Search

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.

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.

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.

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.

Whether dynamic cerebral autoregulation (dCA) is impaired focally in the affected hemisphere or bilaterally in both the affected and nonaffected hemispheres after ischemic stroke remains controversial. We therefore investigated the pattern of dCA in acute ischemic stroke patients with different subtypes.Sixty acute ischemic stroke patients with unilateral anterior circulation infarct [30 with large artery atherosclerosis (LAA), 13 with small vessel disease (SVD), and 17 with coexisting LAA and SVD] and 16 healthy controls were enrolled. Spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations in both bilateral middle cerebral arteries using transcranial Doppler were recorded over 10 minutes. Transfer function analysis was applied to obtain autoregulatory parameters, autoregulation index (ARI), phase difference (PD), and gain.PD was significantly lower on both the ipsilateral and contralateral sides in the LAA group (ipsilateral, 30.74 degrees; contralateral, 29.17 degrees) and the coexisting LAA and SVD group (20.23 degrees; 13.10 degrees) than that in healthy controls (left side, 51.66 degrees; right side, 58.48 degrees) (all P .05), but there were no significant differences between the 2 sides when compared with each other in all groups. However, in the coexisting LAA and SVD group, phase on both sides was significantly lower when compared with that in the LAA and SVD groups, respectively. The results of ARI were consistent with the findings in PD.The results indicate that dCA is bilaterally impaired in acute ischemic patients with LAA, and the coexisting SVD may aggravate the bilateral impairment of dCA.

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: 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.

Background Intracranial arterial calcification (ICAC) is frequently detected on head computed tomography and has been found to be associated with ischemic stroke by recent clinical studies. Aims Based on a hospital-based study, we aimed to compare the occurrence of cerebral microembolic signals (MES) among stroke patients with different degrees of ICAC, which may indicate the potential mechanisms linking ICAC and ischemic stroke in intracranial atherosclerosis patients. Methods This is a post-hoc analysis of our previous clinical study in 2005-2007, recruiting consecutive ischemic stroke patients with middle cerebral artery territory infarctions and good temporal window for MES monitoring. The degrees of ICAC in the Circle of Willis, especially calcification in the ipsilateral intracranial internal carotid artery (iICA), were evaluated both qualitatively and quantitatively on unenhanced head computed tomography. Results Among the 68 recruited patients, MES was detected in 26 patients (38.24%). The overall degree of ICAC in the Circle of Willis was similar between patients with and without MES. For calcification in ipsilateral iICA, the presence of MES was more frequent in the high extent group (widest arc of calcification ≥90°) than in the low extent group (54.2% versus 29.5%, P = .046). Logistic regression found that a high extent ipsilateral iICA calcification was an independent risk factor of MES (odds ratio: 3.134; 95% confidence interval, 1.029-9.543; P = .044). Conclusions MES is frequently detected in patients with a high extent of ipsilateral iICA calcification, which suggests that a high extent of iICA calcification indicates artery vulnerability and accounts for the occurrence of microemboli in the corresponding artery.

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.

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.

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— 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.

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 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.

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that serves as treatment tool to neurological disorders. However, the mechanism of how the stimulation modulates ongoing brain activity and connectivity is still not fully understood. Simultaneous acquisition of neuroimaging data together with brain stimulation could allow a noninvasive examination of the brain dynamic changes during the process. In this pilot study, concurrent tDCS and fMRI was conducted in a healthy subject. Dynamic functional connectivity and effective connectivity were used to reveal the information flow. The results demonstrated that tDCS duration has important effects on the brain connectivity and the causal relationships among the brain regions. These results might reflect the fundamental mechanism of brain processing under the external stimulation.

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

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.

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 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.

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

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

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

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