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Background: Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity. Methods: In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated. Results: Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient −0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values. Conclusions: Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose Of the stroke types, intracerebral hemorrhage is the most debilitating and fatal. The aim of the current study was to determine factors that influence the severity and in-hospital mortality after primary intracerebral hemorrhage. Methods Data were collected retrospectively on 1268 patients with primary intracerebral hemorrhage admitted to stroke units at participating hospitals in Guangzhou between January 2005 and August 2008. Logistic regression analysis was used to determine factors associated with severity on admission and in-hospital mortality. Results Of the 1268 patients, 20·4% were reported to have a severe stroke on admission, and the in-hospital mortality rate was 12·5%. Severity on admission was strongly associated with Glasgow Coma Scale score on admission (odds ratio = 0·89, 95% confidence interval 0·85-0·94) and hematoma location. Notably, basal ganglia hemorrhages were associated with increased severity (odds ratio = 1·40, 95% confidence interval 1·03-1·90), and cerebellar hemorrhages were associated with reduced severity (odds ratio = 0·29, 95% confidence interval 0·10-0·84). In-hospital mortality was not only correlated with Glasgow Coma Scale score on admission (odds ratio = 0·79, 95% confidence interval 0·74-0·84) and basal ganglia location (odds ratio = 0·47, 95% confidence interval 0·26-0·83), but also with dysnatremia (odds ratio = 1·91, 95% confidence interval 1·08-3·40) and comorbidities such as upper gastrointestinal hemorrhage (odds ratio = 2·28, 95% confidence interval 1·33-3·91), pneumonia (odds ratio = 3·50, 95% confidence interval 2·17-5·63), urinary incontinence (odds ratio = 2·22, 95% confidence interval 1·40-3·51), and renal dysfunction (odds ratio = 2·28, 95% confidence interval 1·42-3·65). Conclusion Glasgow Coma Scale score and hematoma locations were independently associated with severity on admission and in-hospital mortality after primary intracerebral hemorrhage. The study also highlights the deleterious effect of comorbidities on in-hospital mortality following primary intracerebral hemorrhage in China. [ABSTRACT FROM AUTHOR]

Summary: Background: Few randomised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis. Microembolic signals, detected by transcranial doppler, are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis. We aimed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke. Methods: The clopidogrel plus aspirin for infarction reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals (CLAIR) trial was a randomised, open-label, blinded-endpoint trial. Between Oct 28, 2003, and Nov 19, 2008, patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were randomly assigned within 7 days of symptom onset to receive clopidogrel (300 mg for the first day, then 75 mg daily) plus aspirin (75–160 mg daily) or aspirin alone (75–160 mg daily) for 7 days. Patients were randomly assigned in blocks of four or six by use of a randomisation website. Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7. The primary endpoint was the proportion of patients who had microembolic signals on day 2. Analysis was by modified intention to treat. All analyses were done by an investigator masked to both patient identity and the day the recording was taken. This trial is registered with the Centre for Clinical Trials, Chinese University of Hong Kong, number CUHK_CCT00164. Findings: 100 patients were randomly assigned to clopidogrel plus aspirin (n=47) or aspirin monotherapy (n=53). 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery: 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group. At day 2, 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler (relative risk reduction 42·4%, 95% CI 4·6–65·2; p=0·025). Adverse events were similar in the two groups. No patients had intracranial or severe systemic haemorrhage, but two patients in the dual therapy group had minor haemorrhages. Interpretation: Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis. Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence. Funding: Research Grant Council Earmarked Grant and Asian Stroke Research Grant, Chinese University of Hong Kong. [Copyright &y& Elsevier]

Abstract: Objective: Inflammatory endothelial activation mediated by intercellular adhesion molecule-1 (ICAM-1) plays a role in the pathogenesis of large- and small-vessel disease. We explored the association between soluble ICAM-1 (sICAM-1) and white matter lesion (WML) as a manifestation of cerebral small-vessel disease. Methods: One hundred and seventy-five elderly individuals aged ≥ 60 without neurological deficits were studied. Subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH) were rated separately. Lesions in each category were then divided into three groups (grade 0-I, grade II, grade III) according to the Fazekas scale. Results: Plasma sICAM-1 levels were positively associated with grades of WML (for SDWMH: 297.4±135.6ng/mL in grade 0-I, 391.3±145.5ng/mL in grade II, and 450.2±232.9ng/mL in grade III, p <0.001; for PVH: 282.5±116.5ng/mL in grade 0-I, 402.3±160.4ng/mL in grade II, and 428.1±227.7ng/mL in grade III, p <0.001). Multivariate analysis showed higher sICAM-1 levels, age and hypertension were the independent risk factors associated with the presence and severity of WML. More than 4-fold increased risk of WML was observed in patients with the highest quartile of sICAM-1 (all WML OR=4.694, 95% CI: 1.805–12.204; moderate WML OR=4.618, 95% CI: 1.543–13.825; severe WML OR=4.893, 95% CI: 1.236–19.368). Conclusion: Increased plasma sICAM-1 suggests inflammatory process may be involved in the pathogenesis of WML. [Copyright &y& Elsevier]

Summary: 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 ≥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. [Copyright &y& Elsevier]

Abstract: Background: This study aimed to compare changes in plasma β-globin DNA and serum S100 protein to diagnose stroke and for predicting mortality and morbidity. Methods: Patients with stroke-like symptoms presenting to the emergency department of a Hong Kong hospital were recruited. Plasma DNA was analyzed for the β-globin gene with fluorescent-based PCR. S100 concentrations were determined using ELISA. Primary outcomes were diagnosis of stroke, mortality, and modified Rankin Score (mRS) after 6 months. Results: One hundred ninety-seven consecutive patients recruited, 118 (60%) ischemic stroke, 35 (18%) hemorrhage and 44 (22%) with no acute neuroimaging changes. Serum S100 and plasma DNA were increased in 126 (p <0.0010) and 36 (p =0.21) stroke patients respectively vs. controls. Median plasma DNA was higher in hemorrhagic stroke than those without (1725 vs. 1050 kilogenome-equivalents/l, p =0.0104). Median plasma DNA was higher in mRS>2 vs. mRS≤2 (1350 vs. 1025, p =0.0103), and higher in non-survivors vs. survivors (1625 vs. 1050, p =0.0070). Median serum S100 higher in mRS>2 patients vs. mRS≤2 (0.152 vs. 0.131 μg/l, p =0.0003). The odds ratio (OR) of discriminating hemorrhagic from non-hemorrhagic stroke with DNA was 4.24 (95% CI 1.88–9.56); S100 and DNA together give an OR of 16.55. Conclusion: For stroke diagnosis, S100 performs better than DNA; DNA is a better marker for hemorrhage. For diagnosis of hemorrhagic stroke, combined S100 and DNA performs better than either alone. Plasma DNA and serum S100 predict morbidity and mortality in stroke. [Copyright &y& Elsevier]

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 Wgenotype (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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of the non-ergot dopamine agonist pramipexole in untreated and levodopa-treated Chinese patients with early or advanced Parkinson''s disease. Methods: This randomized, double-blind, placebo-controlled, parallel-group study, which was conducted in Hong Kong and Taiwan, comprised a screening period of at least 1 week, a dose-escalation period of 7 weeks, and a maintenance period of 8 weeks (total duration of treatment: 15 weeks). During the dose-escalation period, the dose of pramipexole (or number of placebo tablets) was escalated in a blinded fashion according to a predetermined schedule to the optimum tolerated dose of pramipexole, administered three times a day (minimum dose=0.375 mg/day; maximum dose=4.5 mg/day). This dose was then maintained for the duration of the maintenance period. Efficacy was primarily assessed by the Unified Parkinson''s Disease Rating Scale (UPDRS). Safety and tolerability were evaluated by treatment-emergent adverse event reports, clinical laboratory test results (blood chemistry, hematology, and urinalysis), vital signs, and electrocardiograms. Results: Pramipexole was significantly more effective than placebo in reducing the total scores of the UPDRS Part II, Part III, and Parts II and III combined. Approximately 70% of both the placebo- and pramipexole-treated patients evaluated in this analysis were on levodopa. Regardless of levodopa use, the mean UPDRS total scores showed a consistently greater improvement in pramipexole patients than in placebo patients. Mean scores for pramipexole patients not on levodopa showed a greater improvement than did pramipexole patients on levodopa. The mean improvement for the pramipexole/no levodopa group relative to the placebo/no levodopa group at week 15 was 10.93 points (i.e., −14.43 points minus −3.50 points). The mean improvement for the pramipexole/levodopa group relative to the placebo/levodopa group at week 15 was 9.04 points (i.e., −10.26 points minus −1.22 points). Pramipexole was also superior to placebo as measured by improvement in the modified Hoehn and Yahr Scale and a reduction in the number of “off” hours for patients on concomitant levodopa therapy. Conclusions: Pramipexole is an effective and well-tolerated therapy, with or without concomitant levodopa, for Chinese patients with Parkinson''s disease. [Copyright &y& Elsevier]

Background: The Oxfordshire Community Stroke Project (OCSP) classification is a stroke classification based on clinical features collected at bedside. Previous studies reported good correlation between vascular abnormalities and OCSP mainly in populations not at risk of intracranial atherosclerosis. There have been limited data on the relationship between intracranial atherosclerosis and the OCSP classification. Methods: Consecutive Chinese patients admitted to a regional hospital with acute ischemic stroke were studied in Hong Kong. Stroke subtype was classified as total or partial anterior circulation infarct (TACI or PACI), posterior circulation infarct (POCI), or lacunar infarct (LACI), according to the OCSP method. Transcranial Doppler (TCD) was performed whenever possible to evaluate the intracranial arteries as well as the carotid arteries. National Institute of Health Stroke Scale (NIHSS) was used to assess the severity of stroke on admission. Results: Six hundred and ninety-nine consecutive patients were studied. On admission, 24 patients were classified as TACI (3.4%), 96 PACI (13.7%), 111 POCI (15.9%), and 468 LACI (67.0%). Of the 345 patients who had TCD evidence of intracranial or carotid artery abnormalities, 75% had intracranial involvement only, 5% extracranial involvement only and 20% had both intracranial and extracranial involvement. The frequencies of arterial abnormalities were found in 58% of TACIs, 48% of PACIs, 48% of POCIs and 50% of LACIs. There was no evidence that the frequencies of arterial abnormalities were different between the OCSP groups (P=0.8). Middle cerebral artery velocity was abnormal in 9 TACIs (38%), 32 PACIs (33%), 35 POCIs (32%) and 177 LACIs (38%) (P=0.6). Vertebrobasilar velocities were abnormal in 4 TACIs (17%), 20 PACIs (21%), 29 (26%) and 87 LACIs (19%) (P=0.3). The OCSP subtypes were associated with POCIs the severity of stroke. NIHSS score of ≥9 was found in 83% of TACIs, 18% of PACIs, 9% of POCIs, and 12% of LACIs (P<0.0001). Conclusions: OCSP classification is not significantly related to the presence of vascular abnormalities among patients with predominantly intracranial atherosclerosis. [Copyright &y& Elsevier]

Background: Few randomised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis. Microembolic signals, detected by transcranial doppler, are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis. We aimed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke. Methods: The clopidogrel plus aspirin for infarction reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals (CLAIR) trial was a randomised, open-label, blinded-endpoint trial. Between Oct 28, 2003, and Nov 19, 2008, patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were randomly assigned within 7 days of symptom onset to receive clopidogrel (300 mg for the first day, then 75 mg daily) plus aspirin (75-160 mg daily) or aspirin alone (75-160 mg daily) for 7 days. Patients were randomly assigned in blocks of four or six by use of a randomisation website. Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7. The primary endpoint was the proportion of patients who had microembolic signals on day 2. Analysis was by modified intention to treat. All analyses were done by an investigator masked to both patient identity and the day the recording was taken. This trial is registered with the Centre for Clinical Trials, Chinese University of Hong Kong, number CUHK_CCT00164. Findings: 100 patients were randomly assigned to clopidogrel plus aspirin (n=47) or aspirin monotherapy (n=53). 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery: 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group. At day 2, 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler (relative risk reduction 42.4%, 95% CI 4.6-65.2; p=0.025). Adverse events were similar in the two groups. No patients had intracranial or severe systemic haemorrhage, but two patients in the dual therapy group had minor haemorrhages. Interpretation: Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis. Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence. [ABSTRACT FROM AUTHOR]

This Practice Point commentary discusses an observational study by Wahlgren et al. that examined the use of intravenous alteplase in a routine clinical setting 3-4.5 h after onset of stroke. The study recruited patients from the SITS-ISTR thrombolysis registry. The outcomes of 664 patients treated with intravenous alteplase at between 3 h and 4.5 h after stroke onset were compared with those of 11,865 patients treated within 3 h. No significant differences were noted between the two cohorts at 3 months regarding the rate of symptomatic intracerebral hemorrhage, mortality, or functional independence. The study provides invaluable information about the safety of alteplase for acute stroke when used within this extended time frame, although the investigation lacked comprehensive central auditing of the data, and it was difficult to ascertain whether all patients treated in the participating centers were included in the dataset and to verify that no biased reporting occurred. [ABSTRACT FROM AUTHOR]

A response by Ka Sing Lawrence Wong and colleagues to a letter to the editor about their article "Early Dual Versus Mono Antiplatelet Therapy for Acute Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack: An Updated Systematic Review and Meta-Analysis," published in the previous issue, is presented.

The article presents a case study of 83-year old Chinese woman suffering from atrial fibrillation and dementia who was hospitalized due to cardiac arrest. Her magnetic resonance imaging scan before removal of middle cerebral artery (MCA) and after removal was performed for histological comparisons. The results showed hyper intense signal in left MCA and confirmed intraplaque hemorrhage.

Background: Despite doubts about their efficacy and concern about their safety, antithrombotic agents are often used to treat acute ischemic stroke. Recent experience in patients with other thromboembolic disorders suggests that low-molecular-weight heparin, which requires only subcutaneous administration once or twice daily, may be more effective and safer than standard (unfractionated) heparin. Methods: We conducted a randomized, double-blind, placebo-controlled trial comparing two dosages of low-molecular-weight heparin with placebo in the treatment of ischemic stroke. Patients were randomly assigned within 48 hours of the onset of symptoms to receive high-dose nadroparin (4100 anti–factor Xa IU twice daily), low-dose nadroparin (4100 IU once daily), or placebo subcutaneously for 10 days. The primary measure of outcome was death or dependency regarding activities of daily living six months after randomization. Secondary outcomes were death, hemorrhagic transformation of the infarction, and other complications at 10 days, and death or dependency at 3 months. Results: A total of 2750 patients were screened for the study. Among 312 patients randomized, 306 had outcomes that were analyzed at six months. Forty-five patients (45 percent) in the high-dose group, 53 patients (52 percent) in the low-dose group, and 68 patients (65 percent) in the placebo group died or became dependent. There was a significant dose-dependent effect among the three study groups in favor of low-molecular-weight heparin (P = 0.005 by the chi-square test for trend). No significant differences among the groups in the occurrence of secondary outcomes were observed at 10 days. Conclusions: For patients with ischemic stroke treated within 48 hours of the onset of symptoms, low-molecular-weight heparin was effective in improving outcomes at six months. (N Engl J Med 1995;333:1588-93.) [ABSTRACT FROM AUTHOR]

Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping. Peripheral neuropathy in particular is often misdiagnosed or underdiagnosed because of a lack of awareness amongst both patients and physicians. Furthermore, crude screening tools, such as the 10‐g monofilament, only detect advanced neuropathy and a normal test will lead to false reassurance of those with small fiber mediated painful neuropathy. The underestimation of peripheral neuropathy is highly prevalent in the South‐East Asia region due to a lack of consensus guidance on routine screening and diagnostic pathways. Although neuropathy as a result of diabetes is the most common cause in the region, other causes due to infections (human immunodeficiency virus, hepatitis B or C virus), chronic inflammatory demyelinating polyneuropathy, drug‐induced neuropathy (cancer chemotherapy, antiretrovirals and antituberculous drugs) and vitamin deficiencies (vitamin B1, B6, B12, D) should be actively excluded. [ABSTRACT FROM AUTHOR]

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50–69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70–99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) 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. [ABSTRACT FROM AUTHOR]

With over 2 million new cases annually, stroke is associated with the highest disability-adjusted life-years lost of any disease in China. The burden is expected to increase further as a result of population ageing, an ongoing high prevalence of risk factors (eg, hypertension), and inadequate management. Despite improved access to overall health services, the availability of specialist stroke care is variable across the country, and especially uneven in rural areas. In-hospital outcomes have improved because of a greater availability of reperfusion therapies and supportive care, but adherence to secondary prevention strategies and long-term care are inadequate. Thrombolysis and stroke units are accepted as standards of care across the world, including in China, but bleeding-risk concerns and organisational challenges hamper widespread adoption of this care in China. Despite little supporting evidence, Chinese herbal products and neuroprotective drugs are widely used, and the increased availability of neuroimaging techniques also results in overdiagnosis and overtreatment of so-called silent stroke. Future efforts should focus on providing more balanced availability of specialised stroke services across the country, enhancing evidence-based practice, and encouraging greater translational research to improve outcome of patients with stroke. [ABSTRACT FROM AUTHOR]

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries.Methods: Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA).Results: In total, 318 patients were analyzed. Spearman’s correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p < 0.001 individually. Similar correlation was also found between IAC Agatston score and high VBA velocity/high VBA PI, p ≤ 0.001 individually. Multiple logistic regression analysis showed IAC Agatston score was an independent risk factor for high MCA velocity (OR 1.533; 95% CI 1.235-1.903), high VBA velocity (OR 1.964; 95% CI 1.381-2.794), and high VBA PI (OR 1.200; 95% CI 1.016-1.418), respectively.Conclusion: Heavier IAC might cause generalized artery flow velocity changes and increased pulsatility index, which may indicate high resistance within cerebrovasculature. [ABSTRACT FROM AUTHOR]

Background: CT perfusion (CTP) imaging provides quantitative evaluation of cerebral perfusion flow and volume. Our previous findings showed that benign oligemia caused by intracranial large artery disease may be existent in subacute stroke. Aims: We aimed at comparing the topographic patterns and clinical outcome of stroke patients with and without persistent benign oligemia as defined by CTP imaging. Methods: Consecutive ischemic stroke patients who were referred for CTP in 2009 were screened. The topographic patterns (cortical, borderzone or perforating artery territory infarcts) were assessed by diffusion-weighted imaging (DWI). The clinical outcome was defined by modified Rankin score at 6 months after stroke onset. Results: Totally, 26 stroke patients were recruited. Benign oligemia in subacute stage was detected in 15 patients. The occurrence of borderzone infarction was higher in stroke patients with benign oligemia than those without (p = 0.036). Conclusions: The topographic pattern of DWI may be different between the intracranial arterial disease patients with and without benign oligemia on CTP in subacute stroke. [ABSTRACT FROM AUTHOR]

Background and Purpose: Intracranial vessel wall imaging using MRI has great potential as a clinical method for assessing intracranial atherosclerosis. The purpose of the current study was to compare three 3T MRI vessel wall sequences with different contrast weightings (T1w, PD, T2w) and dedicated sagittal orientation perpendicular to the middle cerebral artery, to the reconstructed sagittal image from a transverse 3D T1w volumetric isotropically reconstructed turbo spin-echo acquisition (VIRTA), and provide a clinical recommendation. Materials and Methods: The above-mentioned sequences were acquired in 10 consecutive Chinese ischemic stroke or TIA patients (age: 68 years, sex: 4 females) with angiographic-confirmed MCA stenosis at 3T. Institutional review board approval was obtained. Two raters qualitatively scored all images on overall image quality, presence of artifacts, and visibility of plaques. Data were compared using Repeated measures ANOVA and Sidak’s adjusted post hoc tests. Results: All sequences except the T2w sequence were able to depict the walls of the large vessels of the Circle of Willis (p<0.05). T1w sagittal oblique VIRTA showed significantly more artifacts (p<0.01). Peripherally located plaques were sometimes missed on the sagittal sequences, but could be appreciated on the transverse T1w VIRTA. Conclusion: With the 3T multi-sequence vessel wall protocol we were able to assess the intracranial plaque with two different image contrast weightings. The sequence of preference to include in a clinical protocol would be the transverse 3D T1w VIRTA based on absence of artifacts, larger coverage including the whole Circle of Willis, and excellent lesion depiction. [ABSTRACT FROM AUTHOR]

Objective: Success in clinical trials of intracranial atherosclerosis (ICAS) is related to accurate identification of high-risk patients. Noninvasive computational fluid dynamics (CFD) of stenotic lesions may enhance therapeutic decision-making. We determined whether physiologic parameters change downstream cerebral hemodynamics in patients with ICAS.Methods: Consecutive ICAS patients who underwent both CT angiography (CTA) and digital subtraction angiography were enrolled. CFD models were made using CTA source images. Inlet boundary conditions were defined using three ranges of systolic blood pressure (BP) (109.2, 158, and 225 mmHg) and hematocrit (27.3, 40.2, and 48.8). Ratios of pressure, shear strain rates (SSR), and flow velocity across the lesion were calculated using CFD simulations. A linear mixed model was used for the statistical analysis of repeated simulations.Results: Among the 56 patients, 32 had moderate stenosis (50-69%) and 24 had severe stenosis (70-99%). A linear mixed model revealed that the ratio of pressure was predicted by systolic BP and stenosis group interaction (P = .036). These pressure decreases were associated with systolic BP (P < .001) and stenosis group (P < .001), but not with hematocrit (P = .337). Post-hoc analysis revealed that pressure decreases were more profound in the severe stenosis than the moderate stenosis group when comparing high and low systolic BP (P = .0108). Ratios of SSR and velocity were only associated in the stenosis group.Conclusions: Our study showed that systolic BP along with the degree of stenosis was associated with pressure decreases across stenotic lesions. Physiologic conditions may superimpose further changes in post-stenotic or downstream blood flow. [ABSTRACT FROM AUTHOR]

Background: Collateral pathways are important in maintaining adequate cerebral blood flow in patients with carotid stenosis. We aimed to evaluate the hemodynamic patterns in relation to carotid stenosis in acute stroke patients.Methods: Consecutive 586 stroke patients in a hospital based cohort were included in the present study. Carotid duplex was performed to identify patients with absolute minimal diameter reductions of 50% or greater in their internal carotid arteries (ICAs). Color velocity imaging quantification ultrasound (CVIQ) was used to measure extracranial arterial blood flow volume (BFV) in bilateral common carotid arteries (CCAs) and bilateral vertebral arteries (VAs). The absolute values of BFV and the ratios were compared between patients with and without ICA stenosis.Results: Among 586 acute ischemic stroke patients (mean age: 67.5 ± 12.4y), ICA stenosis was detected in 112 patients (19.1%), including unilateral ICA stenosis in 81 patients (13.8%) and bilateral ICA stenosis in 31 patients (5.3%). Among patients with unilateral ICA stenosis, the BFV in contralateral CCA was significantly higher than that in ipsilateral CCA (325.5 ± 99.8 mL/min vs. 242.2 ± 112.2 mL/min, P < 0.001). Among patients with bilateral ICA stenosis, the sum of BFV in bilateral VAs accounted for 22% of the whole cerebral blood flow, which was significantly higher than that in those without ICA stenosis (14.8%, P < 0.001) or with unilateral ICA stenosis (16.9%, P = 0.007).Conclusions: In patients with unilateral carotid stenosis, contralateral carotid blood flow increases to compensate decreased blood flow, while posterior circulation may compensate for the decreased brain perfusion in those with bilateral carotid stenosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims The purpose of this study was to discuss the relationship between blood pressure and prognosis of patients with symptomatic intracranial arterial stenosis. Methods Data on 2426 patients with symptomatic intracranial large artery stenosis and occlusion who participated in the Chinese Intracranial Atherosclerosis ( CICAS) study were analyzed. According to the JNC 7 criteria, blood pressure of all patients was classified into one of the four subgroups: normal, prehypertension, hypertension stage I, and hypertension stage II. Poor outcomes were defined as death and functional dependency ( mRS 3-5) at discharge or at 1 year. Results For patients with intracranial stenosis of 70% to 99%, the rate of poor outcome at discharge was 19.3%, 23.5%, 26.8%, and 39.8% ( P = 0.001) for each blood pressure subgroup. For patients with intracranial large artery occlusion, the rates were 17.6%, 22.1%, 29.5%, and 49.8%, respectively ( P < 0.0001). The rate of poor outcome at 12-month follow-up was 12.6%, 15.3%, 28.5%, and 27.9% ( P = 0.0038) in patients with stenosis of 70% to 99% for each blood pressure subgroup and 11.6%, 21.5%, 23.9%, 35.1% ( P < 0.0001) in patients with occlusion. Conclusions For patients with severe intracranial arterial stenosis or occlusion, higher hypertension stages are associated with an increased risk of poor outcome at discharge and 12-month follow-up. [ABSTRACT FROM AUTHOR]

Objective: Diabetic patients with acute coronary syndrome (ACS) are at higher risk of poor outcome than are non-diabetic patients with ACS. Few studies have focused on sex-related ACS incidence, ACS-related mortality or risk factors to affects sex specific ACS in Chinese with Type 2 diabetes mellitus (T2DM). Based on a hospital-based cohort of Chinese patients with T2DM, we aimed to investigate whether there was sex difference in ACS or ACS-related mortality or risk factors of ACS. Methods: Totally 2,135 Hong Kong Chinese with T2DM were recruited during 1994-1996 and followed up until August 2012. We systematically analyzed sex-related ACS incidence and ACS-related mortality and risk factors with χ2-squared test, descriptive statistics and survival analysis. Results: Regular follow-up was completed in 2,105 subjects (98.6%), with a median period of 14.53 years. The occurrence of ACS was recorded among 414 patients (19.7%) and ACS-related death among 104 patients (4.9%). ACS incidences increased with age in both men and women, and men had a higher prevalence of ACS than women across different age categories and different follow-up periods (log rank χ2=20.32, P<0.001). The transition of ACS incidences from slow to rapid increase were about 5 years earlier in men (at 51-55 years) than in women (55-60 years). Among ACS patients, cumulative ACS-related mortalities was similar between men and women (log rank χ2=0.063, P=0.802). Besides age and albuminuria, different profiles of risk factors accounted for the occurrence of ACS between men and women. Conclusions: Our findings demonstrated sex differences in ACS incidence and risk factors, but not in ACS-related mortality in Chinese patients withT2DM. These findings suggest that screening and prevention campaigns should be optimized for men and women, which may help to identify diabetic patients at higher risk of coronary heart disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. Methods In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. Results Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year ( p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. Interpretation A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence. Ann Neurol 2015;77:478-486 [ABSTRACT FROM AUTHOR]

Objective: To investigate whether asymptomatic middle cerebral artery (MCA) stenosis is associated with risk of cardiovascular disease (CVD) in Chinese with type 2 diabetes. Methods: In this prospective cohort study, 2,144 Hong Kong Chinese with type 2 diabetes and without history of stroke or atrial fibrillation were recruited in 1994–1996 and followed up for a median of 14.51 years. Participants were assessed at baseline for MCA stenosis using transcranial Doppler. We performed survival analysis to assess the association between asymptomatic MCA stenosis and first CVD event, defined as ischemic stroke, acute coronary syndrome (ACS) or cardiovascular death. Results: Of the 2,144 subjects, MCA stenosis at baseline was detected in 264 (12.3%). Rates of stroke, ACS and cardiovascular death per 100 were, respectively, 2.24, 2.92 and 1.11 among participants with stenosis, higher than among those without stenosis. Ten-year cumulative occurrence of stroke, ACS and cardiovascular death in subjects with MCA stenosis was 20%, 24% and 10%, respectively, higher than the corresponding values for subjects without stenosis(all P<0.001). After adjusting for covariates, MCA stenosis was found to be an independent predictor of stroke [hazard ratio (HR) 1.40, 95%CI 1.05–1.86; P = 0.02], ACS (HR 1.35, 95%CI 1.04–1.75; P = 0.02) and cardiovascular death(HR 1.56, 95%CI 1.04–2.33; P = 0.03). Conclusions: Asymptomatic MCA stenosis is a risk factor for CVD in Chinese with type 2 diabetes, and detection of asymptomatic MCA stenosis by transcranial Doppler can identify diabetic individuals at high risk of future CVD. This finding is particularly important for diabetic individuals in Asia, where intracranial atherosclerosis is common. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset. Methods: Patients with a symptomatic ICAS lesion of 70–99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year. Results: Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (−2.46–0.79), 4.5 (2.2–20.6), and 7.4 (5.2–12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004–1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002–1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594–0.903; P = 0.014) and 0.776 (95% CI, 0.594–0.903; P = 0.002) in receiver operating characteristic analysis. Conclusions: Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70–99% luminal stenosis. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Abstract: Background and Purpose: Our previous study found that cortical gray matter (cGM) volume predicted vascular cognitive impairment independent of age-related white matter changes (WMC). We aimed to investigate predictors for cGM volume in ischemic stroke patients with confluent WMC. Methods: One-hundred post-stroke patients with confluent WMC were recruited into the study. All volumetric measures were standardized by intracranial volume as volume ratio. Univariate analyses and multivariate linear regression models were used to test relationship of cGM volume with basic demography, vascular risk factors, APOE status, WMC volume (periventricular and deep WMC), infarct measures (volume, number and location) and microbleed (number, presence and location). Results: After controlling for significant variables in the univariate analyses, multivariate linear regression models found that old age (β =−0.288, p =0.001), low triglyceride (β =0.194, p =0.027), periventricular WMC (PVWMC) (β =−0.392, p <0.001) and presence of thalamic microbleed (β =−0.197, p =0.041) were independently predictive of less cGM volume ratio. Conclusions: Age, PVWMC and left thalamic microbleed predict less cGM volume. [Copyright &y& Elsevier]

Summary: 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 &y& Elsevier]

Background and purpose Vascular cognitive impairment (VCI) affects up to half of stroke survivors and predicts poor outcomes. Valid and reliable assessement for VCI is lacking, especially for the Chinese population. In 2005, the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) Harmonisation workshop proposed a set of three neuropsychology protocols for VCI evaluation. This paper is to introduce the protocol design and to report the psychometric properties of the Chinese NINDS-CSN VCI protocols. Methods Fifty patients with mild stroke (mean National Institute of Health Stroke Scale 2.2 (SD=3.2)) and 50 controls were recruited. The NINDS-CSN VCI protocols were adapted into Chinese. We assessed protocols' (1) external validity, defined by how well the protocol summary scores differentiated patients from controls using receiver operating characteristics (ROC) curve analysis; (2) concurrent validity, by correlations with functional measures including Stroke Impact Scale memory score and Chinese Disability Assessment for Dementia; (3) internal consistency; and (4) ease of administration. Results All three protocols differentiated patients from controls (area under ROC for the three protocols between 0.77 to 0.79, p<0.001), and significantly correlated with the functional measures (Pearson r ranged from 0.37 to 0.51). A cut-off of 19/20 on MMSE identified only one-tenth of patients classified as impaired on the 5-min protocol. Cronbach's α across the four cognitive domains of the 60-min protocol was 0.78 for all subjects and 0.76 for stroke patients. Conclusions The Chinese NINDS-CSN VCI protocols are valid and reliable for cognitive assessment in Chinese patients with mild stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND Age-related white matter changes (WMC) increase risk of cognitive and functional decline. They are considered as target for preventive trials. However, using magnetic resonance imaging (MRI) to screen for subclinical WMC is not cost-effective. We explored the clinical utility of transcranial Doppler ultrasound (TCD) in the evaluation of WMC. We hypothesized that the pulsatility index (PI) of TCD correlates with severity of WMC. METHODS Among 100 stroke patients with WMC, we obtained the mean PI of middle cerebral artery (MCA) and vertebral basilar artery (VB). We investigated the association between PI and WMC volume. We also obtained PI of 50 subjects who had no WMC on MRI and explored the ability of PI values in differentiating subjects with and without WMC. RESULTS Multivariate linear regressions found that mean MCA PI and mean VB PI were independent predictors for total WMC volume (beta = .43, P < .001 and beta = .37, P < .001, respectively). Mean MCA PI significantly differentiated patients with WMC from those without WMC (area under curve [AUC] .85 [95% confidence interval .78-.91]) with an optimal cut-off value at 1.15 that yielded sensitivity and specificity of 73.7% and 82%, respectively. AUC for mean VB PI was .81 (95% confidence interval .74-.88) with cut-off value at 1.06 that yielded sensitivity and specificity of 70% and 75%, respectively. CONCLUSIONS PI correlates with volume of WMC. It may help to differentiate those with and without WMC in stroke patients. Further study evaluating the clinical utility of TCD in screening for subclinical WMC among community elderly is warranted. [ABSTRACT FROM AUTHOR]

Background: Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis. Methods: We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study. Angiograms were graded systematically in a blinded fashion for antegrade and collateral flow, using Thrombolysis in Cerebral Infarction (TICI) and American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading, respectively, and integrated to a simple composite circulation score. Demographic and clinical variables, modified Rankin Scale (mRS) scores at 3 months, recurrent stroke or TIA in 12 months were collected. Uni- and multivariate analyses were performed to identify independent predictors of good outcome (mRS 0-2) and recurrence in a logistic regression model. Results: Among 69 patients with pure intracranial atherosclerosis ≥50%, compromised antegrade flow (TICI 0-2a) was observed in 26 (36%) patients and was associated with more severe arterial stenosis (mean 86 vs. 74%, p = 0.001). Poor collateral compensation resulting in a poor composite circulation score was observed in 8 (12%) patients. Patients with a good circulation score (n = 61, 88%) had preserved flow, which was associated with more favorable outcome (OR 7.50, 95% CI 1.11-50.7, p = 0.04) and less recurrent TIA or stroke (OR 0.18, 95% CI 0.04-0.96, p = 0.04). Prognosis was not significantly associated with antegrade or collateral grade per se. Conclusion: Good collateral compensations are more important in patients with symptomatic intracranial stenosis and compromised antegrade flow, and are associated with favorable outcome and less recurrence risk. The feasibility of composite flow assessment should be explored in future studies to identify high-risk intracranial stenosis with compromised hemodynamics. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: 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 2months after acute ischemic stroke. Methods: 34 consecutive acute ischemic stroke patients within 7days 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 2months 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. 2months 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 &y& Elsevier]

Background Cerebral microbleeds may contribute to cognitive deficits in stroke. Cognitive impairment that does not meet the criteria for dementia (cognitive impairment no dementia) is common in stroke, and patients with such impairment can revert to normal cognition. Aims and hypothesis This study examined the association between cerebral microbleeds and the reversion of cognitive impairment no dementia. Method A total of 328 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. All subjects were assessed for cognitive impairment no dementia with a neuropsychological test battery at three- and 15 months following the index stroke. Of the 180 patients with cognitive impairment no dementia at three-months poststroke, 143 (79·4%) attended the 15-month follow-up. Twenty-nine subjects had reverted from cognitive impairment no dementia to normal cognitive status (reverters), 98 were nonreverters and 16 had progressed to dementia. Results In univariate analysis, the reverters were found to be younger, less likely to have hypertension and cerebral microbleeds, and to have smaller white matter hyperintensity volumes. In multivariate analysis, the absence of cerebral microbleeds remained an independent predictor of reversion with an odds ratio of 4·3. Absence of deep cerebral microbleeds predicted the reversion of the language domain, whereas the absence of lobar cerebral microbleeds predicted the reversion of the visuomotor speed domain. Conclusions The results suggest that the absence of cerebral microbleeds may be associated with a higher likelihood of a reversible cognitive impairment in stroke patients. The mechanism of how this occurs is not well understood. [ABSTRACT FROM AUTHOR]

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, p¼0.017) 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Polymorphisms of the transforming growth factor-β1 (TGFB1) gene have not been associated with asymptomatic atherosclerosis previously. We investigated the relationship between a single nucleotide polymorphism (SNP) rs4803455 in TGFB1 and atherosclerosis identified by the presence of carotid plaque and increased intima–media thickness (IMT) in an older Chinese population. Methods: 1996 subjects (992 (49.7%) men aged 50–85 years) from the Guangzhou Biobank Cohort Study-Cardiovascular Subcohort (GBCS-CVD) were genotyped. Carotid plaque and IMT were assessed by B-mode ultrasonography. Results: In male subjects, the C allele of TGFB1 rs4803455 was significantly associated with prevalence of carotid plaque (adjusted OR: 2.49, 95% CI: 1.16–5.36, P =0.03). The C allele was related to increased number of common carotid artery (CCA) plaques (P =0.03) and larger carotid plaque area (P =0.02) in men. The homozygous carriers of allele C in male subjects also had a higher risk of having carotid IMT ≥1mm (adjusted OR: 1.75, 95% CI: 1.05–2.93, P =0.03). These associations were independent of age, smoking, physical activity, body mass index, blood pressure, lipid profile, fasting glucose and high sensitivity C-reactive protein. Conclusion: This is the first study to show that the C allele in TGFB1 was associated with increased risk of atherosclerosis in older Chinese men. Further investigations on the linkage between the TGFB1 gene and progression of atherosclerosis in asymptomatic populations are warranted. [Copyright &y& Elsevier]

Background/Aims: This study aimed to determine the clinical and neuroimaging correlates of the presence of neuropsychiatric symptoms in stroke patients with age-related confluent white matter hyperintensities (WMH). Methods: The Neuropsychiatric Inventory was utilized to detect the presence of 12 symptoms. Multivariate logistic regression models were used to identify clinical and neuroimaging correlates of the presence of symptoms. Results: Seventy-seven stroke patients (mean WMH volume: 39.5 cm3) were recruited. Thirty patients (39%) had ≥1 neuropsychiatric symptom. Poor executive function was associated with the presence of any symptoms and symptoms other than depression. More severe left frontal WMH was associated with depression. Conclusion: Executive dysfunction and left frontal WMH are correlated with neuropsychiatric symptoms in these patients. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]