Randomised controlled trial to evaluate the efficacy and usability of a computerised phone-based lifestyle coaching system for primary and secondary prevention of stroke.

BACKGROUND: One of the most effective current approaches to preventing stroke events is the reduction of lifestyle risk factors, such as unhealthy diet, physical inactivity and smoking. In this study, we assessed the efficacy and usability of the phone-based Computer-aided Prevention System (CAPSYS) in supporting the reduction of lifestyle-related risk factors. METHODS: A single-centre two-arm clinical trial was performed between January 2013 and February 2014, based on individual follow-up periods of six months with 94 patients at high risk of stroke, randomly assigned to an intervention group (IC: 48; advised to use the CAPSYS system) or a standard care group (SC: 46). Study parameters, such as blood pressure, blood values (HDL, LDL, HbA1c, glycaemia and triglycerides), weight, height, physical activity as well as nutrition and smoking habits were captured through questionnaires and medical records at baseline and post-intervention and analysed to detect significant changes. The usability of the intervention was assessed based on the standardised System Usability Scale (SUS) complemented by a more system-specific user satisfaction and feedback questionnaire. RESULTS: The statistical evaluation of primary measures revealed significant decreases of systolic blood pressure (mean of the differences = -9 mmHg; p = 0.03; 95% CI = [-17.29, -0.71]), LDL (pseudo-median of the differences = -7.9 mg/dl; p = 0.04; 95% CI = [-18.5, -0.5]) and triglyceride values (pseudo-median of the differences = -12.5 mg/dl; p = 0.04; 95% CI = [-26, -0.5]) in the intervention group, while no such changes could be observed in the control group. Furthermore, we detected a statistically significant increase in self-reported fruit and vegetable consumption (pseudo-median of the differences = 5.4 servings/week; p = 0.04; 95% CI = [0.5, 10.5]) and a decrease in sweets consumption (pseudo-median of the differences = -2 servings/week; p = 0.04; 95% CI = [-4, -0.00001]) in the intervention group. The usability assessment showed that the CAPSYS system was, in general, highly accepted by the users (average SUS score: 80.1). CONCLUSIONS: The study provided encouraging results indicating that a computerised phone-based lifestyle coaching system, such as CAPSYS, can support the usual treatment in reducing cerebro-cardiovascular risk factors and that such an approach is well applicable in practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02444715.

Stroke awareness in luxemburg: deficit concerning symptoms and risk factors.

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.

Advice on lifestyle changes (diet, red wine and physical activity) does not affect internal carotid and middle cerebral artery blood flow velocity in patients with carotid arteriosclerosis in a randomized controlled trial.

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.

A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial.

BACKGROUND: Physical exercise and a Mediterranean diet improve serum lipid profile. The present work studied whether red wine has an effect on top of a lipid-lowering lifestyle in patients with carotid atherosclerosis. METHODS: A prospective randomised unblinded trial was performed from 2009 to 2011 in 108 patients with carotid atherosclerosis, 65% of whom were already on statin therapy with a low mean LDL of 104.9 mg/dl. Half of them were advised to follow a modified Mediterranean diet and to perform moderate physical exercise during 30 min/day (lifestyle changes) for 20 weeks. Within these two groups half of the patients were randomised either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. RESULTS: LDL was significantly lowered by 7% in the lifestyle-changes group compared to the no-lifestyle-changes group (p = 0.0296) after 20 weeks. Lifestyle changes lowered the LDL/HDL ratio after 20 weeks by 8% (p = 0.0242) and red wine independently by 13% (p = 0.0049). The effect on LDL/HDL ratio after 20 weeks was, however, more pronounced in the non-LC group. Total cholesterol (-6%; p = 0.0238) and triglycerides (-13%; p = 0.0361) were lowered significantly by lifestyle changes after 20 weeks compared to the no-lifestyle-changes group. Lipoprotein (a) was not significantly affected by any intervention. The given results are per ITT analysis. CONCLUSIONS: Lifestyle changes including a modified Mediterranean diet and physical exercise as well as a glass of red wine daily improve independently the LDL/HDL ratio in patients with carotid arteriosclerosis even though the vast majority of them was already on statin therapy.

A daily glass of red wine and lifestyle changes do not affect arterial blood pressure and heart rate in patients with carotid arteriosclerosis after 4 and 20 weeks.

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.

Activated monocytes capture platelets for heterotypic association in patients with severe carotid artery stenosis.

Inflammation 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.

Microembolic signals on transcranial Doppler ultrasound are correlated with platelet activation markers, but not with platelet-leukocyte associates: a study in patients with acute stroke and in patients with asymptomatic carotid stenosis.

BACKGROUND: The in vivo correlates of microembolic signals (MES) are still unknown. Platelet-associates (PA) with monocytes or granulocytes or platelet aggregates only may represent these correlates. METHODS: Thirty patients with asymptomatic carotid stenosis >50% and 16 patients with acute (<4 days) atherothrombotic stroke were investigated. PA, P-selectin and thrombospondin expressions on platelets were assessed by flow cytometry. Soluble P-selectin (sPS) levels were assessed. MES detections were performed by transcranial Doppler sonography for 1 hour. PA, P-selectin and thrombospondin expressions on platelets and sPS levels were compared between MES-positive (MES+) and MES-negative (MES-) patients. RESULTS: Eight patients (27%) with asymptomatic carotid stenosis had 1-26 MES/h. Degree of stenosis was 78 +/- 10% in MES- and 88 +/- 8% in the MES+ (p=0.01). There were no differences in percentages of PA. P-selectin and thrombospondin surface expression was lower in MES+, but this was not significant. sPS levels were higher in MES+ (122 +/- 27 ng/ml versus 80 +/- 25 ng/ml in MES-, p=0.01). Seven (44%) patients with stroke had 1-39 MES/h. There were no differences in percentages of PA. MES+ had higher sPS levels (178 +/- 43 versus 121 +/- 44 ng/ml, p=0.02) and less P-selectin surface expression than MES- (9.0 +/- 3.4 versus 4.5 +/- 1.6%, p=0.004). CONCLUSION: High levels of sPS in MES+ and lower expression of platelet activation markers on platelets' surface suggest shedding of activation markers from the platelets' surface and thus enhanced activation of platelets of MES+ compared with MES-. PA are probably not the clinical correlates of MES, but platelets seem to be the main cellular element of solid cerebral microemboli.

Clinical utility of contrast-enhanced ultrasound in neurosonology.

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.

[Restless legs syndrome]. / Le syndrome des jambes sans repos (restless legs syndrome).

About 7% of the population are affected by the restless legs syndrome (RLS). The most invalidating subjective complaints are dysesthesia / pain / an urge to move the legs (46%), an alteration of sleep (38%), and difficulties in performing activities of daily life (7%). The onset of the disease is variable, ranging from childhood (often unrecognised) to old age. The clinical course is generally chronic with phases of spontaneous remission. The cause of RLS is probably mainly genetic with a dysfunction of iron and dopamine metabolism accentuated by peripheral factors (neuropathy, radiculopathy, and temperature). There are secondary forms of RLS, such as iron deficiency (under debate), side effects of drugs (that can be stopped), renal insufficiency, radiculopathy, and neuropathy. RLS can come up during pregnancy, in particular in the last trimenon. Treatment of aggravating factors and sleep hygiene are general measures. Drug treatment of the RLS comprises levodopa, dopaminergic drugs, opioids, and antiepileptic drugs; however, drug treatment is only necessary in about a third of the affected.

Diffusion weighted MRI imaging and MES detection in the assessment of stroke origin.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial.

BACKGROUND AND PURPOSE: The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. METHODS: As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps+/-values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator). RESULTS: For the reference tape, the cumulative ps+/-value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative rho=0.84; P<0.001). CONCLUSIONS: Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.

Benefit of echocontrast-enhanced transcranial arterial color-coded duplex ultrasound.

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.

Surgical closure of combined symptomatic patent foramen ovale and atrial septum aneurysm for prevention of recurrent cerebral emboli.

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.

Comparison of a 1-MHz and a 2-MHz probe for microembolus detection using transcranial Doppler ultrasound.

OBJECTIVES: 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. METHODS: After defining detection thresholds of > or = 12 dB (1 MHz) and > or = 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. RESULTS: 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. DISCUSSION: 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.

Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial.

BACKGROUND: Evidence for efficacy of dual antiplatelet therapy in stroke is limited. Symptomatic carotid stenosis patients are at high risk of early recurrent stroke. In this group, asymptomatic microembolic signals (MES), detected by transcranial Doppler ultrasound (TCD), are markers of future stroke and transient ischemic attack (TIA) risk. They offer a surrogate marker to evaluate antiplatelet therapy, but no multicenter study has evaluated the feasibility of this approach. METHODS AND RESULTS: Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) is a randomized, double-blind study in subjects with recently symptomatic > or =50% carotid stenosis. Patients were screened with TCD, and if MES were detected, they were randomized to clopidogrel and aspirin or aspirin monotherapy. Repeated TCD recordings were made on days 2 and 7. MES were detected in 110 of 230 patients by online analysis at baseline, of whom 107 were randomized. Intention-to-treat analysis revealed a significant reduction in the primary end point: 43.8% of dual-therapy patients were MES positive on day 7, as compared with 72.7% of monotherapy patients (relative risk reduction 39.8%; 95% CI, 13.8 to 58.0; P=0.0046). The secondary end point of MES frequency per hour was reduced (compared with baseline) by 61.4% (95% CI, 31.6 to 78.2; P=0.0013) in the dual-therapy group at day 7 and by 61.6% (95% CI, 34.9 to 77.4; P=0.0005) on day 2. There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis; 2 additional ipsilateral TIAs occurred before treatment started. MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without (mean+/-SD: 24.4+/-27.7 versus 8.9+/-11.5 per hour; P=0.0003). CONCLUSIONS: In patients with recently symptomatic carotid stenosis, combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization. Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies.

Measuring carotid artery stenosis--comparison of postmortem arteriograms with the planimetric gold standard.

OBJECTIVE: Five different calliper methods for assessing the degree of carotid artery stenosis and visual estimation ("eyeballing") of postmortem carotid arteriograms were compared with the planimetric gold standard of the area reduction at the site of the stenosis. METHODS: During autopsy 53 carotid specimens were removed in toto from 31 neurological patients. Carotid arteries were ligated and redistended to a physiological degree for standardised three-plane arteriography. Afterwards, the entire specimen was filled with an embedding medium under the same conditions and sectioned. Slices at the site of stenoses were histologically processed. Computerised planimetric analysis of the lumen area reduction was performed and compared with the arteriographic findings. Arteriograms were evaluated by two independent observers by means of linear Common Carotid Artery (CC), the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and squared measurements (NASCET2, ECST2) after applying the pi r2 function. Further, three independent observers performed eyeballing of the degree of stenosis from the postmortem arteriographies. RESULTS: Planimetry was carried out in 29 internal carotid artery (ICA) and 17 common carotid artery (CCA) stenoses ranging from 8.5 to 100%. The smallest mean differences of the degree of stenosis in % between planimetry and arteriography were -0.5 and 0.6%. The narrowest 95 %-limits of agreement covered a range of +/-24.1 and 26.3% of stenoses, and the highest correlation coefficients were both 0.9 for the CC and ECST2 techniques, respectively. By eyeballing, the degree of stenosis was underestimated by 13.5 to 15.8% on average. The narrowest limits of agreement between two observers for eyeballing covered a range of 35%. CONCLUSION: Three-plane arteriography has only a moderate accuracy and reproducibility in detecting and measuring carotid artery stenosis independent of the technique of measurement used.

[Cerebral apoplexy--importance of diagnosis and therapy in acute stroke]. / De Gehirschlag--en Noutfall Bedeutung, Diagnostik und Therapie des akuten Schlaganfalls.

Every day occur about 4 strokes in the Grand-Duchy of Luxemburg. Stroke is the third cause of death and the first cause of acquired handicap. Stroke constitutes a major individual and social problem. Stroke and TIA are neurological emergency conditions that warrant immediate hospitalisation on a stroke unit, where a dedicated equipe of neurologists, nurses, speech and occupational therapists, physiotherapists and social workers in collaboration with other medical and surgical specialties provide up-to-date diagnostic and therapeutic measures. These include the diagnostic work-up of stroke aetiology and the vascular status, monitoring to ensure the maintenance of homeostasis, thrombolysis and revascularisation, antithrombotic drug treatment relying on individual stroke pathophysiology, treatment of risk factors and early rehabilitation. By treatment on a stroke unit, death and disability can be reduced by 27%, in the case of intravenous thrombolysis even by 45%.

Microembolic signal predicts recurrent cerebral ischemic events in acute stroke patients with middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Cerebral embolism is a common cause of stroke. Microembolic signals (MES) detected by transcranial Doppler represent ongoing embolisms, but the lack of reliable data about its clinical relevance hinders its widespread use in clinical practice. METHODS: We prospectively monitored 114 consecutive acute ischemic stroke patients with middle cerebral artery (MCA) stenosis for MES. The signals on digital audio tape were analyzed by an independent observer who was blinded to all other data. All patients were followed-up for the occurrence of recurrent stroke or transient ischemic attack (TIA) in the indexed MCA territory. RESULTS: MES was detected in 25 (22%) patients. The mean number of MES was 18 (range, 1 to 102). MES were more common in patients with severe stenosis (10/21, 48%) than in those with mild-moderate stenosis (4/26, 15%) (Pearson chi2 P=0.02). During follow-up for a mean of 13.6 months (range, 1 to 32), 12 (12%) patients had further ischemic events (10 strokes and 2 TIAs) in the affected MCA region during follow-up. Among these, 7 (58%) had recurred within 1 month (1 recurred within 1 week, the other 6 patients had recurrences in week 3 or 4 after discharge), 3 within 6 months, 1 within 6 to 12 months, and the remaining 1 recurred after 1 year. The presence of MES was the only predictor of a further ischemic stroke/TIA by Cox regression (adjusted odds ratio, 8.45; 95% CI, 1.69 to 42.22; P=0.01) even after controlling for age, sex, diabetes, hypertension, previous stroke, smoking, and acute treatment. CONCLUSIONS: In acute stroke patients with MCA stenosis, MES predicts further cerebral ischemia. This procedure should be considered as part of routine investigation and might identify a group of patients who are most likely to benefit from antithrombotic treatment.

Clinical utility of echocontrast agents in neurosonology.

INTRODUCTION: Neurosonological investigations of the extracranial and intracranial brain supplying arteries are helpful in the assessment of stroke and stroke-prone patients. METHODS: In this paper we review the indications, application and advantages of second-generation (gas-filled) microbubble contrast agents such as SonoVue. RESULTS: 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. CONCLUSIONS: 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.