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Goals: This study aimed to determine whether the plasma levels of free fatty acid (FFA) are associated with ischemic lesion characteristics in nonarterial-origin embolic stroke., Materials and Methods: We prospectively recruited 254 patients with acute cerebral infarction caused by cardioembolic stroke (CES, n=121) or with embolic stroke of undetermined source (ESUS, n=133). Plasma levels of FFA were measured during the acute stage (median of 2days after stroke onset). Acute ischemic lesions on diffusion-weighted imaging were measured in terms of size, composition, and pattern. Transthoracic echocardiography parameters were evaluated in all patients., Findings: Plasma levels of FAA were not different in CES and ESUS patients (mEq/L, 0.78±0.52 vs. 0.67±0.61, P=0.120). Echocardiography parameters, including left atrium volume index and E/e', were higher, and the ischemic lesion volume was larger in patients with CES than in those with ESUS. The ischemic lesion volume and the proportion of patients with mixed (small and large) and large cortical lesions increased with FFA quartile in both CES and ESUS groups. In a multivariable analysis, FFA level (coefficient, 5.249; standard error, 3.447; P=0.001), atrial fibrillation (coefficient, 7.673; standard error, 1.855; P<0.001), and fasting glucose (coefficient, 0.104; standard error, 0.023; P<0.001) were associated with ischemic lesion volume in nonarterial-origin embolic stroke., Conclusion: Elevated plasma FFA levels are associated with larger ischemic lesion volumes and a higher prevalence of large cortical infarcts in patients with nonarterial-origin embolic stroke regardless of the presence of a high-risk cardioembolic source., (Copyright © 2017. Published by Elsevier B.V.)

Background and Purpose: Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome., Methods: This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients., Results: ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01-1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05-1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88-2.74) and 1.72 (1.17-2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71-2.30) and 1.95 (1.27-2.99), respectively., Conclusions: ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome., (© 2017 American Heart Association, Inc.)

Background and Purpose: Although high-resolution magnetic resonance imaging (HR-MRI) is considered optimal for the diagnosis of intracranial vertebral artery dissection (IVAD), it is not readily available for all patients with suspected IVAD. The purpose of our study was to determine the factor related to IVAD lesions that are not definitively diagnosed by conventional MRI., Methods: This study included IVAD lesions that were evaluated with both of 3 T conventional MRI and HR-MRI. Definitive dissection was defined as the presence of one or more pathognomonic radiological findings including crescentic intramural hematoma, intimal flap, and double lumen. A total of 30 IVAD lesions definitively diagnosed by HR-MRI were included and grouped into a conventional MRI true-positive group (n = 17) or false-negative group (n = 13) based on the presence of definitive findings on conventional MRI., Results: Clinical characteristics did not differ between the two groups. The absence of vertebral artery aneurysmal dilatation was more common in the conventional MRI false-negative group (84.6% vs. 35.3%; P = .010). Ipsilesional vertebral hypoplasia was observed more frequently in the conventional MRI false-negative IVAD group (53.8% vs. 17.6%; P = .056). In logistic regression, absence of vertebral artery aneurysmal dilatation was independently associated with conventional MRI false-negative IVAD (OR, 16.37; 95% CI, 1.39-192.30; P = .026). Ipsilesional vertebral artery hypoplasia showed only a trend as a predictor of conventional MRI false-negative IVAD (OR, 7.24; 95% CI, .73-71.51; P = 0.090)., Conclusions: HR-MRI may be useful for diagnosing IVAD without aneurysmal dilatation or with ipsilesional vertebral hypoplasia., (Copyright © 2016 by the American Society of Neuroimaging.)

Objective: We sought to identify the clinical outcome and predictors for ischemic stroke recurrence in adults with symptomatic moyamoya disease (MMD)., Methods: We analyzed 104 adult MMD patients with ischemic stroke or TIA registered at our institution. All patients underwent digital subtraction angiography and single photon emission computed tomography to measure disease severity and cerebral vascular reserve (CVR). A Cox regression model was used to identify predictors of recurrent ischemic stroke., Results: Fifty-nine patients were non-surgically treated and 45 patients were surgically treated. In the non-surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 1.6% in the first year and 11.8% in the 5th year. Hypertension (hazard ratio [HR]=0.07, 95% confidence interval [CI] 0.01-0.99), diabetes (HR=35.16, 95% CI 2.61-474.16), presence of steno-occlusive lesion in posterior cerebral arteries (HR=17.53, 95% CI 2.02-152.43), and extended or global decreased CVR (HR=13.62, 95% CI 1.55-119.84) were independent predictors of recurrence. In the surgical group, the Kaplan-Meier estimate of ischemic stroke recurrence was 24.4% in the first year and 24.4% in the 5th year. Half of the recurred patients experienced recurrent ischemic strokes postoperatively. Diabetes was the only predictor of recurrent ischemic stroke (HR=6.17, 95% CI 1.31-29.14)., Conclusions: In non-surgically treated MMD, PCA stenosis and CVR were identified as predictors of ischemic stroke recurrence. Diabetes was an independent predictor of recurrent ischemic stroke in both non-surgical and surgically treated MMD groups., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Currently, intensive lipid lowering is recommended in patients with atherosclerotic ischemic stroke or transient ischemic attack. However, the role of statin in cardioembolic stroke is unclear. We investigated the association of statin with pretreatment collateral status in cardioembolic stroke., Methods: A collaborative study from two stroke centers in distinct geographic regions included consecutive patients with acute middle cerebral artery (MCA) infarction due to atrial fibrillation (AF) who underwent cerebral angiography. The relationship between pretreatment collateral grade and the use/dose of statin at stroke onset was assessed. The angiographic collateral grade was evaluated according to the ASITN/SIR Collateral Flow Grading System., Results: Ninety-eight patients (76 statin-naïve, 22 statin users) were included. Compared with statin-naïve patients, statin users were older and more frequently had hypertension, hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3-4) were more frequently observed in statin users (11 patients, 50%) than in statin-naïve patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg equivalent or higher doses of statin was associated with excellent collaterals (p for trend = 0.025). In multiple regression analysis, prestroke statin use was independently associated with excellent collaterals (odds ratio, 7.841; 95% confidence interval, CI, 1.96-31.363; p = 0.004)., Conclusions: Premorbid use of statin in AF patients is associated with excellent collateral flow. Although most statin trials excluded patients with cardioembolic stroke, our data suggests the possibility that statin may be beneficial in AF-related stroke

Background and Purpose: The clinical significance of microembolic signals (MES) in the posterior circulation remains unclear. The aim of this study was to investigate the sources and consequences of MES in acute posterior circulation cerebral ischemia., Methods: We evaluated a total of 140 consecutive patients (93 males, mean age 62.9 years) who had acute posterior circulation cerebral ischemia. The MES monitoring was conducted at the basilar artery through the suboccipital window for a 30-minute period., Results: MES were detected in 18 (12.9%) of the 140 patients. Clinical characteristics and laboratory data did not differ between the MES-positive and MES-negative groups. Intracranial vertebrobasilar artery (VBA) stenosis was independently associated with the presence of MES (odds ratio, 9.85; 95% confidence interval, 1.22-79.48; P=0.032), whereas the patients with vertebral artery stenosis that was limited to the extracranial portion did not show an association. Microembolic signals occurred significantly more frequently in patients with severe degree of VBA stenosis compared to those with nonsignificant stenosis (odds ratio, 9.88; 95% confidence interval, 1.23-79.07; P=0.031). In a subgroup analysis of the 79 patients who had lesions on diffusion-weighted images and relevant VBA stenosis, the MES-positive group showed more frequent embolic infarction (P=0.010) and multiple lesion patterns (P=0.007) than single perforating infarctions., Conclusions: In acute posterior circulation cerebral ischemia, intracranial and severe VBA stenosis is associated with MES and may be its root causes. The presence of MES in VBA stenosis suggests that multiple and embolic type infarctions are the mechanisms of stroke.

Aims: This study was conducted to evaluate the clinical and MRI profiles in acute cancer strokes, and to demonstrate our experience with thrombolytic therapy in cancer stroke patients., Methods: We prospectively studied active cancer patients with acute ischemic stroke who underwent MRI within 48 h of the onset of symptoms. Patients were grouped based on the presence of conventional stroke mechanisms (CSM). Clinical characteristics and MRI profiles were evaluated., Results: A total of 70 patients were finally included in this study. Patients without CSM were more frequently presented with encephalopathy than those with CSM (29.4 vs. 2.8%, p = 0.002). The diffusion-perfusion mismatch pattern was more prevalent in patients with CSM (21 patients, 58.3%) than in patients without CSM (8 patients, 23.5%). Patients who had a higher tertiles of D-dimer level were significantly less likely to have the diffusion-perfusion mismatch pattern (p = 0.015). Among patients who presented within 6 h of the onset of stroke, revascularization therapy was performed in 4 of 16 (25%) patients with CSM, but none of the patients without CSM., Conclusion: Based on the stroke mechanisms, the optimal strategy of thrombolytic therapy should be considered differently in cancer patients with acute ischemic stroke., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: Collaterals sustain the ischemic penumbra to limit growth of the infarct core before revascularization, yet the impact of baseline collateral flow on hemorrhagic transformation (HT) after endovascular therapy remains unknown., Methods: A collaborative study from 2 stroke centers in distinct geographic regions included 222 consecutive patients who received endovascular therapy for acute cerebral ischemia. The influence of collaterals on HT was analyzed in distinct case scenarios relative to baseline collateral grade at angiography (0 to 1 versus 2 to 4) and recanalization (Thrombolysis in Myocardial Ischemia scale, 0 to 1 versus 2 to 3): good collaterals and successful recanalization (n=98), poor collaterals with successful recanalization (n=43), good collaterals and no recanalization(n=46), and poor collaterals and no recanalization (n=35)., Results: HT after endovascular therapy occurred in 103 (46.4%) patients; 42 (18.9%) were symptomatic. HT was more frequently observed in patients with poor collaterals and recanalization than in other groups (P=0.048). When revascularization was achieved, patients with poorer collaterals were more likely to have symptomatic worsening with HT (r=-0.181, P=0.032). Multiple logistic regression analysis identified aggressive treatment (OR, 2.558 for Merci clot retrieval; 95% CI, 1.153 to 5.678; OR, 3.618 for combined fibrinolytics and mechanical therapy; 95% CI, 1.551 to 8.437; and OR, 2.085 for intravenous thrombolysis before endovascular therapy; 95% CI, 1.096 to 3.969), poor collaterals and recanalization (OR, 2.666; 95% CI, 1.163 to 6.113), and serum glucose levels (OR, 1.007; 95% CI, 1.000 to 1.014) as independent predictors of HT., Conclusions: Angiographic grade of collateral flow strongly influences the rate of HT after therapeutic recanalization for acute ischemic stroke. Collateral status readily available from baseline angiography may therefore refine therapeutic decision-making in acute cerebral ischemia.

Background and Purpose: Collaterals sustain the penumbra before recanalization and offset infarct growth, yet the influence of baseline collateral flow on recanalization after endovascular therapy remains relatively unexplored., Methods: We analyzed consecutive patients who received endovascular therapy for acute cerebral ischemia from 2 distinct study populations. We assessed the relationship between pretreatment collateral grade and vascular recanalization (Thrombolysis In Myocardial Ischemia [TIMI] scale). In addition, we assessed infarct growth on serial MRI., Results: A total of 222 patients was included, 138 from the United States and 84 from South Korea. Complete revascularization occurred in 14.1% (11 of 78) patients with poor pretreatment collateral grades, whereas it was observed in 25.2% (26 of 103) patients with good collaterals and 41.5% (17 of 41) patients with excellent collaterals (P<0.001). This relationship was consistently observed in both study populations, although the mode of endovascular therapy was different between them. After adjustment for other factors, including mode of endovascular therapy, prior use of intravenous tissue plasminogen activator, and site of occlusion, pretreatment collateral grade was independently associated with recanalization. When revascularization was achieved, greater infarct growth occurred in patients with poor collaterals than in those with good collaterals (P=0.012)., Conclusions: Our data indicate that angiographic collateral grade determines the recanalization rate after endovascular revascularization therapy. When therapeutic revascularization was achieved, beneficial effects were not observed in patients with poor collaterals. Angiographic collateral grade may therefore help guide treatment decision-making in acute cerebral ischemia.

Background: Clinical response immediately after revascularisation therapy differs among patients. Although reperfusion is the deciding factor with respect to this dramatic response to revascularisation therapy, the influence of pre- and post-treatment diffusion-perfusion status on the speed and degree of recovery are unknown., Methods: Consecutive stroke patients who were eligible for revascularisation therapy underwent serial diffusion-perfusion MRI. Tmax perfusion maps were generated, and stroke severity and recovery were assessed up to day 90. The relationship of diffusion and perfusion lesion indices with the speed and degree of recovery were evaluated., Results: 69 patients (42 men; aged 66.3±15.9 years) were included; National Institutes of Health Stroke Scale (NIHSS) score was 13.3±6.4 points. 19 received intravenous tissue plasminogen activator (tPA) and 50 received endovascular therapy with/without intravenous tPA. Early dramatic improvement (NIHSS score reduction of ≥40% within 24 h) was observed in 24 (34.8%) patients. Among the other 45 patients, 18 (40%) showed good outcomes (modified Rankin score 0-2 at day 90), suggesting delayed recovery. The volume of post-treatment perfusion delay was similar between the early and delayed recovery groups (p=0.329) but smaller than in the non-responders group (p<0.05). Multivariate testing revealed that smaller post-treatment perfusion delay volumes were independently associated with both early dramatic improvement and delayed recovery. In addition, initial diffusion weighted imaging lesion volume was smaller in the former than in the latter (p=0.029) and was independently associated with early dramatic recovery., Conclusions: A significant proportion of patients with a lack of early dramatic improvement (40%) showed delayed recovery. Both pretreatment infarct volume and post-treatment reperfusion correlated with the degree and speed of recovery.

Objective: It has been reported that embolic signal (ES) detected by transcranial Doppler (TCD) has clinical significance, especially in patients with recent stroke attributable to arterial or cardiac embolism. Therefore, we conducted this study to determine whether the prevalence of ES is high in ischemic stroke patients with cancer and related to hypercoagulopathy., Methods: We prospectively studied cancer patients with acute ischemic stroke within the middle cerebral artery (MCA) distribution on diffusion-weighted imaging. Conventional stroke mechanisms (CSMs) were determined using cardiologic and vascular studies. Additionally, the coagulation status was assessed based on the serum D-dimer levels, and TCD monitoring was performed on both MCAs for 30 minutes to detect ES. Clinical features including vascular risk factors, characteristics of ischemic stroke, and cancer and laboratory findings associated with the presence of ES were evaluated., Results: A total of 74 patients were finally included in this study. ES was more commonly observed in patients without CSMs (22 of 38 patients, 57.9%) than in those with CSMs (12 of 36 patients, 33.3%) (p = 0.034). Moreover, ES was more commonly detected in patients with high D-dimer levels (p < 0.001), and D-dimer levels were significantly correlated with the number of ESs in patients without CSMs (r = 0.732, p < 0.001), but were poorly correlated in patients with CSMs (r = 0.152, p = 0.375). Higher levels of D-dimer (odds ratio [OR], 1.082 per 1 microg/ml increase; 95% confidence interval [CI], 1.014-1.154) and adenocarcinoma (OR, 3.829; 95% CI, 1.23-13.052) were independently associated with the presence of ES. The use of anticoagulants dramatically decreased the D-dimer levels., Interpretation: A high prevalence of ES was observed in cancer patients with ischemic stroke, especially in those without CSMs. Elevated D-dimer levels were independently associated with ES, and decreased dramatically with the use of anticoagulants. ANN NEUROL 2010;68:213-219.

Background: Smoking is a well-known risk factor for ischaemic stroke or transient ischaemic attack. Paradoxically, smokers have been reported to have better prognosis after myocardial infarction when compared to nonsmokers. This study examined the independent effect of smoking status on long-term prognosis after ischaemic stroke in male patients., Methods: A total 476 male patients with acute cerebral infarction within the middle cerebral artery territory were reviewed. Baseline characteristics and long-term prognosis were compared among smokers, ex-smokers, and nonsmokers., Results: Although the baseline severity of stroke did not differ among the groups, poor long-term outcome (Barthel index<60 or modified Rankin score>3) at 6 months after ischaemic stroke was more frequently observed in nonsmokers than in smokers (P=0.013); the outcome for ex-smokers was intermediate. After adjustment for age and other variables, current smoking was negatively correlated to poor long-term outcome (odds ratio, 0.286; 95% confidence interval, 0.119-0.686; P=0.005). On subgroup analysis, the impact of smoking on stroke prognosis was significant only in younger patients (<65 years of age) and those with atherosclerotic stroke., Conclusions: There was a strong independent correlation between smoking status and long-term outcome in patients with ischaemic stroke. Further studies about the impact of smoking habit on stroke outcome depending on the characteristics of patients (ie. age and stroke subtype) are needed.

We present two patients with reversible neurologic deficits after carotid artery stenting. The patients showed diffuse cortical sulcal effacement without parenchymal hypoattenuation on brain non-contrast CT as well as mild hyperperfusion on perfusion imaging. There was no white matter edema or intracerebral hemorrhage in either patient. We speculated that hyperperfusion after carotid artery stenting could be the underlying cause of the cortical sulcal effacement on brain CT in the absence of prominent cytotoxic or vasogenic edema.