Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis.
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ABSTRACT:
SUBMITTER: Quandt F
PROVIDER: S-EPMC7446560 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Two positive randomized trials established carotid endarterectomy (CEA) as a superior treatment to medical management alone for the treatment of asymptomatic carotid artery stenosis. However, advances in medical therapy have led to an active and spirited debate about the best treatment for asymptomatic carotid stenosis. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST 2) trial aims to better define the best treatment for the average patient with severe asymptomatic carotid stenosis. Enrollment in the trial may be hampered by strong opinions on either side of the debate. It is important to realize that equipoise exists and that neither the old data on CEA nor the new data on optimal medical therapy provide a rigorous answer. The assumption that medical therapy has already been proven superior to revascularization procedures may hinder both enrollment in the trial and technical advancements in revascularization procedures.
| S-EPMC5440242 | biostudies-literature
Project description:Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70?mg/dl and systolic blood pressure <140?mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217.
| S-EPMC5987521 | biostudies-literature
Project description:RATIONALE:For patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may independently impair cognition. Whether revascularization of a hemodynamically significant carotid stenosis can alter the course of cognitive decline has never been investigated in the context of a randomized clinical trial. HYPOTHESIS:Among patients randomized in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) trials, the magnitude of treatment differences (revascularization versus medical management alone) with regard to cognition will differ between those with flow impairment compared to those without flow impairment. SAMPLE SIZE:We will enroll approximately 500 patients from CREST-2, of which we anticipate 100 will have hemodynamic impairment. We estimate 93% power to detect a clinically meaningful treatment difference of 0.5 SD. METHODS AND DESIGN:We will use perfusion-weighted magnetic resonance imaging to stratify by hemodynamic status. Linear regression will compare treatment differences, controlling for baseline cognitive status, age, depression, prior cerebral infarcts, silent infarction, white matter hyperintensity volume, and cerebral microbleeds. STUDY OUTCOMES:The primary outcome is change in cognition at one year. Secondary outcomes include silent infarction, change in white matter hyperintensity volume, number of cerebral microbleeds, and cortical thickness over one year. DISCUSSION:If cognitive impairment can be shown to be reversible by revascularization, then we can redefine "symptomatic carotid stenosis" to include cognitive impairment and identify a new population of patients likely to benefit from revascularization. TRIAL REGISTRATION:US National Institutes of Health (NIH) clinicaltrials.gov NCT03121209.
| S-EPMC6384010 | biostudies-literature
Project description:BackgroundAsymptomatic carotid artery stenosis (aCAS) impairs haemodynamic and cognitive functions; however, the relationship between these changes and brain network connectivity remains largely unknown. This study aimed to determine the relationship between functional connectivity and neurocognition in patients with aCAS.MethodsWe compared functional status in 14 patients with aCAS and 15 healthy controls using resting state functional magnetic resonance imaging sequences. The subjects underwent a full range of neuropsychological tests and a graphical theoretical analysis of their brain networks.ResultsCompared with controls, patients with aCAS showed significant decline in neuropsychological functions, particularly short-term memory (word-memory, p = .046 and picture-memory, p = .014). Brain network connectivity was lower in patients with aCAS than in the controls, and the decline of functional connectivity in aCAS patients was mainly concentrated in the left and right inferior frontal gyri, temporal lobe, left cingulate gyrus, and hippocampus. Decreased connectivity between various brain regions was significantly correlated with impaired short-term memory. Patients with aCAS showed cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. The cognitive defects were mainly manifested in the short-term memory of words and pictures.ConclusionsThis study is the first of its kind to identify an association between disruption of functional connections in left carotid stenosis and impairment of short-term memory. The findings suggest that alterations in network connectivity may be an essential mechanism underlying cognitive decline in aCAS patients.Clinical trial registration-urlUnique identifier: 04/06/2019, ChiCTR1900023610 .
| S-EPMC8436468 | biostudies-literature
Project description:IntroductionRevascularization procedures in carotid artery stenosis have shown a positive effect in the restoration of cerebral oxygen metabolism as assessed by T2' (T2 prime) imaging as well as capillary homeostasis by measurement of capillary transit time heterogeneity (CTH); however, data in patients with asymptomatic carotid stenosis without manifest brain lesions are scarce.Patients and methodsThe effect of revascularization on the hemodynamic profile and capillary homeostasis was evaluated in 13 patients with asymptomatic high-grade carotid stenosis without ischemic brain lesions using dynamic susceptibility contrast perfusion imaging and oxygenation-sensitive T2' mapping before and 6-8 weeks after revascularization by endarterectomy or stenting. The cognitive performance at both timepoints was further assessed.ResultsPerfusion impairment at baseline was accompanied by an increased CTH (p = 0.008) in areas with a time to peak delay ≥ 2 s in the affected hemisphere compared to contralateral regions. Carotid intervention improved the overall moderate hemodynamic impairment at baseline by leading to an increase in normalized cerebral blood flow (p = 0.017) and a decrease in mean transit time (p = 0.027), oxygen extraction capacity (OEC) (p = 0.033) and CTH (p = 0.048). The T2' values remained unchanged.ConclusionThis study presents novel evidence of a state of altered microvascular function in patients with high-grade carotid artery stenosis in the absence of ischemic brain lesions, which shows sustained normalization after revascularization procedures.
| S-EPMC8894147 | biostudies-literature
Project description:Even clinically "asymptomatic" carotid stenosis is associated with multidomain cognitive impairment, gray matter (GM) atrophy, and silent lesion. However, the links between them remain unclear. Using structural MRI data, we examined GM asymmetry index (AI) and white matter hyperintensity (WMH) in 24 patients with severe asymptomatic carotid stenosis (SACS), 24 comorbidity-matched controls, and independent samples of 84 elderly controls and 22 young adults. As compared to controls, SACS patients showed worse verbal memories, higher WMH burden, and right-lateralized GM in posterior middle temporal and mouth-somatomotor regions. These clusters extended to pars triangularis, lateral temporal, and cerebellar regions, when compared with young adults. Further, a full-path of WMH burden (X), GM volume (atrophy, M1), AI (asymmetry, M2), and neuropsychological variables (Y) through a serial mediation model was analyzed. This analysis identified that left-dominated GM atrophy and right-lateralized asymmetry in the posterior middle temporal cortex mediated the relationship between WMH burden and recall memory in SACS patients. These results suggest that the unbalanced hemispheric atrophy in the posterior middle temporal cortex is crucial to mediating relationship between WMH burden and verbal recall memories, which may underlie accelerated aging and cognitive deterioration in patients with SACS and other vascular cognitive impairment.
| S-EPMC8559457 | biostudies-literature
Project description:Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA. Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed. Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features. Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
| S-EPMC8651616 | biostudies-literature
Project description:Background and purposeHigh-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere.MethodsWe used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis.ResultsAmong 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032).ConclusionsOur findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.
| S-EPMC9911846 | biostudies-literature
Project description:Asymptomatic carotid artery stenosis (CAS) and occlusion (CAO) disrupt cerebral hemodynamics. There are few studies on the brain network changes and compensation associated with the progression from chronic CAS to CAO. In the current study, our goal is to improve the understanding of the specific abnormalities and compensatory phenomena associated with the functional connection in patients with CAS and CAO. In this prospective study, 27 patients with CAO, 29 patients with CAS, and 15 healthy controls matched for age, sex, education, handedness, and risk factors underwent neuropsychological testing and resting-state functional magnetic resonance (rs-fMRI) imaging simultaneously; graph theoretical analysis of brain networks was performed to determine the relationship between changes in brain network connectivity and the progression from internal CAS to CAO. The global properties of the brain network assortativity (p = 0.002), hierarchy (p = 0.002), network efficiency (p = 0.011), and small-worldness (p = 0.009) were significantly more abnormal in the CAS group than in the control and CAO groups. In patients with CAS and CAO, the nodal efficiency of key nodes in multiple brain regions decreased, while the affected hemisphere lost many key functional connections. In this study, we found that patients with CAS showed grade reconstruction, invalid connections, and other phenomena that impaired the efficiency of information transmission in the brain network. A compensatory functional connection in the contralateral cerebral hemisphere of patients with CAS and CAO may be an important mechanism that maintains clinical asymptomatic performance. This study not only reveals the compensation mechanism of cerebral hemisphere ischemia but also validates previous explanations for brain function connectivity, which can help provide interventions in advance and reduce the impairment of higher brain functions. This trial is registered with Clinical Trial Registration-URL http://www.chictr.org.cn and Unique identifier ChiCTR1900023610.
| S-EPMC7530486 | biostudies-literature
Project description:Purpose: Previous studies have found that there are significant changes in functional network properties for patients with moderate to severe carotid artery stenosis. Our study aimed to explore the topology properties of brain functional network in asymptomatic patients with carotid plaque without significant stenosis. Methods: A total of 61 asymptomatic patients with carotid plaque (mean age 61.79 ± 7.35 years) and 25 healthy control subjects (HC; 58.12 ± 6.79 years) were recruited. General data collection, carotid ultrasound examination and resting state functional magnetic resonance imaging were performed on all subjects. Graph-theory was applied to examine the differences in the brain functional network topological properties between two groups. Results: In the plaque group, Eloc(P = 0.03), γ (P = 0.01), and σ (P = 0.01) were significantly higher than in the HC group. The degree centrality of left middle frontal gyrus and the nodal efficiency of left middle frontal gyrus and right inferior parietal angular gyrus were significantly higher in the plaque group than in HC. The degree centrality and betweenness centrality of right middle temporal gyrus, as well as the nodal efficiency of right middle temporal gyrus, were significantly lower in the plaque group than in HC. Conclusions: The brain functional networks of patients with carotid plaques differ from those of healthy controls. Asymptomatic patients with carotid plaques exhibit increased local and global connectivity, which may reflect subtle reorganizations in response to early brain damage.
| S-EPMC8375554 | biostudies-literature