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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.

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.

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

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.

Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries. Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA). In total, 318 patients were analyzed. Spearman’s correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p

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.

External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion in ischemic stroke. However, the response of beat-to-beat heart rate variability (HRV) in patients with ischemic stroke during ECP remains unknown.Forty-eight patients with unilateral ischemic stroke at the subacute stage and 14 healthy controls were recruited. Beat-to-beat heart rate before, during, and after ECP was monitored. The frequency components of HRV were calculated using power spectral analysis. Very low frequency (VLF;.04 Hz), low frequency (LF; .04-.15 Hz), high frequency (HF; .15-.40 Hz), total power spectral density (TP;.40 Hz), and LF/HF ratio were calculated.In stroke patients, although there were no statistical differences in all of the HRV components, the HRV at VLF showed a trend of increase during ECP compared with baseline in the left-sided stroke patients (P = .083). After ECP, the HRV at LF and TP remained higher than baseline in the right-sided stroke patients (LF, 209.4 versus 117.9, P = .050; TP, 1275.6 versus 390.2, P = .017, respectively). Besides, the HRV at TP also increased after ECP compared with baseline in the left-sided stroke patients (563.0 versus 298.3, P = .029).Irrespective of the side of the ischemia, patients showed an increased beat-to-beat HRV after ECP. Additionally, sympathetic and parasympathetic cardiac modulations were increased after ECP in patients after right-sided subacute stroke.

Cerebral autoregulation (CA) is a protective mechanism that maintains cerebral blood flow at a relatively constant level despite fluctuations of cerebral perfusion pressure or arterial blood pressure. It is a universal physiological mechanism that may involve myogenic, neural control as well as metabolic regulations of cerebral vasculature in response to changes in pressure or cerebral blood flow. Traditionally, CA has been represented by a sigmoid curve with a wide plateau between about 50 mm Hg and 170 mm Hg of steady-state changes in mean arterial pressure, defined as static CA. With the advent of transcranial Doppler, measurement of cerebral blood flow in response to transient changes in arterial pressure has been used to assess dynamic CA. However, a gold standard for measuring CA is not currently available. Stroke has been the leading cause of long-term adult disability throughout the world. A better understanding of CA and its response to pathological derangements can help assess the severity of stroke, guide management decisions, assess response to interventions and provide prognostic information. The objective of this review is to provide a comprehensive insight about physiology of autoregulation, measurement methodologies and clinical applications in stroke to help build a consensus for what should be included in an internationally agreed protocol for CA testing and monitoring, and to promote its translation into clinical bedside practice for stroke management.

Objective To examine the relation between neuroticism and fatigue in Chinese patients with stroke. Design Cross-sectional study. Setting Acute stroke unit. Participants Survivors of ischemic stroke (N=191) recruited from the acute stroke unit between May 1, 2010, and September 1, 2011. Interventions Not applicable. Main Outcome Measures 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. Results 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. Conclusions 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.

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

Aggression and agitation are common after a stroke. The association between agitation/aggression following stroke and Health-Related Quality of Life (HRQoL) in stroke survivors is unknown. This study aimed to examine the association between agitation/aggression and HRQoL in Chinese stroke survivors.Three hundred and twenty-four stroke patients entered this cross-sectional study. Agitation/aggression was assessed using the Chinese version of Neuropsychiatric Inventory (CNPI). HRQoL was measured with the Stroke Specific Quality of Life (SSQoL).Three months after the index stroke, agitation/aggression was found in 60 (18.5%) patients. In the agitation/aggression group, 44 patients (73.3%) showed passive agitation/aggression, whereas 16 (26.7%) displayed passive and active agitation/aggression. No patients showed only active agitation/aggression. Patients with agitation/aggression were more likely to have history of diabetes and greater severity of depression, as well as lower SSQoL total score and Personality Changes and Social Role scores. Controlling for diabetes and depression severity did not alter the above results. The Energy and Thinking scores of the SSQoL were significantly lower in the passive/active agitation/aggression group relative to the passive agitation/aggression group (adjusted for CNPI aggression/agitation score).In this study sample, agitation/aggression was preponderantly of the passive type and was associated with poorer HRQoL independently from depression or medical conditions. Patients with both passive and active agitation/aggression had lower Quality of Life (QoL) than patients with only passive agitation/aggression. The causality of the association between low QoL and agitation/aggression needs to be explored in future studies.

Background and purpose Baseline collateral status has been correlated with outcomes of acute ischaemic stroke patients receiving intravenous thrombolysis (IVT) in previous studies. We carried out the current systematic review and meta-analysis to synthesize currently available evidence regarding such correlations. Methods Full-text articles published since 2000 were retrieved and screened. The overall effect sizes of good versus poor collateral status over a series of outcomes and certain baseline features were estimated by random-effects models and presented in risk ratios (RRs) or mean differences. Results Overall, 28 (3057 patients) and 14 (1584 patients) studies were included in qualitative and quantitative synthesis, respectively. Compared with poor pre-treatment collateral status, good collaterals showed a beneficial effect over the primary outcome of a favorable functional outcome at 3 or 6 months [RR, 2.45; 95% confidence interval, 1.94–3.09; P 4.5 h (up to 7 h), with the RRs being 2.21, 2.48 and 5.00, respectively (I2 = 53%). Good pre-treatment collaterals were also associated with a smaller infarct size at baseline, and a lower rate of symptomatic intracranial hemorrhage and a higher rate of neurological improvement early after IVT treatment. Conclusions The present study has demonstrated the prognostic value of baseline collateral circulation for outcomes of acute ischaemic stroke patients receiving intravenous reperfusion therapies, studied with different time windows of up to 7 h after ictus for IVT therapy.

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 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.

Autonomic dysregulation is common in post-stroke patients. We aimed to correlate beat-to-beat blood pressure variability (BPV) and heart rate variability (HRV) with Ewing's test classification. We enrolled patients with acute ischemic stroke. Autonomic function was assessed by Ewing battery and dichotomized into minor or significant group. Beat-to-beat blood pressure and heart rate were monitored for calculating the frequency components of BPV and HRV using power spectral analysis [very low frequency (VLF;0.04 Hz); low frequency (LF; 0.04-0.15 Hz); high frequency (HF; 0.15-0.40 Hz); power spectral density (PSD;0.40 Hz) and LF/HF ratio]. In minor autonomic dysregulation group, BPV and HRV were similar with those in controls (all p 0.05). However, LF/HF ratio in BPV and HRV significantly reduced in significant autonomic dysregulation group compared with that in controls (all p 0.05). LF BPV in significant group was lower than that in controls. In patients, LF and LF/HF BPVs were positively correlated with parasympathetic parameters, while VLF HRV was negatively correlated with sympathetic parameters and the others were positively correlated with parasympathetic parameters. With cut-off values of 1.80 for LF/HF diastolic BP, 0.96 for the LF/HF systolic BP and 1.80 for LF/HF HRV, the sensitivity (53.80%, 69.20% and 53.80%, respectively) and specificity (92.50%, 80.00% and 92.50%, respectively) of these parameters were observed to predict autonomic dysregulation. Autonomic dysregulation is associated with lower variation of blood pressure and heart rate in acute ischemic stroke. Non-invasive monitoring of beat-to-beat BPV and HRV may be an alternative to autonomic dysregulation measure.

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

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.

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.

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 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 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.

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.

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.

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.

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.

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.

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.

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.