Besides the established factors “presence of symptoms” and “degree of stenosis”, plaque echolucency is considered to be associated with increased risk of stroke in patients with carotid artery disease. An evaluation was carried out as to whether the prevalence and number of microembolic signals (MES) detected by transcranial Doppler ultrasound were higher in patients with echolucent carotid plaques. One hundred and five patients with carotid artery stenosis from 20%-99% or occlusion underwent clinical investigations, duplex ultrasound of the carotid arteries, and a 1 hour recording from the middle cerebral artery downstream to the carotid artery pathology using the four gate technique. The presence of MES was more frequent and the number greater in symptomatic patients (21 out of 64 patients (33%); mean number of MES in all 64 patients 3.1) than in asymptomatic patients (four out of 41 patients (10%); mean number of MES in all 41 patients 0.3) (p=0.007, and p=0.006, respectively). Echogenicity of the lesions did not affect either number or presence of MES. Positivity for MES and the number of MES increased with increasing degree of stenosis (both p=0.002). Four out of 12 patients with carotid artery occlusion showed MES. No MES could be detected in carotid artery stenosis below 80%. There was a decline in positivity of MES and of the number of MES with the time after the ischaemic event. After 80 days or more after the index event, only one patient showed MES. In conclusion, increasing degree of stenosis and presence of symptoms similarly affect macroembolic and microembolic risk. Thus MES may be a surrogate parameter for risk of stroke. The presence of MES in a few asymptomatic patients suggests that clinically silent circulating microemboli may give additional information on the pending embolic potential of carotid artery stenoses. Echolucency of the plaque was not related to an increased number of MES.
- carotid artery disease
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In extracranial carotid artery stenosis, besides the presence of symptoms and the degree of stenosis, low plaque echogenecity has been claimed to be also associated with future stroke risk.1-6
Clinically silent circulating cerebral microemboli can be detected as high pitched signals within the transcranial Doppler (TCD) frequency spectrum.7 8 The presence of such microembolic signals (MES) proves ongoing embolisation into the cerebral arteries, gives information on the frequency of embolisation, and helps to localise the embolic source.
In this study we evaluated the clinical and the ultrasonic features of patients with different degrees of extracranial carotid artery occlusive disease in relation to the presence and frequency of circulating microemboli in the dependent middle cerebral artery (MCA) using the four gate technique.9 In particular, we wanted to show that the above established risk factors for macroembolisation (presence of symptoms and degree of stenosis) and the debated risk factor “echolucency” are also risk factors for microembolisation.
Patients and methods
One hundred and five patients, aged from 29 to 86 years, were investigated (mean age 62 (SD 11 years) There were 27 women and 78 men. They were inpatients and outpatients of our department and underwent routine clinical investigations. All of them had extracranial carotid artery stenosis ⩾20% or internal carotid artery (ICA) occlusion on ultrasound. Sixty four of them had presented at least one transient or permanent ipsilateral ocular or cerebral ischaemic event in the carotid artery territory under investigation. The time between the recording and the last event varied from 0 to 3474 days. Five patients were in atrial fibrillation during the recording. Thirty two patients were taking intravenous heparin, one patient subcutaneous heparin, eight oral antiaggregants, and 72 patients were taking aspirin or ticlopidine (some were on two drugs or switched, the previous drug still being active).
In all patients the neck arteries were investigated by color duplex ultrasound (7.5 MHz linear probe, Sonos 2500, Hewlett Packard) and the periorbital arteries by continuous wave Doppler (8 MHz probe, Multidop X, DWL). The extracranial duplex investigation included longitudinal and transverse sections of the plaque and was recorded onto video tape. Furthermore the peak systolic and end diastolic flow velocities in the common carotid artery, in the jet of the stenosis, and in the most distal part of the ICA accessible by B-mode were recorded (angle adjusted). Patients were also examined by TCD (2 MHz probe, Multidop X, DWL).
The carotid plaque was classified as follows: (1) uniformly echolucent, (2) predominantly echolucent, (3) predominantly echogenic, (4) uniformly echogenic.1 10 The stenosis was classified in categories of 10% taking into account the peak systolic velocity in the jet of the stenosis, broadening of the poststenotic spectrum, peak systolic velocity in the poststenotic ICA, direction of ophthalmic flow, presence of collateral flow via communicating arteries, asymmetry in pulsatility, and absolute velocity in the common carotid artery and in the MCA. A peak systolic velocity of at least 120 cm/s was the threshold for a stenosis ⩾50% excluding subtotal stenosis with a variable signal. In the case of indirect haemodynamic criteria, the stenosis was classified to have ⩾80%. Occlusion was diagnosed in the complete absence of detectable flow in and above the stenosis and the presence of corresponding indirect haemodynamic criteria. Plaques with stenosis <50% were classified according to their lumen reduction on B-mode.11-13
For the TCD embolus detection, the MCA main stem downstream to the affected carotid artery was insonated through the temporal window for 1 hour. For all studies, the same transcranial pulsed Doppler ultrasound device (TC4040, Nicolet-EME, Kleinostheim) with a 2 MHz four gate transducer was used. A detection threshold of ⩾5 dB was used for all studies taking into account that only a small percentage of the natural fluctuations of the Doppler spectrum occurred in this range. Details of the technique are described elsewhere.9 In addition, the audio Doppler signal of all four channels was continuously recorded onto an eight channel digital audio tape deck recorder (TA-88, TEAC Corporation) with normal speed.
An experienced observer’s analysis of MES consisted of (1) on line analysis during the recording, (2) visual and acoustic off line verification of the events preselected by the algorithm, and (3) off line analysis of the tapes. During the analysis of the tapes, the investigator was blinded to the information regarding the degree of stenosis, the presence of symptoms, and the echogenicity of the plaque. Conflicting results were re-evaluated and discussed.
ANALYSIS AND STATISTICS
The number of MES as well as the number of embolus positive patients in symptomatic patients and asymptomatic carotid artery disease were compared using the non-parametric Mann-WhitneyU test. The number and presence of MES were investigated in the four echogenicity categories by a Kruskal-Wallis one way analysis of variance (ANOVA). The impact of the degree of stenosis on the number of MES and on embolus positivity was also evaluated using a Kruskal-Wallis one way ANOVA. For these analyses, the 12 patients with ICA occlusion were excluded. Significance was assumed at a value of p<0.05.
The distribution of degrees of stenosis and presence of symptoms is given in the figure.
Thirty plaques were uniformly echolucent, 34 plaques were predominantly echolucent, 37 plaques were predominantly echogenic, and four were uniformly echogenic. In 46 patients a cross flow via the anterior communicating artery was present. Contralateral carotid artery high grade stenosis was present in nine patients, 12 patients had a contralateral ICA occlusion. No intracranial ICA or MCA stenoses were detected. Out of the 40 patients with either oral or intravenous anticoagulation, all but two had a stenosis⩾0%.
The total number of MES was 212, ranging from 0–38 in the individual patients. Twenty one out of 64 symptomatic patients (33%) and four out of 41 asymptomatic patients (10%) showed MES. Symptomatic patients were more likely to have emboli (p=0.007) than asymptomatic patients. The number of MES was higher in the symptomatic patients (mean 3.1 (SD 7.7)) compared with the asymptomatic patients (mean 0.3 (SD 1.0); p=0.006). These values refer to the whole groups of patients, not only those embolus positive.
Positivity for MES and the number of MES increased with increasing degree of stenosis; there were no MES in patients with ⩽80% stenosis (p=0.015 and p=0.019, respectively).
There was a decline of MES positivity and of the number of MES with the time after the ischaemic event; only one patient showed MES more than 80 days after the index event.
Echogenicity of the lesion did not affect either the number or presence of MES (p=0.56 and p=0.49, respectively). Eight patients out of 30 with plaques uniformly echolucent had MES (mean number of MES for the whole group of 30 patients 0.97 (SD 2.82), 10 patients out of 34 with plaques predominantly echolucent showed MES (mean number of MES 1.91 (SD 4.11)), seven out of 37 patients with predominantly echogenic plaques showed MES (mean number of MES 3.19 (SD 9.21)), and none of the four patients with uniformly echogenic plaques.
Out of the 25 patients with MES, four had possibly competing embolic sources. Two of these patients were in atrial fibrillation and two patients had a cross flow via the anterior communicating artery with a high grade carotid artery on the contralateral side.
The degree of stenosis and the presence of ocular or cerebral ischaemic events were associated with a higher number and with a higher presence of MES in the present study. Therefore, our study suggests that the presence and number of clinically silent circulating MES may be surrogate parameters for macroembolic (stroke) risk. Valtonet al described a non-significant trend towards a higher number of MES with increasing degree of stenosis.14 Babikian et aldescribed a higher prevalence of MES in patients with a stenosis of more than 50% compared with patients with ⩽50% stenosis.15 The table gives a summary of the studies performed so far in this field.
The decline of the MES number with time has also been reported by other authors.17-19 The low frequency of MES after about 80 days may indicate the time needed for plaque healing after disruption.20-22
The presence of MES in a few asymptomatic patients suggests that clinically silent circulating microemboli may give additional information on the impending embolic potential of carotid artery stenoses not covered by the patient’s history. At present, there is still insufficient evidence to operate on clinically asymptomatic stenoses only relying on the presence of MES. So far no large study has unequivocally shown MES to be a risk factor for stroke, as the number of patients is high and the observation time needed is long.23 Our study indirectly further supports this possible relation of microembolic events and macroembolic risk. We showed an increase in microembolic risk with increasing degree of stenosis and presence of symptoms, a relation which is well known for macroembolic risk from clinical endarterectomy trials.24-27
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