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Rationale: The effect of the head position as a non-pharmacological therapy on acute ischaemic stroke (AIS) remains inconclusive. Our recent Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis (HOPES 2) suggested the safety, feasibility and potential benefit of the head-down position (HDP) in AIS., Aim: To investigate the benefit of HDP in acute moderate ischaemic stroke patients with large artery atherosclerosis (LAA)., Sample Size Estimates: Based on a two-sided 0.05 level of significance, 600 patients are expected to yield the superiority hypothesis with 80% power, stratified by age, sex, history of diabetes, baseline systolic blood pressure, location of index vessel, National Institutes of Health Stroke Scale Score at randomisation, onset to randomisation time, progression to moderate neurological deficit due to early neurological deterioration and degree of responsible vessel stenosis., Design: Head dOwn-Position for acutE moderate ischaemic Stroke with large artery atherosclerosis(HOPES 3) is a prospective, randomised, open-label, blinded endpoint and multicentre study. Eligible patients who had an ischaemic stroke will be randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg plus standard medical care in compliance with national guidelines, or control group only receiving standard medical care in compliance with national guidelines., Outcome: The primary outcome is favourable functional outcome, defined as modified Rankin Scale 0-2 at 90 days. Safety outcomes are HDP-related adverse events. All outcomes will have blinded assessment and will be analysed on the intention-to-treat basis., Conclusions: The results of HOPES 3 will provide evidence for the effect of HDP in acute moderate ischaemic stroke patients with LAA within 24 hours of onset or in patients with progression from mild neurological deficit within 24 hours., Trial Registration Number: NCT06010641., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The optimal treatment for patients with acute large vessel occlusion (LVO) secondary to intracranial atherosclerotic disease (ICAD) is unclear. Adjunctive rescue therapy with balloon angioplasty or stenting may be necessary to ensure vessel patency. We aimed to compare the safety and clinical outcomes of adjunctive rescue therapy vs lone thrombectomy for ICAD-related-LVO., Methods: A retrospective propensity score matching analysis was performed in acute stroke patients who had endovascular thrombectomy between 2008 and 2021. We included patients with acute ICAD-related-LVO. The location of ICAD and exposure to thrombolysis were used to generate propensity score matching to estimate the likelihood of treatment by adjunctive rescue therapy. The primary clinical outcome (90-day modified rankin scale 0-2) and safety outcomes (symptomatic intracerebral hemorrhage) were assessed between the two groups., Results: One-hundred and forty-four patients were included. The median (IQR) age was 68(59-76) and 52(36 %) were females. The baseline NIHSS was 12.5(8-19). Sixty-seven (47 %) patients had ICAD in M1 or M2 segments. Forty-six patients (67 %) had lone thrombectomy and twenty-one (28 %) had adjunctive rescue therapy. Propensity score matching did not demonstrate significant differences in 90-day modified Rankin Score 0-2 between lone thrombectomy (38.8 %) and adjunctive rescue therapy (39.3 %) (p = 0.3). Lone thrombectomy, compared to adjunctive rescue therapy, did not result in significantly more symptomatic intracerebral hemorrhages (2.8 % vs 8.3 %, p = 0.6), nor progressive occlusion (17 % vs 19 %, p = 0.8)., Conclusion: We did not find significant differences in clinical outcomes and safety between lone thrombectomy and adjunctive rescue therapy. Randomized controlled studies are required to resolve the equipoise in treatment of ICAD-related-LVO., Competing Interests: Declaration of competing interest All authors disclose no real or potential conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool., Methods: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-T max . The correlations between cognitive function and abnormal perfusion were explored., Results: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function., Conclusion: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: Cerebral hemodynamics are important for the management of intracranial atherosclerotic stenosis (ICAS). The quantitative flow ratio (QFR) is a novel angiography-derived index for assessing the functional relevance of ICAS without pressure wires and adenosine. Good diagnostic yield with the hyperemic fractional flow reserve (FFR) have been reported, while data on the comparison of QFR to FFR are scarce., Methods: In this prospective study 56 patients with anterior circulation symptomatic ICAS who received endovascular treatment were included. The new method of computing QFR from a single angiographic view, i.e., the Murray law-based QFR (μQFR), was applied to the examined vessels. An artificial intelligence algorithm was developed to realize the automatic delineation of vascular contour. Pressure gradients were measured before and after treatment within the lesion vessel using a pressure guidewire and the FFR was calculated., Results: There was a good correlation between μQFR and FFR. Preoperative FFR predicted DWI watershed infarction (FFR optimal cut-off level: 0.755). Preoperative μQFR predicted DWI watershed infarction (μQFR optimal cut-off level: 0.51). Preoperative FFR predicted CTP hypoperfusion (FFR best predictive value: 0.62). Preoperative μQFR predicted CTP hypoperfusion (μQFR best predictive value: 0.375)., Conclusion: The μQFR based on DSA images can be used as an indicator to assess the functional status of the lesion in patients with ICAS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: This study aimed to compare clinical and perfusion imaging profiles in acute ischemic stroke with large vessel occlusion (AIS-LVO) between patients with intracranial atherosclerotic disease (ICAD) and non-ICAD who underwent endovascular treatment (EVT)., Methods: Data from AIS-LVO patients over the anterior circulation undergoing EVT across two stroke centers were retrospectively analyzed. Clinical profiles and perfusion parameters from automated processing of perfusion imaging were compared between ICAD and non-ICAD groups. Ischemic core was defined as relative cerebral blood flow < 30 % on CT perfusion or apparent diffusion coefficient ≤ 620 × 10 -6 mm 2 /s on MR diffusion weighted imaging., Results: A total of 111 patients were included (46 ICAD, 65 non-ICAD). The ICAD group exhibited a higher male proportion (60.9 % vs. 35.4 %), more M1 segment occlusions (78.3 % vs. 56.9 %), lower atrial fibrillation rates (17.4 % vs. 63.1 %), and lower baseline NIH Stroke Scale (NIHSS) scores (median [IQR]: 13 [8.75-18] vs. 15 [10-21]) at presentation compared to non-ICAD (all p < 0.05). However, there was no difference in NIHSS scores at discharge or in good functional outcomes (modified Rankin Scale 0-2) at 3 months between the two groups. ICAD patients also had smaller median ischemic core volumes (0 [IQR 0-9.7] vs. 4.4 [0-21.6] ml, p = 0.038), smaller median Tmax >6s tissue volulmes (89.3 [IQR 51.1-147.1] vs. 124.4 [80.5-178.6] ml, p = 0.017) and lower median HIR (hypoperfusion intensity ratio defined as Tmax >10s divided by Tmax >6s; 0.28 [IQR 0.09-0.42] vs. 0.44 [0.24-0.60], p = 0.003). Higher baseline NIHSS scores correlated with larger Tmax >6s lesion volumes as well as higher HIR value in non-ICAD patients, but not in ICAD patients., Conclusions: In anterior circulation of AIS-LVO, ICAD patients exhibited distinct clinical presentations and perfusion imaging characteristics when compared to non-ICAD patients. Perfusion imaging profiles may serve as indicators for identifying ICAD patients before EVT., Competing Interests: Declaration of competing interest Hung-Yu Liu, Jeremy J. Heit, Nicole Yuen, Chung-Han Yang, Michael Mlynash, Aroosa Zamarud, Ronda Lun and Maarten G. Lansberg declare no conflicts of interest. Gregory W. Albers has served as a consultant for Genentech and iSchemaView., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Intracranial atherosclerotic disease (ICAD) of the large cerebral arteries, a leading cause of stroke worldwide, is increasingly implicated in cognitive impairment and neurodegeneration among the general population; however, the underlying pathophysiologic mechanisms in this relationship remain unknown., Methods: In this narrative review, we aim to provide an overview of the epidemiology and pathophysiology of ICAD, the evidence that relates ICAD to neurodegeneration, putative mechanisms, and future research directions. We synthesized available evidence on PubMed up to August 2024., Results and Conclusions: ICAD, a common cause of stroke, is characterized as a chronic, inflammatory, fibroproliferative disease of the cerebral large arteries. Numerous lines of evidence have related ICAD to clinical, neuroimaging, and pathology-based markers of cognitive impairment and Alzheimer's disease; however, little data exists on plausible pathophysiological links. Based on ongoing and adjacent work, we hypothesize hypoperfusion, arterial stiffness, and inflammation to play a role, but further research is needed. Conventional classification of ICAD often infers from symptomatic coronary artery disease and relies on degree of luminal stenosis, but unique anatomic features of the intracranial circulation may be relevant and a more comprehensive description that includes arterial wall features and plaque morphology may be needed to fully understand its relationship with cognitive impairment and neurodegeneration., Competing Interests: Declaration of competing interest Dixon Yang declares no financial or non-financial competing interests. Laurel Cherian declares no financial or non-financial competing interests. Konstantinos Arfanakis declares grant funding from the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Julie A Schneider declares grant funding from the NIA and the NINDS. Neelum T Aggarwal declares grant funding from the NIA. Jose Gutierrez declares grant funding from the NIA and compensation for contributions to UpToDate articles on intracranial atherosclerosis and as an expert witness., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment., Methods: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories., Results: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (r s =-0.765; P <0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts., Conclusions: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis., Competing Interests: Disclosures None.

Artery-to-artery embolism (AAE) is a common stroke mechanism in intracranial atherosclerotic disease (ICAD), associated with a considerable risk of recurrent stroke. We aimed to investigate cerebral hemodynamic features associated with AAE in symptomatic ICAD. Patients with anterior-circulation, symptomatic ICAD confirmed in CT angiography (CTA) were recruited. We classified probable stroke mechanisms as isolated parent artery atherosclerosis occluding penetrating artery, AAE, hypoperfusion, and mixed mechanisms, largely based on infarct topography. CTA-based computational fluid dynamics (CFD) models were built to simulate blood flow across culprit ICAD lesions. Translesional pressure ratio (PR = Pressure post-stenotic /Pressure pre-stenotic ) and wall shear stress ratio (WSSR = WSS stenotic-throat /WSS pre-stenotic ) were calculated, to reflect the relative, translesional changes of the two hemodynamic metrics. Low PR (PR ≤ median) and high WSSR (WSSR ≥ 4th quartile) respectively indicated large translesional pressure and elevated WSS upon the lesion. Among 99 symptomatic ICAD patients, 44 had AAE as a probable stroke mechanism, 13 with AAE alone and 31 with coexisting hypoperfusion. High WSSR was independently associated with AAE (adjusted OR = 3.90; P = 0.022) in multivariate logistic regression. There was significant WSSR-PR interaction on the presence of AAE (P for interaction = 0.013): high WSSR was more likely to associate with AAE in those with low PR (P = 0.075), but not in those with normal PR (P = 0.959). Excessively elevated WSS in ICAD might increase the risk of AAE. Such association was more prominent in those with large translesional pressure gradient. Hypoperfusion, commonly coexisting with AAE, might be a therapeutic indicator for secondary stroke prevention in symptomatic ICAD with AAE., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Fractional flow reserve is widely used in coronary disease management, with a threshold of 0.80. However, similar thresholds are unclear in functional assessment of intracranial atherosclerotic stenosis (ICAS)., Objective: To investigate the potential threshold values in functional assessment of ICAS by studying the relation between pressure-derived indexes and perfusion parameters derived from arterial spin labeling (ASL)., Methods: Patients were consecutively screened between June 2019 and December 2020. The translesional gradient indices were measured by pressure guidewire under resting-state conditions and recorded as mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa-Pd). Preoperative and postoperative cerebral blood flow (CBF) bilaterally and the relative cerebral blood flow ratio (rCBF) were measured and recorded by ASL imaging. Patients were defined as having reversible hemodynamic insufficiency only if the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Preoperative and postoperative Pd/Pa or Pa-Pd values of those patients were used to calculate the threshold., Results: Twenty-five patients (19 men, 6 women) with a mean age of 56.7±9.4 years were analyzed. Seventeen patients (68%) had lesions at the M1 segment of the middle cerebral artery, eight patients (32%) had lesions in the intracranial internal carotid artery. In 14 of the 25 patients, the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Cut-off values of Pd/Pa=0.81 and Pa-Pd=8 mm Hg were suggested to be associated with hemodynamic insufficiency., Conclusions: In a highly selected subgroup with ICAS, cut-off values of translesional pressure gradients (Pd/Pa=0.81 or Pa-Pd=8 mm Hg) were preliminarily established, which may facilitate clinical decision-making in the management of ICAS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cerebral infarction is a health problem of global concern and brings a particular burden to medical treatment., Objective: To analyze the correlation between insulin resistance (IR) levels and changes in cerebral atherosclerosis (AS) degree in non-diabetic patients with cerebral infarction., Methods: A total of 134 non-diabetic patients with cerebral infarction who visited the Department of Neurology of our hospital from May 2019 to October 2020 were selected and underwent MRA/CTA (Magnetic resonance angiography/Computed tomography angiography) of cerebral arteries to refine the cerebrovascular imaging data, and according to the results of cerebral AS load, the patients were divided into mild AS group and severe AS group, and the insulin resistance index was calculated with HOMA-IR (homeostasis model assessment of insulin resistance) to evaluate the IR level and HOMA-IR was compared between the two groups. Spearman correlation was used to analyze the correlation between the levels of IR in patients and the changes in cerebral AS load., Results: 54 individuals had severe AS and 80 patients had mild AS, according to an MRA/CTA of the cerebral arteries. There was a significant difference (P< 0.05) in HOMA-IR between the difficult and gentle AS groups. A significant link between HOMA-IR and the severity of cerebral AS in patients was found using Spearman correlation analysis (r= 0.850, P< 0.05)., Conclusion: The IR phenomenon was prevalent in non-diabetic patients with cerebral infarction, and the level of IR was closely related to the severity of cerebral AS.

Introduction: Anterior and posterior circulation atheroscleroses differ in vascular risk factors and stroke patterns. Posterior circulation stroke has worse clinical outcomes. However, few studies described the differentiation of plaque features between anterior and posterior circulation atheroscleroses via high-resolution vessel wall imaging (HR-VWI). We aimed to compare the plaque imaging features between anterior and posterior circulations to highlight the relevance of plaque imaging features to clinical events of ischemic stroke., Methods: Prospective data from a HR-VWI cohort of adult patients with acute ischemic stroke or transient ischemic attack were retrospectively analyzed. Quantitative and qualitative measurements of atherosclerotic plaques along the middle cerebral arteries (MCAs), the basilar artery (BA), and the vertebral arteries (VAs) were conducted on HR-VWI. Vessels with stenotic degrees over 30% were identified on the matched time-of-flight magnetic resonance angiography (TOF-MRA) and visually classified into normal, irregular, stenotic, and occluded. The sensitivity, specificity, positive and negative predictive values for TOF-MRA in detecting abnormal vessels were calculated by using quantification on the basis of HR-VWI findings as the reference standard., Results: One hundred and one patients (median age, 64 years old; 62.4% males) were included in this study. A total of 292 plaques were identified, with 152 in the MCAs, 35 in the BA, and 105 in the VAs. The VAs possessed significantly higher enhancement index (EI) (median 38.37 vs. 18.40, p &lt;0.001), more plaques with positive remodeling (76.2% vs. 57.2%, p = 0.002) and intraplaque hypo-intensity (43.8% vs. 12.5%, p &lt;0.001) than the MCAs. The MCAs presented with more intraplaque hemorrhage (IPH) (20.4% vs. 8.6%, p = 0.014) than the VAs. The sensitivity and specificity of TOF-MRA for evaluating luminal stenosis were 89.0 (82.5-93.4) and 66.7 (24.1-94.0) in anterior circulation, respectively, and were 75.2 (66.7-82.2) and 27.3 (7.3-60.7) in posterior circulation, respectively., Conclusion: Our findings might elucidate the clinical events and outcomes in anterior and posterior circulation stroke. Posterior circulation atherosclerosis had higher EI and more plaques with hypo-intensity, suggesting a heavier atherosclerosis burden. Positive remodeling pattern in posterior circulation atherosclerosis might create an impression of "wider" vascular lumen, leading to possible underestimation of atherosclerosis burden of posterior circulation on TOF-MRA as compared to HR-VWI. Besides, anterior circulation atherosclerosis with IPH might be associated with plaque rupture and artery-to-artery embolism. Future studies are needed to verify these findings., (© 2023 S. Karger AG, Basel.)

Background and Purpose: The purpose of this study was to test the hypothesis that hemodynamically compromised brains exhibit transient changes in magnetic susceptibility throughout the cardiac cycle, and to model these changes using Linear System Theory to extract an index that reflects cerebrovascular reserve., Materials and Methods: Eleven patients with angiographically-confirmed intracranial atherosclerotic disease with >50% stenosis were imaged with susceptibility weighted, cardiac-gated single shot images of cerebral Oxygen Extraction Fraction (OEF) at different timepoints of the cardiac cycle. Cardiac gating of the OEF acquisition allowed interrogation of oxygenated blood and the detection of changes throughout the cardiac cycle. Independent component analysis (ICA) of raw k-space data across the cardiac phase allowed MRI signal decomposition into dynamic and static components for image reconstruction. An asymmetry index score of the resultant parametric images were compared to test the hypothesis that variation in hemoglobin-induced susceptibility across the cardiac cycle indeed reflects pathophysiology of cerebrovascular disease. A mathematical model was derived to parameterize physiologic changes induced by the presence of a hemodynamically significant stenosis in the brain as a tissue impulse response parameter (β)., Results: OEF was elevated in the affected hemisphere (50.34 ± 12.13% vs 46.93 ± 12.34%), but failed to reach statistical significance (p < .0796). Transient changes in the OEF signal showed significant distinction between healthy and compromised tissue (0.56 ± 0.067 vs 0.44 ± 0.067, p < .019)). The derived tissue impulse response function was found to be significant as well (10.72 ± 3.48 10 -3  ms -1 , 9.69 ± 3.51 10 -3  ms -1 ; p < .037)., Conclusion: In this pilot study, we found transient OEF and β to be significant predictors of hemispheric compromise., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intracranial atherosclerosis is a common cause of stroke with a high recurrence rate. Haemodynamically significant lesions are associated with a particularly high risk of recurrence. Computational fluid dynamics (CFD) is a tool that has been investigated to identify haemodynamically significant lesions. CFD in the intracranial vasculature benefits from the precedent set by cardiology, where CFD is an established clinical tool. This precedent is particularly important in CFD as models are very heterogenous. There are many decisions-points in the model-creation process, usually involving a trade-off between computational expense and accuracy., Objectives: This study aimed to review published CFD models in intracranial atherosclerosis and compare them to those used in cardiology., Methods: A systematic search for all published computational fluid dynamics models applied to intracranial atherosclerosis was performed. Each study was analysed as regards to the different steps in creating a fluid dynamics model and findings were compared with established cardiology CFD models., Results and Conclusion: 38 papers were screened and 12 were included in the final analysis. There were important differences between coronary and intracranial atherosclerosis models in the following areas: area of interest segmented, use of transient models vs steady-state models, boundary conditions, methods for solving the fluid dynamics equations and validation. These differences may be high-yield areas to explore for future research., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Background: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD., Methods: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event., Results: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01)., Conclusions: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD., Competing Interests: Declaration of Competing Interest V.J. Del Brutto has salary support from the Florida Regional Coordinating Center for the NINDS Stroke Trials Network; S. Prabhakaran has research salary support for role as PI (MPI) of MYRIAD from NIH/NINDS (1R01NS084288). Receives compensation from AHRQ/NIH grants, Abbvie consulting, and UpToDate royalties; D.S. Liebeskind has research salary support for role as PI (MPI) of MYRIAD from NIH/NINDS (1R01NS084288); I. Campo-Bustillo has salary support from R01 grant NIH/NINDS (1R01NS084288) to the University of Miami for role as MyRIAD Project Manager; G. Cotsonis has research salary support for role as biostatistician of MYRIAD from NIH/NINDS (1R01NS084288); A. Nizam has research salary support for role as biostatistician of MYRIAD from NIH/NINDS (1R01NS084288); J.G. Romano has research salary support for role as PI (MPI) of MYRIAD from NIH/NINDS (1R01NS084288), (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta Stroke Program Early CT Score, onset to groin puncture time, occlusion site, and final recanalization. Out of 3025 patients with MT, 182 (6%) patients required RT because of underlying ICAS. Balloon angioplasty was performed on 122 patients, and 117 patients had intracranial stenting. In the matched analysis, 141 patients who received RT matched to a similar number of controls. The number of thrombectomy passes was higher (3 versus 1, P <0.001), and procedural time was longer in the RT group (52 minutes versus 36 minutes, P =0.004). There was a higher rate of symptomatic hemorrhagic transformation in the RT group (7.8% versus 4.3%, P =0.211), however, the difference was not significant. There was no difference in 90-day modified Rankin scale of 0 to 2 (44% versus 47.5%, P =0.543) between patients in the RT and control groups. Conclusions In patients with ELVO with underlying ICAS requiring RT, despite longer procedure time and a more thrombectomy passes, the 90 days favorable outcomes were comparable with patients with embolic ELVO.

Background and Purpose: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence., Methods: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence., Results: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P <0.01), diabetes (32.6% versus 14.6%, P =0.05), index stroke (31.3% versus 4.6%, P =0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P =0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P <0.01), and borderzone infarct pattern (63.6% versus 25.0%, P =0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89-0.98], P <0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36-7.71], P <0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation)., Conclusions: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02121028.

Vascular dysfunctions, including arterial stiffness and endothelial dysfunction, are prevalent in hypertensive subjects. We aimed to study their relations to subclinical intracranial vascular health in this study. A total of 200 older hypertensive males without overt cardiovascular or cerebrovascular diseases were recruited. Arterial elasticity was measured as carotid-femoral pulse wave velocity (cfPWV) and endothelial function was measured as digital reactive hyperemia index (RHI). Cerebrovascular health was evaluated using MRI in four aspects: intracranial atherosclerosis, brain perfusion as cerebral blood flow (CBF), vascular rarefaction analyzed as visible arterial branches on angiography using a custom-developed analysis technique and small vessel disease measured as white matter hyperintensity (WMH). There was a significant negative association between cfPWV and CBF, suggesting a link between arterial stiffness and CBF decline. Higher cfPWV was also associated with presence of intracranial stenotic plaque and greater WMH volume. RHI was positively related to CBF, indicating that endothelial dysfunction was associated with reduced CBF. All the associations remained significant after adjustment for confounding variables. Arterial stiffness and endothelial dysfunction are associated with reduced brain perfusion in older hypertensive males. Arterial stiffness is also associated with global cerebral vascular injury, affecting both small and medium-to-large arteries.

Background and Purpose: Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns., Methods: A single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model., Results: Of 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R 2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016)., Conclusions: Increased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives/background: Medical therapy is the first line of treatment for intracranial atherosclerotic disease (ICAD). Percutaneous transluminal angioplasty and stenting (PTAS) are mainly considered for those patients with severe stenosis and recurrent events despite aggressive medical therapy. In this review, we discuss the application of PTAS as a treatment option for ICAD and its future prospect., Materials and Methods: We did the literature review of the key articles and guidelines to elaborate on the role of PTAS in the management of ICAD based on the current data and expert opinion. We searched PubMed, Google Scholar, and Scopus up to August 2020, and included articles published only in the English language., Results: Since the publication of the results from SAMMPRIS and VISSIT trials, stenting is no longer recommended for secondary stroke prevention in patients with symptomatic ICAD. However, recent clinical studies on intracranial stenting for a subgroup of ICAD patients have shown promising results, likely due to better patient selection and continued advancement of endovascular techniques., Conclusion: There exists a lack of consensus regarding the best endovascular treatment approach (e.g., angioplasty alone or balloon mounted stent vs. self-expanding stent with or without prior angioplasty) or management of in-stent restenosis. Another area of clinical controversy relates to the ideal use and duration of antiplatelet therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism., Methods: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks., Results: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes., Conclusions: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes., Trial Registration: ClinicalTrials.gov: NCT02121028., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs., Materials and Methods: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed., Results: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency., Conclusions: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease., Methods: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated., Results: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005)., Conclusions: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke., Objective: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF., Methods: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission., Results: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END., Conclusions: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS., (© 2021 S. Karger AG, Basel.)

Background and Purpose: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort., Methods: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status., Results: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7])., Conclusions: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Background: The prognosis of acute ischemic stroke is related to collateral circulation, which is different with different pathogenesis., Objective: To explore the prognosis of acute large atherosclerotic (LAA) cerebral infarction with different pathogenesis by assessing the establishment of collateral circulation., Methods: 108 patients with acute LAA cerebral infarction in our hospital, who failed to thrombolytic or thrombectomy in the acute phase were selected and classified by Chinese ischemic stroke subclassification (CISS). They were evaluated by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). CT angiography (CTA) of head and neck were used to evaluate the collateral circulation for patients with large vessel stenosis or occlusion within one week of admission. The CTA collateral scores (CS) were recorded in a dichotomized fashion (ie, poor vs good)., Results: Patients with good CS had significantly lower NIHSS score and good prognosis at 2 weeks and 3 months than patients with poor CS (P < 0.001). The arterial-to-arterial embolization mechanism was the highest in the ratio of good CS and good prognosis at 3 months (P < 0.001). Multivariate Logistic regression analysis showed that baseline NIHSS score (OR=1.407, 95%CI:1.153-1.717, P=0.001) was an independent factor affecting poor CS. The NIHSS score at baseline (OR=0.604, 95%CI:0.436-0.837, P=0.002) and good CS (OR=39.552, 95%CI:8.908-175.618, P=0.000) were important predictors of good prognosis at 3 months., Conclusion: The prognosis and collateral circulation of acute LAA cerebral infarction with different pathogenesis was different. Baseline NIHSS score and collateral circulation had great impact on prognosis at 3 months., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion. Methods and Results The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial of ORG 10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4-dimensional computed tomography angiography. A total of 387 large artery occlusion patients were analyzed (229 men and 158 women; mean age, 71±14 years), including 77 (19.9%) with large artery atherosclerosis (LAA), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients with LAA than in those with cardioembolism (85.7% versus 42.2%, P <0.001). Multivariable logistic regression revealed that presence of antegrade flow was significantly associated with cuse of LAA after adjusting for confounding factors, when setting cardioembolism as reference (odds ratio, 5.650; 95% confidence interval, 2.451-13.158; P <0.001). The sensitivity, specificity, and positive and negative predictive values of the antegrade flow for predicting LAA were 43.1%, 91.5%, 85.7%, and 57.8%, respectively. Conclusions Using 4-dimensional computed tomography angiography, antegrade flow can be identified in more than half of acute anterior large artery occlusion patients and occurs more frequently in those with LAA as the cause of stroke.

Rationale: Intracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction., Methods and Design: This is a prospective observational study of patients with recently symptomatic (<21 days) ICAD with 50-99% stenosis treated medically and monitored for up to 1 year. An estimated 110 participants are recruited at 10 sites to identify the association between the presence of each mechanism of ischemia and recurrent stroke. The primary outcome is ischemic stroke in the territory of the symptomatic artery. Secondary outcomes include new cerebral infarction on MRI at 6-8 weeks and recurrent TIA in the territory of the symptomatic artery., Discussion: MyRIAD is positioned to define the role of specific mechanisms of recurrent ischemia in patients with symptomatic ICAD. This knowledge will allow the development and implementation of effective and specific treatments for this condition., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated., Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed., Results: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year., Conclusions: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.

Objectives: To identify whether intracranial atherosclerotic disease large vessel occlusion strokes differ compared to embolic large vessel occlusion strokes in angiographic response to mechanical thrombectomy and clinical course., Methods: Retrospective analysis of acute ischemic stroke patients with large vessel occlusion, due to intracranial atherosclerotic disease or embolic etiology, who underwent mechanical thrombectomy in a primary stroke center from 11/2015 to 4/2018. We categorized patients into intracranial atherosclerotic disease or embolic large vessel occlusion based on the procedural findings. We compared pretreatment, procedural variables, and post-procedural outcomes., Results: Ninety-five patients were included, 13 with intracranial atherosclerotic disease large vessel occlusion strokes and 82 with embolic large vessel occlusion strokes. Between the two groups, there was no statistically significant difference in angiographic success (100% for intracranial atherosclerotic disease and 89% for embolic large vessel occlusion strokes); first pass success (38% for intracranial atherosclerotic disease and 34% for embolic large vessel occlusion strokes); puncture-to-first-pass time; puncture-to-recanalization time (68 minutes for intracranial atherosclerotic disease and 62 minutes for embolic large vessel occlusion strokes); number of passes; or clinical outcomes. Intracranial angioplasty was performed in 6 (46%) of intracranial atherosclerotic disease large vessel occlusion patients, and in 5 (6%) of embolic large vessel occlusion patients (p < 0.0001)., Conclusions: Similar angiographic success and procedural time metrics are achievable with intracranial atherosclerotic disease large vessel occlusion and embolic large vessel occlusion therapy. This occurred with more frequent intracranial angioplasty for intracranial atherosclerotic disease large vessel occlusion strokes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Asymptomatic intracranial atherosclerotic stenosis (AICAS) is a common cause of stroke. Elderly women were more likely than men to develop AICAS, although it indicated that a lifelong exposure to estrogen could lower the risks of cardiovascular disease (CVDs)., Objective: The present study aims to ascertain whether postmenopausal time is a risk factor of AICAS. Fostering a correct perception of menopause is of great significance for the overall well-being of the elderly women., Methods: All participants received a questionnaire, physical examination, laboratory testing and transcranial Doppler. The menopausal population (n = 701) was divided into three groups by tertiles of postmenopausal time. Two-tailed testing and trend test were used to reveal the relationship between postmenopausal time and newly discovered AICAS. Other potential risk factors were also analyzed to ascertain whether there was a relation between postmenopausal time and the newly discovered ICAS., Results: Both mean age and mean postmenopausal time were gradually increased from G0 to G2. The same trend occurred in hypertension, diabetes mellitus, total cholesterol, triglyceride, C-reactive protein and serum homocysteine. Adjusting for various confounding factors, postmenopausal time was not a risk factor for newly discovered AICAS. Multifactor analysis and stratifying analysis showed no correlation between newly discovered AICAS and postmenopausal time., Conclusions: Postmenopausal time is not an independent risk factor of AICAS. No relationship was detected between postmenopausal time and newly discovered AICAS, while vigorous control of body weight, blood pressure/glucose/lipids and smoke cessation are vital for preventing the occurrence of AICAS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up.

Background: Branch atheromatous disease is an ischemic stroke, involving occlusion or severe stenosis of the perforating artery, causing neurologic symptoms and serious sequelae. We aimed to investigate initial morphometric and hemodynamic characteristics of the vertebral artery immediately post-onset to predict lesion expanding., Methods: This case-control study collected demographic, historical, and physical examination data from 44 patients with branch atheromatous disease in the pons at admission. The maximum ischemic pons area and stenosis rate in the basilar artery were calculated using magnetic resonance images. Diameter, velocity, and flow volume of the vertebral arteries were measured using carotid artery ultrasonography. Correlations between ischemic lesion extent and these parameters were investigated., Results: Patients were assigned to groups of less (Group 1) or more (Group 2) than the median maximum ischemic area in the pons, calculated from magnetic resonance images (121.6 mm 2 ). Modified Rankin scale scores were significantly worse in Group 2. Blood pressure and blood findings were similar between groups. Group 2 showed significantly higher basilar artery stenosis rates. Flow volume, velocity, peak systolic velocity, and end-diastolic velocity in the vertebral artery on both sides were significantly decreased in Group 2., Conclusions: Deteriorated vertebral artery hemodynamics caused a more extensive ischemic lesion in branch atheromatous disease in the pons. Evaluation of the vertebral using carotid artery ultrasonography in the acute phase may be useful for predicting disease progression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The associations between blood pressure parameters and intracranial vulnerable plaques have not been fully elucidated. The purpose of this study was to investigate the associations between systemic blood pressure parameters, as well as their variability, and intraplaque hemorrhage (IPH) in stroke patients with intracranial atherosclerosis. We retrospectively analyzed the high-resolution MRI data set of intracranial atherosclerosis from a comprehensive stroke center. The atherosclerotic plaque burden and presence of IPH in each vessel were obtained from vessel wall imaging. Blood pressure parameters in the first week of admission were used. The systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and their variability (standard deviation [SD] and coefficient of variation [CV]) were compared between the IPH (+) and IPH (-) groups. Logistic regression analysis was used to demonstrate the correlations between different blood pressure parameters and IPH. The results indicated that SBP and PP were associated with multiple plaques and severe luminal stenosis after adjusting for confounders, with OR = 1.071, 95% CI: (1.044-1.098) and OR = 1.039, 95% CI: (1.019-1.060) for SBP and OR = 1.058, 95% CI: (1.027-1.089) and OR = 1.044, 95% CI: (1.019-1.070) for PP, respectively. SBP was associated with IPH after adjusting for cardiovascular risk factors, with OR = 1.021, 95% CI: (1.003-1.038), but not after correcting for plaque burden, with OR = 1.014, 95% CI: (0.996-1.032). No associations between blood pressure variability and atherosclerotic plaque burden or IPH were detected in this study. In conclusion, SBP is associated with IPH after adjusting for cardiovascular risk factors but not after further correction for atherosclerotic plaque burden. The association between blood pressure variability and intracranial atherosclerosis requires further study.

Background and Purpose- There is debate over an optimal systolic blood pressure (SBP) in secondary stroke prevention of patients with symptomatic intracranial atherosclerotic stenosis (sICAS). We investigated whether translesional pressure gradient across sICAS would alter the relationship between SBP and risk of recurrent stroke in such patients. Methods- We recruited patients with sICAS (50%-99% stenosis) confirmed in computed tomography angiography. We simulated blood flow across sICAS with computed tomography angiography-based computational fluid dynamics models. Translesional pressure ratio (PR=Pressure post-stenotic /Pressure pre-stenotic ) was calculated in each case. Pressure ratio (PR) ≤ median was defined as low PR, indicating larger translesional pressure gradient across sICAS. All patients received optimal medical treatment. We investigated the interaction of translesional PR and mean SBP during follow-up (SBP FU ) in determining the risk of the primary outcome, recurrent ischemic stroke in the same territory within 1 year. Results- Among 157 patients with sICAS, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBP FU interaction on the primary outcome ( P =0.008): in patients with normal PR, risk of primary outcome significantly decreased with lower SBP FU (hazard ratio for 10 mm Hg decrement =0.46; P =0.018); however, in those with low PR, SBP FU ≤130 mm Hg was associated with significantly increased risk of primary outcome, compared with 130FU <150 mm Hg (hazard ratio=5.08; P =0.043). Conclusions- Low SBP level may be associated with increased risk of stroke recurrence in patients with sICAS with a large translesional pressure gradient. Translesional PR by computational fluid dynamics models may yield a promising indicator to guide more individualized blood pressure management in patients with sICAS, warranting future studies.

Purpose: To compare clinical characteristics and treatment outcomes of intra-arterial thrombectomy (IAT) in acute basilar artery occlusion (BAO) with and without underlying intracranial atherosclerotic stenosis (ICAS) and to investigate the usefulness of preprocedural CT angiography findings in the diagnosis of ICAS., Materials and Methods: Twenty patients who received IAT for acute BAO between September 2014 and March 2019 were included. Additional therapies such as angioplasty, stent placement, and tirofiban infusion were provided while treating ICAS. Clinical and angiographic results of treatment were recorded. Preprocedural CT angiography findings in ICAS and non-ICAS groups were compared to assess (i) basilar tip opacification, (ii) partial occlusion, (iii) presence of convex border, (iv) occlusion segment longer than two thirds of the basilar artery or 20 mm, (v) dense basilar artery, and (vi) wall calcification in the occluded segment., Results: Among the 20 patients (mean age, 71.3 y; mean stroke score, 24.8), optimal recanalization was achieved in 19 (95%). Three patients had good clinical outcomes. There were 6 patients with underlying ICAS. No difference was observed between ICAS and non-ICAS groups in terms of optimal angiographic recanalization and good outcome. On CT angiography, basilar tip occlusion (100% vs 29%), partial occlusion (100% vs 83%), and long occlusion length (100% vs 14%) significantly differed between the groups (P ≤ .01)., Conclusions: In acute BAO, underlying ICAS does not affect optimal recanalization rate or clinical outcome. Preprocedural CT angiography is a potentially useful tool to detect it., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Intracranial atherosclerotic stenoses (ICAS) are one of the most common causes of first and recurrent cerebrovascular ischaemic events worldwide, with highest prevalence in Asian, Hispanic and African populations. Clinical trials have improved the understanding of epidemiology, risk factors and imaging characteristics of patients with ICAS. Current therapeutic approaches concerning these patients include management of risk factors, best medical therapy, potentially endovascular and rarely surgical therapy. In our review, we elucidate the current epidemiology and evidence in evaluation of risk factors and therapeutic options for providing favourable outcome for patients with ICAS.

Fast cine phase contrast magnetic resonance angiography (PC-MRA) has the potential to provide a quantitative measurement method for the diagnosis and treatment of cerebrovascular disease. To evaluation the changes of cerebral blood flow and the characteristics of artery lesion distribution in the patients of transient ischemic attacks (TIA). In all, 98 normal subjects and 106 TIA patients who underwent MRI examination within 72 h after the last symptom onset including the DWI sequence to exclude acute cerebral infarction were enrolled. The blood flow of the cranial total, the area of the internal carotid artery and vertebral artery, the average velocity, and the average blood flow were obtained and compared in normal subjects and TIA group. Analysis of Variance (ANOVA), t -test, and Kruskal-Wallis test were used for statistical assessments. The total cerebral blood flow of the TIA group and normal control group was no significant statistical difference ( P > 0.05). The total blood flow decreased with increasing age, and the TIA group was much lower than the control group. The blood flow of the right internal carotid artery in the TIA group had a significant difference compared with controls ( P < 0.05). However, the same situation did not happen in both of the left internal carotid artery and vertebral artery. Phase contrast magnetic resonance imaging has the potential to evaluate the change of cerebral blood flow in TIA patients. The decrease in the total blood flow and the symptom onset of TIA is consistent. Phase contrast magnetic resonance imaging could provide guidance to the diagnosis of TIA., Competing Interests: The authors declare no competing interests., (Copyright © 2020 Yuzhao Wang et al.)

Background: The optimal treatment strategy for residual stenosis in patients with acute intracranial atherosclerotic stenosis related occlusion (ICAS-O) after endovascular treatment (EVT) is unknown. This study aims to evaluate the efficacy and safety of low-dose tirofiban in patients with residual stenosis after EVT due to acute ICAS-O., Methods: Retrospective analysis of prospectively enrolled consecutive patients with residual stenosis after EVT due to acute ICAS-O from March 2015 to May 2019. Patients were divided into EVT alone group or EVT plus tirofiban group. The primary endpoint was the favorable functional outcome (defined as modified Rankin scale score of 0-2) at 90 days. The secondary endpoints were the proportions of reocclusion of recanalized arteries within 72 hours after EVT, symptomatic intracranial hemorrhage (sICH), any ICH, and mortality at 90 days. Logistic regression for predictors of reocclusion and functional outcomes were performed., Results: A total of 98 patients, 50 treated with tirofiban and 48 without tirofiban, were enrolled in this study. Compared with patients in EVT alone group, patients in EVT plus tirofiban group had higher favorable functional outcome rate, lower mortality, and a lower reocclusion rate (56.3% versus 30.4%; P = .014, 8.3% versus 28.3%; P = .016, and 10.4% versus 32.6%; P = .011, respectively). The rates of any ICH and sICH were similar between the 2 groups. The use of tirofiban was associated with the favorable functional outcome (odds ratio [OR], 3.417; 95% confidence interval [CI], 1.149-10.163; P = .027) and lower reocclusion rate (OR, 0.145; 95% CI, 0.038-0.546; P = .004) on multivariate logistic regression analysis., Conclusions: In patients with residual stenosis after EVT due to acute ICAS-O, a low-dose of tirofiban is associated with favorable functional outcome and reduced incidence of reocclusion without increasing any ICH and sICH., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Previous studies have demonstrated differences in the distribution of intracranial and/or extracranial atherosclerosis (I-ECAS) by region and race. Despite this, few studies have examined the distribution of arterial stenosis in ischemic stroke patients of the Zhuang population in Guangxi, China. We therefore aimed to investigate the distribution of cerebrovascular stenosis in ischemic stroke patients across different ethnicities in Guangxi province. A total of 1,101 patients were divided into 2 groups according to their ethnicity: the Zhuang group and Han group. All patients underwent 64-slice spiral computed tomographic angiography (CTA) scanning to document the presence of intracranial or extracranial stenosis. Results showed that: (I) intracranial atherosclerosis (ICAS) a higher incidence of ECAS (51.1% vs. 48.9%); (II) I-ECAS was the most common lesion type, followed by ICAS; (III) Zhuang patients had a higher rate of ECAS ( 20.2% vs. 15.2%, P=0.047) and a lower rate of I-ECAS (35.8% vs. 42.3%, P=0.041) than that of the Han group. Furthermore, Zhuang patients had a higher percentage of stenosis in the posterior circulation (23.0% vs. 13.1%, P<0.001) and a lower percentage of stenosis in the anterior circulation (29.3% vs. 41.5%, P<0.001) than Han patients; (IV) large artery atherosclerosis (LAA) was the most commonly identified cause of stroke, and the Zhuang group had a lower proportion of LAA than the Han group (47.7% vs. 55.4%; P=0.020); (V) smoking and drinking were independent risk factors for ICAS; older age, male gender, and drinking were independent risk factors for ECAS; older age, male gender, hypertension, and drinking were independent risk factors for I-ECAS; age, hypertension, diabetes, hyperlipidemia, smoking, and drinking were independent risk factors for LAA. These outcomes indicate that there are ethnicity differences in the distribution of cerebrovascular stenosis in Guangxi. The variability in the risk factors involved may explain the variation in the distribution of cerebral atherosclerosis between ethnic groups.

Background: Atherosclerotic plaque in the middle cerebral artery (MCA) is linked to ischemic stroke events, but the relationship between plaque characteristics and cerebral perfusion is unclear., Purpose: To investigate MCA plaque characteristics between intracranial atherosclerotic patients with and without hypoperfusion area, and to identify the variables affecting hypoperfusion volume., Study Type: Retrospective., Population: Seventy-one patients with MCA stenosis (>50%), and all with ischemic onset in recent 2 weeks., Field Strength/sequence: 3.0T MRI / diffusion-weighted imaging (DWI), time-of-flight magnetic resonance angiography (TOF-MRA), inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions (IR-SPACE), dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI)., Assessment: Plaque characteristics including eccentric index (EI), eccentricity, plaque length, and enhancement on MCA were measured on IR-SPACE. Pial collaterals (PCs) were evaluated on axial TOF-MRA source images. Time-to-maximum (Tmax) maps with a threshold more than 6 seconds were assessed by rapid processing of perfusion and diffusion (RAPID) software., Statistical Tests: Two independent-samples t-tests, Mann-Whitney U-test, chi-square test, Z test, univariate and multivariate logistic analysis, and receiver operating characteristic (ROC) curve were used., Results: Patients with hypoperfusion had fewer eccentric plaque, lower EI, longer plaque length, and poor PCs compared with those without (P = 0.002, 0.016, 0.003, and 0.001). Eccentricity, plaque length, PCs, and hypertension were the factors independently associated with the occurrence of hypoperfusion after adjustment for risk factors of cerebrovascular disease (P = 0.014, 0.017, 0.035, and 0.018). The area under the curve (AUC) (95% confidence interval) was 0.865 (0.763-0.934) for a combination of the above four variables, which was significantly higher than any variable alone (P < 0.001, 0.016, < 0.001, and < 0.001). Patients with lower EI, concentric morphology, and grade 2 enhancement trended to have larger hypoperfusion volume (P = 0.028, 0.037, and 0.009)., Data Conclusion: Plaque eccentricity, plaque length, PCs, and hypertension showed an association with the occurrence of hypoperfusion., Level of Evidence: 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:195-204., (© 2019 International Society for Magnetic Resonance in Medicine.)

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  < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale ( p  = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

Background: Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in β thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis., Aim: In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in β TI patients., Methods: For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries' (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls., Results: Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV., Conclusion: More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients., (© 2020 S. Karger AG, Basel.)

Recent basic studies have clarified that aneurysmal wall inflammation plays an important role in the pathophysiology of intracranial aneurysms. However, it remains an interdisciplinary challenge to visualize aneurysm wall status in vivo. MR-vessel wall imaging (VWI) is a current topic of advanced imaging techniques since it could provide an additional value for unruptured intracranial aneurysms (UIAs) risk stratification. With regard to ruptured intracranial aneurysms, VWI could identify a ruptured aneurysm in patients with multiple intracranial aneurysms. Intraluminal thrombus could be a clue to interpret aneurysm wall enhancement on VWI in ruptured intracranial aneurysms. The interpretation of VWI findings in UIAs would require much caution. Actually aneurysm wall enhancement in VWI was significantly associated with consensus morphologic risk factors. However, aneurysmal wall with contrast enhancement oftentimes associated with atherosclerotic, degenerated and thickened wall structure. It remains ill defined if thin wall without wall enhancement (oftentimes invisible in VWI) could be actually safe or look over wall vulnerability. We reviewed currently available studies, especially focusing on VWI for intracranial aneurysms and discussed the clinical utility of VWI.

Background: Stroke risk stratification in patients with symptomatic intracranial atherosclerotic arterial disease (ICAD) remains an important clinical objective owing to the high 14-19% recurrent stroke rate in these patients on standard-of-care medical management. There thus remains a need for hemodynamic markers that may allow for the selection of personalized therapies for high-risk symptomatic patients., Purpose: To determine if shifting of cerebral blood flow (CBF) territories in response to changes in cerebral perfusion pressure (CPP) may provide a marker for stroke risk in ICAD patients., Study Type: Prospective., Population: Twenty ICAD patients who experienced a stroke within 45 days of study enrollment and 10 healthy controls., Sequence: 3.0T MRI including anatomical imaging (T 1 -weighted, T 2 -weighted/FLAIR), 3D MR angiography, and normocapnic and hypercapnic vessel-encoded CBF-weighted arterial spin labeling., Assessment: Patients were scanned within 45 days of overt stroke and monitored (duration = 13.2 ± 4.4 months) for the endpoint of non-cardioembolic stroke or transient ischemic attack. Flow territory shifting (shifting index) was calculated from the first scan by determining whether a voxel shifted from its primary arterial source from normocapnia to hypercapnia., Statistical Tests: A Mann-Whitney U-test (significance: P < 0.05) was performed to determine whether patients meeting the endpoint had greater shifting indices relative to controls or patients not meeting the endpoint., Results: Shifting indices (mean ± standard error) were significantly higher in patients meeting endpoint criteria relative to controls (P = 0.0057; adjusted P = 0.036) and patients not meeting endpoint criteria (P = 0.0047; adjusted P = 0.036)., Data Conclusion: Flow territory shifting may provide a marker of recurrent stroke risk in symptomatic ICAD patients on standard-of-care medical management therapies., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1441-1451., (© 2019 International Society for Magnetic Resonance in Medicine.)

This review highlights the recent evolution of the imaging, medical management, surgical options and endovascular therapies for symptomatic intracranial atherosclerotic disease (ICAD). Recent imaging developments including optical coherence tomography and other modalities to assess the intracranial arteries for symptomatic ICAD are reviewed, not only to diagnose ICAD but to determine if ICAD plaques have any high-risk features for treatment. Potential future developments in the treatment of ICAD are discussed, including the development of trackable drug-coated balloons for the cerebral circulation to treat primary or restenotic arteries, new iterations of self-expanding intracranial stents with easier delivery systems, and the re-examination of indirect surgical bypass techniques for revascularisation. In addition to these important technological developments, however, is the evolving evidence regarding the best treatment window for these techniques and additional factors in medical management which can improve patient outcomes in this devastating pathology., Competing Interests: Competing interests: MJA is a consultant for Stryker Neurovascular, manufacturer of the Wingspan Stent, which is discussed in the manuscript., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: In patients with atherosclerotic major cerebral artery disease, low blood pressure might impair cerebral perfusion, thereby exacerbate the risk of selective neuronal damage. The purpose of this retrospective study was to determine whether low blood pressure at follow-up is associated with increased selective neuronal damage., Methods: We retrospectively analysed data from 76 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischaemic episodes on a follow-up of 6 months or more. All patients had measurements of the distribution of central benzodiazepine receptors twice using positron emission tomography and 11 C-flumazenil. Using three-dimensional stereotactic surface projections, we quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the middle cerebral artery distribution and correlated these changes in the benzodiazepine receptors index with blood pressure values at follow-up examinations., Results: The changes in the benzodiazepine receptor index during follow-up (mean 27±21 months) were negatively correlated with systolic blood pressure at follow-up. The relationship between changes in benzodiazepine receptor index and systolic blood pressure was different among patients with and without decreased cerebral blood flow at baseline (interaction, p<0.005). Larger increases in benzodiazepine receptor index (neuronal damage) were observed at lower systolic blood pressure levels in patients with decreased cerebral blood flow than in patients without such decreases., Conclusion: In patients without ischaemic stroke episodes at follow-up but with decreased cerebral blood flow due to arterial disease, low systolic blood pressure at follow-up may be associated with increased selective neuronal damage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS)., Methods: This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs., Results: Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005-1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013-1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874-0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086-1.526); P = 0.004] were independently associated with NILs at follow-up., Conclusions: High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)