Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

Clinical Neuroscience, St George's University of London, London, UK.
The Lancet Neurology (Impact Factor: 21.9). 07/2010; 9(7):663-71. DOI: 10.1016/S1474-4422(10)70120-4
Source: PubMed


Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk-benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis.
The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity.
482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2.54 (95% CI 1.20-5.36; p=0.015). For ipsilateral stroke alone, the hazard ratio was 5.57 (1.61-19.32; p=0.007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7.13% in patients with embolic signals and 3.04% in those without, and for ipsilateral stroke was 3.62% in patients with embolic signals and 0.70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2.63 (95% CI 1.01-6.88; p=0.049), and for ipsilateral stroke alone the hazard ratio was 6.37 (1.59-25.57; p=0.009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results.
Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy.
British Heart Foundation.

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    • "With the popularity of TCD in China, increasingly more asymptomatic patients with risk factors were found with intracranial artery stenosis, especially with MCA stenosis. In 2010, the Asymptomatic Carotid Emboli Study (ACES) [10] found that detection of MES with TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischemic attack (TIA). However, there have been few reports on the frequency and clinical significance of MES in asymptomatic MCA stenosis which occurs more common in Asians [1], [4]. "
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    ABSTRACT: Although microembolus monitoring has been widely used for ischemic cerebrovascular disease, the clinical significance of microembolic signal (MES) in asymptomatic middle cerebral artery (MCA) stenosis remains unclear. We aim to investigate the frequency of MES and the value of MES in predicting ischemic stroke secondary to asymptomatic MCA stenosis. From June 2011 to December 2012, microembolus monitoring was performed in 83 asymptomatic and 126 symptomatic subjects. By comparing the demographics and risk factors between the symptomatic and asymptomatic subjects, we found that the ratio of male sexuality and smoking history differed (101/126 vs 43/83, and 88/126 vs 38/83, respectively, p<0.01). The frequency of MES was significantly higher in the symptomatic group than in the asymptomatic group (49/126 vs 2/108, p<0.01). Specifically, the frequency of MES in the symptomatic and asymptomatic groups with mild stenosis, moderate stenosis, severe stenosis and occlusion groups was 4/18 (22.22%) vs 0/30 (0), 13/31 (41.94%) vs 1/28 (3.57%), 30/62 (48.39%) vs 1/39 (2.56%), 2/15 (13.33%) vs 0/11 (0), respectively. Except for the occlusive group, the frequency of MES is correlated with stenosis degree and symptom. Two patients in the asymptomatic group were found positive for MES, and the MES number was 1 for both. During the one-year follow-up, neither of them developed ischemic stroke. In conclusion, MES detected with TCD differs between symptomatic and asymptomatic MCA stenoses. Due to the low frequency, the value of MES as a predictor of subsequent ischemic stroke in patients with asymptomatic MCA stenosis might be limited.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Patients with “asymptomatic” severe carotid stenosis, conventionally defined by free of stroke or transient ischemic attack[1], have been found to have increased susceptibility to cognitive impairment in memory and complex visuospatial perception[1]–[4]. Accumulating data suggest that silent embolic infarctions[5] and perfusion insufficiency[6] may both contribute to such mild cognitive impairment (MCI), [7] namely a subtype of vascular cognitive impairment no dementia (VCIND). However, the consequent neural dysfunction has yet to be elucidated in human studies. "
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    ABSTRACT: Severe asymptomatic stenosis of the internal carotid artery (ICA) leads to increased incidence of mild cognitive impairment (MCI) likely through silent embolic infarcts and/or chronic hypoperfusion, but the brain dysfunction is poorly understood and difficult to diagnose. Thirty cognitively intact subjects with asymptomatic, severe (≧70%), unilateral stenosis of the ICA were compared with 30 healthy controls, matched for age, sex, cardiovascular risk factors and education level, on a battery of neuropsychiatric tests, voxel-based morphometry of magnetic resonance imaging (MRI), diffusion tensor imaging and brain-wise, seed-based analysis of resting-state functional MRI. Multivariate regression models and multivariate pattern classification (support vector machines) were computed to assess the relationship between connectivity measures and neurocognitive performance. The patients had worse dizziness scores and poorer verbal memory, executive function and complex visuo-spatial performance than controls. Twelve out of the 30 patients (40%) were considered to have MCI. Nonetheless, the leukoaraiosis Sheltens scores, hippocampal and brain volumes were not different between groups. Their whole-brain mean fractional anisotropy (FA) was significantly reduced and regional functional connectivity (Fc) was significantly impaired in the dorsal attention network (DAN), frontoparietal network, sensorimotor network and default mode network. In particular, the Fc strength at the insula of the DAN and the mean FA were linearly related with attention performance and dizziness severity, respectively. The multivariate pattern classification gave over 90% predictive accuracy of individuals with MCI or severe dizziness. Cognitive decline in stroke-free individuals with severe carotid stenosis may arise from nonselective widespread disconnections of long-range, predominantly interhemispheric non-hippocampal pathways. Connectivity measures may serve as both predictors for cases at risk and therapeutic targets for mitigating vascular cognitive impairment.
    Full-text · Article · Jan 2014 · PLoS ONE
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    • "For this reason, the identification of vulnerable lesions represents the fundamental step to select patients at risk of cerebrovascular ischemic events from carotid disease where the surgical procedure is indicated. This is a particularly relevant hot topic in literature since optimal management of asymptomatic carotid stenosis still remains controversial [5], while the beneficial effect of CEA is recognized worldwide in symptomatic patients for hemodynamic stenosis. However, the timing of surgery in acute cerebrovascular events is still controversial. "
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    ABSTRACT: The early identification of ischemic stroke pathophysiology may lead to different diagnostic and therapeutical strategies. In 1/3 of patients, stroke is related to carotid disease, when a vulnerable plaque evolves with surface rupture and local apposition of highly embolic/thrombotic material. This being a rapidly evolving dynamic process, the value of its early identification may be underestimated. With the diffusion of high-resolution ultrasound equipments, the possibility of identifying these features of plaque vulnerability has become easily available. These plaque characteristics have to be always considered in the patient management, in order to avoid further worsening of neurological conditions or to prevent recurrent events, and to choose the appropriate strategies.Methods Early ultrasonography was performed with high frequency probes (9, 15, 18 MHz) in patients admitted to emergency area for acute ischemic symptomatology from carotid stenosis.ResultsIn 8 patients admitted to the emergency area few hours after the onset of neurological symptoms, we detected peculiar plaque characteristics closely related to the neurological events and at high risk of further embolic events with local thrombosis, surface plaque rupture and carotid floating thrombi. All these cases were successfully submitted to emergency carotid endarterectomy repair.Conclusions Timing of carotid endarterectomy has always been debated in stroke patients’ clinical management, depending on several factors. All imaging techniques contribute to the identification of plaque morphology features, but early admission of stroke patients to the emergency areas and early US have a crucial leading role in detecting plaque rupture and dynamic changes in real-time. Peculiar characteristics of high unstable plaques allow the identification of those lesions at particularly high risk of further embolic events according to their fragile characteristics that may benefit from early surgery.
    Full-text · Article · Sep 2012 · Perspectives in Medicine
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