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Background Awareness of stroke risk factors is important for stroke prevention. Knowledge of stroke symptoms and awareness regarding the necessity of seeking urgent stroke treatment are vital to provide rapid admission to a stroke unit. Data on this specific knowledge in Luxemburg are lacking. METHODS We investigated 420 patients from the Department of Neurology and their relatives using a questionnaire. There were 44% men and 56% women; 25% were immigrants and 75% Luxemburgish nationals; 13% already had had a stroke or transient ischemic attack (TIA); and the mean age was 55 years ranging from 18 to 87 years. Results A total of 88% of participants knew that a stroke occurs in the head/brain. In all, 10% of participants did not know any symptom of a stroke. The most frequently quoted symptoms (>15%) were paralysis/weakness (36%), speech disorders (32%), cranial nerve deficit (16%), vertigo (15%), and visual disorders (15%). Sensory deficits were mentioned by only 4% of patients. Known risk factors (>15%) were smoking (40%), hypertension (32%), alcohol (32%), poor nutrition (28%), high cholesterol (26%), stress (23%), and lack of exercise (19%). Age (4%), diabetes (6%), carotid stenosis (2%), and heart disease (1%) were less frequently known. In all, 11% of participants did not know any risk factor of a stroke. A total of 89% of participants would correctly call the 112 (emergency phone number). The following groups were better informed: Luxemburgish nationals, younger people, and participants with higher education level. Stroke/TIA patients were better informed concerning stroke symptoms, but unfortunately not concerning how to react in the case of a stroke. There was no relevant gender difference. Discussion Although most of the participants knew what to do in the case of a stroke, they did not know the relevant stroke symptoms and risk factors. Future campaigns should therefore focus on risk factors and symptoms, and should address immigrants, elderly persons, less-educated persons, and patients who had already suffered a stroke/TIA.

Background: A Mediterranean diet, with and without small daily amounts of red wine, and physical activity reduce the risk of cerebrovascular disease and improve cognition. An increase in cerebral blood flow may be the underlying mechanism. Under normal conditions, cerebral blood flow velocity changes in the internal carotid arteries and in large basal cerebral arteries correlate closely with cerebral blood flow changes, as the diameter of these vessels hardly changes and only the smaller vessels downstream change their diameter. Methods: A prospective randomized controlled trial was performed in 108 patients with carotid atherosclerosis (mean age 64 years, 67% men, 66% on statin therapy). Half of them were advised to follow a polyphenol-rich modified Mediterranean diet including 1-2 tomatoes, 3-5 walnuts and a bar of dark chocolate (25 g) a day and to perform moderate physical exercise for 30 min/day (lifestyle changes). Within these two groups, half of the patients were randomized either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. Bilateral middle cerebral and internal carotid blood flow velocity (peak systolic, peak end-diastolic and mean) was measured at baseline and after 4 and 20 weeks using colour-coded duplex ultrasound. Insonation depth and insonation angle were used to identically place the sample volume during follow-up investigations. A general linear model with Tukey-Kramer adjustment for multiple comparisons was used to assess the primary end points. For the analysis we used the mean values of the right and left artery. Results: Neither lifestyle changes nor red wine had an effect on peak systolic, peak end-diastolic or mean cerebral blood flow velocity. Conclusions: Advice on lifestyle changes, including a modified polyphenol-rich Mediterranean diet, a glass of red wine daily and physical exercise, did not affect middle cerebral and internal carotid blood flow velocity in our patient group with carotid atherosclerosis. An increase in cerebral blood flow is thus unlikely to be the cause of the reduced risk of cerebrovascular disease and improved cognitive functioning described in the literature. One possible explanation for the fact that blood flow velocity was not affected by red wine, diet and physical activity advice is that two thirds of our patients were already on statin therapy. Statins increase cerebral blood flow and vasomotor reactivity via nitric oxide.

Background: Regular consumption of small amounts of red wine improves blood lipids. However, there is concern whether this beneficial effect might be counterbalanced by an increase in blood pressure (BP) and heart rate (HR), which are risk factors for cerebro-cardiovascular disease. In particular, we studied whether regular consumption of red wine with and without lifestyle changes (LC; healthy diet and physical activity advice) results in an increase in BP and HR. Methods: A prospective, unblinded randomized trial was performed in 108 patients (67% men) with carotid atherosclerosis documented by ultrasound, a mean BP of 122/79 mm Hg and a mean HR of 71 bpm at inclusion in the study. Sixty-eight percent were known and treated hypertensives. The mean 24-hour BP at baseline was 122/79 mm Hg. Half of the study participants, the control group, was seen by a nurse at baseline, after 4 and after 20 weeks, and was instructed not to change their eating and physical activity habits. In the other half, a dietician performed five sessions of 30 min each (at baseline, after 1 week and after 2, 3 and 4 weeks) giving advice on healthy eating based on a Mediterranean diet and physical exercise. The recommendations given were the following: 5 portions of fruit/vegetables per day, a diet low in absolute fat, a preference of vegetable oil (olive or rapeseed oil), whole-grain products, poultry, low-fat dairy products, 1 fat and 1 lean fish meal per week, reduced consumption of red meat, and avoidance of pork, ready-made meals, sugar and excessive salt intake. In addition, regular consumption of 1 bar of dark chocolate (25 g, >70% of cacao), 1-2 tomatoes, and 3-5 walnuts as well as at least 30 min of moderate daily physical activity were recommended. Within these two groups, half of the patients were randomized either to avoid alcohol completely or to drink 100 ml (women) or 200 ml of red wine (men) daily. Results: Neither LC nor red wine had an effect on the mean systolic and diastolic 24-hour BP and HR after 4 and 20 weeks, as analyzed by general linear modeling. No difference was found for diurnal and nocturnal values. Conclusions: The possible beneficial effect of regular consumption of small amounts of red wine is not counterbalanced in the long term by an increase in the mean BP or HR in mainly normotensive and well-treated hypertensive patients with carotid atherosclerosis, neither in the patients given healthy lifestyle advice nor in those with a standard lifestyle. Yet, we remain cautious about actively advice patients to drink alcohol regularly given the well-known risks.

There is conflicting evidence in the literature as to the potential effect of continuous positive airway pressure (CPAP) on cerebral perfusion. Compromising cerebral perfusion could possibly outweigh the benefit of improved oxygenation. Patients with the obstructive sleep apnea syndrome (OSAS) have been claimed to have a higher cerebrovascular reactivity to changes in end-tidal pC02. In this study, we investigated 23 patients with OSAS and 7 6 healthy young adults in the waking state. Both groups performed a series of lOmin of normal breathing, 20min with 9 cmH20 nasal CPAP, and then TOmin of normal breathing while wearing a nasal CPAP mask. The following parameters were assessed: bilateral transcranial Doppler signal of the middle cerebral artery, systolic and diastolic blood pressure assessed manually, and cerebrovascular reactivity to changes in pC02 during hyperventilation and rebreathing into an airbag. Continuous end-tidal pC02 measurements were performed in 74 subjects. As compared with normal breathing middle cerebral artery blood flow velocity and pC02 remained unchanged during CPAP. Systolic and diastolic blood pressure increased slightly by 1.2mmHg (p = 0.015) and 1.1 mmHg (p = 0.007), respectively. Cerebrovascular reactivity did not differ in the two groups. Nasal CPAP of 9 cmH20 is a safe treatment with respect to the maintenance of cerebral blood flow. Our study gives further evidence for the autoregulation's capacity to maintain cerebral blood flow velocity constant during different levels of intrathoracic pressure and different cerebral perfusion pressures. We could not demonstrate any difference in cerebrovascular reactivity between patients with OSAS and healthy persons. [Neurol Res 1999; 21: 737-741].

SummaryInflammation and thrombosis, two processes influencing each other, are involved in the pathogenesis of cerebrovascular disease. We showed that in patients with acute ischaemic stroke circulating platelets are activated and exhausted. To identify whether activated haemostasis might be cause or effect, we investigated the role of leukocyte and platelet activation in patients with severe asymptomatic and symptomatic carotid artery disease. Flow cytometry analysis demonstrated that monocytes from symptomatic (acute stroke aetiology) and asymptomatic patients were highly activated, shown by significantly enhanced presentation of inflammatory markers CD11b and thrombospondin-1 (TSP-1) on the surface. Both correlated positively with monocyte-platelet association rate. However, increased monocyte activation and elevated levels of monocyte-platelet associates in asymptomatic patients were restricted to patients with echo-lucent plaques, providing a close link between monocyte activation and plaque morphology. Circulating single as well as monocyte-bound platelets from symptomatic patients showed significantly enhanced surface expression of P-selectin and TSP-1, whereas platelets from asymptomatic patients were not significantly activated. These results indicate that monocytes activated by inflammation rather than platelets might be the candidates to initiate platelet-monocyte rosetting during the pathogenesis of atherothrombotic cerebral ischaemia and that haemostasis might be activated secondarily by the first occurring inflammation.

Extracranial and transcranial colour-coded duplex sonography (TCCD) are used routinely in clinical practice to assess physiologic and pathologic arterial blood flow to the brain. Such investigations are straightforward, safe, and cost effective, and can be repeated frequently for patient follow-up. In addition, the portability of extracranial colour-coded duplex sonography and TCCD provides the option of bedside investigations, particularly useful for evaluation of the critically ill patient. However, duplex ultrasound can be hampered by insufficient acoustic penetration, an unfavourable insonation angle, or by conditions of low or no flow. Echocontrast agents capable of surviving pulmonary and capillary transit have been developed, and such agents increase the Doppler signal and, therefore, the success rate of neurosonographic investigations. Approximately 20% of TCCD studies involve poor insonation conditions and, therefore, the use of echocontrast agents is of particular interest for this application. Levovist® and SonoVue® are the two agents currently approved for use in neurosonography. Such agents have a relatively long-lasting effect (up to 7 min), and can be administered as a single injection or, alternatively, a fractionated injection protocol can be used, depending on the quality of the window.

This study compares the additional benefit of diffusion-weighted MRI (DWI) and microembolus detection by transcranial Doppler ultrasonography (TCD) in the assessment of stroke etiology.Fifty-five acute anterior circulation stroke or TIA patients were investigated by both cranial DWI and bilateral TCD of the middle cerebral arteries (1 hour).In one of the 13 patients without acute ischemic lesions visualized on DWI, microembolic signal (MES) detection was positive. However, in 33 out of 44 patients without MES, DWI revealed at least one lesion. In two patients with unilateral territorial infarction and otherwise normal cardiovascular work-up, bilateral MES were found thus localizing the embolic source into the aortic arch or the heart. In a further patient with a dissection, the occurrence of contralateral MES raised doubts on a dissection to be the cause of the infarct.There is a contribution of both techniques to the understanding of stroke etiology. The impact of DWI is, however, superior to that of MES detection. Longer TCD recording times may diminish this discrepancy.

Clinically silent microembolic signals (MES) can be detected by transcranial Doppler sonography (TCD). There is theoretical evidence that lower ultrasound emission frequencies may lead to a higher signal intensity and thus sensitivity to detect MES. We compared a 1-MHz probe with a 2-MHz probe regarding sensitivity in the detection of MES. Moreover, embolus detection by transcranial Doppler ultrasound is very time consuming and semi-automated detection is mandatory. Therefore, we studied an on-line algorithm using the bi-gate technique and the two transmission frequencies.After defining detection thresholds ofor = 12 dB (1 MHz) andor = 10 dB (2 MHz) with eight normal subjects as MES-negative controls, taking into account natural fluctuations of the Doppler spectrum, we studied 36 patients with ischaemic events and five asymptomatic patients with incidental embolic sources. All patients subsequently underwent a 1-hour unilateral embolus detection from the middle cerebral artery (MCA) or the posterior cerebral artery (PCA), respectively, using 1 and 2 MHz for 30 minutes each in a randomized order. The software algorithm was compared with a blinded off-line analysis by an experienced observer as a gold standard.The investigator detected 198 MES (range 0-41 MES) in the recordings of 29 patients out of the 41 patients using the 1-MHz probe and 101 MES (range 0-32 MES) in the recordings of 14 patients using the 2-MHz probe (p = 0.0007). Sensitivity of the software to detect MES confirmed by the investigator was 31% using 1 MHz and 41% using 2 MHz. The positive predictive value was 6 and 30%, respectively.The sensitivity and positive predictive values of the automated algorithm to detect MES were unacceptably low for clinical practice with both frequencies. The use of 1 MHz instead of 2 MHz may, however, be useful when evaluating the recordings off-line by an experienced blinded observer.

BACKGROUND Patients with patent foramen ovale (PFO) have an undefined but certainly considerable risk of repeated cerebral ischemia due to paradoxical embolism. Especially, if a cerebrovascular event has already occurred and the combination with an atrial septum aneurysm (ASA) is present this risk increases tremendously. The aim of this study was to demonstrate that surgical closure of PFO in combination with an ASA is safe and useful in preventing recurrent strokes. METHODS Ten patients with previous cerebral ischemia, proven by CT or MRI, and PFO in combination with an ASA were prospectively scheduled for surgical closure. Patients with extracardiac sources of embolic disease were excluded from this study. However, one patient suffered from a hypercoagulability syndrome. RESULTS All patients (mean age 35.5 +/- 19.1 years) underwent direct suture of the PFO and plication of the ASA with the aid of cardiopulmonary bypass and cardioplegic arrest (n = 3) or ventricular fibrillation (n = 7). Mean operation time was 123.1 +/- 20.2 minutes; mean bypass time was 34.5 +/- 9.9 minutes. There was no mortality or significant postoperative morbidity. Mean hospital stay was 5.1 +/- 1.5 days. During a follow-up of >4 years, no recurrent stroke or transient ischemic attack occurred and no patient received anticoagulation therapy. CONCLUSION Our data suggest that surgical closure of PFO in combination with ASA in patients with previous stroke is safe and efficacious to prevent recurrent strokes and avoids lifelong anticoagulation.

Objectives: Proper assessment of the intracranial arteries by transcranial color-coded duplex sonography (TCCD) is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all. Material and Methods:We investigated 67 temporal windows of 47 patients with insufficient native transtemporal insonation conditions before and after the application of the second-generation (gas-filled) microbubble contrast agent Sonovue® (in 20 patients out of these 47, both temporal windows were insufficient, in the remaining 27 only one side). Results: As compared to the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (p < 0.0001) and for longer lumen segments to be displayed on color mode (p < 0.0001). With the help of contrast medium, flow velocity in the middle cerebral artery could be measured through 65 windows as compared to only 26 windows before contrast was applied (p < 0.0001). Conclusions: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful.

Neurosonological investigations of the extracranial and intracranial brain supplying arteries are helpful in the assessment of stroke and stroke-prone patients.In this paper we review the indications, application and advantages of second-generation (gas-filled) microbubble contrast agents such as SonoVue.Gas-filled microbubbles have a strong echo enhancing effect and produce enhancement for several minutes, enabling the sonographer to perform the investigation with a single injection or two or three repeated injections without the need for continuous administration. Echocontrast agents provide better delineation of normal blood flow, occlusions, pseudo-occlusions, stenoses, and collaterals in the extracranial and intracranial vascular beds. They are of particular value during transcranial color-coded transcranial duplex investigations via the temporal and occipital window.Echocontrast agents give additional information on the patient's vascular situation that is often crucial to planning further diagnostic and therapeutic steps. The use of second-generation gas-filled microbubbles, such as SonoVue in transcranial neurosonology, may help to avoid unnecessary, expensive and potentially harmful additional investigations such as intra-arterial DSA. Future applications include the visualization of brain tissue perfusion.

SummaryPlatelet activation is involved in the pathogenesis of cerebrovascular ischemia, but the major agonist involved has yet to be identified. To investigate the role of thrombin in platelet activation in patients with acute ischemic stroke, and while thrombin is the most likely candidate for activation of the thrombin receptor PAR-1 in vivo, we assessed its cleavage and internalization using the antibodies SPAN12, binding to uncleaved PAR-1, and WEDE15, recognizing cleaved and uncleaved, but not internalized PAR-1. In contrast to healthy age-matched controls, platelets from stroke patients exhibited significant cleavage and internalization of PAR-1 (P

Background and Purpose: The major limitation of native transcranial colour-coded duplex sonography (TCCS) in older stroke patients is the relatively frequent occurrence of an insufficient temporal window. Our goal was to investigate the relationship between the in vivo Doppler ultrasound image quality of the temporal bone, and computed tomography (CT)-determined thickness, density, and homogeneity of cadaver temporal bone. Methods: Thirty-three moribund neurological patients who eventually died were examined by TCCS using the transtemporal approach. The sonographer categorized the quality of the TCCS image (excellent, intermediate, and poor). During autopsy, a rectangular sample of the temporal squama was removed, which corresponded to the area of the in vivo acoustic window. The thickness of the whole temporal bone, cortical, and cancellous (= diploe) bone as well as the density and homogeneity were determined by high-resolution CT. Results: Thirty-seven temporal bones were obtained. The quality of the acoustic window was classified as excellent in 13, intermediate in 6 and poor in 18 cases. A significant correlation between the complete bone thickness, as well as between the absolute thickness of the diploe and the quality of the acoustic window was found: the thinner the bone/diploe, the better the colour Doppler signal. The thickness of the cortical plates and the homogeneity of the bones were identical in the three image quality categories. Conclusion: The transtemporal TCCS image quality depends mainly on the thickness of the cancellous component of the temporal bone.

Clinically silent circulating microembolic signals (MES) can be identified by transcranial Doppler ultrasound (TCD). It is not yet clear whether their occurrence is always linked to the presence of embolic sources. 24 terminally ill patients (7 women, 17 men; mean age 68 years) were investigated by TCD of the middle cerebral arteries. These findings were correlated with a complete post-mortem examination of potential embolic pathways. Four patients out of the 24 under investigation showed MES, 2 of them bilaterally. All these 4 MES-positive patients had a definite embolic source, i. e. bilateral carotid artery occlusive disease, endocarditis with thrombotic valvular adhesions and severe plaques in the aortic arch, dilated left atrium and a patent foramen ovale, or severe plaques in the aortic arch and a dilated left atrium, respectively. In the investigated patient group, we could demonstrate that MES can only be found when an embolic source is present. The finding of MES justifies an extensive clinical and laboratory search for potential embolic sources including extracranial and intracranial colour-coded duplex ultrasound, ECG, Holter-ECG, and TEE.

Objectives – Arterial hypertension is, besides age, the number one risk factor for ischaemic stroke. Patients with arterial hypertension frequently present with additional coexisting vascular risk factors interacting in a complex way. Material and methods – This paper reviews the benefit of antihypertensive treatment, as well as different treatment options of arterial hypertension and their side-effects. Results – Patients with definite arterial hypertension, but also patients with so-called normal or high-normal blood pressure are at increased risk to develop stroke and other cardiovascular complications. Vascular remodelling of small and large vessels provoked by arterial hypertension is the initial step in the development of atherosclerosis and lipohyalinosis. Vascular remodelling can be improved or even normalized by antihypertensive treatment with angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists showing the most convincing effects. Angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists have the lowest rate of side-effects, however, economic restraints hinder their general application. Statins are needed to treat dyslipidaemia. They also lower blood pressure and have a synergistic effect with the above two antihypertensive components in lowering blood pressure. In hypertensive patients, risk of stroke and other cardiovascular complications is determined by the blood pressure level and the presence or absence of target organ damage and the interaction with other risk factors, such as cigarette smoking, dyslipidaemia, and diabetes. These high-risk patients should be treated even more aggressively than usual. Conclusions – In the vast majority of patients and healthy individuals, target blood pressure should be as high as or below 120/80 mmHg to minimize the occurrence of stroke and other cardiovascular complications.

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.

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 > or = 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.

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, chi(2)). The number of microembolic signals predicted the number of acute infarcts on diffusion-weighted magnetic resonance imaging (linear regression, adjusted R(2) =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.

Background. The pathophysiology leading to pulmonary side effects during haemodialysis and haemodiafiltration is not yet fully understood. Chronic microembolization, which can be demonstrated by pulsed Doppler ultrasound, may be one cause. Methods. The study cohort consisted of 24 long-term dialysis patients undergoing haemodialysis (n = 21) and online-haemodiafiltration (n = 3), respectively. The subclavian vein downstream to the venous access was investigated during different phases of the procedure using a 2-MHz pulsed ultrasound device. Results. In all periods investigated (connection, dialysis, disconnection), numerous microembolic signals (MES) were found in the subclavian vein. The numbers of MES detected during haemodiafiltration (314-709 MES per 10 min) were higher than during haemodialysis (0-81 MES per 10 min). Conclusions. The composition (gaseous or solid) and origin (pump, tubing system or shunt) of the microemboli detected remains unclear. Chronic microembolization may be one cause of pulmonary complications of haemodialysis and haemodiafiltration. The detection method described in this article will help us to better understand this process and to determine what role microemboli might play in pulmonary and central nervous system disorders. It may also help to optimize the devices and techniques used.

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 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.

We report the case of a young woman with progressive cognitive decline and epilepsy. She showed ischemic cerebrovascular disease and proximal livedo racemosa. Antiphospholipid antibody (aPL) could not be detected and there were no microemboli on continuous transcranial Doppler ultrasonography monitoring. Histology of cerebral vessels showed intimal hyperplasia in small leptomeningeal venous vessels and micronecrosis of grey and white matter. We subsequently made the diagnosis of aPL-negative Sneddon Syndrome (SNS). Anticoagulation with warfarin could not be initiated because of a drug-resistant epilepsy with the risk of falls and subsequent bleeding; immunosuppression with steroids and azathioprine was ineffective, as was initial antiplatelet therapy with clopidogrel alone. However, when we intensified antiplatelet therapy by combining clopidogrel and ASS, a slowing of disease progression, as assessed by neuropsychological testing and magnetic resonance imaging, was noted on a follow-up after 6 months. Therapeutic options in SNS in both aPL-positive and aPL-negative patients with SNS are discussed.

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.

Background and Purpose: Visualization of normal or pathological flow in the intracranial arteries using transcranial colour-coded duplex sonography (TCCS) is occasionally obstructed by insufficient temporal bone windows, unfavourable insonation angles, or low flow velocities or volumes. SonoVue® (BR1) is a new, long-acting echocontrast agent, which could be helpful in these instances. Methods: SonoVue was studied in two separate multicentre investigations of patients with insufficient bone windows (BR1-014 with 73 patients and BR1-017 with 40 patients) using an identical protocol. The agent was given intravenously as a bolus in four different doses (0.3, 0.6, 1.2 and 2.4 ml). Evaluation was performed on-site and off-site with video clips. Results: The contrast agent was well tolerated. As compared to the precontrast scans, SonoVue facilitated the visualization of vessel patency, stenosis, occlusion, and collateral flow, decreased the need for additional tests, and had an impact on the patient’s treatment. In 66–74%, a non-diagnostic investigation was converted into a diagnostic investigation. The highest dose (2.4 ml) allowed for a clinically useful signal enhancement of a median 1.9–6.3 min. Conclusions: SonoVue at a single dose of 1.2 or 2.4 ml is effective in increasing the detection of normal or pathological flow in the intracerebral arteries in patients who do not have a fully diagnostic unenhanced TCCS examination.

Proper assessment of intracranial arteries by transcranial Doppler sonography (TCD) in patients with intracranial stenoses is occasionally made difficult by an insufficient temporal bone window, an unfavourable insonation angle, or low flow velocity or volume. This condition is frequently found in Chinese. In these cases, echocontrast could be helpful. We investigated 48 temporal windows of 24 acute Chinese stroke patients with insufficient native transtemporal insonation conditions before and after the application of the echo enhancer Levovist® (galactose/palmitic acid) by an injection pump. We classified the signal quality from four segments of the main intracranial arteries: anterior cerebral artery (A1), main stem of the middle cerebral artery (MCA, M1), intracranial segment of the carotid artery (C1), and posterior cerebral artery (P1). The signal quality was classified as follows: 0 = no signal, 1 = poor, envelope curve does not follow spectrum, 2 = adequate, envelope curve follows spectrum. As compared to the pre-contrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography. Before Levovist, only 12% of the segments could be detected, after Levovist 63%. For all arteries, signal quality was better after Levovist, p between 0.0180 and 0.0003. In 3 patients, MCA stenoses with peak systolic Doppler flow velocities above 160 cm/s were found only after Levovist. In patients with poor pre-contrast detection, echocontrast-enhanced TCD allows for more arterial segments to be insonated and for the detection of stenoses unnoted during the non-enhanced investigation.

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 cm 2 , respectively, by ultrasound, and 7.81±1.45 mm and 0.516±0.194 cm 2 , respectively, by planimetric analysis of the unfixed redistended carotid arteries ( R 2 =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.

Electrical cardioversion (CV) of atrial fibrillation (AF) is associated with an increased risk of stroke, and its appropriate prevention is still a matter of debate. It is known that, besides dislodgement of pre-existing intra-atrial thrombi, the ‘stunned’ atrium after CV is an important cause of thrombus formation and subsequent embolism. We investigated whether CV of AF is associated with occurrence of circulating microemboli (ME) representing a sensitive marker of the actual thromboembolic activity. Twenty-nine patients (22 men) aged 54 ± 13 years suffering from valvular (n = 5) or nonvalvular (n = 24) AF were studied. All but 1 patient (with recent-onset AF) had been put on oral anticoagulation (INR >2.0) for at least 3 weeks before and 4 weeks after successful CV. In all patients, exclusion of internal carotid artery stenosis and atrial thrombus was performed prior to CV. Five unilateral 1-hour transcranial Doppler ME monitorings over the middle cerebral artery were performed (1) before CV, and (2) immediately, (3) 4–6 h, (4) 24 h, and (5) 2–4 weeks after CV. Total absence of circulating ME was found before CV as well as during a cumulative monitoring time of 115 h after successful CV. Electrical CV of AF after at least 3 weeks of effective anticoagulation is not associated with occurrence of cerebral circulating ME. This finding requires further investigation including high-risk patients with AF undergoing CV based on different treatment protocols.

Patienten, z.B. fur eine Therapie mit Antikoagulanzien, lassen sich hieraus nicht ableiten. Ein neuer moglicher Ansatz fur eine individuell abgestimmte Behandlung besteht in der Detektion zirkulierender Mikroemboli mittels transkranieller Dopplersonographie. Mit dieser Technik lassen sich kleinste gasformige oder solide Partikel im Blutstrom detektieren, die aufgrund der geringen Grose selbst nicht zu einem klinisch fassbaren thromboembolischen Ereignis fuhren. Ihr Auftreten korreliert aber nach den Ergebnissen zahlreicher Studien eng mit einem klinisch relevanten Embolierisiko. Zur Untersuchung wird ein Schallkopf am Kopf des Patienten befestigt, der dopplersonographisch Flusssignale der Arteria cerebri media erfasst. Diese werden akustisch und optisch auf zirkulierende Mikroemboli ausgewertet. In der Neurologie wird diese Methode bereits fur eine individuelle Risikostratifizierung von Patienten eines Hochrisikokollektivs eingesetzt, z.B. bei der Indikationsstellung zu einer Antikoagulanzientherapie oder Karotisendatherektomie. In der Kardiologie wird die Mikroembolus-Detektion bisher nicht routinemasig eingesetzt und wurde nur in geringem Mas durch klinische Studien evaluiert. In diesem Uberblick sollen die grundlegenden Prinzipien, die methodisch-technischen Voraussetzungen sowie Moglichkeiten und Grenzen der Mikroembolus-Detektion dargestellt werden. Weiterhin werden die wesentlichen Studienergebnisse zum Einsatz dieser Technik bei kardiologischen Erkrankungen und kardiovaskularen Interventionen zusammengefasst.

Background and Purpose —Transcranial color-coded sonography (TCCS) via the suboccipital approach allows direct and continuous visualization of the basilar artery (BA). In this study, we intended to evaluate the ability of native TCCS in visualizing the length of the BA by means of a comparison with postmortem measurements. Methods —The BA was prospectively studied by TCCS shortly before death (median 3 days) in 46 moribund neurological patients (mean±SD age 71.1±13.1 years). The length of the BA was determined by measuring the distance between the vertebrobasilar junction and the deepest available flow signal in the top of the BA. During autopsy, photos of the vertebrobasilar system were taken to evaluate the true anatomic length and variations of the course of BA in situ, eg, straight, curved, or S-shaped. Results —Comparison of the in vivo ultrasound measurements of BA length and postmortem data was possible in 44 of 46 cases. In the 2 remaining patients, the BA was occluded. The mean insonation depth of the vertebrobasilar junction was found at 66.9±7.1 mm. The mean BA length was 21.5±6.8 mm by color-coded duplex and 32.9±6 mm anatomically ( P Conclusions —Color duplex imaging enables correct visualization of the proximal two thirds of the BA, but only exceptionally of its distal one third. A tortuous course of the BA leads to an underestimation of its anatomic length.

In carotid artery stenosis both the degree of the lesion and its plaque morphology are thought to be associated with the carrier's thromboembolic risk. In this study we evaluated the diagnostic preciseness of non-invasively B-mode ultrasound in predicting the histopathological plaque structure. We examined 44 patients with > 50% ICA stenosis by B-mode within 6 weeks prior to carotid endarterectomy. At the affected bifurcations, up to 10 different regions of interest (ROI) per artery were investigated. Plaque appearance was classified according to 6 subtypes considering different ultrasonic plaque features. Postoperatively, plaque specimens were examined histopathologically for their relative content of calcification, fibrous tissue and different soft tissue. B-mode ultrasound was compared with histopathological features in ROI. A total of 265 regions of interest were evaluated. In mainly echolucent types of plaques, atheromatous debris was most frequently seen, whereas fibrosis was rare. Homogeneous echolucent plaques showed a high proportion of cholesterol and/or recent haemorrhage. Thrombosis at the plaque surface was often seen in "completely echolucent" plaque type (each P

The present study was designed to perform follow-up transcranial Doppler investigations for microembolic signals (MES) in acute stroke patients by means of a strict protocol. The number of MES was correlated with stroke etiology and the strength of antithrombotic treatment. Concurrently, we wanted to demonstrate that MES in acute stroke patients are solid in nature and not gaseous. Nineteen patients with middle cerebral artery ischemic events, 16 with completed stroke and 3 with transient ischemic attack (TIA) were investigated within 24 h following the onset of symptoms. Six 1-hour recordings on days 1, 2, 3, 4, 7 and 14 were performed from the affected middle cerebral artery. The four-gate technique and recently established criteria for the identification of MES were used. Eight of 19 patients showed MES in at least one recording. Variability was high and showed no uniform tendency with respect to time since onset of symptoms or treatment. All 3 patients with internal carotid artery dissection showed MES. In 3 patients with lacunar stroke, no MES were detected. Two patients with MES suffered recurrent TIAs during the observation period, whereas none of the patients without MES suffered a recurrent ischemic event. In the acute phase following stroke, ongoing, emerging and vanishing embolization in some patients may reflect individual active processes of remodelling, healing and disruption or disappearance of the embolic source.

Background: The anterior communicating artery is a key collateral pathway in patients with internal carotid artery (ICA) occlusions. Diagnostic balloon or manual occlusion of the ICA is a qualified test for the collateral function of the circle of Willis. The aim of our study was to test whether transcranial Doppler sonography (TCD) with manual carotid compression is able to predict the degree of cross-over flow and tolerance of ICA occlusion. Methods: A prospective study was performed on 88 patients suffering from neck tumors or inoperable ICA aneurysms with planned ligation or permanent balloon occlusion of the ICA. Preceding a balloon occlusion lasting 20 min we performed TCD with manual carotid compression test. Insufficient cross-over flow during transient carotid occlusion was defined angiographically as missing opacification of the middle cerebral artery (MCA) after selective injection of contrast media in the contralateral ICA, and sonographically as a decrease greater than 60% in flow velocity of the MCA ipsilateral to the carotid occlusion. Results: TCD and angiography could be compared in 70 of 88 patients. Angiography showed no or insufficient collateral flow in 26%. All patients (n = 10) with a decrease in MCA velocity greater than 60% on angiography showed missing or poor cross-over flow. A greater than 50% increase in the anterior cerebral artery (ACA) predicted moderate or good cross-over flow in 98%. Clinical observation revealed 11 transient neurological deficits. Eight of them showed insufficient cross-over flow angiographically and sonographically. In 2 of 11 only TCD revealed such low collateral supply. Neither technique predicted hemodynamic ischemia in only 1 of the 11. Conclusion: TCD with carotid compression test is a valid method for predicting interhemispheric flow and clinically relevant hemodynamic compromise in cases of occlusion of the ICA.

B-waves are rhythmic oscillations of intracranial pressure (ICP) with a wavelength of 0.5-2 min. These oscillations are accompanied by corresponding fluctuations of arterial blood pressure (BP). There is controversy in the literature whether the ICP oscillations precede or follow the BP oscillations. This relationship, however, is important for the understanding of the origin and the interactions of ICP B-waves with other parameters. ICP and BP were monitored continuously for one night in nine patients with suspected symptomatic normal pressure hydrocephalus (NPH). Forty-five B-waves were identified and the time delays between the peaks and the onsets of B-waves and their BP-equivalents were measured. The mean (+/- standard deviation) of the time delays between the peaks of ICP B-waves and corresponding BP-oscillations was 4.2 +/- 2.4 sec and between the onsets of the oscillations 10.3 +/- 6.6 sec. In all but two B-waves, the ICP peak preceded the BP peak, in all the 45 B-waves the onset of the ICP increase preceded the BP increase (p0.004). Our study demonstrates that ICP B-waves precede concomitant changes in BP by several seconds.

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.

Background and Purpose —Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and different provocation procedures. Currently, data on an appropriate time window for the appearance of contrast bubbles in the TCD recording after the injection of the contrast medium and the comparison of different provocation maneuvers to increase right-to-left shunting are insufficient. Methods —Forty-six patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with 6 injection modes was applied in a randomized way: (1) injection of 10 mL of agitated saline without Valsalva maneuver, (2) injection of 10 mL of agitated saline with Valsalva maneuver, (3) injection of 10 mL of a commercial galactose-based contrast agent (Echovist) without Valsalva maneuver, (4) injection of 10 mL of Echovist with Valsalva maneuver, (5) injection of 10 mL of Echovist with standardized Valsalva maneuver, and (6) injection of 10 mL of Echovist with coughing. Results —In 20 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt-positive). Sixteen patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 10 patients were only positive on at least 1 TCD investigation but negative during TEE. The amount of microbubbles detected in the various tests decreased in the following order: Echovist and Valsalva maneuver, Echovist with coughing, Echovist and standardized Valsalva maneuver, saline with Valsalva maneuver, Echovist, and saline. With a time window of 20 to 25 seconds for the bubbles to appear in the TCD recording and with a sequence of first Echovist and Valsalva maneuver and then Echovist with coughing, all shunts were reliably identified with a specificity of 65% compared with TEE as the traditional gold standard. The time of first microbubble appearance was not helpful to distinguish between shunts detected on TEE and other shunts. Conclusions —TCD performed twice with 2 provocation maneuvers using Echovist is a sensitive method to identify cardiac right-to-left shunts also identified by TEE.

Objective: Embolus detection by transcranial Doppler ultrasound is very time consuming and semi-automated detection is mandatory. The device studied, a TC4040, Nicolet-EME, uses the four-gate technique and allows for audiovisual off-line verification of the recorded events. Methods: Twenty controls, 10 patients with mechanical prosthetic heart valves and 12 patients with occlusive carotid artery disease were investigated by transcranial colour-coded duplex sonography and, subsequently, underwent a 1-h unilateral embolus detection from the middle cerebral artery using four-gate TCD. We investigated the Doppler spectrum background, microembolic signals (MES) and artefacts produced. A detection threshold of 5 dB or more was defined taking into account natural fluctuations of the Doppler spectrum. Results: Sensitivity of the software was 91.9% and observer–software agreement on MES was 7.8% in the valve patients, and 77.7% and 7.5% in the carotid artery disease patients, respectively. Weaker MES were more likely not to be detected in all four channels. The artefact signal rejection rate was 62%. MES produced either positive or zero time delays in adjacent channels. Artefact signals produced either no delay, or a positive or a negative time delay. Duration of MES ranged from 1–88 ms. Conclusions: Besides refined recognition of MES using the time delay, four gates give faint MES no less than four opportunities to overcome the detection threshold. With this device’s satisfying sensitivity, regions of interest in a 1-h recording can audiovisually be evaluated off-line in a few minutes by an investigator.

Background and Purpose —Cardiac right-to-left shunts can be identified by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and by transesophageal echocardiography (TEE). Systematic data are available on neither the reproducibility of contrast TCD, the comparison of different contrast agents, nor the comparison of simultaneous bilateral to unilateral recordings. Furthermore, we assessed the side distribution of thus provoked artificial cardiac emboli. Methods —Fifty-four patients were investigated by TEE and by bilateral TCD of the middle cerebral artery. The following protocol was performed twice: injection of 9 mL of agitated saline without Valsalva maneuver, injection of 9 mL of agitated saline with Valsalva maneuver, injection of 5 mL of a commercial galactose-based contrast agent without Valsalva maneuver, and injection of 5 mL of the galactose-based contrast agent with Valsalva maneuver. Results —In 18 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-nine patients were negative in both investigations, 1 was positive on TEE and negative on TCD, and 6 patients were only positive on TCD. Both bilateral and repeated recordings increased the sensitivity of contrast TCD. There was a symmetrical distribution of microembolic signals in the right and left middle cerebral artery. Conclusions —TCD performed twice and with the use of saline or a galactose-based contrast agent is a sensitive method in the identification of cardiac right-to-left shunts also identified by TEE. The cardiac microemboli in this study did not show any side preference for one of the middle cerebral arteries.

Background and Purpose —Embolus detection using transcranial Doppler ultrasound is a useful method for the identification of active embolic sources in cerebrovascular diseases. Automated embolus detection systems have been developed to reduce the time of evaluation in long-term recordings and to provide more “objective” criteria. The purpose of this study was to evaluate the critical conditions of automated embolus detection by means of a trained neural network (EMBotec V5.1 One, STAC GmbH, Germany). Methods —In 11 normal volunteers and in 11 patients with arterial or cardiac embolic sources, we performed simultaneous recordings from both middle or both posterior cerebral arteries. In the normal subjects, we produced 1342 additional artifacts to use the latter as false-positives. Detection of microembolic signals (MES) was done offline from digital audiotapes (1) by an experienced blinded investigator used as a reference and (2) by a trained 3-layer–feed-forward neural network. Results —From the 1342 provoked artifacts the neural network labeled 216 events as microemboli, yielding an artifact rejection of 85%. In microembolus-positive patients the neural network detected 282 events as emboli, among these 122 signals originating from artifacts; 58 “real” events were not detected. This result revealed a sensitivity of 73.4% and a positive predictive value of 56.7. The spectral power of the detected artifact signals was 16.5±5 dB above background signal. MES from patients with artificial heart valves had a spectral power of 6.4±2.1 dB; however, in patients with other sources of emboli, MES had an averaged energy reflection of 2.7±0.9 dB. Conclusions —The neural network is a promising tool for automated embolus detection, the formal algorithm for signal identification is unknown. However, extreme signal qualities, eg, strong artifacts, lead to misdiagnosis. Similar to other automated embolus detection systems, good signal quality and verification of MES by an experienced investigator is still mandatory.

Abstract —Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Transcranial Doppler sonography has become a widely used method for detecting cerebral circulating microemboli (ME) arising from the carotid arteries or the heart. Yet, studies on subgroups of patients with distinct cardiac sources of embolism are still limited. The same holds true for investigations on the relationship between microembolization and hemorheological parameters. A total of 142 patients suffering from left ventricular aneurysm (LVA, n = 52), severe left ventricular dysfunction (LVD, n = 43), or chronic atrial fibrillation (AF, n = 47) were enrolled in this study. All patients had been neurologically asymptomatic for at least 1 month. Further relevant embolic disorders of the carotid arteries and the heart had been excluded. Unilateral monitoring for ME over the middle cerebral artery was performed for 30 min. Blood was drawn after each monitoring for determination of plasmatic coagulation parameters, as well as plasma viscosity, and platelet reactivity. The overall prevalence of ME was 31%, with a slightly higher prevalence in patients with LVA (37%) compared to patients suffering from AF (30%) or LVD (26%). With single-factor analysis, a trend towards higher ME prevalences was found with (a) a history of remote embolic events, (b) ineffective anticoagulation, (c) increased platelet aggregation, or (d) increased plasma viscosity (all p > 0.1). The combination of ineffective anticoagulation in conjunction with increased platelet aggregation, however, was significantly associated with higher ME rates even after adjustment for other factors by logistic regression analysis. Our results demonstrate a low ongoing microembolic activity in asymptomatic patients suffering from LVA, LVD and AF. An activated plasmatic coagulation system together with increased platelet aggregation contributes to ME generation.

Besides the degree of carotid artery stenosis, the composition of the plaque may help to predict the thromboembolic risk. Low echogenicity on ultrasound and hemorrhage into the atheroma demonstrated histopathologically have been shown to be associated with a higher risk of embolism. Twenty-nine consecutive patients with carotid artery stenosis and scheduled for carotid endarterectomy were investigated preoperatively by B-mode ultrasound. Post-operatively the endarterectomy specimens were examined histopathologically. Neither atheroma with hemorrhage nor atheroma without hemorrhage were significantly associated with echolucent ultrasound presentation. Out of the 10 lesions echolucent and homogeneous on ultrasound, six corresponded to atheroma with hemorrhage, two corresponded to atheroma with hemorrhage plus thrombus, two corresponded to fibrous plaque plus thrombus, and one corresponded to pure thrombus. Out of the 4 lesions heterogeneous and predominantly echolucent, one corresponded to atheroma without hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage, one corresponded to atheroma with hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage plus fibrous plaque. Seven out of the 18 atheromas with hemorrhage did not present as purely or predominantly echolucent lesions, six of them were even homogeneously echogenic. Plaque surface could not reliably be predicted by ultrasound. In our study, there was no significant correlation between ultrasound and histology of the lesion.

Background and Purpose Different frequencies of asymptomatic Doppler embolic signals have been reported in studies. There has been concern that different criteria for identification may account for some of this variation. A previous reproducibility study between two centers found good agreement, but no studies among large numbers of centers have been performed. We performed an international reproducibility study among nine centers, each of which had published recent studies of embolic signal detection in peer-reviewed journals. Methods Each center performed blinded analysis of a taped audio Doppler signal composed of transcranial Doppler middle cerebral artery recordings from 6 patients with symptomatic carotid artery stenosis. The exact time of any embolic signal was recorded. Six centers also measured the intensity increase of any embolic signals detected. Interobserver agreement was determined by a method based on the proportion of specific agreement. Results Seven centers reported between 39 and 55 signals, but one center reported 142 embolic signals. The probability of agreement between observers was .678, which rose to .791 when the data from the highest reporting center were excluded. Introducing a decibel threshold resulted in a significant increase in the probability of agreement; a decibel threshold of >7 dB resulted in a probability of agreement of .902. Intensity measurements made by different centers were usually highly correlated, but this was not always the case, and 3 of the 15 correlations were not significant. The absolute values of the intensities measured varied between centers by as much as 40%. Conclusions Although most centers report similar numbers of embolic signals, some use less specific criteria and report more events. The use of a decibel threshold improves reproducibility. However, intensity thresholds developed by one center cannot be directly transferred without validation to another center; differing methods of measurement are being used, and this results in different intensity values for the same embolic signals, even when the same equipment is used.

OBJECTIVE: To compare the occurrence of periventricular lesions (PVLs) and deep white matter lesions (DWMLs) in elderly patients with idiopathic normal pressure hydrocephalus (NPH) and in an age-matched control group. METHODS: PVLs and DWMLs were evaluated using T2-weighted magnetic resonance scans of 37 patients with idiopathic NPH and 35 participants from an age-matched control group. All patients with idiopathic NPH included in this study improved after shunting. The control group consisted of 16 healthy elderly persons and 19 patients with depression. To allow quantitative assessment and comparison, scores for PVLs and DWMLs were calculated. Furthermore, possible correlations between white matter lesion scores, ventricular width, and age were investigated. RESULTS: There was a significantly higher incidence of PVLs and DWMLs in patients with idiopathic NPH. The mean total PVL was 12.1 (range, 2-24) in the NPH group and 3.9 (range, 0-10) in the control group (P < 0.001). The mean total DWML score was 12.9 (range, 3-24) in the NPH group and 4.5 (range, 0-16) in the control group (P < 0.001). There were significant correlations between the severity of PVL and DWML scores in both groups. Only a weak positive correlation between the severity of DWMLs and age was found in the NPH group, whereas this correlation was significant in the control group. There was a significant negative correlation between the width of the anterior horns and the severity of both PVLs and DWMLs in patients with NPH; however, positive correlations were found in the control group. CONCLUSION: Elderly patients with idiopathic NPH have more frequent and more severe PVLs and DWMLs than people in age-matched control groups. Our data suggest a frequent co-occurrence of idiopathic NPH and vascular subcortical encephalopathy; however, they do not support a direct causal relationship.

Background and Purpose Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood. Methods Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber. Results Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa). Conclusions The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.