White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion ...recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention.
Newtonian 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.
We 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.
In 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.
Newtonian 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.
Objective
To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid ...dynamics (CFD) model.
Methods
In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA‐based CFD models, translesional pressure ratio (PR = pressurepoststenotic/pressureprestenotic) and translesional wall shear stress ratio (WSSR = WSSstenotic − throat/WSSprestenotic) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year.
Results
Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range IQR = 0.87–0.97); median translesional WSSR was 13.3 (IQR = 7.0–26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio HR = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004).
Interpretation
This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery‐to‐artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752–764
Background
Intracranial atherosclerotic stenosis is an important etiology subtype of ischemic stroke. Stenosis severity was thought to be the main reference index for clinical treatment and research. ...However, stenosis could not reflect the ischemia risk completely, instead the hemodynamic state across the lesion, the extent of collateral circulation, and perfusion impairment downstream the stenosis are more important.
Aims
We write this review aimed to summarize novel angiographic methods applied in the evaluation of functional severity of ICAS, and commented on their limitations and prospects in future research.
Summary of review
The main methods to estimate cerebral blood flow including fractional flow assessed by signal intensity ratio, computational fluid dynamics analysis or pressure wire, quantitative magnetic resonance angiography. Fractional flow as a series cerebral hemodynamic parameters may reflect the status of collateral circulation and cerebral blood flow. But the accuracy of the methods was not validated. The method to calculate fractional flow reserve in cardiovascular disease cannot duplicate in cerebrovascular disease. Fractional flow measurement by floating a pressure guidewire across the intracranial stenosis was technically feasible and safe. In the future researches, a non-invasive method should be established to identify high-risk intracranial lesions and may help in decision-making.
Conclusions
The relationship between stenosis and cerebral blood flow was individualized. Cerebral hemodynamic criteria should be used to screen patients to endovascular treatment, which will optimize the diagnosis and treatment strategies for patients with symptomatic intracranial artery stenosis.
AimCerebral venous sinus thrombosis (CVST) is a less common cerebrovascular disease that predominantly affects young patients. The incidence of CVST is 2–5/10 000 000/year, accounting for 0.5%–1% of ...all stroke. To reduce mortality and morbidity associated with CVST, Chinese Stroke Association commissioned the authors to write the current guideline on the management of CVST.MethodsPubMed (MEDLINE), CNKI and Wanfang database were searched for studies related to CVST from 1 January 1990 to 31 July 2019. Data were synthesised by evidence tables. Each recommendation was fully discussed by the writing group members and reviewed by Chinese Stroke Association Stroke Fellow Committees. Levels of evidence grading algorithm of Chinese Stroke Association was used to grade each recommendation.ResultsThis guideline mainly focuses on the diagnostic evaluation, therapeutic strategies and secondary prevention of CVST. CT/CTV and MRI/MRV are recommended in the initial imaging evaluation of patients with suspected CVST. Anticoagulation therapy with low-molecular weight heparin should be initiated in patients with CVST immediately. After the acute stage, warfarin is recommended for 3–6 months to prevent the recurrence of CVST and other venous thromboembolic events.ConclusionsThe guideline summarises the current evidence regarding the management of CVST, and provides references for diagnosis, treatment and secondary prevention of CVST in China.
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.
Intracranial arterial stenosis (ICAS) is the dominant cause for ischemic stroke worldwide, with hemodynamic compromise as a crucial contributor. Prolonged perfusion is commonly observed in ICAS ...patients on CT perfusion (CTP) maps, while the clinical significance of this perfusion pattern has not been elucidated.
Patients having symptomatic ICAS of 50-99% stenosis with sustained downstream cerebral blood flow (CBF) were enrolled in this study. Prolonged perfusion was defined as increased mean transit time (MTT) in vascular territories of the target ICAS on CTP maps. The primary clinical outcome was recurrence of ipsilateral ischemic stroke, and secondary outcome was any ipsilateral ischemic events at 2 years follow-up.
Of the 95 patients (median age 61y; 70% males) with symptomatic ICAS, 29 patients (30.5%) had prolonged perfusion. Such delayed perfusion was persistent in a majority of patients according to the 1-year imaging follow-up. The prolongation of cerebral perfusion was associated with subsequent risk for ipsilateral ischemic stroke (HR 7.01; 95% CI 1.86-26.46; p = 0.004), but not for any ipsilateral ischemic events (HR 1.52; 95% CI 0.63-3.68; p = 0.348). Further comparison of perfusion measures showed lower CBF (p = 0.034) and higher MTT (p = 0.064) in patients with recurrent ischemic stroke, but not in those with recurrent transient ischemic attack (TIA). Among patients with recurrent stroke, a majority had multiple infarcts along the borderzone regions.
In patients with symptomatic ICAS, persistent prolonged cerebral perfusion might contribute to the relapse of ischemic stroke, but not TIA.
Intracranial arterial stenosis (ICAS) is a predominant cause of ischemic stroke in Asia. Changes in the signal intensities (SIs) across ICAS lesions on time-of-flight magnetic resonance angiography ...(TOF-MRA) have been indicated to partially reflect the hemodynamic significance of the lesions, which we aimed to verify by correlating it with cerebral perfusion features provided by CT perfusion (CTP) imaging.
Ischemic stroke or transient ischemic attack patients with unilateral symptomatic stenosis (≥50%) of intracranial internal carotid artery or middle cerebral artery (MCA) were included in this study. Change of SIs across an ICAS lesion on TOF-MRA was calculated by the distal and proximal SI ratio (SIR). Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) within the MCA territory of ipsilateral and contralateral hemispheres were evaluated on the CTP images at the basal ganglia level. Relative CBV, CBF and MTT were defined as ratios of the values obtained from ipsilateral and contralateral hemispheres. The relationships between SIR and CTP parameters were analyzed.
Fifty subjects (74% male, mean age 62) were recruited. Overall, the mean SIR was 0.77 ± 0.17. SIR of ICAS was significantly, linearly and negatively correlated with ipsilateral CBV (r = -0.335, p = 0.017), ipsilateral MTT (r = -0.301, p = 0.034), and ipsilateral/contralateral MTT ratio (r = -0.443, p = 0.001).
Diminished SIs distal to ICAS on TOF-MRA might be associated with delayed ipsilateral cerebral perfusion. Changes of the SIs across ICAS lesions on TOF-MRA may be a simple marker to reflect cerebral perfusion changes in patients with symptomatic ICAS.
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