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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.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.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 p0.05). 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.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.

Neurological deterioration (ND) after ischaemic stroke has been indicated as an independent risk factor for poor outcome. Previous studies have focussed on ND within the first few days after symptom onset, but many patients are likely to experience deterioration outside of this time frame. We aimed to investigate the predictors of ND during hospitalisation.Data were obtained from the Chinese Intracranial Atherosclerosis (CICAS) Study, and patients who were diagnosed with ischaemic stroke and arrived at the hospital within 72 hours after symptom onset were included in the present study. Neurological deterioration was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 2 points at discharge compared with admission. MR angiography (MRA) and duplex colour Doppler ultrasound were used to document the presence of intracranial or extracranial artery stenosis. Intracranial artery stenosis was defined as a reduction in the artery diameter of ≥ 50% on MRA. Multivariate analyses were conducted to determine the potential predictors of ND during hospitalisation.Of the 1996 patients included in this study, 84 (4.21%) developed ND during hospitalisation. Compared with non-ND patients, ND patients showed higher rates of pneumonia (25.0 vs 9.5%, P 0.001), urinary infection (7.1 vs 1.2%, P 0.01), stroke recurrence (14.3 vs 1.9%, P 0.001), watershed infarct (15.5 vs 5.4%, P = 0.002), intracranial internal carotid artery (ICA) stenosis (11.9 vs 6.0%, P = 0.041), middle cerebral artery (MCA) stenosis (39.3 vs 22.0%, P 0.001) and basilar artery (BA) stenosis (16.7 vs 7.1%, P = 0.011). Multivariate analysis indicated that watershed infarcts (OR, 2.85; 95% CI, 1.04-7.81), MCA (OR, 2.23; 95% CI, 1.17-4.25) and BA (OR, 2.86; 95% CI, 1.19-6.87) stenosis or occlusion were independent risk factors for ND, as was pneumonia (OR, 3.4; 95% CI, 1.46-7.9).Patients with watershed infarcts and MCA or BA stenosis or occlusion should be monitored closely, and various therapeutic strategies should be administered simultaneously to prevent pneumonia during hospitalisation.

Upper limb weakness and incoordination is a common disability following ischemic stroke. Previous studies have showed that the single application of external counterpulsation (ECP) and intermittent theta burst stimulation (iTBS) can effectively enhance the cortical motor excitability and facilitate recovery. However, it remains uncertain if sequential application of these therapies would further augment the recovery. We hypothesize a synergistic effect of ECP followed by iTBS to upper limb function may happen through improvements in both cerebral perfusion and neuron excitability.

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 e4 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 e4/e4 (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 ApoEe4/e4 genotype may be associated with the occurrence of MCA stenosis in the ischemic stroke Chinese patients.

Background and Purpose: Vasa vasorum, which constitutes a network of microvasculature, plays a nutritive and drainable role in vessel walls of arteries. The existence of vasa vasorum within brain vasculature is rarely reported. Based on a series of cerebral artery specimens, we aimed to describe the distribution features of vasa vasorum among intracranial arteries, including middle cerebral arteries (MCAs), basilar arteries (BAs) and vertebral arteries (VAs) and potential effects of vasa vasorum on atherosclerosis morphology. Methods: One hundred and fifty- seven arteries (64 MCAs, 32 Bas and 61 VAs) were obtained from consecutively recruited 32 autopsy cases aged 45 years or above. Routine histology and immunostaining processing were performed to identify the presence of adventitial vasa vasorum and to study the phenotypes and specific components of intracranial atherosclerotic lesions. Results: Among 157 intracranial cerebral arteries, adventitial vasa vasorum were present most frequently in the vertebral arteries (77%), followed by basilar arteries (44%) and middle cerebral arteries (20%). Arteries with adventitial vasa vasorum had greater thickness of tunica adventitia (0.10±0.06 mm vs. 0.06±0.03 mm, p &lt 0.001) and larger size in diameters (3.41± 0.73 mm vs. 2.97± 0.66 mm, p &lt 0.001). The occurrence of adventitial vasa vasorum correlated with high frequency of complicated plaques and higher rate of concentric atherosclerotic lesions (70% vs. 36%, p &lt 0.001). Conclusion: For the first time, our study demonstrated the presence of adventitial vasa vasorum within brain vasculature, especially at vertebral arteries. The correlations between adventitial vasa vasorum and intraplaque hemorrhage, inflammation and calcification suggest that adventitial vasa vasorum may serve as a predictor of unstable atherosclerotic lesions. Further studies are required to explore the biological behavior of adventitial vasa vasorum within cerebral arteries.

Introduction: Intracranial arterial calcification (IAC) is frequently observed on brain computed tomography (CT) in stroke patients. However, the association between IAC and stroke recurrence after hospital discharge has received little attention. In this study, we aim to explore the effect of IAC on the long-term stroke recurrence. Subjects and methods: We prospectively recruited consecutive patients with ischemic stroke or transient ischemic attack during December 2004 and March 2005 from a population-based stroke registry at Prince of Wales Hospital. Demographic characteristics, stroke risk factors, and stroke etiology were recorded at baseline. IAC volume and IAC Agatston score were both measured on 16-slice CT with a semi-automatic system. All patients were regularly followed up for stroke recurrence till July 2016. Results: Total 694 patients (age 71.6±12.4; male sex 50.3%; median follow-up period 8.8 years) were followed up. Stroke recurred in 156 patients (22.5%). Multivariate Cox proportional hazard model found higher IAC Agatston score was predictive factor for both recurrent stroke (HR per 1-SD increment 1.301; 95% CI, 1.084-1.561, p =0.005) and stroke death (HR per 1-SD increment, 1.441; 95% CI, 1.061-1.956, p =0.019). In addition, among different stroke etiological subtypes, IAC Agatston score was independent risk factor of stroke recurrence for index small-vessel occlusive stroke patients (HR per 1-SD increment, 1.674; 95% CI, 1.061-2.639, p =0.027). Conclusions: Quantitative-evaluated IAC scores can predict long-term stroke recurrence and stroke death.

We report a case of thrombotic thrombocytopenic purpura (TTP) with uncommon imaging features, namely concomitant small- and large-vessel thrombosis, atypical locations of posterior reversible encephalopathy syndrome (PRES) and microbleeds. A 58-year-old Chinese woman presented with slurred speech and multiple petechiae over lower limbs. Blood tests showed thrombocytopenia. Neuroimaging showed multiple acute small infarcts and PRES in the subcortical white matter, basal ganglia, thalamus, brainstem and occipital lobe. Microbleeds were noted. She was treated as TTP with infusion of cryo-reduced plasma (CRP). Patient subsequently developed dense right hemiplegia. Computed tomography of brain demonstrated a new major left middle cerebral artery territory infarct. She was stabilized after 2 weeks of treatment with daily CRP infusion, then received rehabilitation for major stroke. Early recognition of TTP provides the best chance of recovery as most lesions are reversible when TTP was treated. However, concurrent large artery thrombosis could cause major morbidity and mortality.

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 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

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.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.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).The risk factors of MBs in strictly deep or lobar regions differ modestly, which may be related to heterogeneous vascular pathologic changes.

© 2017 Yang, Fisher, Zheng, Niu, Paganini-Hill, Zhao, Xu, Wong, Ng and Chen. Background: Anterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature. Methods: Intracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs) (both left and right), vertebral arteries (VAs) (side more affected), and basilar arteries (BAs). Results: Progressive atherosclerotic lesions were present in 91(71%) of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p < 0.05). MCA had more eccentric (vs. concentric) plaques than VA (69 vs. 25%, p = 0.003) and BA (69 vs. 38%; p = 0.03). Lumen thrombi were more frequent in BA, and calcification most commonly occurred in VA atherosclerotic lesions. Conclusion: Intracranial atherosclerotic plaques were commonly present in this sample, but the lesions generally lacked features of complicated plaques. MCA lesions had demonstrable differences compared with VA and BA lesions. Further studies are needed to determine whether these characteristics indicate a distinctive atherosclerotic phenotype for the intracranial vasculature.

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.

Background and purpose Leptomeningeal collateral (LMC) status governs the prognosis of large artery occlusive stroke, although factors determining LMC status are not fully elucidated. The aim was to investigate metrics affecting LMC status in such patients by using computational fluid dynamics (CFD) models based on computed tomography angiography (CTA). Methods In this cross-sectional study, patients with recent ischaemic stroke or transient ischaemic attack attributed to atherosclerotic M1 middle cerebral artery (MCA) stenosis (50%-99%) were recruited. Demographic, clinical and imaging data of these patients were collected. Ipsilesional LMC status was graded as good or poor by assessing the laterality of anterior and posterior cerebral arteries in CTA. A CFD model based on CTA was constructed to reflect focal hemodynamics in the distal internal carotid artery, M1 MCA and A1 anterior cerebral artery. Pressure gradients were calculated across culprit MCA stenotic lesions in CFD models. Predictors for good LMC status were sought in univariate and multivariate analyses. Results Amongst the 85 patients enrolled (mean age 61.5 ± 10.9 years), 38 (44.7%) had good ipsilesional LMC status. The mean pressure gradient across MCA lesions was 14.8 ± 18.1 mmHg. Advanced age (P = 0.030) and a larger translesional pressure gradient (P = 0.029) independently predicted good LMCs. A lower fasting blood glucose level also showed a trend for good LMCs (P = 0.058). Conclusions Our study suggested a correlation between translesional pressure gradient and maturation of LMCs in intracranial atherosclerotic disease. Further studies with more exquisite and dynamic monitoring of cerebral hemodynamics and LMC evolution are needed to verify the current findings.

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.

A 61-year-old woman was admitted due to right limb weakness and newly-diagnosed atrial fibrillation. Brain Magnetic Resonance Imaging and Magnetic Resonance Angiography showed progression of the infarcts and occlusion of part of the internal carotid artery (ICA) respectively. T1-weighted high-resolution magnetic resonance imaging (HRMRI) was conducted after 14 months of medical treatment, showing vessel wall thickness and enhancement that resembled the appearance of vasculitis. This case shows that HRMRI could characterize the morphology of luminal thrombi and vessel wall of chronic intracranial ICA occlusion, which provides a potential tool for investigating the aetiology of stroke due to ICA occlusions.

Background and Purpose— Cerebral microbleeds (CMBs) are common in stroke survivors and community-dwelling elderly. The clinical significance of CMBs in the outcome of poststroke depression (PSD) is unknown. This study examined the association between the 1-year outcome of PSD and CMBs. Methods— The study population comprised 774 Chinese patients with acute ischemic stroke who were admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong. Three and 15 months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Geriatric Depression Scale score of ≥7. Of the 213 patients with PSD at the 3-month follow-up, 135 (63.4%) attended the 15-month follow-up, at which time 89 (65.9%) patients remained depressed (nonremitters), and 46 (34.1%) had recovered (remitters). The presence and location of CMBs were evaluated with magnetic resonance imaging. Results— In comparison with the remitters, nonremitters were more likely to have lobar CMBs (18.4% versus 4.3%; P =0.024). Lobar CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 4.96 ( P =0.039). Conclusions— The results suggest that lobar CMBs may influence the outcome of PSD. The importance of CMBs in the clinical course of depression in stroke survivors warrants further investigation.

Background Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA. Methods Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other's readings: SIR=(mean poststenotic SI − mean background SI)/(mean prestenotic SI − mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index. Results A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92 ± .17 versus .93 ± .17; mean difference −.006 ± .09; P = .496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland–Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers. Conclusions SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.

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 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.

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.

The thalamus plays an important role in different brain functions including memory, emotions, sleep-wake cycle, executive functions, mediating general cortical alerting responses, processing of sensory (including taste, somatosensory, visual, and auditory) information and relaying it to the cortex, and sensorimotor control. Thalamic stroke, both in isolation and in combination with infarcts involving other structures, are not rare. The functional complexity of the thalami nuclei and the not uncommon normal variations of arteries supply the thalamus induce wide variations in presentation of thalami infarcts. In patients with an unusual collection of deficits difficult to explain by a single lesion, in particular where there is impaired vigilance, thalamic disease should be considered which may mimic several different neurological conditions. By researching the literature, we found that the characteristic stroke syndrome of paramedian thalamic infarction is probably underdiagnosed. In addition to thalamic infarct, thalamic lesions can be caused by deep cerebral venous thrombosis with neuropsychological and radiological features that should be considered in the differential diagnosis of intracranial artery occlusion or bleeding, especially in young patients.

Background Intracranial arterial stenosis (ICAS) is the dominant cause for ischemic stroke worldwide, with hemodynamic compromise as a crucial contributor. Prolonged perfusion is commonly observed in ICAS patients on CT perfusion (CTP) maps, while the clinical significance of this perfusion pattern has not been elucidated. Method Patients having symptomatic ICAS of 50-99% stenosis with sustained downstream cerebral blood flow (CBF) were enrolled in this study. Prolonged perfusion was defined as increased mean transit time (MTT) in vascular territories of the target ICAS on CTP maps. The primary clinical outcome was recurrence of ipsilateral ischemic stroke, and secondary outcome was any ipsilateral ischemic events at 2 years follow-up. Results Of the 95 patients (median age 61y; 70% males) with symptomatic ICAS, 29 patients (30.5%) had prolonged perfusion. Such delayed perfusion was persistent in a majority of patients according to the 1-year imaging follow-up. The prolongation of cerebral perfusion was associated with subsequent risk for ipsilateral ischemic stroke (HR 7.01; 95% CI 1.86-26.46; p = 0.004), but not for any ipsilateral ischemic events (HR 1.52; 95% CI 0.63-3.68; p = 0.348). Further comparison of perfusion measures showed lower CBF (p = 0.034) and higher MTT (p = 0.064) in patients with recurrent ischemic stroke, but not in those with recurrent transient ischemic attack (TIA). Among patients with recurrent stroke, a majority had multiple infarcts along the borderzone regions. Conclusion In patients with symptomatic ICAS, persistent prolonged cerebral perfusion might contribute to the relapse of ischemic stroke, but not TIA.

Background This study aimed to evaluate the 1-year clinical and angiographic outcome of angioplasty and stenting of intracranial atherosclerosis using Wingspan and Gateway system. Methods In this prospective study, patients with symptomatic lesions were treated and followed clinically and angiographically by digital subtraction angiography (DSA) for 1 year. The two primary endpoints were recurrent ipsilateral ischemic stroke and in-stent restenosis (ISR) at 1 year. Secondary endpoints included periprocedural death or stroke and all strokes at 1 year. Potential factors correlated with ISR were studied using univariate and multivariate analysis. Results Treatment was attempted in 65 patients and successfully completed in 61 (93.8%). Fifty-nine patients (44 men, 15 women) aged 62.86±11.38 years with 66 stenoses (average degree of stenosis 71.78±11.23%) underwent clinical and DSA follow-up at 1 year. There were 66 stenotic lesions. ISR occurred in 11 of the 66 lesions (16.7%). Luminal gain occurred in 32 of the lesions (48.5%), an unchanged lumen in 4 (6%) and luminal loss in 30 (45.4%). The periprocedural stroke or death rate was 6.1% (4/65), including three hemorrhagic and one ischemic stroke, all of which occurred at the corresponding site and resulted in death. There were no interval strokes between the periprocedural time and the 1-year follow-up. The occurrence of ISR was correlated with the degree of stenosis before treatment and was not correlated with patient age or sex, vessel diameter, location of stenosis or failure to control risk factors for atherosclerosis. Conclusions One-year clinical and angiographic outcomes of angioplasty and stenting are promising for symptomatic intracranial atherosclerosis.

Background and Purpose— Large artery intracranial occlusive disease (LAICOD) is a predominant cause of ischemic stroke in China. Carotid intima-media thickness (CIMT) and presence of carotid plaque are also related to subsequent ischemic stroke. However, the correlation between these and LAICOD is less clear. Methods— This was a community-based cross-sectional study. All subjects underwent carotid duplex ultrasonography and transcranial Doppler. Mean CIMT value of bilateral common carotid arteries was used. Plaque was defined as a focal CIMT of >1.5 mm. LAICOD in transcranial Doppler was defined by peak systolic velocity and age, and presence of turbulence or musical sound was also considered. Results— For the 537 subjects studied (mean age, 54.7±10.1 years; 46.9% males), mean CIMT was 0.74±0.12 mm, with the 75th percentile of 0.80 mm. CIMT ≥1.0 mm was identified in 13 subjects (2.4%). Plaques were detected in 79 subjects (14.7%). Compared with those without LAICOD, the 48 subjects (8.9%) with LAICOD had greater CIMTs (0.77±0.09 versus 0.73±0.12 mm; P =0.044), more with CIMT of higher quartiles ( P =0.007), and more with carotid plaques (25.0% versus 13.7%; P =0.035). However, after adjusting for confounding factors, CIMT and presence of carotid plaque were not significantly associated with LAICOD. Conclusions— The results suggest that CIMT and presence of carotid plaque probably are not independently correlated with LAICOD in Chinese community residents, which supported the existence of pathologic and pathophysiologic differences in atherogenesis of intra- and extracranial arteries.

Objective The caudate nucleus may be involved in the pathogenesis of the fatigue observed in neurological disorders. However, the significance of caudate lesions in poststroke fatigue (PSF) is unknown. This study examined the association between caudate infarcts and PSF. Methods Five hundred 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 participants were assessed for PSF with the Fatigue Severity Scale (FSS) three months after their index stroke. PSF was defined as a mean FSS score of 4.0 or more. Physical functioning and depressive symptoms were measured by the Barthel Index (BI) and the Geriatric Depression Scale (GDS). Results One hundred and twenty-five (25.0%) of the patients had PSF. Compared to the non-fatigue group, the PSF patients were more likely to be women and had hyperlipidemia, lower BI and higher GDS scores. Caudate (8.0% versus 1.3%, p = 0.001) and putamen (19.2% versus 12.0%, p = 0.043) acute infarcts were more common in the PSF group, whereas pons infarcts (13.6% versus 22.2%, p = 0.038) were less common. Acute caudate infarcts remained an independent predictor of PSF in the multivariate analysis, with an odds ratio of 6.4. Conclusions The results suggest that patients with PSF are more likely to have caudate infarcts.

The serotonin receptor 2C (HTR2C) gene has been shown to play a pivotal role in major depression. We examined the association between post-stroke depression (PSD) and polymorphism in HTR2C. A cohort of 223 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a geriatric depression scale score of 7 or above. Possible confounding factors, including previous history of stroke, severity of stroke, level of social support, and recent life events, were investigated. All patients were genotyped for polymorphisms of HTR2C. Separate analyses were performed for males and females. Sixty-one patients were found to have PSD. There were significant associations between the HTR2C gene and PSD status in the male patients, but not in the female ones. After adjusting for possible confounders, the rs12837651 T allele (odds ratio = 4.020) and the rs2192371 G allele (odds ratio = 2.866) were found to be significantly associated with PSD in males. Genetic variation in HTR2C receptors appears to be involved in the pathogenesis of PSD in Chinese males.

Transcranial Doppler ultrasonography (TCD) is the only diagnostic modality that provides a reliable evaluation of intracranial blood flow patterns in real-time. The physiological information obtained from TCD is complementary to the anatomical details obtained from other neuroimaging modalities. TCD is relatively cheap, can be performed bedside, and allows monitoring in acute emergency settings. TCD criteria for intracranial stenosis have been validated against various forms of angiographic studies and serve as reliable tools for screening, diagnostic as well as follow up purposes. TCD findings of intracranial stenosis have acceptable accuracy parameters for anterior as well as posterior circulation. Extended applications of TCD, especially emboli monitoring and assessment of vasomotor reactivity, provide important information about the pathophysiology of cerebrovascular ischemia and risk stratification. Therefore, TCD has become an integral component of the armamentarium of stroke neurologists for understanding stroke etiopathogenesis, planning and monitoring definitive treatment and determining the prognosis. We present the basic principles of TCD, techniques of test performance, diagnostic methods as well as some of the advanced applications of TCD in patients with intracranial stenosis.

Increasing our knowledge about intracranial atherosclerosis (ICAS) natural history and prognostic factors is essential to improve its preventive therapy and thus reduce the dramatic clinical consequences caused by this entity. ICAS is characterized by a chronic and progressive course until it becomes symptomatic, mostly through complication of an unstable intracranial atherosclerotic plaque. Population-based studies in healthy subjects have shown that the prevalence of asymptomatic ICAS is higher in Asian than in Caucasian populations. In both settings, asymptomatic ICAS is associated with classical vascular risk factors and with the metabolic syndrome, and it is burdened with an increasing risk of having incident stroke and cognitive impairment. When it reaches its symptomatic stage, ICAS is a dynamic and aggressive condition, and affected patients are at high risk of having recurrent stroke and other major vascular events. The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has recently shown a robust impact of intensive medical therapy reducing the risk of clinical recurrence of symptomatic ICAS. However, even under best medical therapy and degree of risk factor control, symptomatic ICAS-related recurrence risk continues to be the highest among all stroke etiologic subtypes. The second part of the chapter reviews the current understanding of prognostic factors that may help discriminate the high-risk ICAS patients, divided into local factors (vulnerable ICAS plaque) and systemic factors (vulnerable ICAS patient). Regarding research on local factors, high-resolution magnetic resonance imaging (HRMRI) is an emerging technique that allows in vivo evaluation of intracranial arterial wall, which is displacing our research focus from intracranial stenosis degree towards intracranial atherosclerotic plaque composition and activity. Characterization of the vulnerable ICAS patient may be improved with biomarker research. The latest contributions in this field help support the hypothesis that inflammation determines the risk of progression and complication of this disease, as it occurs in atherosclerosis affecting extracranial arterial beds.

Recent advances in neuroimaging technologies, such as diffusion weighted magnetic resonance imaging (MRI), perfusion weighted computed tomography (CT)/MRI, MR/CT angiography and Doppler ultrasonography allow us to determine the mechanisms of stroke and transient ischemic attack. In addition, high-resolution vessel wall MRI is nowadays increasingly used to understand the stroke mechanism in patients with intracranial atherosclerosis. Artery to artery embolism, hypoperfusion and the combination of the two are the important stroke mechanisms in patients with extracranial atherosclerosis. In addition to the above two, branch occlusion and in-situ thrombotic occlusion are important stroke mechanisms in patients with intracranial atherosclerosis. Branch occlusion leads to subcortical or brainstem infarcts indistinguishable from infarcts caused by small artery disease. In-situ thrombotic occlusion leads to larger territorial infarcts. However, whole territory infarcts are uncommon due to relatively well developed collateral circulation in these patients. The treatment strategy should be based on the correct understanding of the stroke mechanism in individual patients.

Intracranial atherosclerotic occlusive disease is an important and possibly the most common cause of stroke worldwide. Asian, Black and certain Hispanic populations have a high risk of harboring intracranial occlusive disease. In this chapter we review the epidemiology of intracranial occlusive disease by primarily focusing on studies from China, Japan, Korea, and other Asian countries. In addition, we compare and contrast the information from Asian countries with that from North America and related regions. Finally, we explore hypotheses concerning the origin of race-ethnic differences in the distribution of extracranial and intracranial atherosclerotic disease.

Background Computational fluid dynamics (CFD) allows noninvasive fractional flow (FF) computation in intracranial arterial stenosis. Removal of small artery branches is necessary in CFD simulation. The consequent effects on FF value needs to be judged. Methods An idealized vascular model was built with 70% focal luminal stenosis. A branch with one third or one half of the radius of the parent vessel was added at a distance of 5, 10, 15 and 20 mm to the lesion. With pressure and flow rate applied as inlet and outlet boundary conditions, CFD simulations were performed. Flow distribution at bifurcations followed Murray’s law. By including or removing side branches, five patient-specific intracranial artery models were simulated. Transient simulation was performed on a patient-specific model, with a larger branch for validation. Branching effect was considered trivial if the FF difference between paired models (branches included or removed) was within 5%. Results Compared with the control model without a branch, in all idealized models the relative differences of FF was within 2%. In five pairs of cerebral arteries (branches included/removed), FFs were 0.876 and 0.877, 0.853 and 0.858, 0.874 and 0.869, 0.865 and 0.858, 0.952 and 0.948. The relative difference in each pair was less than 1%. In transient model, the relative difference of FF was 3.5%. Conclusion The impact of removing side branches with radius less than 50% of the parent vessel on FF measurement accuracy is negligible in static CFD simulations, and minor in transient CFD simulation.

Supplemental Digital Content is available in the text., 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

To examine the relation between neuroticism and fatigue in Chinese patients with stroke.Cross-sectional study.Acute stroke unit.Survivors of ischemic stroke (N=191) recruited from the acute stroke unit between May 1, 2010, and September 1, 2011.Not applicable.The personality trait of neuroticism was measured with the neuroticism subscale of the Chinese version of the NEO Five-Factor Inventory. The level of fatigue was measured with the Fatigue Assessment Scale. The National Institutes of Health Stroke Scale, Geriatric Depression Scale, Barthel Index, and Mini-Mental State Examination were administered to obtain demographic and clinical information.Fatigue severity 3 months after stroke positively correlated with Geriatric Depression Scale and NEO Five-Factor Inventory neuroticism scores and negatively correlated with the Barthel Index score.Neuroticism, independent of depressive symptoms, is a predictor of fatigue severity 3 months after stroke. Interventions such as psychological screening programs are warranted for early detection of patients at high risk of poststroke depression.

Stroke patients with carotid disease have a high risk of recurrence of disease. By measuring cerebral blood flow volume (BFV) using extracranial duplex technique for clinical estimation of intracranial collaterals, we aimed to investigate the relationship between the presence of intracranial collaterals and stroke recurrence in stroke patients with carotid disease. Consecutive stroke patients indicated for carotid duplex ultrasound investigations in our hospital were recruited during three years' period. Carotid stenosis was diagnosed as ≥50% stenosis and extracranial arterial BFV was measured by using color velocity imaging quantification ultrasound (CVIQ) software. Presence of intracranial collateral flow was defined as a blood flow volume of either ≥370 mL/min in common carotid artery or ≥120 mL/min in vertebral artery. Univariate and multivariate analyses were performed to determine the independent predictors of recurrent stroke. One hundred and twelve stroke patients (19.1%) with ≤50% carotid stenosis were recruited from consecutive ischemic stroke patients. During a mean follow-up of 28.6±13.1 months, recurrent stroke was recorded in 32 (28.6%) out of the total recruited patients. Estimated by blood flow volume measured by CVIQ, the patients with intracranial collateral flow had a lower rate of recurrent stroke than those without (9.5% vs. 33%, P=0.032). After adjusting for potential confounders, the presence of CVIQ-estimated intracranial collateral flow was an independent protector of recurrent stroke (OR, 0.169; 95% CI, 0.034- 0.842; P=0.03). It could be concluded that blood supply through intracranial collateral flow estimated by CVIQ technique may protect stroke patients with carotid stenosis from suffering recurrent stroke.

Objectives The criteria for evaluating cerebral artery stenosis by transcranial Doppler sonography are inconsistent. We aimed to identify the accuracy of transcranial Doppler criteria compared with digital subtraction angiography for diagnosis of anterior circulation artery stenosis. Methods A total of 170 patients who underwent transcranial Doppler sonography and digital subtraction angiography were recruited. The anterior circulation arteries were evaluated by transcranial Doppler sonography and digital subtraction angiography. We defined the best cutoff value for substantial anterior circulation artery stenosis by receiver operating characteristic curve analyses and calculated the sensitivity, specificity, and positive and negative predictive values. Results An anterior circulation artery peak systolic velocity (PSV) of 120 cm/s had the largest area under the receiver operating characteristic curve compared with PSVs of 110, 130, and 140 cm/s and mean flow velocities of 60, 70, and 80 cm/s. The sensitivity, specificity, false-positive rate, false-negative rate, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and Youden index for transcranial Doppler sonography were 90.6%, 85.0%, 15.0%, 9.4%, 87.9%, 87.2%, 88.9%, 6.04, 0.11, and 0.756, respectively. The reliability index included the agreement rate and κ value, which were 87.9% and 0.757. Conclusions A PSV of 120 cm/s combined with additional parameters was an accurate criterion for diagnosing anterior circulation artery stenosis. Transcranial Doppler sonography could be considered a valuable method for screening diagnosis of cerebral artery stenosis.

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.

Xiong L, Leung HW, Chen XY, Han JH, Leung WH, Soo OY, Lau YL, Wong KS. Autonomic dysfunction in ischemic stroke with carotid stenosis. Acta Neurol Scand: 2012: 126: 122–128. © 2011 John Wiley & Sons A/S. Objectives – Impaired autonomic function is common in acute ischemic stroke. Previous limited studies have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the cardiovascular autonomic function. This study sought to investigate cardiovascular autonomic function in patients with ischemic stroke with carotid stenosis. Methods – Eighty-five patients with ischemic stroke (58 ones without carotid stenosis and 27 ones with carotid stenosis, average 6 months after stroke onset) and 37 elderly controls were recruited. All performed Ewing’s battery autonomic function tests. Results – From Ewing’s battery of autonomic function tests, atypical, definite, or severe autonomic dysfunction was identified in 69.0% patients without carotid stenosis and 88.9% with carotid stenosis, with significant difference between the two groups, and the prevalence of autonomic dysfunction in both groups was higher than that in controls (21.6%). Patients with carotid stenosis showed impairment of all parasympathetic tests (all P

Background and Purpose— Cerebral microbleeds (CMB) are common in stroke survivors and the community-dwelling elderly. The clinical significance of CMB in the development of depression after a stroke is unknown. This study examined the association between poststroke depression (PSD) and CMB. Methods— A cohort of 235 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Genetic Depression Scale score of ≥7. The presence and location of CMB were evaluated with MRI. Results— In comparison with the non-PSD group, PSD patients were more likely to have lobar CMB (33.3% versus 19.9%; P =0.022). Lobar CMB remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 2.08 ( P =0.032). Conclusions— The results suggest that lobar CMB may play a role in the development of PSD. The importance of CMB in the pathogenesis of depression in stroke survivors and the general elderly population warrants further investigation.

Tang W-K, Lau CG, Mok V, Ungvari GS, Wong K-S. Burden of Chinese stroke family caregivers: the Hong Kong experience. Objective To ascertain the clinical and sociodemographic factors associated with family caregivers' burden in Chinese patients with stroke in Hong Kong. Design Cross-sectional design. Setting Stroke Clinic. Participants Patients (N=123) from a stroke clinic and their family caregivers. Interventions Not applicable. Main Outcome Measures Predictive factors of family caregivers' burden in Chinese stroke patients in Hong Kong. Caregivers' burden was assessed with the Caregiving Burden Scale (CBS). Patients' and caregivers' sociodemographic data and clinical characteristics were recorded. Physical and psychological conditions were measured and rated with the following instruments: Cumulative Illness Rating Scale, Geriatric Depression Scale (GDS), Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, Lubben Social Network Scale, Modified Life Event Scale (MLES), Hospital Anxiety and Depression Scale (HADS), and a single question about fatigue. Results In the univariate analysis, the CBS score had significant correlations with certain characteristics of caregivers (sex, GDS, HADS, depressive symptoms, fatigue, and MLES) and those of patients' (sex, age, education, GDS). Regression analysis revealed that caregivers' GDS and patients' education were the independent correlates of the CBS. Conclusions The severity of depressive symptoms in Chinese stroke caregivers and patients' education are independent factors associated with the caregivers' burden. Further studies evaluating interventions on caregivers' burden should include the assessment and management of mood disorders.

The aim of this cross-sectional study was to determine the socio-demographic and clinical factors associated with depressive symptoms in the family caregivers of Hong Kong Chinese stroke patients. One hundred and twenty-three patients at a stroke clinic and their family caregivers formed the study sample. The depressive symptoms of both the patients and their family caregivers were rated with the Chinese version of the 15-item Geriatric Depression Scale (GDS). Participants' socio-demographic data and clinical characteristics served as the independent variables in relation to the caregivers' GDS scores. Patients' and caregivers' somatic and psychological conditions were measured with 10 scales. In univariate analysis, caregivers' GDS scores were significantly correlated with certain of their characteristics [Modified Life Event Scale (MLES), Cumulative Illness Rating Scale (CIRS) and Lubben Social Network Scale (LSNS) scores, sex and being a housewife] and those of the patients (GDS score and being a housewife). Multiple regression analysis showed caregivers' MLES and CIRS scores and patients' GDS scores to be independent correlates of caregivers' GDS scores. Adverse events encountered by caregivers in the past 6 months, their current health problems and patients' depressive symptoms were found to be the principal factors associated with caregivers' depressive symptoms.

This study evaluated the impact of cerebral microbleeds (CMBs) on the health-related quality of life (HRQoL) in 458 Chinese patients with first or recurrent acute ischemic stroke. HRQoL was assessed with the Short Form-36 (SF-36). Univariate analysis showed the presence of lobar CMBs to be negatively correlated with patients’ physical functioning (PF; p < 0.01), social function (SF; p < 0.01), and role-emotional (RE; p < 0.05) scores. Subsequent linear regression analysis revealed lobar CMBs to be independently associated with the PF and SF scores (p < 0.05). The limitations of this study include the exclusion of patients with more severe stroke, the lack of longitudinal assessments, the use of a generic rather than stroke-specific HRQoL scale, and the less than optimal sensitivity of the CMB measurement. The study findings suggest that CMBs have a significant impact on the HRQoL of stroke survivors.

Aim: To determine the association between polymorphisms of the multidrug transporter genes ABCC2, ABCC5 and ABCG2, and drug resistance in epilepsy by genotyping comprehensive sets of tagging SNPs. Materials & methods: A total of 25 tagging SNPs from ABCC2, ABCC5 and ABCG2 genes were genotyped in a total of 590 Han Chinese epilepsy patients (262 drug resistant and 328 drug responsive). Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. Results: Genotype distributions of all the selected SNPs were consistent with Hardy–Weinberg equilibrium. None of the polymorphisms, either genotype or allele distributions, were significantly associated with drug resistance. For each gene, no haplotypes of over 1% frequency, and that included all SNPs of the gene, were associated with drug resistance. Conclusion: This gene-wide tagging study revealed no association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy. Original submitted 11 August 2010; Revision submitted 5 November 2010.

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.

OBJECTIVE Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene (APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. METHODS We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. RESULTS The SNP rs662799 (-1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10(-5) ) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up (P = 0·010 and 0·00021, respectively) and in Guangzhou subjects (P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides. CONCLUSION Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism.

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: The association between protein S deficiency (PSD) and ischemic stroke is controversial and warrants further investigation. Methods: We conducted a genotype and MRI correlation study in a Chinese family in which hereditary PSD cosegregated with premature ischemic strokes. Six out of 11 family members inherited PSD type III in an autosomal dominant manner. Results: Among all PSD members, a novel missense mutation 1063C→T in exon 10 of protein S alpha ( PROS1 ) was identified, which encoded a substitution of arginine to cysteine at position 355 (R355C) in the first globular domain of laminin A of protein S. Wild-type PROS1 sequences were retained in non-PSD members. MRI detected deep white matter infarctions predominantly distributed in the borderzone regions. The infarct topography was homogeneous in all adult mutant carriers. By contrast, cerebral infarction was absent in nonmutant carriers. Extensive investigation in the family did not reveal any confounding stroke risk. Haplotype analysis with high-density single nucleotide polymorphism markers revealed a 6.1-Mb minimally rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7 annotated genes in this region, PROS1 is known to be associated with thrombotic disorders. MRI screening in an additional 10 PSD families without R355C showed no cerebral infarction. Conclusions: PROS1 R355C mutation cosegregated with PSD type III and premature white matter infarctions in the index family. The findings substantiate an association between PSD and stroke. Study of the mechanism underlying this association may improve our understanding of premature cryptogenic white matter infarction.

Background and purpose: Although the age-related white matter changes (ARWMC) scale has been advocated to be applicable to both MRI and CT for assessing the severity of WMC, its inter-rater reliability on CT is only fair. We aimed to operationalize the ARWMC scale and investigate the effect of this operationalization on the reliability and validity on MRI and CT. Methods: Operational definitions of the ARWMC scale were derived from Erkinjuntti research criteria for subcortical vascular dementia and Scheltens scale. Using original and operationalized ARWMC scale, eight observers recorded the time for rating per MRI and per CT. We investigated the inter-rater and intrarater reliability as well as validity against volume using data from 97 stroke patients. Results: Inter-rater reliability of the operationalized scale on CT (0.874, 95% confidence interval [0.780–0.934]) was better than the original scale (0.569, 95% confidence interval [0.247–0.775]). Its intrarater reliability on CT (0.869) and reliability on MRI (inter-rater: 0.860; intrarater: 0.838) was comparable with the original scale (CT intrarater: 0.750 and on MRI inter-rater: 0.845; intrarater: 0.853). The time required to administer the operationalized scale (4′2″ for MRI and 1′18″ for CT) was similar to that of the original scale (3′56″ for MRI and 1′16″ for CT). The original scale and operationalized scale also significantly correlated with WMC volume (operationalized scale ρ = 0.613, P

Background and purpose: There is limited data of neurovascular coupling on stroke patients, especially on comparison of different etiologies. We aim to test the hypothesis that patients with small vessel disease (SVD) are impaired on neurovascular coupling rather than stroke patient with large intracranial artery stenosis (LIAS), because small vessel is more associated with microcirculatory function. To assess microcirculatory integrity of stroke patients, we performed a functional transcranial Doppler test using a standardized visual stimulation test. Methods: The neurovascular coupling was measured in the asymptomatic occipital cortex in ischaemic stroke patients with LIAS, SVD, and healthy elder controls. Bilateral posterior cerebral arteries were monitored to measure evoked flow velocity during resting and visual stimulation phase. Peak systolic flow velocity responses were recorded, and time course of hemodynamic response was modeled according to a control system analysis with the parameters gain, natural angular frequency, attenuation, and rate time. Results: Reproduced for both sides, the functionally induced flow velocity changes (gain) were significantly lower in LIAS and SVD compared with controls (P

Background and purpose: Age-related white matter changes (ARWMC) are closely associated with cognitive impairment. Although the ARWMC scale has been widely used to grade white matter changes (WMC) severity, the correlation between this scale and cognitive impairment has not been studied. We aimed to validate the ARWMC scale against cognition in patients with stroke. Methods: We determined the severity of WMC for 172 patients with stroke on MRI by volumetric quantification and the ARWMC scale. Two scores (total score and global score) were derived from the ARWMC scale. We assessed executive function and global cognition using the Mattis dementia rating scale-initiation/perseveration subset (MDRS I/P) and mini-mental state examination (MMSE), respectively. We investigated the association between the three WMC measures (volume, total score, and global score) and clinical variables with cognitive impairment using multivariate regression analysis. Results: Even after adjusting for other clinical variables, total score and global score of ARWMC scale were independently associated with MDRS I/P (beta = −0.248, P = 0.001 and beta = −0.218, P = 0.005, respectively) and MMSE (adjusted odds ratio 1.181, 95%CI [1.038–1.343] and adjusted odds ratio 1.740, 95%CI [1.063–2.847], respectively). Conclusion: The ARWMC scale correlates well with cognitive impairment in patients with stroke.

Summary What is new and Objective: Some evidence suggests that angiotensin-converting enzyme insertion/deletion (I/D) polymorphism may play a role in endothelium-dependent vasodilatation. However, the impact of I/D polymorphism on endogenous nitric oxide production, which may be of great therapeutic significance, has scarcely been studied. This study aimed to investigate this in hypertensives and hypercholesterolaemics. Methods: Adult Han subjects were recruited by cluster sampling from two communities in Shunde, Guangdong province, China. Plasma nitrite and nitrate (NOx) levels were determined by colorimetry assay and angiotensin II and 6-keto-prostaglandin F1-alpha by radioimmunoassay. Angiotensin-converting enzyme gene I/D polymorphism were genotyped by polymer chain reaction-amplified fragment length polymorphism. Results and Discussion: Of the 779 subjects who met our inclusion criteria, 502 were with normotensive and normocholesterolaemic, 76 had hypertension only, 146 hypercholesterolaemia only, and 55 had both hypertension and hypercholesterolaemia. Among subjects with hypertension only, the plasma levels of NOx for genotype DD were significantly lower than those for genotype II (P = 0·034). And the plasma levels of NOx for genotype DD was significantly higher than those for genotype II (P = 0·040) in subjects with hypercholesterolaemia only. What is new and Conclusion: Our results suggest that I/D polymorphism has an impact on in vivo NO production in hypertensives and hypercholesterolaemics at the population level. Hypertensives with allele D may be benefit from l-arginine supplementation and hypercholesterolaemics with allele D may respond better to statins or antioxidants.