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Purpose: Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi. Materials and Methods: After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition. Results: In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9−57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5−53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002). Conclusion: Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction. [ABSTRACT FROM AUTHOR]

Purpose: Interleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi. We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A. Materials and Methods: We performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors. Results: Time to occlusion values did not differ between the IL-17A group and the control group (94.6±86.9 sec vs. 121.0±84.4 sec, p=0.238). However, it was significantly shorter in the IL-17A group of female mice (74.6±57.2 sec vs. 130.0±76.2 sec, p=0.032). In rotational thromboelastometry, the IL-17A group exhibited increased maximum clot firmness (71.3±4.5 mm vs. 66.7±4.7 mm, p=0.038) and greater amplitude at 30 min (69.7±5.2 mm vs. 64.5±5.3 mm, p=0.040) than the control group. In Western blotting, the IL-17A group showed higher levels of coagulation factor XIII (2.2±1.5 vs. 1.0±0.9, p=0.008), monocyte chemoattractant protein-1 (1.6±0.6 vs. 1.0±0.4, p=0.023), and tissue factor (1.5±0.6 vs. 1.0±0.5, p=0.003). Conclusion: IL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model. Materials and Methods: We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy. Results: Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation. Conclusion: Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis. [ABSTRACT FROM AUTHOR]

Purpose: Infarct core can expand rapidly in acute stroke patients receiving intravenous tissue plasminogen activator (IV t-PA). We investigated changes in the extent of infarct core during IV t-PA treatment, and explored the associative factors of this infarct core expansion in patients with proximal artery occlusion. Materials and Methods: We included patients who were considered for sequential intra-arterial therapy (IAT) due to occlusion of intracranial proximal artery after IV t-PA. Patients who had a baseline Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) =6 and who underwent two consecutive CT scans before and shortly after IV t-PA infusion were enrolled. Patients were classified into no, moderate, and marked expansion groups based on decreases in ASPECTS (0-1, 2-3, and =4, respectively) on follow-up CT. Collateral status was graded using CT angiography. Results: Of the 104 patients, 16 (15.4%) patients showed moderate and 13 (12.5%) patients showed marked infarct core expansion on follow-up CT scans obtained at 71.1±19.1 min after baseline CT scan. Sixteen (15.4%) patients had an ASPECTS value <6 on the follow-up CT. None of the patients with marked expansion were independent at 3 months. Univariate analysis and ordinal logistic regression analysis demonstrated that the infarct core expansion was significantly associated with collateral status (p<0.001). Conclusion: Among patients who were considered for IAT after IV t-PA treatment, one out of every seven patients exhibited marked expansion of infarct core on follow-up CT before IAT. These patients tend to have poor collaterals and poor outcomes despite rescue IAT. [ABSTRACT FROM AUTHOR]

Purpose Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. Materials and Methods Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. Results Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p<0.001) and larger infarct in the superficial MCA territory (40.8±62.6 cm3 vs. 10.8±21.8 cm3,p<0.001) than the SM group. A poor functional outcome (mRS >2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246) and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than the SM group. In multivariate analyses, LSA involvement was an independent predictor of poor functional outcomes and stroke mortality. Conclusion LSA territory involvement is predictive of poor long-term outcomes in patients with superficial MCA territory infarction. [ABSTRACT FROM AUTHOR]

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

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

Purpose: The benefits of thrombolytic treatment are time-dependent. We developed a smartphone application that aids stroke patient self-screening and hospital selection, and may also decrease hospital arrival time. Materials and Methods: The application was developed for iPhone and Android smartphones. Map data for the application were adopted from the open map. For hospital registration, a web page (http://stroke119.org) was developed using PHP and MySQL. Results: The Stroke 119 application includes a stroke screening tool and real-time information on nearby hospitals that provide thrombolytic treatment. It also provides information on stroke symptoms, thrombolytic treatment, and prescribed actions when stroke is suspected. The stroke screening tool was adopted from the Cincinnati Prehospital Stroke Scale and is displayed in a cartoon format. If the user taps a cartoon image that represents abnormal findings, a pop-up window shows that the user may be having a stroke, informs the user what to do, and directs the user to call emergency services. Information on nearby hospitals is provided in map and list views, incorporating proximity to the user's location using a Global Positioning System (a built-in function of smartphones). Users can search for a hospital according to specialty and treatment levels. We also developed a web page for hospitals to register in the system. Neurology training hospitals and hospitals that provide acute stroke care in Korea were invited to register. Seventy-seven hospitals had completed registration. Conclusion: This application may be useful for reducing hospital arrival times for thrombolytic candidates. [ABSTRACT FROM AUTHOR]

Purpose: Cerebral ischemic lesions are frequently observed after carotid artery stenting (CAS), and anti-platelet agents are used to prevent stent thrombosis and peri-procedural complications. However, despite the premedication, cerebral ischemic lesions are observed, suggesting that they may rather be related to anti-platelet resistance. We, therefore, investigated the effects of anti-platelet resistance on the development of cerebral ischemic lesions after CAS. Materials and Methods: We retrospectively reviewed patients who received CAS and selected patients for whom brain MRI was performed within 24 hours after CAS and for whom anti-platelet resistance was checked. Anti-platelet resistance was examined by the Verify Now system. We analyzed the correlation between anti-platelet resistance and cerebral ischemic lesions detected on follow-up MRI. Results: Among 76 patients, 45 (59.2%) developed new ischemic lesions after CAS. Twelve (15.8%) patients showed aspirin resistance and 50 (65.8%) patients showed clopidogrel resistance. Patients with a new ischemic lesion demonstrated a significantly greater frequency of clopidogrel resistance than those who had no new ischemic lesion (82.2% versus 41.9%, p=0.001). The frequency of aspirin resistance was not significantly different between the groups of patients with and without new ischemic lesions (20.0% versus 9.7%, p=0.340). In multivariate analysis, clopidogrel resistance was a significant risk factor for post-procedural cerebral ischemia. Conclusion: Anti-platelet resistance can be used to predict new ischemic lesions after CAS. Anti-platelet resistance should be evaluated in all patients prior to CAS to prevent ischemic complications related to CAS. [ABSTRACT FROM AUTHOR]

Purpose: Continuous cardiac monitoring in a stroke unit (SU) may improve detection of atrial fibrillation (AF), and SU care may improve the rate of anticoagulation by better adherence to a standardized treatment protocol in patients with AF. We investigated the effects of the SU on the detection of AF and the rate of warfarin therapy in patients with AF. Materials and Methods: Acute stroke patients who had been admitted before or after the opening of the SU were included in our study. SU patients were monitored continuously with electrocardiography. Rates of AF and warfarin therapy were compared between patients admitted to the SU (SU group) and those admitted to the general ward (GW) prior to the opening of the SU (GW group). Results: Total 951 patients had been admitted to the GW prior to the opening of the SU (from January 2000 to November 2002), and 2349 patients to the SU (from January 2003 to December 2008). AF was found in 149 patients (15.7%) in the GW group and in 487 (20.7%) in the SU group. Most of AF detected during ad- mission was paroxysmal AF (84.8%). The frequency of newly detected AF was higher in the SU group than the GW group (2.5% vs. 0.7%, p=0.001). The rate of anticoagulation consideration was also higher in the SU group. Conclusion: SU care improved the detection of AF and the rate of anticoagulation consideration in acute stroke patients. Our findings support the benefits of continuous cardiac monitoring in the SU for stroke patients. [ABSTRACT FROM AUTHOR]

Purpose: Koreans have been undergoing rapid lifestyle changes that may have an effect on patterns of cerebral artery atherosclerosis. This study was aimed at determining the frequency and distribution of atherosclerosis in the cerebral arteries and associated temporal changes over the past eight-year period among Korean stroke patients. Materials and Methods: By using stroke registry data registered between April 1999 and March 2007, we investigated the presence, severity, and location of cerebral artery atherosclerosis as determined by angiographic findings. Their annual patterns and association with vascular risk factors were investigated. Results: Of 1,955 patients, 1,517 patients (77.6%) demonstrated atherosclerosis in one or more arteries. A significantly increasing trend of atherosclerosis was observed during the past eight years, which was ascribed to an increase of combined extracranial (EC) and intracranial (IC) atherosclerosis. The number of atherosclerotic arteries increased as the number of risk factors increased. In the multivariate analysis, the year and vascular risk factors were independent predictors of the presence of atherosclerosis. Conclusion: We found that the atherosclerotic burden has been increasing for the past eight years in Korean stroke patients, particularly the combined EC and IC subtype. Lifestyle changes and increase in vascular risk factors may be contributing factors. [ABSTRACT FROM AUTHOR]