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N6-methyladenosine (m6A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6A’s effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear.

Aims: The relationship between heme oxygenase‐1 (HO‐1) and human ischemic stroke outcome remains unclear, which was investigated in this study. Methods: Acute ischemic stroke patients admitted within 24 h were enrolled. Serum HO‐1 levels at baseline were measured via ELISA. Poor 3‐month functional outcome was defined as modified Rankin Scale (mRS) score 3–6. Multivariable‐adjusted binary logistic regression and restricted cubic spline models were employed to examine association between serum HO‐1 and functional outcome. HO‐1's additive prognostic utility was assessed by net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: Of 194 eligible patients, 79 (40.7%) developed poor functional outcomes at 3‐month follow‐up. The highest quartile of serum HO‐1 was independently associated with a lower risk of poor functional outcome (adjusted OR 0.13, 95% CI 0.04–0.45; p = 0.001) compared with the lowest HO‐1 category. The relationship between higher HO‐1 levels and reduced risk of poor functional outcome was linear and dose responsive (p = 0.002 for linearity). Incorporating HO‐1 into the analysis with conventional factors significantly improved reclassification for poor functional outcomes (NRI = 41.2%, p = 0.004; IDI = 5.0%, p = 0.004). Conclusions: Elevated serum HO‐1 levels at baseline were independently associated with improved 3‐month functional outcomes post‐ischemic stroke. Serum HO‐1 measurement may enhance outcome prediction beyond conventional clinical factors. [ABSTRACT FROM AUTHOR]

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.

BackgroundChanges of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA.MethodsSymptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other's readings: SIR=(mean poststenotic SI-mean background SI)/(mean prestenotic SI-mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index.ResultsA total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92±.17 versus .93±.17; mean difference -.006±.09; P=.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland-Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers.ConclusionsSIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS.

BackgroundIntracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity.MethodsIn-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated.ResultsThirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient -0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values.ConclusionsChange of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.

Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine. [ABSTRACT FROM AUTHOR]

The methodologies of computational fluid dynamics (CFD) and response surface method (RSM) were integrated to uncover the optimal correlational framework for intricate hydraulic geometric parameters of guide vane centrifugal pumps. Parameters such as blade number, blade wrap angle, blade outlet angle, and relative axial distance between the guide vane and impeller, as well as radial distance, are embraced as optimization design variables. Meanwhile, pump head and efficiency were chosen as responsive variables. An analysis of 46 sets of hydraulic performance data was carried out by using the Box–Behnken experimental design method. Subsequently, response surface approximation models were established between hydraulic parameters and the efficiency, as well as the head. The optimal design point was predicted and a simulation of the hydraulic characteristics for the optimal scheme was conducted; the errors were 0.846% for head and 0.256% for efficiency between the simulation results with predicted results from RSM. The optimized model demonstrates noteworthy enhancements in hydraulic performance in comparison to the original model. By analyzing the internal flow of the optimized model under transient conditions, it was found that, as the internal flow of the flow passage components is relatively disordered at small flow rates, the amplitude of pressure pulsation is affected a lot. At other flow rates, the inside pressure pulsation waveform exhibits pronounced periodicity, and the primary causes of pressure pulsation in various flow components are not the same. Wall dissipation and turbulent dissipation emerge as significant contributors to the entropy generation in this centrifugal pump. The magnitude of entropy generation is correlated with the flow rate and the structural configuration of the pump's components. High-entropy regions concentrate around the leading and trailing edges of the blades. [ABSTRACT FROM AUTHOR]

Background: Stroke caused by acute basilar artery occlusion (BAO) is devastating with high dependency and mortality. Recent trials have demonstrated the efficacy of endovascular treatment (EVT) for acute BAO, while pretreatment collaterals may be a valuable prognostic indicator for post-EVT outcomes. Aims: To systematically review and synthesize evidence on the associations between pretreatment collateral status and outcomes after EVT in acute BAO. Methods: We retrieved relevant full-text articles published in English since 1 January 2010, reporting associations between pretreatment collateral status and outcomes after EVT for BAO, by searching MEDLINE and Embase. The primary outcome was favorable or good 90-day functional outcome (modified Rankin Scale [mRS] 0–2 or 0–3); secondary outcomes included successful recanalization, symptomatic intracranial hemorrhage, final infarct volume, and 90-day mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) for good versus poor collaterals on the outcomes were synthesized using random-effects models. Subgroup and sensitivity analyses were conducted for the primary outcome. Results: Overall, 29 primary studies (2995 participants) were included in qualitative review, among which 16 studies (1447 participants) were meta-analyzed. With different imaging modalities and methods to grade the collateral status, good collaterals were found in 33–85% of patients in the individual primary studies (I2 = 95.2%, p < 0.001), with a pooled proportion of 51% (95% CI: 40–62%) across all studies. Good pretreatment collaterals were associated with a doubled rate of favorable/good 90-day functional outcome (RR = 2.03, 95% CI: 1.63–2.51, p < 0.001), a higher rate of successful recanalization (RR = 1.23, 95% CI: 1.04–1.45, p = 0.015), and reduced 90-day mortality (RR = 0.59, 95% CI: 0.43–0.81, p = 0.001) after EVT for BAO. None of the primary studies reported the associations of good collaterals with the other secondary outcomes. Subgroup analyses revealed possibly more prominent protective effect of good pretreatment collaterals over the primary outcome, in studies with longer time windows in patient eligibility criteria for EVT (p = 0.028 for between-subgroup heterogeneity). Conclusions: In patients with BAO receiving EVT, good pretreatment collateral status was associated with a higher chance of favorable 90-day functional outcome, despite the various methods in grading the collateral circulation. Efforts are needed for more standardized collateral assessment in BAO, for more reliable and generalizable investigations of its clinical implications. [ABSTRACT FROM AUTHOR]

Background: Depicting the time trends of ischemic stroke subtypes may inform healthcare resource allocation on etiology-based stroke prevention and treatment. Aim: To reveal the evolving ischemic stroke subtypes from 2004 to 2018. Methods: We determined the stroke etiologies of consecutive first-ever transient ischemic attack or ischemic stroke patients admitted to a regional hospital in Hong Kong from 2004 to 2018. We analyzed the age-standardized incidences and the two-year recurrence rate of major ischemic stroke subtypes. Results: Among 6940 patients admitted from 2004 to 2018, age-standardized incidence of ischemic stroke declined from 187.0 to 127.4 per 100,000 population (p < 0.001), driven by the decrease in large artery disease (43.0–9.67 per 100,000 population (p < 0.001)), and small vessel disease (71.9–45.7 per 100,000 population (p < 0.001)). Age-standardized incidence of cardioembolic stroke did not change significantly (p = 0.2). Proportion of cardioembolic stroke increased from 20.4% in 2004–2006 to 29.3% in 2016–2018 (p < 0.001). Two-year recurrence rate of intracranial atherothrombotic stroke reduced from 19.3% to 5.1% (p < 0.001) with increased prescriptions of statin (p < 0.001) and dual antiplatelet therapy (p < 0.001). In parallel with increased anticoagulation use across the study period (p < 0.001), the two-year recurrence of AF-related stroke reduced from 18.9% to 6% (p < 0.001). Conclusion: Etiology-based risk factor control might have led to the diminishing stroke incidences related to atherosclerosis. To tackle the surge of AF-related strokes, arrhythmia screening, anticoagulation usage, and mechanical thrombectomy service should be reinforced. Comparable preventive strategies might alleviate the enormous stroke burden in mainland China. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objective. Hematoma expansion is closely associated with adverse functional outcomes in patients with intracerebral hemorrhage (ICH). Prediction of hematoma expansion would therefore be of great clinical significance. We therefore attempted to predict hematoma expansion using a dual-modal machine learning (ML) strategy which combines information from non-contrast computed tomography (NCCT) images and multiple clinical variables. Approach. We retrospectively identified 140 ICH patients (57 with hematoma expansion) with 5616 NCCT images of hematoma (2635 with hematoma expansion) and 10 clinical variables. The dual-modal ML strategy consists of two steps. The first step is to derive a mono-modal predictor from a deep convolutional neural network using solely NCCT images. The second step is to achieve a dual-modal predictor by combining the mono-modal predictor with 10 clinical variables to predict hematoma growth using a multi-layer perception network. Main results. For the mono-modal predictor, the best performance was merely 69.5% in accuracy with solely the NCCT images, whereas the dual-modal predictor could boost the accuracy greatly to be 86.5% by combining clinical variables. Significance. To our knowledge, this is the best performance from using ML to predict hematoma expansion. It could be potentially useful as a screening tool for high-risk patients with ICH, though further clinical tests would be necessary to show its performance on a larger cohort of patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA. Methods: Consecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients). Results: Overall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96−4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; p = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07−3.75; p = 0.031) was independently associated with the composite outcome in older patients. Conclusion: In older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events. [ABSTRACT FROM AUTHOR]

Transfer function analysis (TFA) is extensively used to assess human physiological functions. However, extracting parameters from TFA is not usually optimized for detecting impaired function. In this study, we propose to use data-driven approaches to improve the performance of TFA in assessing blood flow control in the brain (dynamic cerebral autoregulation, dCA). Data were collected from two distinct groups of subjects deemed to have normal and impaired dCA. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) were simultaneously recorded for approximately 10 mins in 82 subjects (including 41 healthy controls) to give 328 labeled samples of the TFA variables. The recordings were further divided into 4,294 short data segments to generate 17,176 unlabeled samples of the TFA variables. We optimized TFA post-processing with a generic semi-supervised learning strategy and a novel semi-supervised stacked ensemble learning (SSEL) strategy for classification into normal and impaired dCA. The generic strategy led to a performance with no significant difference to that of the conventional dCA analysis methods, whereas the proposed new strategy boosted the performance of TFA to an accuracy of 93.3%. To our knowledge, this is the best dCA discrimination performance obtained to date and the first attempt at optimizing TFA through machine learning techniques. Equivalent methods can potentially also be applied to assessing a wide spectrum of other human physiological functions. [ABSTRACT FROM AUTHOR]

In a multicenter registry study, Guo et al. reported a 8.2% 1-year risk of stroke and vascular death, in patients with symptomatic, high-grade ICAD with imaging evidence of downstream hypoperfusion who received stenting treatment. These two studies have stressed the need to understand the pathophysiology in ICAD-related stroke and to treat ICAD and the stroke mechanism(s) rather than a single stenosis. Keywords: stroke; intracranial atherosclerotic disease; imaging; endovascular treatment; stenting EN stroke intracranial atherosclerotic disease imaging endovascular treatment stenting 1 3 3 10/26/21 20211022 NES 211022 Intracranial atherosclerotic disease (ICAD) is an important cause of ischemic stroke and transient ischemic attack (TIA) worldwide ([1]). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background: Although wall shear stress (WSS) and pressure play important roles in plaque vulnerability, characteristics of the two indices in intracranial atherosclerosis (ICAS) have not been fully investigated yet. This study aimed to elucidate this issue by means of establishing a non-invasive computational fluid dynamics method with time-of-flight magnetic resonance angiography (TOF-MRA) of the whole cerebral artery. Materials and Methods: Subjects with symptomatic ICAS in the middle cerebral artery domain were enrolled, excluding those with concomitant internal carotid artery stenosis. Based on patient-specific TOF-MRA images for three-dimensional (3D) meshes and arterial blood pressure with patient-specific carotid artery ultrasonography for inlet boundary conditions, patients' three-dimensional hemodynamics were modeled by a finite element method governed by Navier-Stokes equations. Results: Among the 55 atherosclerotic lesions analyzed by this TOF-MRA based computational fluid dynamics model, the maximum WSS (WSSmax) was most frequently detected at the apex points and the upper half of the upstream sections of the lesions, whereas the maximum pressure was most often located at the lower half of the upstream sections. As the percent stenosis increases, the relative value of WSSmax and pressure drop increased with significantly increasing steep beyond 50% stenosis. Moreover, WSSmax was found to linearly correlate with pressure drop in ICAS. Conclusions: This study on ICAS revealed certain trends of longitudinal distribution of WSS and pressure and the influences of percent stenosis on cerebral hemodynamics, as well as the correlations between WSS and pressure drop. It represents a step forward in applying computational flow simulation techniques in studying ICAS and stroke, in a patient-specific manner. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives:Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. Methods:Patients with symptomatic ICAS (70–99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. Results:Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = −0.398,p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = −0.677,p = 0.032). There was no difference in patients with good collateral circulation (r = −0.279,p = 0.356). Conclusion:An anatomically severe (70–99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this hemodynamic impact, partially explaining the protective effect of collateral circulation against recurrent stroke in such patients. [ABSTRACT FROM PUBLISHER]