups within 3 months of the index stroke (2 [1.1%] versus 4 [4.2%]; hazard ratio [HR], 0.257 [log‐rank P =0.091]) but were significantly lower in the early rhythm control group at 12 months (3 [1.7%] versus 6 [6.3%]; HR, 0.251 [log‐rank P =0.034]). Although the rates of overall mortality, any cause of hospitalizations (25 [14.0%] versus 16 [16.8%]; HR, 0.808 [log‐rank P =0.504]), and arrhythmia‐related adverse events (5 [2.8%] versus 1 [1.1%]; HR, 2.565 [log‐rank P =0.372]) did not differ, the proportion of sustained AF was lower in the early rhythm control group than the usual care group (60 [34.1%] versus 59 [62.8%], P Conclusions The early rhythm control strategy of an acute IS decreased the sustained AF and recurrent IS within 12 months without an increase in the composite adverse outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02285387.

Background and Purpose— Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods— We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results— Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient’s age (21.6%), and clinicians’ experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions— In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients’ age and physicians’ experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.

Background and Purpose— Based on its mechanism, the use of balloon guide catheters (BGCs) may be beneficial during endovascular treatment, regardless of the type of mechanical recanalization modality used—stent retriever thrombectomy or thrombaspiration. We evaluated whether the use of BGCs can be beneficial regardless of the first-line mechanical endovascular modality used. Methods— We retrospectively reviewed consecutive acute stroke patients who underwent stent retriever thrombectomy or thrombaspiration from the prospectively maintained registries of 17 stroke centers nationwide. Patients were assigned to the BGC or non-BGC group based on the use of BGCs during procedures. Endovascular and clinical outcomes were compared between the BGC and non-BGC groups. To adjust the influence of the type of first-line endovascular modality on successful recanalization and favorable outcome, multivariable analyses were also performed. Results— This study included a total of 955 patients. Stent retriever thrombectomy was used as the first-line modality in 526 patients (55.1%) and thrombaspiration in 429 (44.9%). BGC was used in 516 patients (54.0%; 61.2% of stent retriever thrombectomy patients; 45.2% of thrombaspiration patients). The successful recanalization rate was significantly higher in the BGC group compared with the non-BGC group (86.8% versus 74.7%, respectively; P P P P P P =0.038) irrespective of the type of first-line endovascular modality used. Conclusions— Regardless of the first-line mechanical endovascular modality used, the use of BGC in endovascular treatment was beneficial in terms of both recanalization success and functional outcome.

BACKGROUND It remains controversial whether carotid artery stenting (CAS) is needed in cases of tandem cervical internal carotid artery occlusion (cICAO) and intracranial large vessel occlusion (LVO). OBJECTIVE To investigate the efficacy and safety of CAS in combination with endovascular thrombectomy (CAS-EVT) in cICAO-LVO patients and to compare its outcomes with those of EVT without CAS (EVT-alone). METHODS We identified all patients who underwent EVT for tandem cICAO-LVO from the prospectively maintained registries of 17 stroke centers. Patients were classified into 2 groups: CAS-EVT and EVT-alone. Clinical characteristics and procedural and clinical outcomes were compared between 2 groups. We tested whether CAS-EVT strategy was independently associated with recanalization success. RESULTS Of the 955 patients who underwent EVT, 75 patients (7.9%) had cICAO-LVO. Fifty-six patients underwent CAS-EVT (74.6%), and the remaining 19 patients underwent EVT-alone (25.4%). The recanalization (94.6% vs 63.2%, P = .002) and good outcome rates (64.3% vs 26.3%, P = .007) were significantly higher in the CAS-EVT than in the EVT-alone. Mortality was significantly lower in the CAS-EVT (7.1% vs 21.6%, P = .014). There was no significant difference in the rate of symptomatic intracranial hemorrhage between 2 groups (10.7 vs 15.8%; P = .684) and according to the use of glycoprotein IIb/IIIa inhibitor (10.0% vs 12.3%; P = .999) or antiplatelet medications (10.2% vs 18.8%; P = .392). CAS-EVT strategy remained independently associated with recanalization success (odds ratio: 24.844; 95% confidence interval: 1.445-427.187). CONCLUSION CAS-EVT strategy seemed to be effective and safe in cases of tandem cICAO-LVO. CAS-EVT strategy was associated with recanalization success, resulting in better clinical outcome.

Background and Purpose: Aortic plaques are associated with both larger artery and small artery atherosclerosis. However, association between aortic plaque and aortic stiffness in ischemic stroke is unknown. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive technique to measure aortic stiffness. In the present study, we hypothesized that presence of aortic plaques is associated with increased baPWV. Methods: We reviewed 1099 patients diagnosed with acute ischemic stroke, who had both transesophageal echocardiography (TEE) and brachial-ankle pulse wave velocity (baPWV) measurements. Aortic plaques were classified as complex aortic plaques (CAP) or simple aortic plaques (SAP). CAP were defined as plaques protruding into the lumen ≥4 mm and of mobile lesions located in the proximal aorta. SAP represented plaques Results: Among the 1099 patients, aortic atheroma was found in 689 (62.7%) patients. Twenty one (1.9%) patients had only CAP, 142 (12.9%) patients had both SAP and CAP, while 526 (47.9%) patients had SAP without CAP. Mean value of baPWV was 1982±580 cm/sec. baPWV was significantly increased in patients with any aortic atheromas than those without atheromas (2095±577 cm/sec vs. 1793±535 cm/sec, p Conclusion: We found that baPWV was associated with SAP but not CAP in acute ischemic stroke patients. These feature suggests that SAP represent generalized atherosclerosis and aortic stiffness, whereas CAP represent the sole mechanism of stroke.

Introduction: Increased neutrophils, and stress-induced low lymphocyte levels both indicate changes in the immune system. Blood neutrophil/lymphocyte ratio (NLR) is shown to be a simple, reliable and inexpensive inflammatory indicator that can provide important information on many conditions. Recently, NLR has been proposed as a useful biomarker to predict cardiovascular risk. However, little is known about the role of NLR in patients with intracranial aneurysm (IA). Hypothesis: The purpose of present study was to investigate whether NLR values differ in patients with IA. Methods: The study group consisted of patients with IA who had been admitted to the neurology department from January 2008 to December 2016. A total of 406 patients including 198 patients with unruptured IA, 208 patient with ruptured IA were enrolled in this study. The control group consisted of 420 age, sex-matched healthy adults who had not harbor IA by CTA, MRA, DSA. The baseline NLR was calculated as the ratio of neutrophil count to lymphocyte count. WBC count>12.000 cells per μL or 38 ° are excluded from the study. Results: The Mean NLR was significantly higher among persons with cerebral aneurysm compared with controls (P < 0.001). The level of NLR in ruptured IA group were found higher compared to unruptured IA and control group (6.1 ± 4.3 vs 2.7 ± 1.5 vs 1.8 ± 1.1, P < 0.001). Other comorbid conditions were balanced between these three groups. Conclusions: We demonstrated that the NLR is an independent predictor of IA patients. In addition, higher NLR is associated with ruptured IA. Unlike many other inflammatory markers and bioassays, NLR are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm. The clinical implications of NLR on IA remain to be established by future investigations. A long term prospective study is needed to clarify this matter.

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.

Background and Purpose— Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined. Methods— Patients who were treated with a SR as the first endovascular modality for their intracranial large artery occlusion in anterior circulation were retrospectively reviewed. The recanalization rate for each SR pass was calculated. The association between the number of SR passes and a patient’s functional outcome was analyzed. Results— A total of 467 patients were included. Successful recanalization by SR alone was achieved in 82.2% of patients. Recanalization rates got sequentially lower as the number of passes increased, and the recanalization rate achievable by ≥5 passes of the SR was 5.5%. In a multivariable analysis, functional outcomes were more favorable in patients with 1 to 4 passes of the SR than in patients without recanalization (odds ratio [OR] was 8.06 for 1 pass; OR 7.78 for 2 passes; OR 6.10 for 3 passes; OR 6.57 for 4 passes; all P P =0.455; OR 0.33 with 0.02–5.70, P =0.445 for ≥6 passes). Conclusions— The likelihood of successful recanalization got sequentially lower as the number of SR passes increased. Five or more passes of the SR became futile in terms of the recanalization rate and functional outcomes.

BACKGROUND Although several outcome prediction scores incorporated with pretreatment variables have been developed for acute ischemic stroke (AIS) patients, there is not currently a prediction score that includes pretreatment imaging that can show salvageable brain tissue. OBJECTIVE To evaluate whether addition of the collateral grade on computed tomography angiography to previously published prediction scores could increase accuracy of clinical outcome prediction in endovascular thrombectomy (EVT) for AIS. METHODS This study used a retrospective multicenter registry for patients undergoing EVT for anterior circulation large vessel occlusion. Three previously published outcome prediction scores (Houston intra-arterial therapy 2, HIAT2; totaled health risks in vascular events, THRIVE; and Pittsburgh response to endovascular therapy, PRE scores) were tested in this study. Using 482 deprivation cohorts, areas under the receiver operating characteristic curves (AUC-ROCs) were compared between prediction scores with/without collateral grades in predicting the poor outcomes (modified Rankin Scale 4-6 at 3-mo follow-up) after EVT. We developed modified prediction scores by adding the collateral grade, and their advancement of outcome prediction was validated using 208 independent validation cohorts. RESULTS AUC-ROCs of HIAT2, THRIVE, and PRE scores that incorporated with collateral grade were superior in predicting poor outcomes when compared to that of the unmodified scores (P

Background and Purpose— Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. Methods— This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. Results— MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group showed a significantly higher rate of good outcome (modified Rankin Scale score, 0–2; 39.6% versus 22.0%; P =0.031) without increasing symptomatic intracranial hemorrhage (16.7% versus 20.0%; P =0.823) or mortality (12.5% versus 19.0%; P =0.360). Of the RS group, patients who had recanalization success had 54.8% of good outcome, which is comparable to that (55.4%) of recanalization success group with MT. RS remained independently associated with good outcome after adjustment of other factors (odds ratio, 3.393; 95% confidence interval, 1.192–9.655; P =0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31 patients with recanalization success with RS. The stent was patent in 20 (87.0%) of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated with stent patency but not with symptomatic intracranial hemorrhage. Conclusions— RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.

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.

Background and Purpose— Statin is an established treatment for secondary prevention after ischemic stroke. However, the effects of statin intensity and adherence on the long-term prognosis after acute stroke are not well known. Methods— This retrospective cohort study using a nationwide health insurance claim data in South Korea included patients admitted with acute ischemic stroke between 2002 and 2012. Statin adherence and intensity were determined from the prescription data for a period of 1 year after the index stroke. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. We performed multivariate Cox proportional regression analyses. Results— We included 8001 patients with acute ischemic stroke. During the mean follow-up period of 4.69±2.72 years, 2284 patients developed a primary outcome. Compared with patients with no statin, adjusted hazard ratios (95% confidence interval) were 0.74 (0.64–0.84) for good adherence, 0.93 (0.79–1.09) for intermediate adherence, and 1.07 (0.95–1.20) for poor adherence to statin. Among the 1712 patients with good adherence, risk of adverse events was lower in patients with high-intensity statin (adjusted hazard ratio [95% confidence interval], 0.48 [0.24–0.96]) compared with those with low-intensity statin. Neither good adherence nor high intensity of statin was associated with an increased risk of hemorrhagic stroke. Conclusions— After acute ischemic stroke, high-intensity statin therapy with good adherence was significantly associated with a lower risk of adverse events.

Background and Purpose— We investigated whether occlusion type identified with computed tomography angiography (CTA-determined occlusion type) could predict endovascular treatment success using stent retriever (SR) thrombectomy. Methods— Consecutive patients with stroke who underwent CTA and then endovascular treatment for intracranial large artery occlusion were retrospectively reviewed. CTA-determined occlusion type was classified into truncal-type occlusion or branching-site occlusion and compared with digital subtraction angiography–determined occlusion type during endovascular treatment. Three rapidly- and readily-assessable pre-procedural findings (CTA-determined occlusion type, atrial fibrillation, and hyperdense artery sign), which may infer occlusion pathomechanism (embolic versus nonembolic) before endovascular treatment, were evaluated for association with SR success along with stroke risk factors and laboratory results. In addition, the predictive power of the 3 pre-procedural findings for SR success was compared with receiver operating characteristic curve analyses. Results— A total of 238 patients (mean age, 70.0 years; male patients, 52.9%) were included in this study. CTA-determined occlusion type corresponded adequately with digital subtraction angiography–determined occlusion type ( P =0.453). Atrial fibrillation (odds ratio, 2.66; 95% confidence interval, 1.25–5.66) and CTA-determined branching-site occlusion (odds ratio, 8.20; confidence interval, 3.45–19.5) were independent predictors for SR success. For predicting SR success, the area under the receiver operating characteristic curve value for CTA-determined branching-site occlusion (0.695) was significantly greater than atrial fibrillation (0.594; P =0.038) and hyperdense artery sign (0.603; P =0.023). Conclusions— CTA-determined branching-site occlusion was significantly associated with SR success. Furthermore, among the 3 rapidly- and readily-assessable pre-procedural findings, CTA-determined branching-site occlusion had the greatest predictive power for SR success.

Background and Purpose— It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. Methods— This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Results— Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P P =0.003), but not in the dabigatran group (6/19 [31.6%]; P =0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P =0.022), but not related to the hemorrhage frequency. Conclusions— The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.

Introduction: We investigated whether collateral augmentation treatments with acetazolamide (ACZ), head down tilt (HDT), or combination are effective in rats with the transient middle cerebral artery occlusion (MCAO) models. Methods: All animals were induced MCAO for 1h 30min and reperfusion for 24h. ACZ 100 mg/kg solution in 0.9% saline was administered in a single intravenous bolus of 0.5 ml over 3 min, 30 min after onset of MCAO. HDT was administered using a 15° tilted platform for 60 min, 30 min after onset of MCAO. To measure infarct volume, brain water content and neurological score, 58 male Wistar rats were divided into four groups: control (n=17), ACZ (n=15), HDT (n=13) and combination groups (n=14). Infarction volumes were measured after 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurologic deficits were assessed using the Garcia and Longa scores at 24h after MCAO. The following formula was used to quantify the brain water content: brain water content (g) = wet brain weight - dry brain weight. Results: The collateral augmentation groups had smaller infarct volume (control, 30.39 ± 8.18 vs. collateral augmentation groups 16.89 ± 11.45, p=0.005) and less brain water content (control, 1.53 ± 0.11 vs. collateral augmentation groups 1.44 ± 0.10, p=0.081). Neurological scores were better in collateral augmentation group than control group (Garcia score; control, 9.8 ± 2.1 vs. collateral augmentation groups, 12.4 ± 3.0, p=0.001) (Longa score; control, 2.5 ± 0.8 vs. collateral augmentation groups, 1.9 ± 1.1, p=0.026). Among groups, the ACZ group was significantly associated with small infarct volume (ACZ, 11.79 ± 5.40 vs. control, 30.39 ± 8.18, p Conclusion: We found that collateral augmentation was associated with smaller infarction volume and better neurological outcome compared to untreated animal after transient MCAO. Among the treatment methods, the combination group showed the best beneficial effects.

Background: The brain and gut are made up of a network of many neurons and are bidirectional through the vagus nerve. These two nervous systems adjust to each other when food is needed, stressed, and intestinal bacteria are out of balance. Trimethlamine N-oxide (TMAO) is produced by gut microbiota. Gut microbiota derived TMAO are known to be associated with poor outcome in various vascular diseases including coronary artery disease and peripheral artery obstructive disease. Therefore, increased TMAO may be also associated stroke outcome. We sought the association between TMAO level and infarction size in mice ischemic stroke model. Method: Five-week-old male C57BL / 6J mice are fed with Control, 1.2% choline and 0.12% TMAO for 6 weeks. At the 11th week, the transient middle cerebral artery occlusion model (MCAO) was performed. All assessments was blindly conducted. TMAO was measured with mass spectrometry. Infarction size was measured with 2,3,5-Triphenyltetrazolium staining at 1 day after MCAO. Neurological score was assessed with Longa score, Gracia's, and mNHSS. Results: During the 6 weeks of feeding, weighing was performed to confirm the diet feeding. Interestingly, the weight of TMAO group mice was generally high. The concentration of TMAO level also varied from group to group. TMAO and choline fed group had significant increase in the level of circulating TMAO compared to control diet fed group (P Conclusion: We found that the infarction volume was associated with TMAO level. Increased TMAO may be beneficial in acute ischemic stroke.

Background: Systemic cancer is a cause of stroke. However, histologic features of thrombus in stroke patients with cancer are not well-known. We investigated histologic features of intracranial thrombi in acute stroke patients with cancer. Methods: We prospectively collected thrombi that were retrieved during mechanical thrombectomy. This study included 32 consecutive patients with any history of systemic cancer (16 patients with active cancer and 16 patients with inactive cancer.) All patients underwent continuous electrocardiographic monitoring for at least 24 h. Echocardiography was performed in all but three patients. Immunohistochemical staining of thrombus was done using anti-CD42b antibody for platelets, anti-glycophorin antibody for erythrocytes, anti-fibrinogen antibody for fibrin, anti-myeloperoxidase antibody for leukocytes, and anti-Histone H3 antibody for neutrophil extracellular traps. After acquiring images of entire thrombus area using the stereo investigator imaging system, quantitative fraction (%) of different thrombus composition was semi-automatically assessed using ImageJ software. We compared the thrombus composition between the active cancer group and the inactive cancer group. Results: Comparing with the inactive cancer group, the active cancer group showed higher platelet fraction (median [interquartile range], 20.6 [7.3-27.6] vs 6.1 [2.5-9.9], p=0.002) and lower erythrocyte fraction (1.6 [0.8-11.1] vs 20.7 [13.3-23.7], p=0.001). Fractions for fibrin, leukocytes, and neutrophil extracellular traps were not different between the active and inactive cancer groups. Four patients had vegetation on echocardiography and showed very high platelet fraction (29.5 [26.1-33.9]) and very low erythrocyte fraction (0.8 [0.7-0.9]). Of the active cancer group, 6 patients with negative evaluation also showed high platelet fraction and low erythrocyte fraction, but the thrombus composition in 4 patients with determined etiology (3 atrial fibrillation, 1 >50% stenosis) was similar to that in inactive cancer. Conclusion: Thrombi in stroke patients with active cancer were platelet-rich and erythrocyte-poor. These findings may aid to determine the treatment strategy for stroke patients with cancer.

Introduction: The current management of acute ischemic stroke has changed recently with the publication of randomized trials using endovascular therapy (EVT). Rationale/Hypothesis: Limited information is however available on how physicians make decisions regarding patient selection for endovascular therapy (EVT) in the real-world. Methods: We conducted an international web-based cross-sectional survey of stroke physicians and interventionalists to assess the decision to offer EVT. Part 1 of the survey used hierarchical Bayes’ disaggregate discrete choice modelling to analyze ten pairs of patient scenarios, randomly generated from ten key patient characteristics to have respondents choose which scenario was best suited for EVT in their practice. Part 2 of the survey used mixed effects logistic regression modelling to analyze 22 randomly chosen patient scenarios, again randomly generated from several key patient and hospital level characteristics. Results: 607 physicians [mean age of 44 (SD 8.5) years, 83.5% men, 53.6% neurologists, 28.7% neuro-interventionists, 13.3% neurosurgeons, 4.7% other], from 38 countries participated. Using disaggregate discrete choice analysis, the most influential characteristic in deciding about EVT was the extent of ischemic change (ASPECTS)/volume of infarct core (26-28% of the choice). Patient age, premorbid status, baseline NIHSS score, and occlusion location (13-15% each) were the other relevant characteristics. Using mixed effects logistic regression, baseline stroke severity (NIHSS> 15 vs. NIHSS 0-5, OR 6.7; 95% CI 4.8-9.5), ASPECTS (5-7 vs. 0-4, OR 9.4; 95% CI7.4-11.9) and occlusion location (distal M2 vs. ICA/M1, OR 012; 95% CI 0.08-0.17) were the most relevant characteristics in deciding about EVT. Time from stroke onset, sex, comorbidities, time of day (off hours vs. day time) were all less relevant in deciding about EVT in both analyses. Conclusion: Severity of stroke assessed clinically, and extent of brain infarction and location of thrombus assessed on imaging are the dominant characteristics that treating physicians use in the real world when deciding about EVT for patients with an acute ischemic stroke.

Backgroud: Trimethylamine N-oxide (TMAO) is produced by gut microbiota. Gut microbiota derived TMAO are known to be associated with coronary heart disease, congestive heart failure, and chronic kidney disease. Therefore, increased TMAO may be associated stroke outcome. Method: Fasting blood from consecutive 313 stroke patients were analyzed. Plasma TMAO level was measured by mass spectrometry. The patients were followed up for 3 years and major adverse cardiovascular event (MACE) was captured. The cut off value was calculated by Contal & O'Quigley's method. Results: Median TMAO level was 362.4 (IQR 317.5 - 405.6) ng/ml. Cut off value was 563. 25. Older age, men was predominant in patients with higher TMAO level. Moderate to severe renal disease were frequent and creatinine levels were high in patient with higher TMAO group compared to lower TMAO group (1.4±1.8 vs. 0.9 ± 1.1, p = 0.047). Higher level of TMAO was associated with occurrence of MACE in Kaplan-Meier survival analysis (log-rank test, p Conclusion: We found that the TMAO level in patients with acute ischemic stroke was associated with poor long-term outcome. Gut microbiota and brain axis may be a prognostic marker after acute ischemic stroke.

Background and Purpose— We hypothesized that permanent stenting may be a rescue treatment for stentriever-failed anterior circulation large artery occlusion. We compared the outcomes among patients with permanent stenting and those without stenting after stentriever failure. Methods— We retrospectively evaluated 208 patients who underwent stentriever thrombectomy for anterior circulation large artery occlusion between September 2010 and September 2015. Modified thrombolysis in cerebral ischemia 2b-3 recanalization was achieved with stentriever alone or in combination with Penumbra device in 155 patients (74.5%). An additional 8 patients (3.8%) obtained modified thrombolysis in cerebral ischemia 2b-3 with urokinase or glycoprotein IIb/IIIa inhibitor infusion. Of the remaining 45 patients (21.6%), 17 underwent stenting (stenting group; mean age, 68 years), whereas 28 did not undergo stenting (nonstenting group; mean age, 72 years). The rate of modified thrombolysis in cerebral ischemia 2b-3 in stenting group was assessed, and clinical outcomes were compared between groups. Results— There were no differences in clinical and laboratory findings, initial National Institute of Health Stroke Scale score, location of anterior circulation large artery occlusion, and onset-to-puncture time between groups. Modified thrombolysis in cerebral ischemia 2b-3 was achieved in 14 members (83.3%) of the stenting group. Stenting group had more favorable outcomes (modified Rankin Scale score 0–2, 35.3%) and less cerebral herniation (11.8%) than nonstenting group (modified Rankin Scale score 0–2, 7.1%; cerebral herniation, 42.9%; P Conclusions— Permanent stenting may be a rescue modality for stentriever-failed anterior circulation large artery occlusion. A large prospective study is necessary for confirmation because of the small sample size of this study.

Background and Purpose— The evaluation of sources of cardioembolism with transesophageal echocardiography (TEE) in patients with stroke is crucial but semi-invasive. We hypothesized that the size and mechanical function of the left atrium (LA) assessed by transthoracic echocardiography (TTE) could provide useful information on high risk of cardioembolism on TEE in patients with stroke. Furthermore, we sought to define the determinants of LA mechanical dysfunction in these patients. Methods— A total of 248 patients with acute ischemic stroke (147 men; 64±13 years) who underwent 2-dimensional and speckle tracking TTE followed by TEE were analyzed. Results— LA appendage emptying velocity, prevalence of LA or LA appendage thrombus, prevalence of aortic plaques, and incidence of embolic stroke showed significant differences among the 4 groups classified according to the median values of the LA volume index and global LA longitudinal strain (LALS). Patients at high risk of cardioembolism evidenced by TEE revealed significantly larger LA volume index and lower global LALS than those without. Global LALS (cutoff, 11.5%; area under the curve, 0.947; sensitivity, 100%; specificity, 91%; P P =0.04) for LA or LA appendage thrombus than LA volume index (cutoff, 36.2 mL/m 2 ; area under the curve, 0.823; sensitivity, 88%; specificity, 75%; P =0.002). Age, left ventricular systolic function, LA volume index, and pulse wave velocity were independent determinants for global LALS. Conclusions— LA mechanical dysfunction is closely associated with high risks of cardioembolism. Global LALS assessed by speckle tracking TTE well discriminates the presence of LA or LA appendage thrombus on TEE in patients with acute ischemic stroke.

Introduction: Prediction of outcome in stroke patients can help both physicians and patients in making treatment decisions and managing prognostic expectations. Machine learning techniques are being increasingly used in the field of medical research. Hypothesis: We hypothesized that models developed with machine learning techniques are useful for predicting long-term functional outcomes in patients with acute ischemic stroke. Methods: The model was developed with a prospective cohort of acute ischemic stroke patients. This cohort registers stroke patients who were admitted within 7 days from the onset of symptoms. For this study, we included all patients admitted between January 1, 2010, and December 31, 2014. We excluded patients with pre-stroke modified Rankin Scale (mRS) score >2 or missing 3-month mRS score. Univariate analysis was performed to guide in variable selection for machine learning models. Machine learning models were trained to classify patients likely to have unfavorable outcome, defined as 3-month mRS score >2. Developed models included artificial neural network, random forest, support vector machine, and logistic regression models. Area under the receiver-operated characteristic curve (AUC) was used to compare effectiveness of each model. Google’s TensorFlow and scikit-learn toolkit were used for training of machine learning models. Results: Total of 3,524 patients were admitted during the study period. After excluding 454 patients with unavailable 3-month mRS scores, 60 patients with pre-stroke mRS score >2, and 87 patients with missing laboratory tests or clinical data, 2,923 patients were finally enrolled. Of the 2,923 patients, 695 (24%) patients had unfavorable outcome (mRS>2) at 3 months. The AUC was 0.888 for Artificial neural network model, 0.810 for random forest model, 0.836 for support vector machine model, and 0.842 for logistic regression model. We calculated the AUC of ASTRAL score for reference, which showed 0.839 in our study group. Conclusion: Machine learning models, particularly the artificial neural network model, achieved high accuracy of prediction for functional outcome in stroke. This study showed the feasibility of machine learning approach for predicting outcomes in stroke.

Background and purpose: In this study, we investigated the stroke severity was associated with the prior antithrombotic medication including novel Vitamin K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). Methods: We included 801 consecutive acute ischemic stroke or transient ischemic attack patients with NVAF who were admitted to 6 hospitals between August 2013 and January 2017 in the present study. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). Prior antithrombotics before index stroke were categorized into 5 groups: no antithrombotics, only antiplatelet, warfarin with international normalized ratio (INR) Results: A total of 801 acute ischemic stroke or transient ischemic stroke patients with NVAF were enrolled. Among the 801 patients, the 34 (4.2%) had been treated with warfarin with INR ≥2, 146 (18.2%) with warfarin with INR ≥2, 70 (8.7%) with NOACs, 347 (43.3%) with only antiplatelet, and 204 (25.5%) without any antithrombotics. The median NIHSS score was 5 (IQR 1-14). Compared with the no antithrombotics group (9.5, IQR 2-16), the NIHSS was lower in the warfarin with INR ≥2 (4, 1-7.3) and the only antiplatelet group (4, IQR 1-12), while the warfarin with INR Conclusions: Our data indicate that the prior anticoagulation was related with milder initial stroke severity in patients with NVAF.

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.

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.

Introduction: Spontaneous echo contrast (SEC) is frequently observed in patients with atrial fibrillation (AF). SEC represents red blood cell aggregates associated with increased thrombogenecity, which may produce larger thrombus formation. This can result in larger infarctions and severe stroke. Hypothesis: Thrombus characteristics occluding the intracranial artery may differ between AF patients with concomitant SEC and those without. Methods: This was a post hoc analysis of prospective cohort. Acute stroke patients with non-valvular AF who underwent transesophageal echocardiography and thin-section (1 or 1.25 mm) noncontrast CT between January 2008 and December 2014 were considered for this study. The volume and the density of thrombus were measured semi-automatically using three-dimensional image software, and compared between the patients with SEC and those without. Results: Among 368 patients considered, thrombus was identified in 135 patients. Of the135 patients, 67 (49.6%) had SEC. The frequency of SEC was not different between patients with identified thrombi and those without (P=0.146). Thrombus volume was larger in the patients with SEC than those without (median [interquartile range], 75.0 mm 3 [46.1-142.9] versus 55.9 mm 3 [30.3-91.8]; P=0.013). As the degree of SEC increased, the thrombus volume increased (P=0.025). On multivariate analysis, the presence of SEC was independently associated with thrombus volume. (P=0.008) . Linear regression analysis showed positive association between initial National Institute of Health Stroke Scale scores and thrombus volume (P Conclusions: This study suggests that increased thromogenecity by SEC in patients with AF might produce larger intracardiac thrombi and embolization, which resulted in larger thrombi occluding the intracranial artery and more severe stroke.

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.

Introduction: The presence of spontaneous echo contrast (SEC) on transesophageal echocardiography (TEE) is associated with increased thrombogenecity and a risk factor of thromboembolism. The increased thrombogenecity in SEC may produce larger intracardiac thrombi, which result in larger cerebral infarctions and severe stroke. Hypothesis: We hypothesized that infarction volume will be larger in stroke patients with SEC than in those without SEC. Methods: This was a post-hoc analysis using a prospective cohort of acute ischemic stroke. This study included patients with nonvalvular atrial fibrillation (NVAF) who underwent TEE and diffusion weighted imaging (DWI) from Jan. 2008 to Dec. 2014. The volume of cerebral infarction on DWI was measured semi-automatically using 3-dimensional software by an investigator who was blinded to clinical information. The infarction volume was compared between patients with SEC and those without. Results: Of 4252 considered patients, 889 patients had NVAF. After excluding 449 patients without TEE and 39 patients without DWI, 401 patients were included for analysis. Of them, SEC was found in 181 patients (45.1%, 82 mild, 35 moderate, and 64 severe SEC). Infarction volume was larger for the patients with SEC than those without SEC (median [interquartile range], 7226.8 mm 3 [1218.1-28804.6] vs. 4756.8 mm 3 [672.8-14887.8], p=0.015). Infarction volume also increased with SEC severity (p=0.006). Initial National Institute of Health Stroke Scale scores were higher for the patients with SEC than those without SEC (median [interquartile range], 5.0 [2.0-12.0] vs. 3.0 [1.0-8.0]. p=0.008). On multivariate analysis, infarction volume was independently associated with the presence of SEC (p=0.014). Conclusion: Among stroke patients with NVAF, those with co-existing SEC had larger cerebral infarction, which may account for severe stroke. This may be related with increased thrombogenecity in patients with SEC.

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.

Background Intracranial atherosclerotic stenosis (ICAS) is responsible for 9% to 37% of ischemic strokes. Objective To evaluate the clinical outcome and risk factors for in-stent restenosis (ISR) after treatment of ICAS with a Wingspan stent. Methods Seventy-seven patients with 79 total target ICAS > 60% (mean, 79.9 ± 8.4%; symptomatic ICAS, 96.2%) underwent attempted treatment with Wingspan stenting between March 2010 and March 2011. A retrospective review of the prospectively registered data was conducted to assess the risk factors for ISR and the clinical outcomes of these patients. Results The 30-day transient ischemic attack/stroke and death rates were 5.3% (95% confidence interval [CI], 0.1-10.5) and 0%, respectively. All patients but 1 were followed up clinically for a mean of 18.9 months (range, 12-23 months). During the period, cumulative transient ischemic attack/stroke and death rates were 8.1% (95% CI, 1.7-14.5) and 0%, respectively. Only 1 patient suffered a disabling stroke (subarachnoid hemorrhage), which was associated with retreatment of an ISR with a drug-eluting balloon-expandable stent. Follow-up angiography was available in 69 treated vessels (89.6%) at 3 to 24 months (median, 12 months). Binary ISR rate was 24.6%, of which 17.6% (3 of 17 cases) was symptomatic. Rapid balloon inflation (95% CI, 5.490-530.817) and longer length of stenosis (95% CI, 1.093-1.891) were independent risk factors for ISR. Conclusion Wingspan stenting may be effective for appropriately selected ICAS patients. Rapid balloon inflation and longer lengths of stenosis were independent risk factors for ISR.

Background and Purpose: The goal of reperfusion therapy in acute ischemic stroke is to limit the extension of the ischemic core. The objectives of the present study were to assess the relationship between endovascular treatment and final infarct volume. Methods and Results: ESCAPE is a multicenter prospective randomized open-label trial with blinded outcome evaluation that enrolled 315 patients (endovascular treatment n=165; control n=150). Of these, 314 patient infarct volumes at 24 hours on CT or MRI were measured blinded to clinical data. Because infarct volumes were non-normally distributed, final infarct volumes were analysed by quartiles. Final infarct volumes were compared by treatment assignment and recanalization/reperfusion status measured by 2-8h CT angiogram in the control group and by formal angiography in the intervention arm. Results: Median final infarct volume among all study participants was 21 mL (IQR: 7 to 72). Median final infarct volume in endovascular treatment arm at 15.5 mL (IQR: 5 to 46.5) was significantly lower than median final infarct volume in control arm 33.5 mL (IQR: 11 to 95; P=0.0004). Small infarcts, defined as 1st quartile of infarct volumes were more common in the endovascular group compared to control (relative risk [RR] 1.5, CI95 1.02-2.3). Successful recanalization and reperfusion was highly associated with small infarcts (RR 2.2, CI95 1.4-3.4). The proportion of large hemispheric stroke (defined as an infarct volume in the 4th quartile) was much less frequent in the endovascular treatment arm (RR 0.6, CI95 0.3-0.8). Conclusions: This analysis supports the primary results of ESCAPE trial as endovascular treatment was associated with significantly smaller final infarct volumes. Recanalization/reperfusion was associated with smaller final infarct volume.

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.

Background and hypothesis: Post-stroke emotional symptoms are common and adversely influence the patients’ outcome. We aim to evaluate the efficacy of escitalopram in patients with acute stroke for the prevention of various emotional disorders, and for improvement of neurologic, cognitive function and patient quality of life. Method: In this multicenter, placebo-controlled, double-blind trial, 405 stroke patients (within 21 days after onset) were randomized either to the escitalopram (n = 217) (5 mg -10mg) or placebo (n = 188) for 3 months. Depressive symptoms (Montgomery-Asberg Depression Rating Scale [MADRS] and mini-international neuropsychiatric interview [MINI]), emotional incontinence (Kim’s criteria), anger proneness (Modified Spielberger trait), cognition (MOCA test), Modified Rankin scale (MRS), and quality of life (Stroke Specific QOL) were assessed initially, and at 3 and 6-months. Results: Baseline characteristics were similar between the groups. Proportions of patients with MADRS≥16, the primary outcome, were not different at 3-month (placebo vs. escitalopram group, 13.8% vs. 12.0%, p=0.579). However, new development of depression determined by MINI was lower in the escitalopram group (0 vs. 4 patients, P = 0.046). For the secondary outcomes, anger proneness score was lower in the escitalopram group (21.5 vs 20.1 at 3-month, P = 0.011). There were no significant differences in other items at 3-months: emotional incontinence (% of patients, 8.5% vs. 10.2%, p=0.565), MOCA score (21.1±6.8 vs. 20.9±7.2, p=0.704), MRS (3.1±1.2 vs. 3.0±1.3, p=0.822), and patient quality of life (165.0±38.8 vs. 166.7±39.1, p=0.667). When chronological changes of MADRS were analyzed after categorizing patients into normal (0-6), mild (7-15), and moderate/severe (≥16) depression groups, escitalopram significantly improved MADRS of patients with mild depression (10.30 to 7.23 vs. 10.91 to 5.06, p = 0.036). Conclusion: Escitalopram was not effective in the prevention of post-stroke depressive symptoms, and did not improve cognitive function, neurologic severity, and patient quality of life. However, it prevented development of depression defined by MINI, anger-proneness and seems to improve depressive symptoms in patients with mild depression.

Introduction: Blood neutrophil/lymphocyte ratio (NLR) is a simple marker of subclinical inflammation that can be easily obtained. The NLR has recently emerged as a prognostic marker in patients with cancer and coronary artery disease. However, little is known about the role of NLR in patients with intracranial aneurysm (IA). Hypothesis: The purpose of this study was to determine the clinical significance of NLR in patients with IA. Methods: The study group consisted of patients with IA who had been admitted to the neurology department from January 2008 to December 2014. A total of 362 patients including 176 patients with unruptured IA, 186 patient with ruptured IA were enrolled in this study. The control group consisted of 178 age, sex-matched healthy adults who had not harbor IA by CTA, MRA, DSA. The baseline NLR was calculated as the ratio of neutrophil count to lymphocyte count. WBC count>12.000 cells per μL or 38 ° are excluded from the study. Results: The Mean NLR was significantly higher among persons with cerebral aneurysm compared with controls (P < 0.001). The level of NLR in ruptured IA group were found higher compared to unruptured IA and control group (7.0 ± 6.6 vs 2.5 ± 1.5 vs 1.6 ± 0.5, P < 0.001). Other comorbid conditions were balanced between these three groups. Conclusions: Higher NLR is associated with cerebral aneurysm. Unlike many other inflammatory markers and bioassays, NLR are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm.

Introduction: Dabigatran is effective in preventing stroke and reduces the risk of intracerebral hemorrhage when comparing with warfarin in patients with atrial fibrillation. However, it is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is also less frequent in dabigatran users than warfarin users. Hypothesis: We hypothesized that intracerebral HT would occur less frequently following large cerebral infarction in rats pretreated with dabigatran than those with warfarin. We also compared the change of matrix metalloproteinases (MMPs), which play a key role in HT. Methods: We performed randomized, double-blind experiments comparing warfarin and dabigatran in rats. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or normal saline for 7 days, male wistar rats were subjected to permanent middle cerebral artery occlusion (MCAO) using a nylon thread. After 22 hours of MCAO, magnetic resonance imaging (MRI) was undergone (9.4T MR scanner, slice thickness = 0.5 mm). Operative procedures and assessment of MRI findings were performed by investigators who were blind to the group information. The presence of HT was assessed on gradient recalled-echo and infarction volume was measured on diffusion-weighted image. The MMP-2 and MMP-9 activities in brain tissues (obtained 24 hours after MCAO) were investigated using gelatin zymography. Results and Conclusions: Of the 33 rats with MRI, HT was observed less frequently in the dabigatran group than the warfarin group (placebo 14% [2/14], dabigatran 0% [0/10], and warfarin 100% [9/9], p < 0.001 [dabigatran vs warfarin]). The volume of infarction was similar between the groups (placebo 432.45 ± 78.35 mm3, dabigatran 432.42 ± 60.27 mm3, and warfarin 446.55 ± 73.55 mm3). MMP-2 and MMP-9 activities were not different between the groups. In the placebo, dabigatran, and warfarin groups, mean international normalized ratio were 1.38 ± 0.13, 1.73 ± 0.20, and 4.72 ± 2.92, respectively; mean activated partial thromboplastin times were 30.20 ± 7.49, 31.14 ± 7.02, and 55.06 ± 24.05, respectively. The risk of HT after large cerebral infarction was remarkably reduced in rats pretreated with dabigatran. MMPs did not seem to play a major role in reduced risk of HT.

Background and Purpose— The determination of stroke etiology is essential for planning treatment for stroke prevention. However, the etiology of stroke is undetermined in many patients. Methods— During a 10-year period, consecutive patients with acute ischemic stroke were enrolled. The stroke etiology was determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. Long-term mortality and causes of death were identified using death certificates. The standardized mortality ratio was calculated to compare the mortality in patients with stroke and that in the general Korean population. Results— In total, 3278 patients were enrolled and followed-up for a median of 3.4 years (interquartile range, 1.5–5.7). The stroke subtype was undetermined in 37% because of negative evaluation (21.2%), multiple causes (10.6%), and incomplete evaluation (4.8%). Poor functional outcome at 3 months (modified Rankin scale score >2) was more frequent in patients with an incomplete evaluation than in those with the other stroke subtypes (49.6% vs 24.5%; P Conclusions— Long-term mortality in patients with an incomplete evaluation was quite high. Etiologic work-up helps to better define the stroke subtype and determine the prognosis.

Background and Purpose— To date, no large study has been conducted to investigate baseline stroke awareness within a nationally representative sample of the Korean population. Methods— A total of 1000 residents were randomly sampled according to regional demographic characteristics and were interviewed in person by trained interviewers. Structured, open-ended and close-ended questions were asked to assess stroke awareness. Results— Among the respondents, 62% reported at least 1 stroke symptom and 56% reported at least 1 risk factor for stroke in open-ended questioning. Multivariate analysis revealed that completion of ≥12 years of education was independently associated with knowledge of symptoms (OR, 1.527; 95% CI, 1.146–2.034) and risk factors (OR, 1.577; 95% CI, 1.175–2.115). Approximately 31% and 33% of respondents, respectively, had some knowledge of thrombolysis and the proper action (call emergency medical services). Compared with subjects aged 20 to 39 years, those aged 40 to 59 years were more knowledgeable about thrombolysis (OR, 1.433; 95% CI, 1.045–1.964) and proper action (OR, 2.291; 95% CI, 1.646–3.188). The major source of information about stroke was television (59%), and the most reliable source was the respondents' physicians (55%). Among respondents 20 to 39 years of age, the Internet (37%) was the second greatest source of information. Conclusions— Stroke awareness was suboptimal in Korea, especially among younger citizens and those with less education. To improve their knowledge, physicians should exert greater efforts to educate the public about stroke using mass media and the Internet.

Background and Purpose— The CHADS 2 score is used for risk stratification of ischemic stroke in patients with nonvalvular atrial fibrillation and high CHADS 2 scores are associated with increased risk of stroke. Most components of the CHADS 2 score are also risk factors for atherosclerosis. Therefore, high CHADS 2 scores can be associated with concomitant cerebral atherosclerosis and subsequently atherothrombotic stroke. The aim of this study was to determine whether there are differences in the presence and burden of concomitant cerebral atherosclerosis according to CHADS 2 scores in patients with stroke with nonvalvular atrial fibrillation. Methods— We included 780 consecutive patients with nonvalvular atrial fibrillation who had undergone angiographic studies at index stroke between August 1994 and March 2010 in the present study. We investigated the relationships between the CHADS 2 score and the presence, severity, and pattern of cerebral atherosclerosis and stroke mechanism. Results— Of the 780 patients, concomitant arterial stenosis (≥50%) was found in 231 patients (29.6%). The number of arteries with atherosclerosis increased as the CHADS 2 score increased ( P P 2 score was an independent predictor of concomitant cerebral atherosclerosis (OR, 3.121; 95% CI, 1.770 to 5.504) and the presence of proximal stenosis at the symptomatic artery (OR, 3.043; 95% CI, 1.458 to 6.350). Conclusions— The CHADS 2 score can predict the presence of concomitant cerebral artery atherosclerosis. Increased risk of stroke in patients with high CHADS 2 scores may be partly explained by increased frequency and burden of cerebral atherosclerosis.

Background and Purpose— An effective stroke code system that can expedite rapid thrombolytic treatment requires effective notification/communication and an organized team approach. We developed a stroke code program based on the computerized physician order entry (CPOE) system and investigated whether implementation of this CPOE-based program is useful for reducing the time from arrival at emergency departments (ED) to evaluation steps and the initiation of thrombolytic treatment in various hospital settings. Methods— The CPOE-based program was implemented by 10 hospitals. Time intervals from arrival at the ED to blood tests, computed tomography scanning, and thrombolytic treatment during the 1-year period before and the 1-year period after the program implementation were compared. Results— Time intervals from ED arrival to evaluation steps were significantly reduced after implementation of the CPOE-based program. Times from ED arrival to CT scan, complete blood counts, and prothrombin time testing were reduced by 7.7 minutes, 5.6 minutes, and 26.8 minutes, respectively ( P P P Conclusions— The CPOE-based stroke code could be successfully implemented to reduce in-hospital time delay in thrombolytic therapy in various hospital settings. CPOE may be used as an efficient tool to facilitate in-hospital notification/communication and an organized team approach.

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.

Background and Purpose— We assessed the diagnostic performance of 2-phase 64-slice cardiac computed tomographic angiography (CCTA) for the detection of a cardiac source of embolism in stroke patients using transesophageal echocardiography (TEE) as the reference standard. Methods— We selected 137 patients who had experienced a recent episode of stroke and had undergone both 2-phase 64-slice CCTA and TEE within a period of 5 days. A potential cardiac source of embolism detected at both CCTA and TEE was recorded, and echocardiographic findings were categorized into high- and medium-risk sources based on the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Results— Of 137 patients, 100 abnormal findings in 91 patients were found on TEE, and 46 patients had no abnormal finding on TEE. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the 64-slice CCTA for detecting cardiac sources of embolism were 89% (95% CI, 82%, 95%), 100% (95% CI, 90%, 100%), 100% (95% CI, 95%, 100%), and 81% (95% CI, 70%, 92%), respectively. TEE detected a total of 47 high-risk sources of embolism, whereas CT detected 44 lesions. For medium-risk sources of cardiac embolic stroke, TEE detected a total of 53 abnormal findings, whereas CT detected 44 abnormal findings. Of 53 lesions, there were 8 false-negative results on CT (5 patent foramen ovale and 3 atrial septal aneurysm). Conclusions— Two-phase 64-slice CCTA is a noninvasive and useful modality for detecting high-risk cardiac sources of embolism in stroke 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.

To determine whether there is a relationship between aortic plaques and intracranial (IC) atherosclerosis.We reviewed 922 patients with stroke who had both transesophageal echocardiography and cerebral angiography. The plaques of these patients were classified as either complex aortic plaques (CAP), which protrudedor =4 mm or were present as mobile lesions in the proximal aorta, or simple aortic plaques (SAP), which were4 mm or present in the descending aorta. Cerebral artery atherosclerosis was classified as either an IC or extracranial (EC) atherosclerosis.Among the 922 patients, we found aortic plaques in 237 patients (26%). There were 111 (47%) patients of SAP, 74 (31%) patients with CAP, and 52 (22%) patients that had both SAP and CAP. Angiography showed IC or EC atherosclerosis in 511 patients (55%). The presence of aortic plaques was significantly associated with IC or EC atherosclerosis. The significance appeared to be due to the strong association between the presence of SAP and IC atherosclerosis (51% SAP vs 35% no plaques; odds ratio = 1.94, 95% CI: 1.17 to 3.21). In the multiple logistic regression analysis, SAP were independent predictors of IC atherosclerosisThe presence of simple aortic plaques may be a marker of advanced vascular disease. Detection of simple aortic plaques during transesophageal echocardiography may have clinical implications because patients with these plaques frequently had concomitant intracranial atherosclerosis, a risk factor for stroke.

Immediate reocclusion after successful thrombolysis was angiographically examined in 29 consecutive stroke patients. The reocclusion, which was associated with a high-grade residual stenosis of initially perfused arteries, occurred in four patients. IV abciximab successfully dissolved the thrombus in all four patients. Rapid thrombotic reocclusion after successful thrombolysis is commonly observed in patients after an acute stroke. Administration of abciximab may lead to reperfusion of the reoccluded artery.

We appreciate the interest of Dr Tsuda in our recently published article.1 In our study, we showed that higher levels of alkaline phosphatase (ALP) were associated with a poor functional outcome after acute stroke, but phosphate was not. Dr Tsuda wanted to know whether the levels of ALP/phosphate were correlated with changes in bone mineral density (BMD) and serum vitamin D levels. Dr Tsuda’s questions were based on evidence that (1) there was an association between BMD and stroke; (2) lower serum 25-hydroxyvitamin D levels were associated with carotid atherosclerosis and fatal …