Cross-sectional studies suggest that impaired cerebral haemodynamics is associated with symptomatic status in patients with carotid stenosis and occlusion, but there is relatively little prospective data confirming this association. Transcranial Doppler ultrasonography was used to determine the reactivity of the middle cerebral artery to 8% carbon dioxide in air in 107 patients with either carotid occlusion (n = 48) or asymptomatic carotid stenosis (n = 59). Subjects were followed prospectively until stroke, transient ischaemic attack (TIA), death or study end. Mean duration of follow-up was 635 days. No patients dropped out due to operation before an end-point was reached, or were lost to follow-up. There were 11 ipsilateral ischaemic events during follow-up (six strokes, five TIAs). Exhausted ipsilateral middle cerebral artery reactivity (>20% increase in ipsilateral middle cerebral flow velocity in response to 8% carbon dioxide) predicted ipsilateral stroke and TIA risk in the whole group (P: < 0.00001) and in the carotid occlusion (P: = 0.019) and carotid stenosis (P: = 0.015) groups alone. It also predicted the risk of ipsilateral stroke alone in all three groups. Cox regression was performed, controlling for age, gender, hypertension, diabetes, smoking, ipsilateral CT infarct, degree of contralateral stenosis and the presence of ipsilateral stenosis versus occlusion. Exhausted reactivity remained an independent predictor of ipsilateral stroke and TIA (odds ratio 14.4, 95% confidence interval 2.63-78.74, P: = 0.0021). In contrast, the pulsatility index of the middle cerebral artery was a poor predictor of the risk of stroke. Reactivity to 6% carbon dioxide also predicted the risk of stroke and TIA, but slightly less effectively than reactivity to 8% carbon dioxide. Severely reduced cerebrovascular reactivity predicts the risk of ipsilateral stroke and TIA in patients with carotid occlusion, and to a lesser extent in asymptomatic carotid stenosis. Particularly in the former group, a study is required to determine whether revascularization reduces the risk of stroke in patients with exhausted reactivity.

SummaryBackgroundWhether 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.MethodsThe 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.Findings482 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.InterpretationDetection 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.FundingBritish Heart Foundation.

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Background and Purpose-The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. Methods-In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. Results-In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of Ն7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity Ͼ95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of Ն7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give Pϭ0.84, which was similar to that of the software. Conclusions-By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts (Stroke. 2000;31:1335-1341.)