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Background and purposeSymptomatic intracranial atherosclerotic stenosis (sICAS) is associated with a considerable risk of recurrent stroke despite contemporarily optimal medical treatment. Severity of luminal stenosis in sICAS and its haemodynamic significance quantified with computational fluid dynamics (CFD) models were associated with the risk of stroke recurrence. We aimed to develop and compare stroke risk prediction nomograms in sICAS, based on vascular risk factors and these metrics.MethodsPatients with 50%–99% sICAS confirmed in CT angiography (CTA) were enrolled. Conventional vascular risk factors were collected. Severity of luminal stenosis in sICAS was dichotomised as moderate (50%–69%) and severe (70%–99%). Translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified via CTA-based CFD modelling; the haemodynamic status of sICAS was classified as normal (normal PR&WSSR), intermediate (otherwise) and abnormal (abnormal PR&WSSR). All patients received guideline-recommended medical treatment. We developed and compared performance of nomograms composed of these variables and independent predictors identified in multivariate logistic regression, in predicting the primary outcome, recurrent ischaemic stroke in the same territory (SIT) within 1 year.ResultsAmong 245 sICAS patients, 20 (8.2%) had SIT. The D2H2A nomogram, incorporating diabetes, dyslipidaemia, haemodynamic status of sICAS, hypertension and age ≥50 years, showed good calibration (P for Hosmer-Lemeshow test=0.560) and discrimination (C-statistic 0.73, 95% CI 0.60 to 0.85). It also had better performance in risk reclassification and provided larger net benefits in decision curve analysis, compared with nomograms composed of conventional vascular risk factors only, and plus the severity of luminal stenosis in sICAS. Sensitivity analysis in patients with anterior-circulation sICAS showed similar results.ConclusionsThe D2H2A nomogram, incorporating conventional vascular risk factors and the haemodynamic significance of sICAS as assessed in CFD models, could be a useful tool to stratify sICAS patients for the risk of recurrent stroke under contemporarily optimal medical treatment.

Objective: Intracranial arterial calcification (IAC) is a risk factor of ischemic stroke. However, the relationship between IAC patterns and clinical outcome of ischemic stroke remains controversial. We aimed to investigate the correlation between IAC patterns and the effects of reperfusion therapy among acute stroke patients. Methods: Consecutive acute ischemic stroke patients who underwent reperfusion therapy were included. IAC was categorized as intimal or medial. Based on its involvement, IAC was further classified as diffuse or focal. Neurologic dysfunction was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed. Results: Of 130 patients, 117 had IAC. Intimal IAC was identified in 74.6% of patients and medial IAC was present in 64.6% of patients. Diffuse IAC was present in 31.5% of patients. All diffuse IACs were medial pattern. Diffuse IAC was associated with higher baseline NIHSS (p = 0.011) and less FNO (p = 0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p = 0.002) and less FNO (p = 0.024). Multivariable linear regression (p < 0.001) and logistic regression (p = 0.027) suggested that multiple diffuse IAC was associated with higher baseline NIHSS and less FNO. No significant association was found between END and different IAC patterns. Interpretation: Multiple diffuse medial IAC may predict severer neurologic dysfunction and less favorable neurologic outcome after reperfusion therapy in acute stroke patients.

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

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., Diabetic neuropathy has a major impact on morbidity and mortality. However, the diagnosis and management of diabetic neuropathy is South‐East Asia is limited. Clear guidance is required to diagnose and manage patients with diabetic and other neuropathies.

Background and PurposeDynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke.MethodsForty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain.ResultsThe cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R2 = 0.108, P = 0.038).ConclusionThe degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation.

Background and PurposeIntracranial arterial calcification (IAC) may be present in the intimal or medial arterial layer. This study aimed to elucidate the link between the calcification and atherosclerotic disease in the intracranial vasculature.MethodsConsecutive patients with acute ischemic stroke were included. Bilateral intracranial segment of the internal carotid artery, M1 segment of the middle cerebral artery, intracranial segment of the vertebral artery, and the basilar artery were visualized by the multi-detector computed tomography (CT) and vessel-wall magnetic resonance imaging (vwMRI) within 14 days after stroke onset. IAC was into the intimal or medial pattern. Subsequently, on the vwMRI, we assessed the luminal stenosis, eccentricity, plaque burden, and intraplaque hemorrhage (IPH) as markers of atherosclerosis at each IAC site.ResultsAmong 69 patients with stroke, IAC was identified in 35% of (161/483) artery segments, of which 61.5% were predominantly intimal calcification and 38.5% were predominantly medial calcification. About 79.8% of intimal calcifications and 64.5% of medial calcifications co-existed with atherosclerotic plaques. Intimal calcification was associated with luminal stenosis (p = 0.003) caused by atherosclerotic lesions. Compared with the medial IAC, intimal IAC was more often accompanied by eccentric plaques (p = 0.02), larger plaque burden (p = 0.001), and IPH (p = 0.001).ConclusionOur multimodal imaging-based comparison study on intracranial arteriosclerosis demonstrated that intimal IAC, compared with medial IAC, was more often accompanied by the luminal stenosis, larger plaque burden, eccentricity, and IPH, providing strong evidence for clinical evaluation on the mechanism, risk, and prognosis of ischemic stroke.

BackgroundNewtonian fluid model has been commonly applied in simulating cerebral blood flow in intracranial atherosclerotic stenosis (ICAS) cases using computational fluid dynamics (CFD) modeling, while blood is a shear-thinning non-Newtonian fluid. We aimed to investigate the differences of cerebral hemodynamic metrics quantified in CFD models built with Newtonian and non-Newtonian fluid assumptions, in patients with ICAS.MethodsWe built a virtual artery model with an eccentric 75% stenosis and performed static CFD simulation. We also constructed CFD models in three patients with ICAS of different severities in the luminal stenosis. We performed static simulations on these models with Newtonian and two non-Newtonian (Casson and Carreau-Yasuda) fluid models. We also performed transient simulations on another patient-specific model. We measured translesional pressure ratio (PR) and wall shear stress (WSS) values in all CFD models, to reflect the changes in pressure and WSS across a stenotic lesion. In all the simulations, we compared the PR and WSS values in CFD models derived with Newtonian, Casson, and Carreau-Yasuda fluid assumptions.ResultsIn all the static and transient simulations, the Newtonian/non-Newtonian difference on PR value was negligible. As to WSS, in static models (virtual and patient-specific), the rheological difference was not obvious in areas with high WSS, but observable in low WSS areas. In the transient model, the rheological difference of WSS areas with low WSS was enhanced, especially during diastolic period.ConclusionNewtonian fluid model could be applicable for PR calculation, but caution needs to be taken when using the Newtonian assumption in simulating WSS especially in severe ICAS cases.

Background and Purpose: Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability.Materials and Methods: Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression.Results: Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, P = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036–8.517; P = 0.043).Conclusion: Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.

Background and Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source). Methods: Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort). Results: Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41–1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57–1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32–12.01]). Conclusions: The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

Background: Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality. Methods: Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors. Results: During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08–1.56, p = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06–1.96, p = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke. Conclusions: IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels.

Objective: Contrast enhancement is a vital feature of the intracranial atherosclerotic plaque on high-resolution magnetic resonance imaging (HRMRI), but its clinical significance is still unclear. We aimed to quantitatively assess plaque enhancement patterns in the middle cerebral artery (MCA) atherosclerotic plaque.Methods: We conducted a cross-sectional study by prospectively recruiting stroke or transient ischemic attack patients with >30% of MCA stenosis of either side. All patients underwent contrast-enhanced HRMRI scans. Enrolled patients were classified into acute phase (12 weeks) groups based on the time interval from stroke onset to imaging scan. Plaque enhancement index was calculated for each MCA lesion at the maximal narrowing site.Results: We identified a total of 89 MCA plaques [53 (60%) symptomatic and 36 (40%) asymptomatic; 57 (64%) acute, 18 (20%) subacute and 14 (16%) chronic] in 58 patients on HRMRI. Among the acute lesions, symptomatic plaques had a significantly stronger plaque enhancement than asymptomatic plaques (symptomatic vs. asymptomatic: 38.9 ± 18.2 vs. 18.2 ± 16.2, p < 0.001). Among the symptomatic lesions, plaque enhancement diminished with increasing time after stroke onset (38.9 ± 18.2, 22.0 ± 22.8, and 5.0 ± 10.1 for acute, subacute, and chronic phase, respectively; p = 0.001).Conclusion: Plaque enhancement in the acute atherosclerotic plaque is closely related to recent ischemic events. In symptomatic atherosclerosis, plaque enhancement regresses over time after ischemic stroke, which may offer the potential to monitor the plaque activity in intracranial atherosclerosis using HRMRI.

Background and Purpose— Posterior circulation ischemic stroke (IS) is generally considered an illness with a poor prognosis. However, there are no effective rating scales to predict recurrent stroke following it. Therefore, our aim was to identify clinical or radiological measures that could assist in predicting recurrent cerebral ischemic episodes. Methods— We prospectively enrolled 723 noncardiogenic posterior circulation IS patients with onset of symptoms Results— A total of 40 patients (5.5%) had recurrent IS or TIA within 1 year of posterior circulation IS. Multivariate Cox regression identified chief complaint with dysphagia (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.69–10.2; P =0.002), repeated TIAs within 3 months before the stroke (HR, 15.4; 95% CI, 5.55–42.5; P P =0.05), multisector infarcts (HR, 5.38; 95% CI, 1.25–23.3; P =0.02), and not on antithrombotics treatment at discharge (HR, 3.06; 95% CI, 1.09–8.58; P =0.03) as independent predictors of recurrent IS or TIA. Conclusions— Some posterior circulation IS patients are at higher risk for recurrent IS or TIA. Urgent assessment and preventive treatment should be offered to these patients as soon as possible.

Background: Tandem stenoses were widely observed in acute stroke cases. High pressure drop and low fractional flow (FF) indicate the risk of ischemia caused by intracranial atherosclerotic stenosis. Low wall shear stress (WSS) and high low-density lipoprotein (LDL) filtration rate indicate the risk of atherosclerotic plaque growth. High WSS is related to the risk of plaque rupture. The hemodynamic parameters (pressure drop, FF, WSS, and LDL filtration rate) could be estimated using computational fluid dynamics (CFD) simulation. Few studies have investigated the hemodynamics of intracranial tandem stenoses. This study aims to estimate the clinical risks of intracranial tandem stenoses using CFD simulation.Methods: With identical radius and length, 4 cylindrical tube models were developed with different stenoses (severity in area: 75% single, 75%-84% tandem, 75%-84%-89% tandem, and 89% single). The pressure drop and FF of each stenosis were derived from static CFD simulation and compared between models. A transient CFD simulation was performed on a patient-specific intracranial arterial model with three (56.2%, 51.3%, and 89.8%) tandem stenoses using boundary conditions derived from patient-specific measurements. For the three stenoses, pressure drop, FF, WSS, and LDL filtration rate were calculated and compared.Results: Independent from other stenoses, 89% single stenosis caused comparable pressure drops in four tube models (difference less than 10%), larger than those of 75%-84% tandem stenoses. 89% stenosis had the lowest FF (less than 0.85). In the patient-specific model, the 56.2% and 51.3% stenoses had pressure drops less than 2mmHg with FFs higher than 0.98, while the 89.8% stenosis caused a pressure drop more than 10mmHg with FF lower than 0.90, where a high WSS belt extended distally. Compared with low WSS (less than 0.5Pa), high LDL filtration rate appeared in smaller areas on arterial wall, with less temporal fluctuations.Conclusions: 1. Tandem stenoses are independent in pressure drop and FF. Pressure drop increases sharply with the severity of stenosis. 2. Compared with low WSS, high LDL filtration rate is more specific and stable in reflecting the risk of intracranial atherosclerotic plaque growth. 3. The risks of both plaque growth and rupture should be considered in severe stenoses.

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

Background: Previous studies conflicted in the association between intracranial atherosclerotic stenosis (ICAS) and the severity of white matter changes (WMC).Aims: We aimed to investigate the relationships between the severity of luminal stenosis and the hemodynamic significance of middle cerebral artery (MCA) stenosis, and the severity of ipsilateral WMC.Methods: In this cross-sectional study, patients with a recent ischemic stroke or transient ischemic attack and a 50–99% MCA-M1 stenosis in the Chinese Intracranial Atherosclerosis study cohort were analyzed. The post- to pre-stenotic signal intensity ratio (SIR) was obtained in time-of-flight MR angiography (MRA) to represent the hemodynamic significance of MCA-M1 stenosis, with a lower SIR indicating a hemodynamically more severe lesion. The severity of ipsilesional WMC was assessed by an age-related WMC (ARWMC) scale in T2-weighted fluid attenuated inversion recovery MR imaging. The relationships between the degree of MCA-M1 stenosis, SIR, and ipsilesional ARWMC scale were analyzed. The MCA-M1 lesion with a higher percentage of stenosis was chosen for analyses in patients with bilateral MCA-M1 stenoses.Results: Among 180 subjects (mean age, 64 years), a lower SIR of MCA-M1 stenosis (Spearman correlation coefficient, −0.543; p < 0.001), but not the degree of stenosis (p = 0.93), was significantly linearly correlated with a higher ipsilateral ARWMC. Multivariate ordinal logistic regression identified older age (OR = 1.037; 95% CI, 1.008–1.066; p = 0.011) and lower SIR (OR = 0.010; 95% CI, 0.002–0.058; p < 0.001) as independent predictors for more severe ipsilateral WMC.Conclusion: Patients with hemodynamically more severe ICAS are more likely to have more severe ipsilateral WMC. Longitudinal studies with sequential imaging exams may further reveal the impact of hemodynamic significance of ICAS on the development and progression of WMC.

Though dysfunction of neuromuscular junction (NMJ) is associated with congenital myasthenic syndrome (CMS), the proteins involved in neuromuscular transmission have not been completely identified. In this study, we aimed to identify a novel CMS gene in a consanguineous family with limb-girdle type CMS. Homozygosity mapping of the novel CMS gene was performed using high-density single-nucleotide polymorphism microarrays. The variants in CMS gene were identified by whole-exome sequencing (WES) and Sanger sequencing. A 20 MB-region of homozygosity (ROH) was mapped on chromosome 6q15–21. This was the only ROH that present in all clinically affected siblings and absent in all clinically unaffected siblings. WES showed a novel variant of AK9 gene located in this ROH. This variant was a start-gain mutation and introduced a cryptic 5′-UTR signal in intron 5 of the AK9 gene. The normal splicing signal would be interfered by the cryptic translation signal leading to defective splicing. Another 25 MB-ROH was found on chromosome 11p13–q12 in all siblings. WES showed a homozygous RAPSN pathogenic variant in this ROH. Since RAPSN-associated limb-girdle type CMS was only manifested in AK9 homozygous variant carriers, the disease phenotype was of digenic inheritance, and was determined by the novel disease modifier AK9 which provides NTPs for N-glycosylation. This is the first time that this specific genotype–phenotype correlation is reported. Importantly, the AK9-associated nucleotide deficiency may replete by dietary supplements. Since AK9 is a disease modifier, enhancing N-glycosylation by increasing dietary nucleotides may be a new therapeutic option for CMS patients.

Background and Purpose— High signal on T1-weighted fat-suppressed images in middle cerebral artery plaques on ex vivo magnetic resonance imaging was verified to be intraplaque hemorrhage histologically. However, the underlying plaque component of low signal on T1-weighted fat-suppressed images (LST1) has never been explored. Based on our experience, we hypothesized that LST1 might indicate the presence of lipid core within intracranial plaques. Methods— 1.5 T magnetic resonance imaging was performed in the postmortem brains to scan the cross sections of bilateral middle cerebral arteries. Then middle cerebral artery specimens were removed for histology processing. LST1 presence was identified on magnetic resonance images, and lipid core areas were measured on the corresponding histology sections. Results— Total 76 middle cerebral artery locations were included for analysis. LST1 showed a high specificity (96.9%; 95% confidence interval, 82.0%–99.8%) but a low sensitivity (38.6%; 95% confidence interval, 24.7%–54.5%) for detecting lipid core of all areas. However, the sensitivity increased markedly (81.2%; 95% confidence interval, 53.7%–95.0%) when only lipid cores of area ≥0.80 mm 2 were included. Mean lipid core area was 5× larger in those with presence of LST1 than in those without (1.63±1.18 mm 2 versus 0.32±0.31 mm 2 ; P =0.003). Conclusions— LST1 is a promising imaging biomarker of identifying intraplaque lipid core, which may be useful to distinguish intracranial atherosclerotic disease from other intracranial vasculopathies and to assess plaque vulnerability for risk stratification of patients with intracranial atherosclerotic disease. In vivo clinical studies are required to explore the correlation between LST1 and clinical outcomes of patients with intracranial atherosclerotic disease.

Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies.

Background and Purpose: The risk of recurrent stroke following a transient ischemic attack (TIA) or minor stroke is high, despite of a significant reduction in the past decade. In this study, we investigated the feasibility of using artificial neural network (ANN) for risk stratification of TIA or minor stroke patients. Methods: Consecutive patients with acute TIA or minor ischemic stroke presenting at a tertiary hospital during a 2-year period were recruited. We collected demographics, clinical and imaging data at baseline. The primary outcome was recurrent ischemic stroke within 1 year. We developed ANN models to predict the primary outcome. We randomly down-sampled patients without a primary outcome to 1:1 match with those with a primary outcome to mitigate data imbalance. We used a 5-fold cross-validation approach to train and test the ANN models to avoid overfitting. We employed 19 independent variables at baseline as the input neurons in the ANN models, using a learning algorithm based on backpropagation to minimize the loss function. We obtained the sensitivity, specificity, accuracy and the c statistic of each ANN model from the 5 rounds of cross-validation and compared that of support vector machine (SVM) and Naïve Bayes classifier in risk stratification of the patients. Results: A total of 451 acute TIA or minor stroke patients were enrolled. Forty (8.9%) patients had a recurrent ischemic stroke within 1 year. Another 40 patients were randomly selected from those with no recurrent stroke, so that data from 80 patients in total were used for 5 rounds of training and testing of ANN models. The median sensitivity, specificity, accuracy and c statistic of the ANN models to predict recurrent stroke at 1 year was 75%, 75%, 75%, and 0.77, respectively. ANN model outperformed SVM and Naïve Bayes classifier in our dataset for predicting relapse after TIA or minor stroke. Conclusion: This pilot study indicated that ANN may yield a novel and effective method in risk stratification of TIA and minor stroke. Further studies are warranted for verification and improvement of the current ANN model.

Background and Objectives: External counterpulsation (ECP) is a non-invasive method used to augment cerebral blood flow of patients with ischaemic stroke via induced hypertension. We aimed to investigate whether the cerebral augmentation index (CAI) evaluated by ECP can predict clinical outcomes after acute ischemic stroke. Methods: We enrolled acute ischemic stroke patients within 7 days after stroke onset. Bilateral middle cerebral arteries of patients were monitored using transcranial Doppler (TCD). Flow velocity changes before, during and after ECP were, respectively, recorded for 3 mins. The cerebral augmentation index (CAI) was the increase in percentage of the middle cerebral artery mean flow velocity during ECP compared with baseline. TCD data were analysed based on the side ipsilateral or contralateral to the infarct. The modified Rankin Scale (mRS) (good outcome: mRS 0∼2; poor outcome: mRS 3∼6) was evaluated 3 months after the index stroke. Results: 200 patients were included (mean age, 64.5±8.9 years; 86.5% males). At month 3 after stroke onset, univariate analysis showed that the National Institutes of Health Stroke Scale at recruitment was significantly higher in the poor outcome group, while the bilateral CAIs were significantly lower in the good outcome group than those in the poor outcome group (ipsilateral 3.72±2.94 vs 7.92±6.25, p=0.032; contralateral 4.04±3.82 vs 6.98±6.05, p=0.048). Multivariate logistic regression showed that bilateral CAIs were independently correlated with an unfavorable functional outcome after adjusting for confounding factors. Conclusions: The higher degree of cerebral blood flow velocity augmentation on the both sides ipsilateral and contralateral to the infarct induced by ECP is independently correlated with an unfavorable functional outcome after acute ischemic stroke.

Background and Purpose— Intracranial artery calcification detected by computed tomography is associated with ischemic stroke as an indicator of intracranial atherosclerosis. However, little is known about its histopathology. This study aimed to explore the intracranial calcification patterns and their associations with atherosclerotic plaques. Methods— We recruited 32 adult autopsy cases to assess the calcification patterns and distributions in the middle cerebral artery, vertebral artery, and basilar artery. The relationships of calcification patterns with plaque phenotype and luminal stenosis were evaluated. The calcification patterns on computed tomography were correlated with that on histology. Results— Visible calcifications were detected within 37 (39%) segments, including 25 segments with intimal calcification, 6 segments with internal elastic lamina calcification, 3 segments with adventitial calcification, and 3 segments with concurrent calcification. Calcification occurred more often in the vertebral artery (51%), followed by the middle cerebral artery (35%) and basilar artery (14%; P P P Conclusions— Our histological findings indicate that the presence of intracranial artery calcification has 3 patterns, including intimal, internal elastic lamina, and adventitial calcifications. But only intimal calcification is related with progressive atherosclerotic lesions, indicative of a proxy for intracranial atherosclerosis.

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

Objective Repeated testing using the Montreal Cognitive Assessment (MoCA) increases risks for practice effects which may bias measurements of cognitive change. The objective of this study is to develop two alternate versions of the MoCA (Hong Kong version; HK-MoCA) and to investigate the validity and reliability of the alternate versions in patients with DSM-5 Mild Neurocognitive Disorder (Mild NCD) and cognitively healthy controls. Methods Concurrent validity and inter-scale agreement were examined by Pearson correlation of the total scores between the original and alternate versions and the Bland-Altman Method. Criterion validity of the two alternate versions in differentiating patients with Mild NCD was tested using receiver operating characteristic curve (ROC) analysis. One-month test-retest and inter-rater reliability were examined in 20 participants. Internal consistency of the alternate versions was measured by the Cronbach’s α. Results 30 controls (age 73.4 [4.5] years, 60% female) and 30 patients (age 75.4 [5.5] years, 73% female) with Mild NCD were recruited. Both alternate versions significantly correlated with the original version (r = 0.79–0.87, p

BACKGROUND AND PURPOSE Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. METHODS We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. RESULTS Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P

Background and Purpose— Clinical trial studies show that plaque eccentricity (symmetry) is among the plaque features that have been associated with more frequent cerebrovascular events. Plaque eccentricity of intracranial atherosclerotic disease is unclear because of lacking of cerebral artery specimens. Methods— 1.5T magnetic resonance imaging was performed in the postmortem brains to scan the cross sections of middle cerebral artery. Plaque eccentricity of histology-verified middle cerebral artery atherosclerosis was calculated on T1-weighted fat-suppressed sequence. Results— Validated by histology, concentric atherosclerotic plaques were identified in 46 middle cerebral arteries (63.9%) on magnetic resonance imaging and eccentric plaques in 26 arteries (26.1%). Eccentric plaques showed higher maximum wall thickness and lower minimum wall thickness than concentric plaques (both P Conclusions— Intracranial atherosclerosis presents as eccentric or concentric in geometry, which may be not linked to intracranial plaque risk. Further in vivo imaging studies are needed to identify morphological features of intracranial plaques and to verify its association with brain infarctions.

AIM: Pulse wave velocity (PWV) has been regarded as the “gold standard” measurement of arterial stiffness (AS), but it is still only used in the assessment of central and peripheral arteries. We constructed a new method to evaluate cerebral AS by measuring PWV using transcranial Doppler (TCD). METHODS: In all, 90 healthy subjects who received annual health screening were consecutively enrolled in this study between January 2011 and June 2013. Data on clinical characteristics, brachium–ankle (ba) PWV, and carotid–cerebral (cc) PWV measured with our newly constructed method by two experienced operators were recorded. cc PWV was calculated as the distance between two points in the common carotid artery and proximal part of ipsilateral middle cerebral artery, which was divided by the pulse transit time between these two points where the pulse was measured using TCD. RESULTS: The value of cc PWV was 499.3 ± 78.6 cm/s. Correlation between cc PWV and ba PWV in the assessment of AS was r = 0.794 (P < 0.001). The concordance between both the above mentioned methods was good. Interobserver and intraobserver reliability using interclass correlation for measuring cc PWV were 0.815 (P < 0.001) and 0.939 (P < 0.001), respectively. In multivariable analysis, older age (β = 4.51, P < 0.001) and increased diastolic blood pressure (β = 2.39, P < 0.001) were independently associated with higher cc PWV. CONCLUSION: cc PWV measured using TCD may be a promising method for the assessment of human cerebral AS, which is independently associated with age and diastolic blood pressure.

Symptomatic vertebrobasilar artery (VBA) stenosis has a poor prognosis. Intravascular stents provide a new therapeutic approach, but the long-term outcome of stenting compared with medical outcome is controversial. External counterpulsation (ECP) is a noninvasive method to improve perfusion of vital organs. We report two cases of this combination with ECP treatment in addition to receiving endovascular stenting. Two patients experienced posterior ischemic stroke. Digital subtraction angiography revealed a severe basilar or vertebral artery stenosis. Computed tomographic perfusion revealed significantly decreased perfusion of posterior artery territories. Both of them underwent combined ECP treatment and endovascular stenting of the stenosed basilar or vertebral artery, without recurrent stroke within 30 days after stenting. The two patients were independent (modified Rankin scale ≤2) at the 12-month follow-up time. Combined ECP treatment and endovascular stent placement may be effective and safe for patients with symptomatic VBA stenosis who failed aggressive medical treatment.

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.

© 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— 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.

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.

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.

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

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.

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.

Surgery is recommended for pharmacoresistant temporal lobe epilepsy (TLE), but seizures recur in approximately one third of patients postsurgery. P-glycoprotein is an efflux multidrug transporter that is overexpressed in a range of epileptogenic pathologies. We hypothesized that increased expression of P-glycoprotein in the epileptogenic temporal lobe might be a marker for recurrence of pharmacoresistant seizures postsurgery. We performed immunohistochemistry on temporal lobe tissues resected from 69 patients who underwent anterior temporal lobectomy for pharmacoresistant TLE with histopathological proven hippocampal sclerosis. P-glycoprotein expression was rated by three pathologists independently. Patients with seizure recurrence (n=22) had greater number of positively stained capillaries (p=0.001) and higher P-glycoprotein immunoreactive score in capillaries (p=0.002) in the white matter of resected temporal lobe. The differences remained significant in multivariate analysis (p=0.002 and 0.006, respectively). The results suggest that P-glycoprotein expression in temporal lobe may be associated with seizure recurrence after surgery for pharmacoresistant TLE.