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Background and Purpose: Symptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics (CFD) models were associated with the risk of stroke recurrence. We aimed to develop and compare stroke risk prediction nomograms in sICAS, based on vascular risk factors and these metrics., Methods: Patients with 50%-99% sICAS confirmed in CT angiography (CTA) were enrolled. Conventional vascular risk factors were collected. Severity of luminal stenosis in sICAS was dichotomised as moderate (50%-69%) and severe (70%-99%). Translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified via CTA-based CFD modelling; the haemodynamic status of sICAS was classified as normal (normal PR&WSSR), intermediate (otherwise) and abnormal (abnormal PR&WSSR). All patients received guideline-recommended medical treatment. We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression, in predicting the primary outcome, recurrent ischaemic stroke in the same territory (SIT) within 1 year., Results: Among 245 sICAS patients, 20 (8.2%) had SIT. The D 2 H 2 A nomogram, incorporating diabetes, dyslipidaemia, haemodynamic status of sICAS, hypertension and age ≥50 years, showed good calibration (P for Hosmer-Lemeshow test=0.560) and discrimination (C-statistic 0.73, 95% CI 0.60 to 0.85). It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis, compared with nomograms composed of conventional vascular risk factors only, and plus the severity of luminal stenosis in sICAS. Sensitivity analysis in patients with anterior-circulation sICAS showed similar results., Conclusions: The D 2 H 2 A nomogram, incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models, could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to develop a sensitive index from transcranial Doppler (TCD) signals for quantitatively evaluating the effects of long-term external counterpulsation (ECP) treatment on stroke rehabilitation. We recruited 27 patients with unilateral ischemic stroke and a good acoustic window within 7 days of stroke onset. 15 of them received 35 daily 1-hour ECP treatment (ECP group) and the others underwent conventional therapy without ECP treatment (No-ECP group). We monitored blood flow in middle cerebral arteries on both sides by TCD, and analyzed them via discrete wavelet analysis method. The overall changes of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index were assessed. A 'big-wave' phenomenon was observed in TCD signals of patients in ECP group after 35 days' treatment, with significant fluctuation in frequency interval from 0.010 to 0.034 Hz as main feature. A new index, which was denoted as I , was derived from this phenomenon. The I was significantly higher for patients in ECP group than that for patients in No-ECP group after 35-days' treatment ( 0.01). And the I was positively correlated with NIHSS change in ECP group ( ). The new index could be used as an effective indicator for evaluating enhancement of endothelial metabolism and neurogenic activity after long-term ECP treatment.

Background and Purpose- Poststroke autonomic dysfunction portended an unfavorable prognosis. We investigated whether blood pressure variability (BPV), heart rate variability, and baroreflex sensitivity might predict stroke functional outcome. Methods- We calculated BPV, heart rate variability, baroreflex slope, and baroreflex effectiveness index from a 5-minute beat-to-beat blood pressure and heart rate monitoring within 7 days from the stroke onset. We compared the parameters between patients with a good outcome (modified Rankin Scale score, 0-2) and those with a poor outcome. Results- Among 142 patients (mean age, 63.9±10.2 years; 88.0% men), functional outcome was good in 112 (78.9%) and poor in 30 (21.1%). There were significant differences in admission National Institutes of Health Stroke Scale, prior stroke, high-frequency systolic BPV, low/high-frequency ratio of BPV, baroreflex sensitivity-up, and baroreflex sensitivity-total between the 2 groups (all P <0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316-2.125]; P <0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250-0.973]; P =0.041), and baroreflex effectiveness index-down (OR, 0.958 [95% CI, 0.924-0.992]; P =0.017) independently predicted a poor functional outcome. Conclusions- A decreased low/high-frequency ratio of systolic BPV and impaired baroreflex sensitivity predicted an unfavorable stroke outcome, in addition to the established prognostic factor such as the National Institutes of Health Stroke Scale.

Aim: Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population., Methods: PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals., Results: Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel ( n = 14, 293) or aspirin ( n = 15, 064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53-0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups., Conclusions: The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke., Competing Interests: Maurizio Paciaroni received honoraria as a member of the speaker bureau of Aspen, Sanofi-Aventis, Boehringer Ingelheim, Bayer, Bristol Meyer Squibb, Daiiki Sankyo and Pfizer. Birsen Ince has received honoraria from Pfizer and Sanofi-Aventis within the past 36 months, outside the submitted work. Kursad Kutluk has received honoraria from Boehringer Ingelheim, Pfizer and Sanofi-Aventis within the past 36 months, outside the submitted work. Dara Paek, Jung Min Han, and Michael del Aguila report employment by Doctor Evidence at the time in which this research was conducted, who was contracted by Sanofi to perform the analysis. Shalini Girotra reports employment by Sanofi. All other authors have nothing to disclose., (Copyright © 2019 Maurizio Paciaroni et al.)

Objective: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model., Methods: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressure poststenotic /pressure prestenotic ) and translesional wall shear stress ratio (WSSR = WSS stenotic - throat /WSS prestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year., Results: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004)., Interpretation: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764., (© 2019 American Neurological Association.)

Objectives: Stenosis of the intracranial large arteries, especially the middle cerebral artery (MCA), is common in the Chinese population. We conducted a case-control study to investigate clinical and apolipoprotein E (ApoE) gene polymorphism of MCA atherosclerosis in the Chinese population., Materials and Methods: Polymerase chain reaction-based protocols were used to identify the genotypes of polymorphisms in ApoE genes. Clinical parameters and the genotypes of polymorphisms in the ApoE genes were compared in patients with and without MCA stenosis. The ApoE exon ε4 genotypes with risk factors were compared in the patients with and without MCA stenosis., Results: In total, 337 ischemic stroke patients were recruited, 156 cases with and 181 without MCA stenosis. Univariate analysis showed that the levels of systolic blood pressure and pulse pressure were higher in the MCA-stenosis group. There were no significant differences in the genotype and allele frequencies of the ApoE polymorphism observed between patients with and without MCA stenosis. However, there was a trend that the MCA-stenosis group tended to have more of genotype ε4/ε4 (3.8% vs. 0.6%, P=0.052) than the non-MCA-stenosis group. There was no effect of ApoE genotype and genotype-by-environment interactions on ischemic stroke susceptibility., Conclusions: This present study indicated that the hypertension (ie, systolic blood pressure and pulse pressure) and the ApoEε4/ε4 genotype may be associated with the occurrence of MCA stenosis in the ischemic stroke Chinese patients.

Background and Purpose: Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome., Methods: In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6)., Results: Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group ( P =0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071-8.284; P =0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141-9.335; P =0.027)., Conclusions: Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke., (© 2017 American Heart Association, Inc.)

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA., Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis., Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively)., Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories., (© 2016 American Academy of Neurology.)

Background and Purpose: Intracranial atherosclerosis is a major cause of ischemic stroke worldwide. Intracranial vessel wall imaging is an upcoming field of interest to assess intracranial atherosclerosis. In this study, we investigated total intracranial plaque burden in patients with symptomatic middle cerebral artery stenosis, assessed plaque morphological features, and compared features of symptomatic and asymptomatic lesions using a 3T vessel wall sequence., Methods: Nineteen consecutive Chinese patients with ischemic stroke and transient ischemic attack (mean age: 67 years; 7 females) with a middle cerebral artery stenosis were scanned at 3T magnetic resonance imaging; the protocol included a time-of-flight magnetic resonance angiography and the T1-weighted volumetric isotropically reconstructed turbo spin echo acquisition sequence before and after (83%) contrast administration. Chi-square tests were used to assess associations between different plaque features. Statistical significance was set at P<0.05., Results: Vessel wall lesions were identified in 18 patients (95%), totaling 57 lesions in 494 segments (12% of segments). Lesions were located primarily in the anterior circulation (82%). Eccentric lesions were associated with a focal thickening pattern and concentric lesions with a diffuse thickening pattern (P<0.001). When differentiating between asymptomatic and symptomatic lesions, an association (P<0.05) was found between eccentricity and asymptomatic lesions, but not for enhancement or a specific thickening pattern. Symptomatic lesions did not have any specific morphological features., Conclusions: Our results lead to a 2-fold conclusion: (1) The classification system of both thickening pattern and distribution of the lesion can be simplified by using distribution pattern only and (2) differentiation between symptomatic and asymptomatic atherosclerotic lesions was possible using intracranial vessel wall imaging., (© 2016 The Authors.)

Objective: We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions., Methods: Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted., Results: In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods., Conclusions: Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: External counterpulsation (ECP) is a non-invasive method used to augment cerebral perfusion in ischaemic stroke. We aimed to investigate time-course effects on blood pressure elevation and cerebral blood flow augmentation induced by ECP in ischaemic stroke., Methods: Patients with acute unilateral ischaemic stroke and large artery occlusive disease were recruited to receive 35 daily 1 h ECP treatment sessions. Serial transcranial Doppler monitoring of bilateral middle cerebral arteries was performed on days 3, 5, 7, 10, 14, 21, 28 and 35 after stroke onset. Flow velocity changes before, during and after ECP and continuous beat-to-beat blood pressure data were recorded. The cerebral augmentation index (CAI) is the increase in the percentage of the middle cerebral artery mean flow velocity during ECP compared with baseline., Results: The CAI in patients with stroke was significantly higher on the ipsilateral side and on the contralateral side on day 3 (ipsilateral CAI, 9.3%; contralateral CAI, 7.2%), day 5 (7.0%; 6.7%), day 7 (6.8%; 6.0%), day 10 (6.0%; 5.1%), day 14 (4.7%; 2.6%) and day 21 (4.1%; 2.2%) after stroke onset than that in controls (-2.0%) (all p<0.05). There was a significant trend of decreasing CAI on the ipsilateral and contralateral sides over time after a stroke. Differences in the percentage increase in the mean blood pressure did not change significantly over time in patients with stroke., Conclusions: Blood pressure elevation persists throughout ECP treatment, which consists of 35 sessions. However, cerebral blood flow augmentation may last at least 3 weeks and then appears to return to baseline 1 month after acute stroke onset., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Purpose: Increased cerebral blood flow velocity of basilar artery (BA) is common but often neglected. By using digital subtraction angiography (DSA) to detect intracranial large artery stenosis, we performed transcranial Doppler (TCD) to evaluate cerebral hemodynamic changes of stroke patients., Methods: Acute stroke patients with TCD-detected raised peak systolic velocity (PSV) in BA (≥100 cm/second) were recruited., Results: Among 91 recruited patients, BA stenosis (>50%) was confirmed by using DSA in 29 patients (32%), among which 20 patients (70.0%) had coexistent internal carotid artery (ICA) and vertebral artery (VA) stenoses. Among patients without BA stenosis (n = 62, 68%), severe stenosis or occlusion of ICA was evaluated in 22 patients (22/62, 35.4%) and severe stenosis or occlusion of VA was detected in 22 patients (22/62, 35.4%). Among the values of PSV (120, 140, 160, and 180 cm/second) and the stenotic-to-prestenotic ratio (SPR) (1.5, 2.0, 2.5, and 3.0), 160 cm/second was found to show the highest predictive value (area under the receiver operator characteristic curve: .75, 95% CI: .65-.86), with a sensitivity of .70 and a specificity of .81., Conclusions: Apart from an intrinsic BA stenosis, high-grade steno-occlusion of ICA or VA may contribute a lot to induce an elevated flow velocity in BA. A higher value of cutoff point may increase the accuracy of diagnosing BA stenosis., (Copyright © 2015 by the American Society of Neuroimaging.)

Background: The risk of a subsequent stroke following a minor stroke is high. However, there are no effective rating scales to predict recurrent stroke following a minor one. Therefore, we assessed the risk factors associated with recurrent ischemic stroke or transient ischemic attack (TIA) within one year of minor stroke onset in order to identify possible risk factors., Methods: Eight hundred and sixty-three non-cardioembolic ischemic stroke patients in the Chinese IntraCranial AtheroSclerosis Study that presented with minor stroke, defined as an admission National Institutes of Health stroke scale (NIHSS) score of ≤3, were consecutively enrolled in our study. Clinical information and imaging features upon admission, and any recurrent ischemic stroke or TIA within one year was recorded. Cox regression was used to identify risk factors associated with recurrent ischemic stroke or TIA within the year following stroke onset., Results: A total of 50 patients (6.1%) experienced recurrent ischemic stroke or TIA within one year of minor stroke onset. Multivariate Cox regression model identified lower admission NIHSS score (HR, 1.75; 95% CI, 1.32 to 2.33; P<0.0001), history of coronary heart disease (HR, 2.62; 95% CI, 1.17 to 5.86; P = 0.02), severe stenosis or occlusion of large cerebral artery (HR, 4.68; 95% CI, 1.87 to 11.7; P = 0.001), and multiple acute cerebral infarcts (HR, 2.61; 95% CI, 1.01 to 6.80; P = 0.05) as independent risk factors for recurrent ischemic stroke or TIA within one year., Conclusions: Some minor stroke patients are at higher risk for recurrent ischemic stroke or TIA. Urgent and intensified therapy may be reasonable in these patients.

Background: T2*-weighted gradient echo magnetic resonance imaging is sensitive in detecting cerebral microbleeds (MBs), but there are few reports on the risk factors of MBs in different brain regions. Therefore, we aimed to investigate whether the risk factors associated with the presence of MBs in strictly deep or lobar brain regions were different., Methods: This study consisted of 696 consecutive acute ischemic stroke patients from 6 hospitals in the Chinese IntraCranial AtheroSclerosis Study. We evaluated the number and location of MBs, severity of lacune and leukoaraiosis (LA), and etiologic subtype of ischemic stroke. Multivariable logistic regression was used to analyze risk factors of MBs in different brain regions., Results: Among 696 acute ischemic stroke patients, 162 patients (23.3%) had MBs. Of them, 62 patients had strictly deep brain MBs, 49 patients had strictly lobar MBs. There was a significant correlation between the number of MBs, the number of lacune, and the severity of LA (P < .0001). In multivariable logistic regression analysis, both strictly deep and strictly lobar brain, MBs were significantly associated with history of cerebral hemorrhage (P = .037 and P = .026, respectively), presence of lacune (P = .004 and P = .032, respectively), and severe LA (P = .002 and P = .008, respectively). However, MBs in strictly deep regions were significantly associated with higher mean arterial pressure (P = .030), and those in strictly lobar brain regions were significantly associated with older age (P = .023)., Conclusions: The risk factors of MBs in strictly deep or lobar regions differ modestly, which may be related to heterogeneous vascular pathologic changes., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Fatigue is common in stroke survivors. Lesion location may influence the risk of poststroke fatigue (PSF) but it is uncertain whether location has an impact on the prognosis of PSF. This study examined the association between PSF outcome and infarct location., Methods: The study sample comprised 435 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university affiliated regional hospital in Hong Kong. Three and fifteen months after the onset of the index stroke a research assistant administered the Fatigue Severity Scale (FSS). PSF was defined as a FSS score of 4.0 or above. Of the 139 patients with PSF three months poststroke, 97 (69.8%) attended the 15-month follow-up, when 50 (51.5%) patients still had PSF ('non-remitters') and 47 (48.5%) did not report fatigue ('remitters'). The presence and location of infarcts were evaluated with magnetic resonance imaging., Results: In comparison with the remitters, the non-remitters were more likely to have subcortical white matter infarcts (40.0% vs 21.3%, p = 0.046). These infarcts remained an independent predictor of non-remission of PSF in the multivariate analysis, with an odds ratio of 4.208 (p = 0.011)., Conclusions: The results suggest that subcortical white matter infarcts may influence the outcome of PSF. Further investigations are needed to explore whether infarcts have any impact on the response of PSF to pharmacological or psychological interventions.

Background: Leukoaraiosis (LA) is an indicator of small vessel disease, but little is known about the relationship between the severity of LA and etiologic subtype of ischemic stroke. Our study aimed to investigate the factors associated with the severity of LA and the relationship between the severity of LA and etiologic subtype of ischemic stroke., Methods: A total of 791 patients with first-ever ischemic stroke within 7 days were enrolled in our study. We evaluated cranial magnetic resonance imagings including severity of LA in periventricular and deep white matter, severity of silent lacunar infarcts (SLIs), etiologic subtype of ischemic stroke, and topographic patterns of acute cerebral infarcts. Severity of LA was graded as grade 0 when Fazekas scores = 0, grade 1 when Fazekas scores ranged from 1 to 2, and grade 2 when Fazekas scores were greater than or equal to 3. Multivariable ordinal logistic regression was used to analyze the factors associated with the severity of LA., Results: A total of 748 patients (94.6%) had LA, the numbers and proportions of grade 0, grade 1, and grade 2 LA were 43 patients (5.4%), 413 patients (52.2%), and 335 patients (42.4%), respectively. In multivariable ordinal logistic regression analysis, increasing age, higher diastolic blood pressure, admission National Institutes of Health Stroke Scale scores less than or equal to 3, presence of SLIs, and small artery occlusion (SAO) subtype of ischemic stroke were found to be independently associated with higher grade of LA., Conclusions: LA is prevalent in first-ever ischemic stroke patients. Severe LA is more frequently associated with higher grades of SLIs and ischemic stroke due to SAO., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Few studies have reported on the risk factors of dilated Virchow-Robin Spaces (dVRS) in large samples of ischemic stroke patients. Little evidence exists regarding the relationship between dVRS and etiologic subtype of ischemic stroke or lacune. We aimed to investigate the risk factors associated with the severity of dVRS in a large sample of ischemic stroke patients., Methods: We consecutively enrolled 1,090 patients who experienced an ischemic stroke within the past seven days and underwent a 3.0 T MRI scan in the Chinese IntraCranial AtheroSclerosis Study (ICAS). Clinical data and cranial MRI information of patients included age, sex, vascular risk factors, dVRS, leukoaraiosis, lacune, and etiologic subtype of ischemic stroke. Analyses were performed regarding the risk factors associated with the severity of dVRS by univariate analysis and multivariable ordinal logistic regression analysis., Results: Through multivariable ordinal logistic regression analysis, age, the severity of leukoaraiosis, lacune, admission National Institutes of Health Stroke Scale (NIHSS) ≤3, and the severity of dVRS in the white matter (WM) and hippocampus (Hip) were correlated with the severity of dVRS in basal ganglia (BG); male, history of hypertension, admission NIHSS ≤3, and the severity of dVRS in BG and Hip were correlated with the severity of dVRS in WM; female, the severity of leukoaraiosis, admission NIHSS >3, small artery occlusion subtype of ischemic stroke, and the severity of dVRS in BG and WM were correlated with the severity of dVRS in Hip., Conclusion: dVRS is an indicator of cerebral small vessel diseases such as leukoaraiosis and lacune. However, the risk factors of dVRS differ in various brain regions.

External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion but the optimal use of ECP in ischemic stroke has not been well documented. We aimed to investigate the effects of ECP treatment pressure on cerebral blood flow and blood pressure (BP). We recruited 38 ischemic stroke patients with large artery occlusive disease and 20 elderly controls. We commenced ECP treatment pressure at 150 mmHg and gradually increased to 187.5, 225 and 262.5 mmHg. Mean cerebral blood flow velocities (CBFV) of bilateral middle cerebral arteries and continuous beat-to-beat BP were recorded before ECP and during each pressure increment for 3 minutes. Patient CBFV data was analyzed based on whether it was ipsilateral or contralateral to the infarct. Mean BP significantly increased from baseline in both stroke and control groups after ECP commenced. BP increased in both groups following raised ECP pressure and reached maximum at 262.5 mmHg (patients 16.9% increase versus controls 16.52%). The ipsilateral CBFV of patients increased 5.15%, 4.35%, 4.55% and 3.52% from baseline under the four pressures, respectively. All were significantly higher than baseline but did not differ among different ECP pressures; contralateral CBFV changed likewise. Control CBFV did not increase under variable pressures of ECP. ECP did increase CBFV of our patients to a roughly equal degree regardless of ECP pressure. Among the four ECP pressures tested, we recommend 150 mmHg as the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications with higher pressures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: Poststroke fatigue (PSF) is a frequent and persistent problem in stroke survivors. The neuroanatomical model of PSF remains unclear. This study examined the association between PSF and cerebral microbleeds (CMBs)., Methods: The sample comprised 199 patients with acute ischemic stroke. A psychiatrist who was blind to the subjects' radiological data administered the Chinese version of the Fatigue Severity Scale. PSF was defined as a Fatigue Severity Scale score of 4.0 or more. The locations of CMBs were evaluated with magnetic resonance imaging within 7 days of admission., Results: Of the 199 patients screened, 47 (23.6%) had PSF. The PSF group had a higher Geriatric Depression Scale score (p < 0.001) and a trend for a higher age (p = 0.074). The proportion of patients with deep CMBs was significantly higher in the PSF group (66.0 vs. 48.7%; p = 0.038). The presence of deep CMBs was a significant independent predictor of PSF with an odds ratio of 2.68 (p = 0.016)., Conclusion: The results suggest that deep CMBs are associated with a higher risk of PSF. Further studies are needed to clarify whether CMBs affect the clinical presentation, treatment response and outcome of PSF., (© 2014 S. Karger AG, Basel.)

Background: Emerging studies suggest that early administration of dual antiplatelet therapy may be better than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in acute ischemic stroke and transient ischemic attack (TIA). We performed a meta-analysis of randomized, controlled trials evaluating dual versus mono antiplatelet therapy for acute noncardioembolic ischemic stroke or TIA., Methods and Results: We assessed randomized, controlled trials investigating dual versus mono antiplatelet therapy published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), for efficacy and safety outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60-0.80; P<0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63-0.81; P<0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70-2.59, P=0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results., Conclusions: For patients with acute noncardioembolic ischemic stroke or TIA, dual therapy was more effective than monotherapy in reducing risks of early recurrent stroke. The results of the CHANCE study are consistent with previous studies done in other parts of the world.

Background and Purpose: Geographic variation and sex difference in the distribution of intracranial atherosclerosis (ICAS) have not been fully discussed before in Chinese patients with cerebral ischemia. We performed this study with the aim to investigate geographic and sex difference in the distribution of ICAS in China., Methods: In this prospective multicenter study, we evaluated 2864 consecutive patients who experienced an acute cerebral ischemia within 7 days of symptom onset in 22 hospitals in China. All the inclusive patients underwent 3-dimensional time-of-flight MR angiography and duplex color Doppler ultrasound or contrast-enhanced MR angiography to document the presence of intracranial or extracranial stenosis. Intracranial large-artery atherosclerosis was defined as ≥50% diameter reduction on MR angiography., Results: The proportion of patients with ICAS was significantly higher in north China than in south China (50.22% versus 41.88%; P<0.0001). Patients in the north were likely to consume more alcohol and smoke more cigarettes and had significantly higher proportion of diabetes mellitus, family history of stroke, history of cerebral ischemia, heart disease, and higher body mass index. In patients aged >63 years, the percentage of ICAS in women was notably higher than in men (51.51% versus 45.40%; P=0.028). In elderly patients, women had higher proportion of diabetes mellitus, hypertension, hyperlipidemia, and heart disease than men., Conclusions: There exists geographic and sex difference in the distribution of symptomatic ICAS in China. Public health measures should strengthen improving social determinants of health and risk factor prevention/control in high-risk populations for decreasing stroke risk.

Background: Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke., Methods: We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis., Findings: Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events., Interpretation: There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised., Funding: MRC., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: Computed tomography angiography is an accurate noninvasive method to diagnose intracranial steno-occlusive disease (ICAD) at initial presentation for stroke. We aimed to identify features of computed tomography angiography associated with unfavorable outcome., Methods: We identified patients with ICAD in the Screening Technology and Outcomes Project in Stroke Study, a prospective imaging-based study of stroke outcomes, in consecutive patients with ischemic stroke or transient ischemic attack (TIA) presenting to 2 academic medical centers. All patients underwent computed tomography angiography, which were graded by 2 neuroradiologists independently. Univariate and multiple logistic regression was used to evaluate predictors of favorable outcome at 6 months, defined as a modified Rankin Scale ≤ 2., Results: Among 539 patients that met study entry criteria, ICAD was identified in 212 patients (39%); 116 patients (22%) had concurrent extraintracranial lesions, and 66 patients (12%) had multiple sites of ICAD. Patients with ICAD had more severe stroke (median National Institutes of Health Stroke Scale, 9 versus 3; P<0.001), worse outcomes at 6 months (modified Rankin Scale, 0-2; 57% versus 73%; P<0.001), and higher mortality (18% versus 8%; P=0.001). In the multivariate model, age (odds ratio [OR], 0.75 per decade; 95% confidence interval [CI], 0.65-0.87), female sex (OR, 0.49; 95% CI, 0.32-0.73), multiple sites of ICAD (OR, 0.53; 95% CI, 0.29-0.97), complete occlusion (OR, 0.42; 95% CI, 0.25-0.72), and concurrent extraintracranial lesions (OR, 0.51; 95% CI, 0.31-0.84) negatively predicted favorable outcome., Conclusions: Findings of multiple sites of ICAD from computed tomography angiography, concurrent extraintracranial lesions, and complete occlusion are independent predictors of unfavorable outcome at 6 months.

Objective: To evaluate the relation between poststroke pain and suicidality (SI) in Chinese patients with first or recurrent stroke., Design: Cross-sectional survey., Setting: Acute stroke unit of a university-affiliated general hospital., Participants: Patients (N=496) with acute ischemic stroke admitted to the Acute Stroke Unit., Interventions: Not applicable., Main Outcome Measures: Patients were interviewed 3 months after the index stroke. SI was assessed with the Geriatric Mental State Examination. Pain was evaluated with the Faces Pain Rating Scale-Revised (FPS-R). The association between FPS-R scores and SI was examined and adjusted for potential confounders, including marital status, depression, neurologic deficits assessed by the National Institute of Health Stroke Scale, and functioning measured by the Barthel Index., Results: Thirty-seven (7.5%) of the patients had SI (the SI group). Compared with the non-SI group, patients in the SI group were more likely to experience pain (59.5% vs 37.7%), had a higher mean FPS-R score (6.0±2.5 vs 4.5±2.3), and had an FPS-R score of >4 (43.2% vs 15.9%). After adjustment for possible confounders, the FPS-R score of >4 (odds ratio=2.9) remained a significant predictor of SI in the subsequent forward logistic regression models., Conclusions: These findings should alert clinicians that the early identification and treatment of pain may reduce suicide risk in patients with stroke., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: High serum bilirubin predicts depression in non-stroke subjects, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between the risk of PSD and bilirubin level., Methods: Six hundred and thirty-five patients with acute ischemic stroke in Hong Kong were recruited. Serum total bilirubin, alanine transaminase and alkaline phosphatase levels were measured in all patients during their hospital stay. A psychiatrist gave the Structured Clinical Interview for DSM-IV to all patients 3 months after the index stroke, with 61 patients diagnosed with PSD: 27 with major depression, 24 with minor depression and 10 with dysthymia., Results: In the full sample, the 25%, 50% and 75% percentile bilirubin levels were 7.0, 10.0 and 14.0 μmol/L, respectively. Significant differences were found between the PSD and non-PSD groups in terms of bilirubin level (P = 0.006). In post-hoc comparisons, the proportion of patients with bilirubin ≥14.1 μmol/L was significantly higher in the PSD group (37.7% vs 19.7%, P = 0.001). In the final regression model, bilirubin level (≥14.1 μmol/L) remained a significant independent predictor of PSD, with an odds ratio of 2.4., Conclusions: High bilirubin level is associated with PSD. Further investigations are needed to clarify the underlying pathophysiological link between bilirubin level and PSD., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

Background: International guidelines recommend oral anticoagulation in patients with atrial fibrillation according to their level of stroke risk. This study aimed to determine oral anticoagulation use in atrial fibrillation patients with recent ischemic stroke and examine factors that impact such management in China., Methods: Among the patients with acute ischemic stroke (n = 4782) from the China QUality Evaluation of Stroke Care and Treatment study, a multicenter, prospective, 62-hospital registry in China, there were 499 (10%) (mean age 70 ± 12 years, 49% female) with documented atrial fibrillation with outcome data over 12 months of follow-up. Logistic regression analysis was used to identify the independent predictors of oral anticoagulation use in these patients., Results: Of the 499 stroke patients with atrial fibrillation, oral anticoagulation use was 20% overall but varied from 8% prestroke and 11% in-hospital (poststroke), to 13% and 10% at three-months and 12 months, respectively. Oral anticoagulation use was independently associated with younger age (odds ratio 0.95, 95% confidence interval 0.93-0.97, P < 0.001), nonmanual occupation (odds ratio 0.44, 95% confidence interval 0.25-0.80, P = 0.006), and less cardiovascular risk factors (odds ratio 0.81, 95% confidence interval 0.68-0.96, P = 0.02)., Conclusions: These data indicate oral anticoagulation use is lower in stroke patients with atrial fibrillation in China than that in Western countries, being applied more often in those of younger age, nonmanual occupation, and having less cardiovascular risk factors., (© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.)

Background and Purpose: Inflammation exists in inception, progression, and reperfusion of acute ischemic stroke. Insightful understanding of correlation in inflammatory mediators and stroke severity with intracranial artery stenosis may improve rational stroke therapy., Methods: We prospectively recruited 977 patients with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to mild (<50%), moderate (50-69%), severe (70-99%), or occlusive (100%). The peripheral levels of WBC, homocysteine (HCY), and high sensitivity C-reactive protein (hs-CRP) were recorded. All patients were assessed of 1-year outcome by mRS as favorable (0-2) or poor (3-6)., Results: The levels of WBC, HCY, and hs-CRP had no significant differences in patients with categorized MCA stenosis (all P > 0.05). Higher levels of WBC, HCY, and hs-CRP were found in patients with 1-year poor outcome (all P < 0.05), but only hs-CRP is an independent predictor (OR 1.06, 95% CI 1.027-1.093, P = 0.0003). The combination of any two of increased hs-CRP (>3 mg/L), WBC (>6.91 × 10(9)/L), and HCY (>15  μ mol/L) had higher power in predicting 1-year poor outcome than the single elevated mediator., Conclusions: Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke. The combination of increased hs-CRP, WBC, or HCY had a stronger predictive value in poor outcome than individual elevated mediator.

Background and Purpose: Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions., Methods: A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities., Results: After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039)., Conclusions: Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD., Clinical Trial Registration: http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.

Objective: Cerebral microbleeds (CMBs) are common in stroke survivors. The clinical significance of CMBs in the development of suicidality (SI) following stroke is unknown. This study examined the association between SI and CMBs. The aim of the study reported here was to determine the relationship between CMBs and SI in ischemic stroke survivors., Methods: A cohort of 367 patients with acute ischemic stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. SI was assessed with the geriatric mental state examination at three months following the subjects' index stroke. Depressive symptoms were assessed using the geriatric depression scale (GDS). A qualified psychiatrist administered the Chinese version of the Structured Clinical Interview for DSM-IV to diagnose depressive disorders. The presence and location of CMBs were evaluated with magnetic resonance imaging (MRI)., Results: Compared with the non-SI patients, SI patients were more likely to have CMBs in any brain region (36.6% vs. 20.2%, p = 0.017), specifically more lobar (29.3% vs. 13.5%, p = 0.008) and thalamic CMBs (19.5% vs. 7.5%, p = 0.018). Presence of CMBs (odds ratio was 2.5, p = 0.026) and lobar CMBs (odds ratio 2.6, p = 0.034) were independent predictors of SI in the multivariate analysis., Conclusions: The results suggest that lobar CMBs may play roles in the development of SI. The importance of CMBs in the pathogenesis of SI in stroke survivors warrants further investigation., (Copyright © 2012 The Academy of Psychosomatic Medicine. All rights reserved.)

Background and Purpose: Impaired autonomic function is common in the acute poststroke phase but little is known about its effects on functional outcome after acute ischemic stroke. This study sought to investigate the impact of autonomic dysfunction by Ewing's classification on functional outcome 2 months after acute ischemic stroke., Methods: 34 consecutive acute ischemic stroke patients within 7 days after onset were enrolled. On admission, autonomic function was assessed by Ewing's battery tests. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), autonomy in activities of daily living by the Barthel Index (BI), and global disability by the modified Rankin Scale (mRS). BI and mRS were also evaluated 2 months after ischemic stroke onset., Results: On admission, eight patients were diagnosed as minor autonomic dysfunction and 26 patients as relatively severe autonomic dysfunction. The prevalence of relatively severe autonomic dysfunction in ischemic stroke patients was 76.5%. There were no significant differences in baseline characteristics between the minor and severe autonomic dysfunction groups. 2 months after stroke onset, the mean BI score of patients with minor autonomic dysfunction and severe autonomic dysfunction increased from 76.3±15.3 on admission to 95.0±7.1, 66.5±15.2 on admission to 74.8±15.9 respectively. The mean BI score after 2-month stroke onset and the change in BI from admission to 2-month outcome (delta BI) in patients with severe autonomic dysfunction were lower than those in patients with minor autonomic dysfunction (all P<0.05)., Conclusions: Autonomic dysfunction occurs in acute stroke patients. Relatively severe autonomic dysfunction is related to an unfavorable functional outcome in patients with acute ischemic stroke., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background and Purpose: The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies., Methods: The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries., Results: Compared with aspirin, LMWH improved outcome among older patients >68 years (P=0.043; OR, 1.86; 95% CI, 1.02-3.41) without ongoing antiplatelet treatment on admission (P=0.029; OR, 1.85; 95% CI, 1.06-3.21) and with symptomatic posterior circulation arterial disease (P=0.001; OR, 5.76; 95% CI, 2.00-16.56)., Conclusions: Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis., Clinical Trial Registration: URL: www.strokecenter.org/trials. Unique identifier: registration no. 493.

Objectives: Insomnia is a common complaint in stroke survivors. The purpose of this study was to investigate the clinical and magnetic resonance imaging (MRI) correlates of insomnia symptoms in Chinese ischemic stroke survivors., Methods: A comprehensive psychiatric assessment was performed involving 508 ischemic stroke patients 3 months after their first-ever or recurrent acute stroke. Insomnia symptoms were evaluated with a standard insomnia questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS).The evaluation of the MRI scans focused on infarctions, white matter lesions, and microbleeds., Results: One hundred and eight-six patients (36.6% of the sample) had insomnia symptoms. Sixty-four patients (12.6%) had insomnia symptoms with daytime consequences. In the multivariate logistic regression analysis, GDS score (OR = 1.157, p < 0.001) and acute frontal lobe infarction (OR = 1.933, p = 0.039) were significant predictors of insomnia symptoms, while the GDS score (OR = 1.251, p < 0.001) and diabetes mellitus (OR = 1.959, p = 0.017) were significant predictors of insomnia symptoms with daytime consequences., Conclusions: Insomnia symptoms have a multi-factorial origin in stroke. Besides depressive symptoms, frontal lobe infarction and diabetes mellitus predict insomnia symptoms., (Copyright © 2010 John Wiley & Sons, Ltd.)

Despite extensive research into poststroke depression (PSD), the role played by lesion location in the pathogenesis of PSD remains uncertain. The aim of this study was to estimate the magnetic resonance imaging (MRI) correlates of PSD in Chinese patients with first or recurrent stroke. A total of 591 patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong were recruited. A psychiatrist assessed all the patients 3 months after the stroke. The psychiatrist used the Structured Clinical Interview for Diagnostic and Statistical Manual, fourth edition (DSM-IV) to confirm whether the patients met the criteria of a depressive disorder. In addition, a host of demographic, clinical, and radiological variables were examined. A tota; of 475 and 116 patients had first and recurrent strokes, respectively. In all, 75 (12.7%) patients received a diagnosis of PSD. In univariate analysis of the MRI findings, the presence of infarcts in the frontal subcortical circuits ([FSC], 66.7% vs 53.3%) was significantly associated with PSD (P = .03) compared to the patients without PSD. The FSC infarct-PSD association remained significant (odds ratio = 2.6) in subsequent logistic regression analysis after adjusting for gender, history of depression, neurological impairment, level of social support, and major life events. In conclusion, FSC infarcts are independent predictors of PSD. Further work is needed to clarify whether these infarcts have an impact on the clinical presentation, treatment responses, and prognosis of PSD.

Background and Purpose: The ABCD(2) score is able to predict the short-term risk of stroke after a transient ischemic attack/minor stroke. We aimed to explore its predictive value for long-term recurrent stroke., Methods: Consecutive patients with a transient ischemic attack/minor stroke, hospitalized during a 2-year period, were followed up to document any further stroke and death stratified by a 7-point ABCD(2) score. Result- A total of 490 patients were followed for an average of 40.5 months (SD, 10.7 months). Further stroke were identified in 76 (15.5%) patients and 62 (12.7%) patients died during follow-up. Multivariate Cox regression analysis showed that an ABCD(2) score >4 was found to be an independent risk factor for further stroke (hazard ratio, 2.27; 95% CI, 1.36 to 3.80) and for death (hazard ratio, 1.68; 95% CI, 0.99 to 2.85)., Conclusions: In addition to predicting short-term stroke risk, ABCD(2) score is a useful tool to predict long-term stroke risk after a transient ischemic attack or minor ischemic stroke.

Lesions located in the basal ganglia (BG) are thought to be involved in the fatigue observed in neurological disorders. However, the significance of the location of infarcts in poststroke fatigue (PSF) is unknown. This study examined the association between BG infarcts and PSF. A total of 334 Chinese patients with acute ischemic stroke consecutively admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. At admission, a host of demographic and clinical characteristics was collected and the number and location of acute infarcts were evaluated with MRI. All participants were assessed for PSF with the fatigue severity scale (FSS) 3 months after their index stroke. PSF was defined as a mean FSS score of 4.0 or more. Depressive symptoms were measured by the geriatric depression scale (GDS). Seventy-eight (23.4%) patients had PSF. In the univariate analysis, the PSF group included more females, had higher GDS scores, and a higher number of acute infarcts, and the PSF patients were more likely to have acute infarcts at the BG. Acute BG infarct remained an independent predictor of PSF in the multivariate analysis. In conclusion, these results suggest that BG infarcts may play a role in the development of PSF.

Background: The pathogenesis of frontal lobe atrophy (FLA) in stroke patients is unclear. We aimed to ascertain whether subcortical ischemic changes were more associated with FLA than with parietal lobe atrophy (PLA) and temporal lobe atrophy (TLA)., Methods: Brain magnetic resonance images (MRIs) from 471 Chinese ischemic stroke patients were analyzed. Lobar atrophy was defined by a widely used visual rating scale. All patients were divided into non-severe, mild-moderate, and severe atrophy of the frontal, parietal, and temporal lobe groups. The severity of white matter lesions (WMLs) was rated with the Fazekas' scale. Clinical and radiological features were compared among the groups. Subsequent logistic regressions were performed to determine the risk factors of atrophy and severe atrophy of the frontal, parietal and temporal lobes., Results: The frequency of FLA in our cohort was 36.9% (174/471). Severe FLA occurred in 30 (6.4%) patients. Age, previous stroke, and periventricular hyperintensities (PVH) (odds ratio (OR)=1.640, p=0.039) were independent risk factors of FLA. Age and deep white matter hyperintensities (DWMH) (OR=3.634, p=0.002) were independent risk factors of severe FLA. PVH and DWMH were not independent risk factors of PLA and TLA., Conclusion: Frontal lobe atrophy in ischemic stroke patients may be associated with small vessel disease. The association between WMLs and FLA was predominant over atrophy of the parietal and temporal lobes, which suggests that the frontal lobe may be vulnerable to subcortical ischemic changes.

We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 x 10(-10)). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.

Background and Purpose: We aimed to investigate the feasibility and therapeutic effect of external counterpulsation (ECP) in ischemic stroke., Methods: The trial was a randomized, crossover, assessment-blinded, proof-of-concept trial. ECP treatment consisted of 35 daily 1-hour sessions. Patients were randomized to either early (ECP weeks 1 to 7 and no ECP weeks 8 to 14) or late group (no ECP weeks 1 to 7 and ECP weeks 8 to 14). Primary outcomes were an overall change in National Institutes of Health Stroke Scale (NIHSS) and cerebral blood flow estimated by color velocity imaging quantification. Secondary outcomes were change in NIHSS, color velocity imaging quantification, favorable functional outcome (modified Rankin scale, 0 to 2), and stroke recurrence at weeks 7 and 14, respectively., Results: Fifty patients were recruited. At week 7, there was a significant change in NIHSS (early 3.5 vs late 1.9; P=0.042). After adjusting for treatment sequence, ECP was associated with a favorable trend of change in NIHSS of 2.1 vs 1.3 for non-ECP (P=0.061). Changes of color velocity imaging quantification were not significant but tended to increase with ECP. At week 14, a favorable functional outcome was found in 100% of early group patients compared to 76% in the late group (P=0.022)., Conclusions: ECP is feasible for ischemic stroke patients with larger artery disease.

Background: Despite the rapid progress in stroke prevention, effective acute stroke treatment except for thrombolysis is still lacking. Hypoperfusion is related to unfavorable functional outcome, further strokes and long-term mortality. Therefore, the need for a safe and effective way of increasing the cerebral blood flow seems obvious. Currently, there is a growing body of evidence to suggest that external counterpulsation (ECP) may enhance the blood supply to the brain and thus may be beneficial to patients with ischemic stroke., Methods: A MEDLINE search in combination with a search for papers in Chinese literature in the Wan Fang and China Academic Journal databases was carried out., Results: Preliminary investigations suggested that ECP may improve the clinical outcome of stroke patients. However, well-designed clinical studies exploring the therapeutic effects of ECP in ischemic stroke are very limited., Conclusions: Randomized-controlled trials with a large sample size are needed to further define the efficacy and safety of ECP in acute stroke management. Future studies should provide insight into the value of ECP in ischemic stroke as well as its possible mechanisms., ((c) 2008 S. Karger AG, Basel.)

Background and Purpose: Calcification in cerebral arteries is understudied, although frequently observed on computed tomography of the brain (CT brain). We aimed to assess the incidence of intracranial artery calcification in ischemic stroke patients and to evaluate its correlation with ischemic stroke., Methods: Our study included ischemic stroke patients and age-gender-matched nonischemic stroke patients referred for CT brain., Results: One hundred and seventy-five ischemic stroke patients and 182 controls were enrolled. The highest prevalence of calcification was seen in intracranial internal carotid artery (IICA) (80.4%), and less commonly in the vertebral artery (35.6%). There was a higher prevalence of intracranial artery calcification in ischemic stroke patients than controls (92.6% vs. 76.4%, P < .001). Hypertension (OR = 2.056, 95% CI: 1.129 approximately 3.745), diabetes (OR = 2.483, 95% CI: 1.233 approximately 5.001), smoking (OR = 2.844, 95% CI: 1.542 approximately 5.243), intracranial artery calcification (OR = 3.172, 95% CI: 1.252 approximately 8.036), hyperlipidemia (OR = 6.714, 95% CI: 3.302 approximately 13.650), and atrial fibrillation (OR = 7.941, 95% CI: 2.790 approximately 22.599) were found to be independently associated with ischemic stroke., Conclusions: We demonstrated a higher incidence of intracranial artery calcification in ischemic stroke patients. Besides traditional risk factors, intracranial artery calcification was found to be an independent risk factor of ischemic stroke.

Background: Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD., Methods: Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493)., Findings: Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively)., Interpretation: Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.

Background and Purpose: Small subcortical infarcts (SSI, maximum lesion diameter < or =2.0 cm) are usually considered as infarcts caused by small vessel disease. However, SSI can also be associated with large artery occlusive disease such as middle cerebral artery (MCA) stenosis. We performed a prospective study to investigate the relationship between MCA stenosis and SSI distribution and further to investigate the mechanism of SSI caused by MCA stenosis., Methods: Magnetic resonance angiography (MRA) and diffusion-weighed MRI (DWI) of consecutive acute ischemic stroke patients with recent SSI were studied. The distribution of acute infarcts on DWI was categorized as cortical infarct (CI), border zone infarct (BI), or perforating artery infarct (PAI)., Results: Totally, 93 cases were recruited, among which 12 had single SSI with MCA stenosis (group 1) and 26 patients had multiple SSI with MCA stenosis (group 2), while 55 patients without MCA stenosis had single SSI (group 3). For patients with single SSI and MCA stenosis, 6 had BI and 6 had PAI; for patients with multiple SSI and MCA stenosis, 25 had BI, 4 had PAI and 9 had CI (compared with group 1: P= .001); for patients with single SSI but without MCA stenosis, 20 had BI and 35 had PAI (compared with group 1: P= .58)., Conclusion: Multiple acute infarcts along the border zone are the commonest pattern in small infarcts with MCA stenosis, especially among those with multiple acute infarcts. Our data suggest that hemodynamic compromise and artery-to-artery embolism may be both important factors for infarcts in patients with MCA stenosis.

Background and Purpose: Cerebral embolism is a common cause of stroke. Microembolic signals (MES) detected by transcranial Doppler represent ongoing embolisms, but the lack of reliable data about its clinical relevance hinders its widespread use in clinical practice., Methods: We prospectively monitored 114 consecutive acute ischemic stroke patients with middle cerebral artery (MCA) stenosis for MES. The signals on digital audio tape were analyzed by an independent observer who was blinded to all other data. All patients were followed-up for the occurrence of recurrent stroke or transient ischemic attack (TIA) in the indexed MCA territory., Results: MES was detected in 25 (22%) patients. The mean number of MES was 18 (range, 1 to 102). MES were more common in patients with severe stenosis (10/21, 48%) than in those with mild-moderate stenosis (4/26, 15%) (Pearson chi2 P=0.02). During follow-up for a mean of 13.6 months (range, 1 to 32), 12 (12%) patients had further ischemic events (10 strokes and 2 TIAs) in the affected MCA region during follow-up. Among these, 7 (58%) had recurred within 1 month (1 recurred within 1 week, the other 6 patients had recurrences in week 3 or 4 after discharge), 3 within 6 months, 1 within 6 to 12 months, and the remaining 1 recurred after 1 year. The presence of MES was the only predictor of a further ischemic stroke/TIA by Cox regression (adjusted odds ratio, 8.45; 95% CI, 1.69 to 42.22; P=0.01) even after controlling for age, sex, diabetes, hypertension, previous stroke, smoking, and acute treatment., Conclusions: In acute stroke patients with MCA stenosis, MES predicts further cerebral ischemia. This procedure should be considered as part of routine investigation and might identify a group of patients who are most likely to benefit from antithrombotic treatment.

The 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene 677C --> T polymorphism causes an A222V amino acid change which affects MTHFR enzyme activity and can increase homocysteine, a vascular disease risk factor. This polymorphism was examined for association with stroke. In a case-control study of 241 ischemic stroke patients and 304 controls in Hong Kong, the V allele increased in stroke [28% vs. 20%, odds ratio (OR) 1.5, p=0.003]. A lack of significance for the increase in the VV genotype (7.5% vs. 4.6%, OR 1.7, p = 0.16) may be due to its rarity in this region. V -allele carriers had more severe strokes (according to the NIH stroke scale). The association of the V allele with stroke occurred mostly in women or older subjects and was due to decreasing V allele frequency with age, as seen in other studies. This V frequency decline with age might be due to a loss of V -carrying controls from a higher risk of cancer, vascular disease, bone fracture, and kidney failure when folate is sparse. Examination of previous studies revealed that the association of VV genotype with stroke appeared stronger in Japan than elsewhere, possibly due to dietary differences. Perhaps folate supplementation for stroke prevention would particularly benefit VV individuals in such high-risk regions.

Background: Small subcortical infarct (SSI) occurs more frequently among Chinese than Caucasians. Apart from small vessel disease, SSI is also associated with intracranial large artery disease. We aimed to study the frequency of SSI with and without intracranial large artery disease among Chinese stroke patients., Methods: Magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) were performed among consecutive Chinese stroke patients admitted to our acute stroke unit over a 6-month period., Results: Among the 257 patients with ischemic stroke, 71 patients (27.6%) had SSI. Twelve patients (16.9%) had relevant intracranial large artery disease and three patients (4.2%) had lone relevant extracranial carotid artery disease. No patient had an identifiable cardiac embolic source or other miscellaneous cause. Excluding patients with relevant intracranial large artery disease and extracranial carotid artery disease, the frequency of SSI associated with presumed small vessel disease among patients with ischemic stroke was 21.7%. Patients with SSI associated with intracranial large artery disease had greater number of acute infarcts and slightly greater stroke severity and cognitive impairment than those with presumed small vessel disease., Conclusion: Our present study suggests that the higher frequency of SSI among Chinese may be in part related to a higher frequency of intracranial large artery disease rather than to a higher frequency of small vessel disease.

Background and Purpose: Cerebral microbleeds (MBs) detected by gradient-echo MRI are considered evidence of advanced microangiopathy with potential for further bleeding. The goal of this study was to determine whether the presence of MBs is a risk factor for subsequent intracerebral hemorrhage among patients with acute ischemic stroke., Methods: We prospectively examined patients hospitalized with acute cerebral infarction with gradient-echo T2*-weighted MRI for the presence of MBs. We recorded demographics, medical history, and stroke severity. Patients were then followed up for the development of stroke, other vascular events, and death., Results: One hundred twenty-one consecutive patients with a mean age of 67.96+/-10.97 years were recruited. MBs were present in 43 patients (35.5%). During follow-up of 27.15+/-11.68 months, 16 patients had recurrent stroke. There was no difference between patients with or without MB for the development of ischemic stroke (5 and 6 respectively, P=0.841). However, 4 patients (9.3%) with MBs and 1 patient (1.3%) without an MB had intracerebral hemorrhage during follow-up (P=0.053). Of the 5 patients who developed subsequent intracerebral hemorrhages, 3 were treated with aspirin and 2 with anticoagulation. Two of the intracerebral hemorrhages occurred in the site where asymptomatic MBs were found at baseline., Conclusions: MBs appear to be a risk factor for subsequent intracerebral hemorrhage among patients with ischemic stroke in this small cohort of Chinese stroke patients. A large cohort study is required to confirm this observation.

Diabetes can cause more than double risk of ischemic stroke and is associated with with poor long-term prognosis after ischemic stroke. Surprisingly, intensively treating hyperglycemia has not been shown to have beneficial outcomes in either primary or secondary prevention in stroke disease. Encouragingly, multifactorial management of risk factors of ischemic stroke, in particular, lifestyle, glucose concentration, hypertension, and dyslipidemia will prevent a substantial number of ischemic stroke and improve the prognosis in diabetic patients. Antithrombotic treatment and carotid surgery are also essential for primary and secondary stroke prevention in selected diabetic patients. Evidence for primary and secondary prevention of ischemic stroke in diabetic patients is steadily evolving, and it is imperative that clinicians are actively informed regarding the latest advance in order to better implement stroke prevention in diabetic patients. [ABSTRACT FROM AUTHOR]