Intracranial arterial stenosis in Caucasian versus Chinese patients with TIA and minor stroke: two contemporaneous cohorts and a systematic review.

BACKGROUND: Intracranial arterial stenosis (ICAS) is an important cause of stroke worldwide. Separate reports in Caucasians and Asians with stroke/transient ischaemic attack (TIA) have suggested lower ICAS prevalence in Caucasians, but there has been no direct comparisons of the two ethnic groups with the same criteria to define ICAS. METHODS: Acute minor stroke or TIA patients in two cohorts respectively recruiting patients in Oxford (2011-2018, predominantly Caucasians) and Hong Kong (2011-2015, predominantly Chinese) were compared. ICAS was defined as ≥50% stenosis/occlusion in any major intracranial artery in MR/CT angiography. Prevalence, distribution and risk factors of ICAS were compared between the two cohorts. We also systematically reviewed literature on ICAS prevalence in stroke/TIA patients in different populations. RESULTS: Among 1287 patients from Oxford and 691 from Hong Kong (mean age 69 vs 66), ICAS prevalence was higher in Chinese than in Caucasians (43.0% vs 20.0%; OR 3.02; 95% CI 2.47 to 3.70; p<0.001), independent of age (age-adjusted OR 3.73; 95% CI 3.00 to 4.63; p<0.001) and vascular risk factors (multivariable-adjusted OR 3.21; 95% CI 2.56 to 4.02; p<0.001). This ethnic difference was greater (p interaction=0.005) at age <70 years (OR 5.33; 95% CI 3.79 to 7.50; p<0.001) than at ≥70 years (OR 2.81; 95% CI 2.11 to 3.74; p<0.001). ICAS prevalence increased with age and with vascular risk factors in both cohorts, with equivalent prevalence in Chinese aged <60 years and Caucasians aged ≥80, and in Chinese with no vascular risk factor and Caucasians with two vascular risk factors. ICAS locations also differed between Chinese and Caucasian patients. CONCLUSIONS: Chinese are more susceptible to ICAS than Caucasians, with an earlier onset age and a higher prevalence, independent of vascular risk factors.

Stroke Outcome Prediction by Blood Pressure Variability, Heart Rate Variability, and Baroreflex Sensitivity.

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<0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316-2.125]; P<0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250-0.973]; 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.

Hemodynamics and stroke risk in intracranial atherosclerotic disease.

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.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs. METHODS: In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs. RESULTS: A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH. CONCLUSIONS: In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

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.

Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies.

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

Impact of intracranial artery calcification on cerebral hemodynamic changes.

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

Impact of Side Branches on the Computation of Fractional Flow in Intracranial Arterial Stenosis Using the Computational Fluid Dynamics Method.

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

Prediction of Recurrent Stroke or Transient Ischemic Attack After Noncardiogenic Posterior Circulation Ischemic Stroke.

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 <7 days. Stroke risk factors, admission symptoms and signs, topographical distribution and responsible cerebral artery of acute infarcts, and any recurrent IS or transient ischemic attack (TIA) within 1 year were assessed. Cox regression was used to identify risk factors associated with recurrent IS or TIA within the year after posterior circulation IS. 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<0.0001), responsible artery stenosis ≥70% (HR, 7.91; 95% CI, 1.00-62.6; 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.

Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

BACKGROUND AND PURPOSE: In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis. METHODS: Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model. RESULTS: A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61). CONCLUSIONS: The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Impaired cerebral autoregulation: measurement and application to 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.

Location of Acute Infarcts and Agitation and Aggression in Stroke.

The role of the infarct location in the development of poststroke agitation (PSA) is largely unknown. This study examined the association between the locations of infarcts and PSA at 9 months following the index stroke in 213 patients with the Chinese version of the Neuropsychiatric Inventory. Compared with the non-PSA group, PSA patients had a higher number and volume of acute pontine infarcts. Ventral pontine and lateral cerebellar infarcts were independent predictors of PSA in the multivariate analysis.

Neuroticism and Fatigue 3 Months After Ischemic Stroke: A Cross-Sectional Study.

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.

Benign Oligemia in Subacute Stage Is Associated with Borderzone Infarction in Stroke Patients Caused by Intracranial Large Artery Disease.

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.

High Extent of Intracranial Carotid Artery Calcification Is Associated with Downstream Microemboli in Stroke Patients.

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.

Is Dynamic Cerebral Autoregulation Bilaterally Impaired after Unilateral Acute Ischemic Stroke?

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Postmortem Study of Validation of Low Signal on Fat-Suppressed T1-Weighted Magnetic Resonance Imaging as Marker of Lipid Core in Middle Cerebral Artery Atherosclerosis.

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.

In Vitro Assessment of Histology Verified Intracranial Atherosclerotic Disease by 1.5T Magnetic Resonance Imaging: Concentric or Eccentric?

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<0.001). Plaque burden and brain infarctions were similar between concentric and eccentric plaques. 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.

Magnetic Resonance Imaging of Plaque Morphology, Burden, and Distribution in Patients With Symptomatic Middle Cerebral Artery Stenosis.

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<0.05. RESULTS: Vessel wall lesions were identified in 18 patients (95%), totaling 57 lesions in 494 segments (12% of segments). Lesions were located primarily in the anterior circulation (82%). Eccentric lesions were associated with a focal thickening pattern and concentric lesions with a diffuse thickening pattern (P<0.001). When differentiating between asymptomatic and symptomatic lesions, an association (P<0.05) was found between eccentricity and asymptomatic lesions, but not for enhancement or a specific thickening pattern. Symptomatic lesions did not have any specific morphological features. CONCLUSIONS: Our results lead to a 2-fold conclusion: (1) The classification system of both thickening pattern and distribution of the lesion can be simplified by using distribution pattern only and (2) differentiation between symptomatic and asymptomatic atherosclerotic lesions was possible using intracranial vessel wall imaging.