Dirk W. Droste

Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study.

Although most therapeutic efforts and experimental stroke models focus on the concept of complete occlusion of the middle cerebral artery as a result of embolism from the carotid artery or cardiac chamber, relatively little is known about the stroke mechanism of intrinsic middle cerebral artery stenosis. Differences in stroke pathophysiology may require different strategies for prevention and treatment. We prospectively studied 30 consecutive acute ischemic stroke patients with middle cerebral artery stenosis detected by transcranial Doppler and magnetic resonance angiography. Patients underwent microembolic signal monitoring by transcranial Doppler and diffusion‐weighted magnetic resonance imaging. Characteristics of acute infarct on diffusion‐weighted magnetic resonance imaging were categorized according to the number (single or multiple infarcts) and the pattern of cerebral infarcts (cortical, border zone, or perforating artery territory infarcts). The data of microembolic signals and diffusion‐weighted magnetic resonance imaging were assessed blindly and independently by separate observers. Diffusion‐weighted magnetic resonance imaging showed that 15 patients (50%) had single acute cerebral infarcts and 15 patients had multiple acute cerebral infarcts. Among patients with multiple acute infarcts, unilateral, deep, chainlike border zone infarcts were the most common pattern (11 patients, 73%), and for single infarcts, penetrating artery infarcts were the most common (10 patients, 67%). Microembolic signals were detected in 10 patients (33%). The median number of microembolic signals per 30 minutes was 15 (range, 3–102). Microembolic signals were found in 9 patients with multiple infarcts and in 1 patient with a single infarct (p = 0.002, χ2). The number of microembolic signals predicted the number of acute infarcts on diffusion‐weighted magnetic resonance imaging (linear regression, adjusted R2 =0.475, p < 0.001). Common stroke mechanisms in patients with middle cerebral artery stenosis are the occlusion of a single penetrating artery to produce a small subcortical lacuna‐like infarct and an artery‐to‐artery embolism with impaired clearance of emboli that produces multiple small cerebral infarcts, especially along the border zone region.

Optimizing the Technique of Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts

Background and Purpose— A cardiac right-to-left shunt (RLS) can be identified by transesophageal echocardiography and transcranial Doppler ultrasound (TCD) with contrast agents and a Valsalva maneuver (VM) as a provocation procedure. This article applies the modalities of these tests detailed in previous studies to a large patient cohort and compares 2 contrast agents (saline and Echovist-300). Methods— Eighty-one patients were investigated by both transesophageal echocardiography and bilateral TCD of the middle cerebral arteries. The following protocol with injections of 10 mL agitated saline was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, and (3) repetition of the test with VM if the first test with VM was negative. The VM was performed for 5 seconds starting exactly 5 seconds after the beginning of saline injection. Thereafter, the same protocol was repeated with 10 mL Echovist-300 instead of saline. Results— Thirty-one patients had a cardiac RLS. The Echovist-300 investigation disclosed all these 31 shunts, but saline disclosed only 29 of them. Twenty-two had an RLS only in at least 1 of the above TCD tests, some of them even with a considerable shunt volume. Conclusions— Contrast TCD performed with Echovist-300 but not with saline yields a 100% sensitivity to identify transesophageal echocardiography-proven cardiac RLSs. The TCD test should be repeated if negative the first time. This article gives detailed information for the optimization of the contrast TCD technique. Extracardiac shunts detected only during contrast TCD can have a considerable shunt volume and may allow for paradoxical embolism.

Accuracy of In Vivo Carotid B-Mode Ultrasound Compared With Pathological Analysis Intima-Media Thickening, Lumen Diameter, and Cross-Sectional Area

Background and Purpose— This study aimed to determine the correlation of in vivo ultrasound measurements of intima-media thickening (IMT), lumen diameter, and cross-sectional area of the common carotid artery (CCA) with corresponding measurements obtained by gross pathology and histology. Methods— Sixty-six moribund neurological patients (mean age 71 years) underwent B-mode ultrasound of the CCA a few days before death. During autopsy, carotid specimens were removed in toto. Carotid arteries were ligated and cannulated for injection of a hydrophilic embedding material under standardized conditions. The carotid bifurcation was frozen and cut manually in 3-mm cross slices. Digital image analysis was carried out to determine the diameter and the cross-sectional area of the frozen slices of the CCA. IMT was assessed by light microscope. Ultrasonic and planimetric data were compared. Results— Mean measurements of lumen diameter and cross-sectional area were 7.13±1.27 mm and 0.496±0.167 cm2, respectively, by ultrasound, and 7.81±1.45 mm and 0.516±0.194 cm2, respectively, by planimetric analysis of the unfixed redistended carotid arteries (R2=0.389 and 0.497). The mean IMT was 1.005±0.267 mm by ultrasound and 0.67±0.141 mm histologically, resulting in a mean difference of −31%. Conclusions— Transcutaneous B-mode ultrasound provides a reliable approach for in vivo measurements of the cross-sectional area and, less exactly, of the lumen diameter of the CCA. Compared with histological results, in vivo ultrasound measurements of the IMT are systematically larger.

Clinically Silent Circulating Microemboli in 20 Patients with Carotid or Vertebral Artery Dissection

Background and Purpose: Carotid and vertebral artery dissections are frequently complicated by cerebral embolism. Detection of clinically silent circulating microemboli by transcranial Doppler sonography (TCD) is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. Methods: In 20 patients with carotid (n = 17) or vertebral (n = 2) artery dissection, or both (n = 1), we performed a 1-hour microembolus detection downstream to the dissection in the middle or in the posterior cerebral artery, respectively. Results: Five patients with a carotid artery stenosis of ≧90% or with carotid artery occlusion showed microembolic signals at a rate of up to 15 events/h. In all these patients, the onset of the dissection was within the last 58 days. Patients with lower degrees of stenosis or onset of symptoms beyond 58 days did not show microembolic signals at all. Three patients who had presented with recurrent ischaemic events prior to TCD monitoring unexceptionally had microembolic signals. Conclusion: Microembolic signals occur in patients with high-grade stenosis or occlusion due to acute cervical artery dissection. Patients with microemboli seem to be at increased macroembolic risk, i.e. stroke recurrence, and may require close-meshed clinical follow-up and possibly stronger antithrombotic treatment.

Carotid artery auscultation - Anachronism or useful screening procedure?

Abstract Carotid bruits are supposed to indicate the presence of high-grade common carotid or extracranial internal carotid artery stenosis in a large proportion of patients. Using a stethoscope, we prospectively auscultated 273 carotid arteries of 145 patients blinded to the results of a complete extracranial and intracranial Doppler investigation including extracranial color-coded duplex ultrasound. Fifty-four arteries showed stenosis of ≥ 50%-99%, or occlusion of the extracranial internal or the common carotid artery. In 25 of these arteries, a bruit was present. In 9 out of 16 patients with extracranial stenosis from 70%-99%, a bruit was detected. In one additional patient with a middle-grade external carotid artery stenosis, a bruit was also present. In seven additional patients, a bruit was present in the absence of any carotid artery stenosis, cardiac vitium or goiter. The sensitivity of carotid auscultation for the detection of a 70%-99% stenosis of the common or extracranial internal carotid artery was 56% and specificity was 91%. The positive predictive value of a bruit found during carotid auscultation was 27%, and the negative predictive value of a normal auscultation was 97%. Carotid auscultation is a useful screening procedure in the detection of carotid stenosis or occlusion, but requires confirmation by carotid ultrasound.

Microembolus detection by transcranial doppler sonography.

Microembolic signals can be detected by transcranial ultrasound as signals of high intensity and short duration. These signals represent circulating gaseous or solid particles. To optimize the differentiation from artefacts and the background signal and to facilitate the clinical use, several attempts have been made to automatize the detection of microemboli. Microemboli occur spontaneously in various clinical situations but their clinical impact and possible therapeutical implications are still under debate. This article provides a review of the actual literature concerning the current state of technical and clinical aspects of microembolus detection.

Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts: Comparison of Echovist®-200 and Echovist®-300, Timing of the Valsalva Maneuver, and General Recommendations for the Performance of the Test

Background and Purpose: Cardiac right-to-left shunts (RLS) can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents, such as Echovist®-200 or Echovist®-300 in conjunction with a Valsalva maneuver (VM) as provocation procedure. Both Echovist preparations are in use. Currently, the appropriate timing of the VM is still under debate. Methods: Sixty-four patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) no VM, (2) VM for 5 s starting with the beginning of Echovist-300 injection, (3) VM for 5 s starting 5 s after the beginning of Echovist-300 injection, (4) VM for 5 s starting 10 s after the beginning of Echovist-300 injection, and (5) VM for 5 s starting 5 s after the beginning of Echovist-200 injection. Results: In 27 patients, an RLS was demonstrated by both TEE and contrast TCD (shunt-positive). Twenty-two patients were negative in both investigations, no patient was positive on TEE but negative on TCD, 15 patients were only positive on at least one TCD investigation but negative on TEE. Tests 3 and 5 were the most appropriate ones; test 3 was slightly superior to test 5. Conclusions: TCD using Echovist-300 or Echovist-200 is a sensitive method to identify TEE-proven cardiac RLS. To achieve the best diagnostic accuracy, the VM should be performed for a duration of 5 s starting at 5 s following the beginning of contrast injection.

Circulating Microemboli in 33 Patients with Intracranial Arterial Stenosis

Background: Intracranial arterial stenosis is a rare cause of stroke in Caucasians. Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. Methods: In 33 patients with intracranial internal carotid (n = 12), middle cerebral (n = 18), posterior cerebral (n = 2), or basilar artery stenosis (n = 1), we performed a 1-hour microembolus detection downstream to the stenosis in the middle or in the posterior cerebral artery, respectively. The stenosis was assessed by transcranial Doppler and duplex ultrasound. 18 patients had been symptomatic in the dependent territory. Results: Five patients with ischaemic symptoms within the last 8 days and with a peak systolic flow velocity of ≧210 cm/s in the stenosis showed microembolic signals at a rate of 3–25 events/h, despite effective anticoagulation. All these 5 patients had a lesion pattern on cranial CT or MRI scan suggesting embolic origin. All the asymptomatic patients (n = 15) and all the patients with a peak systolic intrastenostic velocity of 160 to <210 cm/s (n = 13) did not show microembolic signals at all. Conclusion: Microembolic signals occur in recently symptomatic patients with high-grade intracranial arterial stenosis indicated by a sonographically measured stenotic peak flow velocity of ≧210 cm/s. Therapeutic anticoagulation was not sufficient to suppress microemboli formation.

Evaluation of Progression and Spread of Atherothrombosis

Symptomatic atherothrombosis in one vascular bed is usually indicative of disseminated disease. Indeed, involvement of multiple beds is common in everyday clinical practice, and these patients are at much higher risk of ischaemic events. The prevention of manifestations following atherothrombosis is therefore an important therapeutic goal in these patients. Some causative risk factors demonstrate affinities to particular arterial domains. Cigarette smoking, for example, is particularly associated with atherothrombotic involvement of the pelvic and lower limb arteries, whereas arterial hypertension is associated with the intracranial cerebral arteries. The degree, spread and progression of atherosclerosis can be assessed using various non-invasive and invasive modalities: high-resolution Doppler ultrasound, ankle-brachial index (ABI) measurement, magnetic resonance (MR), computed tomography (CT) and intra-arterial angiography. Indicators of atherothrombotic risk include increased carotid artery intima-media thickness, microembolic signals on transcranial Doppler ultrasonography and low ABI. There is a strong rationale for the inclusion of the ABI measurement as part of the routine clinical examination to assess the cardiovascular risk in patients with identified risk factors. Furthermore, detection of a low ABI should serve as a trigger for patient management with aggressive antiplatelet therapy. The generalized nature of atherothrombosis and the methods for evaluating the spread of disease are illustrated through the case history of a patient with disseminated atherothrombotic disease.

Detection of Carotid Artery Stenosis by In Vivo Duplex Ultrasound: Correlation With Planimetric Measurements of the Corresponding Postmortem Specimens

Background and Purpose— The correct detection and quantification of carotid artery disease are of decisive impact on patient prognosis and adequate treatment. In this study, we evaluated the ability of ultrasonography to detect and to grade carotid artery stenosis through a comparison of the in vivo ultrasound findings with the planimetric analysis of the corresponding postmortem specimens. Methods— Shortly before their death, 59 critically ill neurological patients (mean age, 70 years) were prospectively examined by extracranial and intracranial Doppler sonography and color-coded duplex ultrasound. Carotid stenosis was classified by hemodynamic and morphological ultrasound criteria. Carotid specimens were removed in toto during autopsy. Under standardized conditions, specimens were redistended, sectioned, and histologically processed. Computerized planimetric measurements of the arteries were carried out and compared with the ultrasound findings. Correlation of the ultrasound and postmortem planimetric findings was available in 93 carotid bifurcations. Results— Through both techniques, 46 carotid arteries were found to be normal. Steno-occlusive carotid lesions ranged from 8.5% to 100% lumen reduction. Overall, r =0.96 and adjusted R2=0.90. For the steno-occlusive carotid lesions, r =0.91. Conclusions— Extracranial and intracranial Doppler and color-coded duplex ultrasound permits reliable detection and quantification of carotid artery stenoses and occlusions even under difficult examination conditions in critically ill patients.