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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.

Introduction Cardioembolic (CE) risks is usually considered as the main mechanism of ischemic stroke in non-valvular atrial fibrillation (NVAF) patients. However, a substantial number of ischemic strokes in NVAF patients are related to non-CE mechanisms. The aim of this study was to investigate the non-CE risk factors in ischemic stroke patients had NVAF. Methods We included 401 patients (65.6% male, 68.6 ± 9.6 years old) who had been hospitalized due to ischemic stroke and had a known or newly diagnosed NVAF. The CE (intracardiac thrombus, dense spontaneous echo contrast, or low left atrial appendage flow velocity) and non-CE (complex aortic plaque, significant carotid stenosis, or intracranial arterial stenosis) risk factors were investigated at the time of the index stroke. Results The number of CE and non-CE risk factors increased with increasing CHA2DS2-VASc scores (p for trends < 0.001). The presence of CE risk factors was independently associated with persistent atrial fibrillation (p < 0.001), body mass index (p = 0.003), heart failure (p = 0.003), and left atrial volume index (p < 0.001). In contrast, the presence of non-CE risk factors was independently associated with age (p < 0.001), hypertension (p = 0.049), diabetes (p = 0.030), and coronary artery calcium score (CACS; p < 0.001). CACS had the added value in predicting non-CE risk factors of ischemic stroke regardless of the CHA2DS2-VASc risk category (p < 0.001). Conclusion Non-CE risk factors in ischemic stroke patients with NVAF are associated with high CHA2DS2-VASc score and CACS. Atherosclerotic non-CE risk factors should be considered as potential mechanisms of stroke even in patients with AF-associated ischemic stroke.

BACKGROUND AND PURPOSE Atherosclerosis and osteoporosis are two major public health problems. It is still uncertain whether an abnormal carotid ultrasonography, either increased intima-media thickness (IMT) or plaque thickness, is associated with osteoporosis in acute ischemic stroke patients. To investigate the possible relationships between osteoporosis and carotid atherosclerosis, we evaluated the correlation between carotid IMT/plaque thickness and bone mineral density (BMD) in acute ischemic stroke patients. METHODS Patients having their first ischemic stroke within seven days were screened for the study. The IMT was scanned approximately 10 mm proximal to the beginning of the dilatation of the carotid bulb. The plaques were measured in both common and internal carotid arteries. The BMD was measured at total hip and lumbar spine in the anterior-posterior projection, using dual-energy x-ray absorptiometry. RESULTS A total of 155 patients were enrolled in the study and the mean age was 68.3 ± 10.34 years. Multiple linear regression analysis reveals that age (P < .001), smoking (P = .016), and osteoporosis (P = .001) were significantly associated with increased carotid IMT/plaque thickness. Old age, current smoking, and osteoporosis were significantly related to increased IMT/plaque thickness in acute ischemic stroke patients. In women, IMT/plaque thickness was significantly related to age (P = .01) and osteoporosis (P = .025). In men, though there was no significant relationship, a trend toward old age and having osteoporosis was observed in increased IMT/plaque thickness (P = .051, P = .086). CONCLUSIONS This study showed that carotid IMT/plaque thickness was inversely related to the BMD in female but not in male patients with acute ischemic stroke.

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.

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

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

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

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

Background The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH. Methods We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6–9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3. Results Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12–2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15–2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association. Conclusion The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

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

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background: The pronator drift test (PDT), a neurological examination, is widely used in clinics to measure motor weakness of stroke patients. Objective: The aim of this study was to develop a PDT tool with machine learning classifiers to detect stroke symptoms based on quantification of proximal arm weakness using inertial sensors and signal processing. Methods: We extracted features of drift and pronation from accelerometer signals of wearable devices on the inner wrists of 16 stroke patients and 10 healthy controls. Signal processing and feature selection approach were applied to discriminate PDT features used to classify stroke patients. A series of machine learning techniques, namely support vector machine (SVM), radial basis function network (RBFN), and random forest (RF), were implemented to discriminate stroke patients from controls with leave-one-out cross-validation. Results: Signal processing by the PDT tool extracted a total of 12 PDT features from sensors. Feature selection abstracted the major attributes from the 12 PDT features to elucidate the dominant characteristics of proximal weakness of stroke patients using machine learning classification. Our proposed PDT classifiers had an area under the receiver operating characteristic curve (AUC) of .806 (SVM), .769 (RBFN), and .900 (RF) without feature selection, and feature selection improves the AUCs to .913 (SVM), .956 (RBFN), and .975 (RF), representing an average performance enhancement of 15.3%. Conclusions: Sensors and machine learning methods can reliably detect stroke signs and quantify proximal arm weakness. Our proposed solution will facilitate pervasive monitoring of stroke patients. [J Med Internet Res 2017;19(4):e120]

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.

Background and Purpose Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process. Methods After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared. Results The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]. Conclusions PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

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 (

Aim First, we objectively quantified the handwriting size of Parkinson's disease (PD) patients. Second, we investigated the efficacy of the external visual cueing on Korean handwriting in PD. Methods We recruited 57 patients diagnosed with PD and 37 community-dwelling normal older adults. All participants were asked to write a target word on a blank sheet of paper. For investigating the external visual cueing, 24 PD patients wrote the target word in square grids. The size of each syllable of the word was measured using a public domain software program. In order to measure the area of a syllable, the upper, lower, left and right margins of the syllable were outlined with a rectangle. The area of selection in square pixels or in calibrated square units was used to spatially calibrate the image automatically. Results The PD group showed significantly smaller writing size than the normal group in all syllables of the free writing. The writing size in the square grids of the PD patients was bigger than their free writing. Conclusion The present study is noteworthy, because it is the first attempt to use a software program to objectively quantify parkinsonian handwriting size. This measuring system would help clinicians monitor handwriting size throughout the disease course. From the perspective of rehabilitation, language-appropriate external visual cues might be useful in daily communication (i.e. handwriting) activities in Korean patients with PD. Geriatr Gerontol Int 2015; 15: 647–651.

Background: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. Methods: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. Results: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm3 (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm3). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤4.9 cm3 (p = 0.002). Significant treatment effects were observed in the cilostazol group. Conclusions: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

BackgroundEtiology is unknown in approximately one-quarter of stroke patients after evaluation, which is termed cryptogenic stroke (CS). The prognosis of CS patients is largely undetermined. We created a novel index from transcranial Doppler parameters including mean flow velocity (MV) and pulsatility index (PI) and investigated whether the calculation of asymmetry in the novel parameter can predict functional outcomes in CS patients.MethodsWe made the middle cerebral artery (MCA) index (%) as a novel parameter, which was calculated as 100 X (MCA MV + MCA PI X 10) / (MCA MV-MCA PI X 10). The MCA asymmetry index (%) was also calculated as 100 X (|Rt MCA index-Lt MCA index|) / (Rt MCA index + Lt MCA index) / 2. Poor functional outcomes were defined as modified Rankin Scale score (mRS) ≥3 at 3 months after stroke onset.ResultsA total of 377 CS patients were included. Among them, 52 (13.8%) patients had a poor outcome. The overall MCA asymmetry index was two-fold higher in CS patients with a poor outcome (10.26%) compared to those with a good outcome (5.41%, p = 0.002). In multivariable analysis, the overall MCA asymmetry index (OR, 1.054, 95% CI, 1.013-1.096, p = 0.009) and the cutoff value of the overall MCA asymmetry index >9 were associated with poor outcomes at 3 months (OR, 3.737, 95% CI, 1.530-9.128, p = 0.004).ConclusionWe demonstrated that the novel asymmetric MCA index can predict short-term functional outcomes in CS patients.

Background and purpose Increased arterial stiffness causes vessel damage in the end-organs. Therefore small vessels in the brain may be susceptible to increased arterial stiffness. Cerebral microbleeds (CMBs) are topographically or pathophysiologically categorized as deep or infratentorial type and strictly lobar type. Whether the presence and location of CMBs are associated with brachial-ankle pulse wave velocity (baPWV) which represents a measure of arterial stiffness was investigated. Methods Between June 2006 and January 2012, 1137 consecutive patients diagnosed with non-cardioembolic acute ischaemic stroke and who underwent baPWV measurement and brain gradient-echo imaging were enrolled. CMBs were classified as deep or infratentorial or strictly lobar according to their location. Severity of leukoaraiosis was determined using the Fazekas scoring system. Results CMBs were found in 30.7% of the included patients. These patients were older than those without CMBs. Mean baPWV was higher in patients with CMBs than in those without (20 ± 5 m/s vs. 19 ± 5 m/s; P = 0.001). When comparing baPWV according to the location of the CMB, it was higher in the deep or infratentorial CMB group than in the strictly lobar CMB group (22 ± 5 m/s vs. 20 ± 5 m/s; P = 0.001). In univariate and multivariate multinomial logistic regression analyses, baPWV was found to be independently associated with deep or infratentorial CMBs. Conclusions Arterial stiffness was independently associated with deep or infratentorial CMBs but not lobar CMBs. These findings suggest a pathophysiological association between arterial stiffness and CMBs in the deep or infratentorial region.

a Neurology, b Biostatistics, and Background and Purpose Widespread use of thrombolytic treatments, along with improved chances of survival after an initial ischemic stroke, increases the possibility of repeated thrombolysis. There are few reports, however, regarding repeated thrombolysis in patients who have suffered acute ischemic stroke. We explored the number and outcome of patients with repeated thrombolytic therapy in the era of multimodal thrombolytic treatments. Methods We investigated patients with acute ischemic stroke who had received thrombo- lytic treatments for a period of 10 years. Number of thrombolysis was determined in each patient. Recanalization was defined as Thrombolysis in Cerebral Infarction grading ≥ 2a. Symptomatic hemorrhagic transformation was defined as any increase in the National Insti- tutes of Health Stroke Scale score that could be attributed to intracerebral hemorrhage. A good outcome was defined as a modified Rankin scale score ≤ 2. Results Of the 437 patients who received thrombolytic treatments, only 7 underwent re- peated thrombolysis (1.6%). The median age at the time of repeated thrombolytic therapy was 71 years old; 4 of the patients were female. All patients had 1 or more potential sources of cardiac embolism. Recanalization was achieved in all patients, in both the first and the second thrombolysis. No symptomatic intracranial hemorrhage occurred after repeated thrombolytic treatments. Five patients (71.4%) showed good outcomes at 3 months. Conclusions Repeated thrombolysis for recurrent acute ischemic stroke appears to be safe and feasible. Among patients who experience recurrent acute ischemic stroke, thrombolytic therapy could be considered even if the patient has had previous thrombolytic treatments.

Object Carotid artery stenting (CAS) can be an alternative option for carotid endarterectomy in the prevention of ischemic stroke caused by carotid artery stenosis. The purpose of this study was to evaluate the influence of stent design on the incidence of procedural and postprocedural embolism associated with CAS treatment. Methods Ninety-six symptomatic and asymptomatic patients, consisting of 79 males and 17 females, with moderate to severe carotid artery stenosis and a mean age of 69.0 years were treated with CAS. The stent type (48 closed-cell and 48 open-cell stents) was randomly allocated before the procedure. Imaging, procedural, and clinical outcomes were assessed and compared. The symptomatic subgroup (76 patients) was also analyzed to determine the influence of stent design on outcome. Results New lesions on postprocedural diffusion-weighted imaging (DWI) were significantly more frequent in the open-cell than in the closed-cell stent group (24 vs 12, respectively; p = 0.020). The 30-day clinical outcome was not different between the 2 stent groups. In the symptomatic patient group, stent design (p = 0.017, OR 4.173) and recent smoking history (p = 0.036, OR 4.755) were strong risk factors for new lesions on postprocedural DWI. Conclusions Stent design may have an influence on the risk of new embolism, and selecting the appropriate stent may improve outcome.

Background and purpose CHADS2 and CHA2DS2-VASc scores are measurement tools that stratify thromboembolic risk in patients with non-valvular atrial fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and ischaemic heart disease. Patients with higher CHADS2 and CHA2DS2-VASc scores are more likely to have had an akinetic/hypokinetic left ventricular segment or a recent myocardial infarction, all of which are associated with coronary artery disease (CAD). Most of the CHADS2 score components are also risk factors for atherosclerosis. Thus, CHADS2 and CHA2DS2-VASc scores may be predictive of CAD. Methods In all, 1733 consecutive patients with acute ischaemic stroke who underwent multi-slice computed tomography coronary angiography were enrolled. The association of CHADS2 and CHA2DS2-VASc scores with the presence and severity of CAD was investigated. Results Of the 1733 patients, 1220 patients (70.4%) had any degree of CAD and 576 (33.3%) had significant CAD (≥50% stenosis in at least one coronary artery). As the CHADS2 and CHA2DS2-VASc scores increased, the presence of CAD also increased (P

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 Multiple potential causes of stroke may coexist in ischemic stroke patients, which may affect long-term outcome. Aim We investigated whether there are differences in long-term mortality among stroke patients with coexisting potential causes. Methods We evaluated the long-term all-cause mortality and stroke or cardiovascular mortality of ischemic stroke patients with multiple potential stroke mechanisms, large artery atherosclerosis, cardioembolism, small vessel occlusion, and negative evaluation admitted to a single center between January 1996 and December 2008. Mortality data were obtained from a National Death Certificate system. Results Total 3533 patients were included in this study: 286 multiple potential mechanisms (138 large artery atherosclerosis + cardioembolism, 105 small vessel occlusion + large artery atherosclerosis, 43 small vessel occlusion + cardioembolism), 1045 large artery atherosclerosis, 701 cardioembolism, 606 small vessel occlusion, and 895 negative evaluation. During a mean follow-up of 3·9 years, as referenced to small vessel occlusion mortality rate, the adjusted mortality hazard ratio was 4·387 (95% confidence interval 3·157–6·096) for large artery atherosclerosis + cardioembolism group, 3·903 (95% confidence interval 3·032–5·024) for cardioembolism group, and 2·121 (95% confidence interval 1·655–2·717) for large artery atherosclerosis. The risk of long-term ischemic stroke mortality or cardiovascular mortality also showed comparable findings: highest in the large artery atherosclerosis + cardioembolism, followed by cardioembolism, and large artery atherosclerosis groups. However, the outcome of small vessel occlusion + large artery atherosclerosis or small vessel occlusion + cardioembolism group was not significantly different from that of small vessel occlusion. Conclusions Coexisting potential causes of ischemic stroke impact on long-term mortality. Identification of coexisting potential causes may help to predict stroke outcomes and to guide planning secondary prevention strategies.

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

SummaryVascular leakage due to compromised integrity of the endothelial barrier is closely associated with brain damage in several neurological disorders, including ischaemic stroke. Saxatilin, a snake venom disintegrin containing the Arg-Gly-Asp (RGD) motif, exerts thrombolytic and antiplatelet effects by interacting with multiple integrins on platelets. Integrin signalling is indispensable for regulation of endothelial permeability. Saxatilin may play a role in vascular leakage after ischaemia because it has high affinity for endothelial integrins. Here, we determined whether Fc-saxatilin, an Fc-fusion protein of saxatilin, could prevent vascular leakage under hypoxic or ischaemic conditions. In mouse brain microvascular endothelial cells, hypoxia increased the permeability to FITC-dextran, and this effect was attenuated by Fc-saxatilin treatment. Fc-saxatilin also blocked vascular leakage of Evans Blue in the ischaemic brain induced by middle cerebral artery occlusion in mice. Furthermore, the expression of occludin, a tight junction protein, was reduced by hypoxia in endothelial cells. This downregulation of occludin was attenuated by Fc-saxatilin treatment. We also determined the activity of matrix metalloproteinases (MMPs) 2 and 9 because they are implicated in the degradation of occludin and of the microvascular basal lamina. Hypoxia increased MMP-9 activity, and this increase was attenuated by Fc-saxatilin treatment. Fc-saxatilin specifically bound to integrin αvβ3 of the endothelial cells and inhibited hypoxia-induced activation of FAK, a downstream signalling molecule in integrin-dependent signal transduction. Taken together, these results provide new insights into the mechanism via which Fc-saxatilin, as an integrin antagonist, prevents vascular leakage under ischemic conditions by regulating occludin expression in endothelial tight junctions.Supplementary Material to this article is available online at www.thrombosis-online.com.

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.

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.

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.

Purpose: Smoking cessation is strongly recommended for every smoker after ischemic stroke, but many patients fail to quit smoking. An improved smoking cessation rate has been reported with intensive behavioral therapy during hospitalization and supportive contact after discharge. The aim of this study was to demonstrate the usefulness of the timely interventions for smoking cessation in men with acute ischemic stroke. Methods: Patients who participated in the timely interventions strategy (TI group) were compared with those who received conventional counseling (CC group). In the TI group, a certified nurse provided comprehensive education during admission and additional counseling after discharge. Outcome was measured by point smoking success rate and sustained smoking cessation rate for 12 months. Results: Participants, 157 men (86 of the TI group and 71 of the CC group), were enrolled. Mean age was 58.25 ± 11.23 years and mean initial National Institutes of Health Stroke Scale score was 4.68 ± 5.46. The TI group showed a higher point smoking success rate compared with the CC group (p = .003). Multiple logistic regression analysis showed that the TI group was 2.96-fold (95% CI, 1.43~6.13) more likely to sustain smoking cessation for 12 months than the CC group. Conclusion: Findings indicate that multiple interventions initiated during hospital stay and regular follow-up after discharge are more effective than conventional smoking cessation counseling in men with acute ischemic stroke.

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: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). Results: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. Conclusions: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

BACKGROUND AND PURPOSE Cerebral microbleeds (CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation (OA)-related intracranial haemorrhage (ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS(2) scores or CHA(2) DS(2) -VASc scores in non-valvular atrial fibrillation (NVAF) patients. METHODS We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging (MRI) with gradient-recalled echo (GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS(2) scores and CHA(2) DS(2) -VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up. RESULTS The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS(2) scores or CHA(2) DS(2) -VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS(2) scores or CHA(2) DS(2) -VASc scores were not. CONCLUSIONS Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs.

Osteoprotegerin (OPG) is known to regulate processes involved in vascular injury and inflammation. We investigated the relationship between plasma OPG levels and stroke subtype, stroke severity at admission and functional outcome at 3 months in 172 patients with acute ischaemic stroke. Patients with large artery atherosclerosis and those with multiple causes had higher plasma OPG levels than patients with lacune. Increased plasma OPG levels were independently associated with more severe stroke and poor functional outcome. These results suggest pleiotropic roles of OPG in mediating atherosclerosis and ischaemic brain injury. OPG is a potential biomarker for predicting neurologic outcome in stroke.

The ankle-brachial blood pressure index (ABI) is an established clinical test for assessment of peripheral arterial disease and an indicator of generalized atherosclerosis. We investigated whether low ABI is associated with long-term functional outcome in patients with acute cerebral infarction.We included 775 patients with acute cerebral infarction who were admitted within 7 days from stroke onset and had completed an ABI measurement during admission. Poor functional outcome was defined as a modified Rankin Scale of more than 2 at three months from stroke onset. The association between low ABI and poor functional outcome was analyzed using logistic regression analysis.A low ABI (0.9) was present in 10.1% of patients. At three months from stroke onset, 16.9% of patients showed poor functional outcome (mRS2). After adjusting for conventional cardiovascular risk factors and the presence of cerebral atherosclerosis, a low ABI was independently associated with poor functional outcome (odds ratio 2.523, 95% CI 1.330-4.785, p = 0.005).The presence of a low ABI was associated with an increased risk of poor functional outcome in patients with acute cerebral infarction. Screening for low ABI among stroke patients may be necessary to identify individuals at increased risk of poor functional outcome. Proper and individualized treatment for patients with a low ABI may improve long-term functional outcome following acute cerebral infarction.

Previous studies have evaluated intracranial internal carotid artery calcifications (ICACs) qualitatively using different visual grading scales, which could lead to inconsistent results. The purpose of this study was to evaluate the feasibility of ICAC volume measurement and to correlate the volume with visual grading scales. We included 49 patients (>50 years) who underwent unenhanced cranial CT. Two observers evaluated four visual grading scales and measured ICAC volumes semi-automatically, and interobserver agreements were assessed. Differences in ICAC volume between visual grades of each scale were tested. The relationship between the visual grading and volume was assessed. Interobserver agreements ranged from 0.841 to 0.901 for visual grading and 0.997 for volume measurement. Mean volumes were not significantly different between the visual grades (P > 0.05) except when comparing grade 4 with the other grades. The grades of each visual grading correlated well with ICAC volumes (Spearman's ρ = 0.849–0.881, P

Background: A low ankle–brachial index (ABI) is predictive of peripheral arterial disease (PAD). For unknown reasons, patients with PAD demonstrate higher vascular mortality during follow-up than do those without. Initial stroke severity is a strong predictor of long-term outcome and may be different between patients with and without PAD. Thus, we investigated whether a low ABI was associated with severe stroke presentation. Methods: We enrolled 1147 first-ever ischaemic stroke patients who underwent ABI measurements during hospitalization. Patients were categorized into the normal (≥ 0.90) or the abnormal (

SummaryThe degree of thrombus resolution directly indicates the effectiveness of a thrombolytic drug. We investigated the degree of thrombus resolution and factors associated with thrombus resolution after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) using thin-section noncontrast computed tomography (NCT). Thin-section NCTs were performed before and immediately after IV rt-PA infusion in acute stroke patients. The thrombus volume and Hounsfield unit were measured using three-dimensional imaging software. Immediate recanalisation was assessed immediately after IV rt-PA infusion using CT angiography. During a three-year study period, 130 patients were prospectively enrolled. On baseline thin-section NCT, no thrombi were found in 30 patients (23%). Among the 100 patients with confirmed thrombus, the median volume decreased by 20% on the follow-up NCT. The thrombus was completely resolved in 8%. Of note, an increase in thrombus volume was observed in 20 patients. Independent predictors of thrombus resolution were total rt-PA dose, thrombus location in the M2 segment of the middle cerebral artery, and time from baseline to follow-up NCT. Thrombus resolution increased by 9% per each 10-mg increase in rt-PA (p = 0.045). Immediate complete recanalisation was achieved in 12% of patients. Total dose of rt-PA was independently associated with complete recanalisation [odds ratio [OR] 4.52, 95% confidence interval [CI] 1.345–15.184) and good functional outcome at three months (modified Rankin scale score