Photon echoes using atomic frequency combs in Pr:YSO - experiment and semiclassical theory.

Photon echoes in rare-earth-doped crystals are studied to understand the challenges of making broadband quantum memories using the atomic frequency comb (AFC) protocol in systems with hyperfine structure. The hyperfine structure of Pr3+ poses an obstacle to this goal because frequencies associated with the hyperfine transitions change the simple picture of modulation at an externally imposed frequency. The current work focuses on the intermediate case where the hyperfine spacing is comparable to the comb spacing, a challenging regime that has recently been considered. Operating in this regime may facilitate storing quantum information over a larger spectral range in such systems. In this work, we prepare broadband AFCs using optical combs with tooth spacings ranging from 1 MHz to 16 MHz in fine steps, and measure transmission spectra and photon echoes for each. We predict the spectra and echoes theoretically using the optical combs as input to either a rate equation code or a density matrix code, which calculates the redistribution of populations. We then use the redistributed populations as input to a semiclassical theory using the frequency-dependent dielectric function. The two sets of predictions each give a good, but different account of the photon echoes.

TCD-Profiling Using AVERAGE. A New Technique to Evaluate Transcranial Doppler Ultrasound Flow Spectra of Subjects with Cerebral Small Vessel Disease.

BACKGROUND: There is an unmet need for screening methods to detect and quantify cerebral small vessel disease (SVD). Transcranial Doppler ultrasound (TCD) flow spectra of the larger intracranial arteries probably contain relevant information about the microcirculation. However, it has not yet been possible to exploit this information as a valuable biomarker. METHODS: We developed a technique to generate normalized and averaged flow spectra during middle cerebral artery Doppler ultrasound examinations. Second, acceleration curves were calculated, and the absolute amount of the maximum positive and negative acceleration was calculated. Findings were termed 'TCD-profiling coefficient' (TPC). Validation study: we applied this noninvasive method to 5 young adults for reproducibility. Degenerative microangiopathy study: we also tested this new technique in 30 elderly subjects: 15 free of symptoms but with MRI-verified presence of cerebral SVD, and 15 healthy controls. SVD severity was graded according to a predefined score. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) study: TPC values of 10 CADASIL patients were compared with those of 10 healthy controls. Pulse wave analysis and local measurements of carotid stiffness were also performed. CADASIL patients were tested for cognitive impairment with the Montreal Cognitive Assessment scale. White matter and basal ganglia lesions in their cerebral MRI were evaluated according to the Wahlund score. RESULTS: Validation study: the technique delivered reproducible results. Degenerative microangiopathy study: patients with SVD had significantly larger TPCs compared with controls (SVD: 2,132; IQR 1,960-2,343%/s vs. CONTROLS: 1,935; IQR 1,782-2,050%/s, p = 0.01). TPC values of subjects with SVD significantly correlated with SVD severity scores (R = 0.58, n = 15, p < 0.05). CADASIL study: TPC values of CADASIL patients were significantly higher than values of the controls (CADASIL: 2,504; IQR 2,308-2,930%/s vs. controls 2,084; 1,839-2,241%/s, p = 0.008), and also significantly higher than the TPC values of the patients with SVD from the degenerative microangiopathy study (p = 0.007). CADASIL patients had significantly worse cognitive test results than healthy controls. CONCLUSION: TCD-profiling detects impairment of the cerebral microcirculatory state. The suitability of the TCD-profiling for the evaluation of cerebral microangiopathy was confirmed.

Supraventricular premature beats and short atrial runs predict atrial fibrillation in continuously monitored patients with cryptogenic stroke.

BACKGROUND AND PURPOSE: Supraventricular premature beats (SPBs) may help to assess the risk of atrial fibrillation (AF) in patients with cryptogenic stroke and therefore guide therapy. METHODS: An internal loop recorder was implanted in consecutive patients with acute cryptogenic stroke. The occurrence and quantity of SPBs and short supraventricular runs (SVRs) in 24-hour ECG in patients with and without future AF were analyzed. We evaluated the relative risk of the upper quartile of SPB and SVR patients against the remainder and used binary logistic regression to evaluate a possible independent influence of SPBs and SVRs on AF occurrence. RESULTS: Twelve of 70 included patients (mean age, 59±13 years) experienced development of AF during a mean monitoring duration of 536±212 days. Patients with AF had a median of 22.8 SPBs/h versus 1.2 SPBs/h (P<0.0001) in patients without AF and a median of 0.7 SVRs/h (AF) versus 0 SVR/h (non-AF). Patients in the upper quartile of SPBs (>14.1/h) and SVRs (>0.2/h) demonstrated a relative risk of 4.0 (95% confidence interval, 1.1-14.6; P=0.04) and 6.9 (95% confidence interval, 1.8-26.7; P=0.005) for future AF, respectively. In binary logistic regression, SPBs (P=0.02) and SVRs (P=0.05) remained significant independent predictors for occurrence of AF. CONCLUSIONS: Numerous SPBs and SVRs demonstrated a high risk for future AF in patients with cryptogenic stroke.

Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2.

OBJECTIVE: The outbreak of hemolytic-uremic syndrome and diarrhea caused by Shiga toxin-producing Escherichia coli O104:H4 in Germany during May to July 2011 involved severe and characteristic neurologic manifestations with a strong female preponderance. Owing to these observations, we designed a series of experimental studies to evaluate the underlying mechanism of action of this clinical picture. METHODS: A magnetic resonance imaging and electroencephalographic study of patients was performed to evaluate the clinical picture in detail. Thereafter, combinations of different experimental settings, including electrophysiological and histological analyses, as well as calcium imaging in brain slices of rats, were conducted. RESULTS: We report on 7 female patients with neurologic symptoms and signs including bilateral thalamic lesions and encephalopathic changes indicative of a predominant involvement of the thalamus. Experimental studies in rats revealed an enhanced expression of the Shiga toxin receptor globotriaosylceramide on thalamic neurons in female rats as compared to other brain regions in the same rats and to male animals. Incubation of brain slices with Shiga toxin 2 evoked a strong membrane depolarization and intracellular calcium accumulation in neurons, associated with neuronal apoptosis, predominantly in the thalamic area. INTERPRETATION: These findings suggest that the direct cytotoxic effect of Shiga toxin 2 in the thalamus might contribute to the pathophysiology of neuronal complications in hemolytic-uremic syndrome.

Modified phased radiofrequency ablation of atrial fibrillation reduces the number of cerebral microembolic signals.

AIMS: Phased radiofrequency (RF) ablation for atrial fibrillation is associated with an increased number of silent cerebral lesions on magnetic resonance imaging and cerebral microembolic signals (MESs) on transcranial Doppler ultrasound imaging compared with irrigated RF. The increased rate of embolic events may be due to a specific electrical interference of ablation electrodes attributed to the catheter design. The purpose of this study was to elucidate the effect of deactivating the culprit electrodes on cerebral MESs. METHODS AND RESULTS: Twenty-nine consecutive patients (60 ± 11 years, 10 female) underwent their first pulmonary vein isolation using phased RF energy. Electrode pairs 1 or 5 were deactivated to avoid electrical interference between electrodes 1 and 10 ('modified'). Detection of MESs by transcranial Doppler ultrasound was performed throughout the procedure to assess cerebral microembolism. Results were compared with the numbers of MESs in 31 patients ablated using all available electrodes ('conventional') and to 30 patients undergoing irrigated RF ablation of a previous randomized study. Ablation with 'modified' phased RF was associated with a marked decrease in MESs when compared with 'conventional' phased RF (566 ± 332 vs. 1530 ± 980; P < 0.001). This difference was mainly triggered by the reduction of MES during delivery of phased RF energy, resulting in MES numbers comparable to irrigated RF ablation (646 ± 449; P = 0.7). Total procedure duration as well as time of RF delivery was comparable between phased RF groups. Both times, however, were significantly shorter compared with the irrigated RF group (123 ± 28 vs. 195 ± 38; 15 ± 4 vs. 30 ± 9; P < 0.001, respectively). CONCLUSION: Pulmonary vein isolation with 'modified' phased RF is associated with a decreased number of cerebral microembolism especially during the delivery of ablation impulses, supporting the significance of electrical interference between ablation electrodes 1 and 10. Deactivation of electrode pairs 1 or 5 might increase the safety of this approach without an increase in procedure duration or RF delivery time.

Occult atrial fibrillation in cryptogenic stroke: detection by 7-day electrocardiogram versus implantable cardiac monitors.

BACKGROUND AND PURPOSE: A significant number of patients with cryptogenic stroke suffer from intermittent atrial fibrillation (iAF) which was not detected during the standard diagnostic procedures. We investigated whether implantation of an insertable cardiac monitor (ICM) is feasible in patients with cryptogenic stroke, and compared the iAF detection rate of the ICM with 7-day Holter monitoring. METHODS: Sixty patients (median age 63; interquartile range, 48.5-72 years) with acute cryptogenic stroke were included. ICM was implanted 13 days (interquartile range; 10-65 days) after the qualifying event. Seven-day Holter was performed after the ICM was implanted. RESULTS: The iAF was detected by the ICM in 10 patients (17%; 95% CI, 7% to 26%). Only 1 patient (1.7%; 95% CI, 0% to 5%) had iAF during 7-day Holter monitoring as well (P=0.0077). Episodes of iAF lasting 2 minutes or more were detected 64 (range, 1-556) days after implantation. There were no recurrent strokes during the observation period. The implantation procedure was well tolerated with no adverse events; the daily data transmission protocol was easy to handle by the patients. CONCLUSIONS: ICM implantation for the detection of iAF during outpatient follow-up is feasible in patients with cryptogenic stroke. ICMs offer a much higher diagnostic yield than 7-day Holter monitoring.

Predictors of Atrial Fibrillation in Patients with Embolic Stroke of Unknown Etiology and Implantable Loop Recorders-Further Insights of the TRACK AF Study on the Role of ECG and Echocardiography.

Aims-Electrocardiography (ECG) and echocardiographic left atrial (LA) parameters may be helpful to assess the risk of atrial fibrillation (AF) in embolic stroke of unknown etiology (ESUS) and could therefore guide intensity of ECG monitoring. Methods-1153 consecutive patients with ischemic stroke or transient ischemic attack (TIA) were analyzed. An internal loop recorder (ILR) was implanted in 104 consecutive patients with ESUS. Multiple morphologic P-wave parameters in baseline 12-channel ECG and echocardiographic LA parameters were measured and analyzed in patients with and without ILR-detected AF. Using logistic regression, we evaluated the predictive value of several ECG parameters and LA dimensions on the occurrence of AF. Results-In 20 of 104 (19%) patients, AF was diagnosed by ILR during a mean monitoring time of 575 (IQR 470-580) days. Patients with AF were significantly older (72 (67-75) vs. 60 (52-72) years; p = 0.001) and premature atrial contractions (PAC) were more frequently observed (40% vs. 2%; p < 0.001) during baseline ECG. All morphologic P-wave parameters did not show a significant difference between groups. There was a non-significant trend towards a larger LA volume index (31 (24-36) vs. 29 (25-37) mL/m2; p = 0.09) in AF patients. Conclusions-Age and PAC are independently associated with incident AF in ESUS and could be used as markers for selecting patients that may benefit from more extensive rhythm monitoring or ILR implantation. In our consecutive cohort of patients with ESUS, neither morphological P-wave parameters nor LA size were predictive of AF.

Heart rate monitoring on the stroke unit. What does heart beat tell about prognosis? An observational study.

BACKGROUND: Guidelines recommend maintaining the heart rate (HR) of acute stroke patients within physiological limits; data on the frequency and predictors of significant deviations from these limits are scarce. METHODS: Demographical data, stroke risk factors, NIH stroke scale score, lesion size and location, and ECG parameters were prospectively assessed in 256 patients with ischemic stroke. Patients were continuously monitored for at least 24 hours on a certified stroke unit. Tachycardia (HR ≥ 120 bpm) and bradycardia (HR <45 bpm) and cardiac rhythm (sinus rhythm or atrial fibrillation) were documented. We investigated the influence of risk factors on HR disturbances and their respective influence on dependence (modified Rankin Scale ≥ 3 after three months) and mortality. RESULTS: HR ≥ 120 bpm occurred in 39 patients (15%). Stroke severity (larger lesion size/higher NIHSS-score on admission), atrial fibrillation and HR on admission predicted its occurrence. HR <45 bpm occurred in 12 patients (5%) and was predicted by lower HR on admission. Neither HR ≥ 120 nor HR <45 bpm independently predicted poor outcome at three moths. Stroke location had no effect on the occurrence of HR violations. Clinical severity and age remained the only consistent predictors of poor outcome. CONCLUSIONS: Significant tachycardia and bradycardia are frequent phenomena in acute stroke; however they do not independently predict clinical course or outcome. Continuous monitoring allows detecting rhythm disturbances in stroke patients and allows deciding whether urgent medical treatment is necessary.

Blood pressure threshold violations in the first 24 hours after admission for acute stroke: frequency, timing, predictors, and impact on clinical outcome.

BACKGROUND AND PURPOSE: Admission blood pressure (BP) and significant decreases in BP after acute stroke have been correlated with outcome. Few data are available on the impact of extreme values at any time point within the first 24 hours. METHODS: BP was measured hourly for 24 hours in 325 consecutive patients with acute ischemic stroke. Predefined endpoints were systolic BP >or=200, diastolic BP >or=110, or systolic BP <100 mm Hg during the first 24 hours, and significant systolic BP decreases by >26 mm Hg within 4 hours after admission. Multiple logistic regression analysis identified independent predictors of each end point and determined the impact on dependency at 3 months defined as modified Rankin scale score >or=3. RESULTS: Upper threshold violations occurred in 70% of cases during the admission process, and more frequently in patients arriving early after stroke; 30% of cases exhibited such values at a later time point. History of hypertension (P<0.01) and higher NIHSS on admission (P<0.05) were independent predictors. Systolic BP <100 mm Hg occurred at random and was associated with younger age (P<0.05). Night time admission was the strongest independent predictor of systolic BP decreases >26 mm Hg (P<0.0001). Diabetes, NIHSS on admission, and age were associated with adverse outcome at 3 months, whereas threshold violations and decreases were not. There was a trend for administration of antihypertensives being associated with poor outcome (P<0.1). CONCLUSIONS: External stimuli, premorbid risk factors, diurnal BP variations, and disease-immanent mechanisms all influence the course of BP after acute stroke. Monitoring should precede any medical BP treatment.

Fiberoptic endoscopic Dysphagia severity scale predicts outcome after acute stroke.

BACKGROUND AND PURPOSE: Fiberoptic endoscopic evaluation of swallowing (FEES) is a suitable method for dysphagia assessment after acute stroke. Recently, we developed the fiberoptic endoscopic dysphagia severity scale (FEDSS) for acute stroke patients, grading dysphagia into 6 severity codes (1 to 6; 1 being best). The purpose of this study was to investigate the impact of the FEDSS as a predictor of outcomes at 3 months and intermediate complications during acute treatment. METHODS: A total of 153 consecutive first-ever acute stroke patients were enrolled. Dysphagia was classified according to the FEDSS, assessed within 24 h after admission. Intermediate outcomes were pneumonia and endotracheal intubation. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months. Multivariate regression analysis was used to identify whether the FEDSS was an independent predictor of outcome and intercurrent complications. Analyses were adjusted for sex, age and National Institutes of Health Stroke Scale (NIH-SS) on admission. RESULTS: The FEDSS was found to predict the mRS at 3 months as well as but independent from the NIH-SS. For each additional point on the FEDSS, the likelihood of dependency at 3 months (mRS > or = 3) raised by approximately 50%. Each increase of 1 point on the FEDSS conferred a more than 2-fold increased chance of developing pneumonia. The odds for the necessity of endotracheal intubation raised by a factor of nearly 2.5 with each additional point on the FEDSS. CONCLUSIONS: The FEDSS strongly and independently predicts outcome and intercurrent complications after acute stroke. Thus, a baseline FEES examination provides valuable prognostic information for the treatment of acute stroke patients.

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.

Prevalence and prognostic impact of microembolic signals in arterial sources of embolism. A systematic review of the literature.

OBJECTIVE: To compile available studies using microembolic signal (MES) detection by transcranial Doppler sonography in varying sources of arterial brain embolism. We investigated prevalences of MES and whether MES detection is of proven use for risk stratification. METHOD: Studies reporting prevalences of MES and the risk of cerebral ischemic events were pooled for patients with symptomatic or asymptomatic carotid stenosis, intracranial artery stenosis, cervical artery dissection, and aortic embolism. RESULTS: MES were reported in 43% of 586 patients with symptomatic and in 10% of 1066 patients with asymptomatic carotid stenosis. Presence of one MES indicated an increased risk of future events [odds ratio (OR): 7.5, 95% confidence interval (CI): 3.6-15.4, p<0.0001 for symptomatic, and OR: 13.4, 95% CI: 6.5-27.4, p<0.0001 for asymptomatic disease). MES were reported in 25% of 220 patients with symptomatic vs. 0% of 86 patients with asymptomatic intracranial stenosis (p<0.0001), Of 82 patients with cervical artery dissection presenting with TIA or stroke, 50% had MES compared with 13% of 16 patients with local symptoms (p=0.006), In patients with aortic embolism, patients with plaques >or= 4 mm more frequently had MES compared with patients with smaller plaques (p=0.04), Data were insufficient to reliably predict future events in patients with intracranial stenosis, cervical artery dissection, and aortic embolism. CONCLUSION: MES are a frequent finding in varying sources of arterial brain embolism, MES detection is useful for risk stratification in patients with carotid stenosis.

Attitudes and current practice of primary care physicians in acute stroke management.

BACKGROUND AND PURPOSE: Stroke patients often report that primary care physicians (PCPs) are their first medical contact after onset of symptoms. We studied PCP attitudes and current practice in early management of suspected stroke patients. METHODS: A cross-sectional survey was conducted among 714 general practitioners, internists, and neurologists providing acute primary care for stroke patients in 4 different regions in Germany. PCP attitudes and practices were assessed with standardized questionnaires and case vignettes presenting suspected stroke patients contacting PCPs either by phone or in practice. Factors influencing the decision of the PCPs to admit patients with clear stroke symptoms as medical emergency to hospital were assessed using multivariate analysis. RESULTS: In total, 395 PCPs participated in the study (55.3%). Most PCPs agreed that stroke (94.7%) and transient ischemic attack (84.8%) were medical emergencies. In case vignettes, admission to hospital as medical emergency was preferred management after first contact to patients with clear stroke symptoms by phone or in practice (68.9% and 65.6%, respectively). Outpatient clarification was the preferred option of PCPs in patients with unclear stroke symptoms contacting PCPs by phone or in practice (54.7% and 75.5%, respectively) and in transient ischemic attack patients (50.9%). Working as general practitioner (odds ratio, 0.3; 95% confidence interval, 0.2 to 0.6) and practice location outside metropolitan area (P=0.002) independently decreased probability of admitting suspected stroke patients as medical emergency when first contact to PCPs was by phone. PCP agreement that all stroke and transient ischemic attack patients must be admitted to hospital increased probability for early hospitalization of stroke and transient ischemic attack patients when first contact was in practice (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.3, and odds ratio, 1.8; 95% confidence interval, 1.1 to 2.8, respectively). CONCLUSIONS: Stroke and transient ischemic attack were well recognized as medical emergencies by PCPs in our study. However, only two-thirds of PCP would immediately admit stroke suspected patients with clear symptoms to hospital as medical emergency.

Discrepancy between theoretical knowledge and real action in acute stroke: self-assessment as an important predictor of time to admission.

BACKGROUND: Poor knowledge of stroke symptoms within the general population might be responsible for significant delay between symptom onset and hospital admission in most stroke patients. METHODS: We prospectively evaluated whether theoretical knowledge about stroke influenced time to admission among 102 consecutive acute stroke patients using standardized questionnaires. We assessed in multiple logistic regression models the influence of theoretical knowledge (knowledge about stroke symptoms and knowledge about the appropriate actions to be taken in the case of a stroke) on the real actions taken in the acute situation. Predictors of a delayed hospital admission greater than 2 hours after stroke onset were determined. Models were adjusted for age, gender, level of education, stroke severity, previous history of stroke or transient ischemic attack (TIA), and being alone at symptom onset. RESULTS: Patients arrived significantly later, if the patients themselves were the managers of the emergency situation [odds ratio (OR): 4.7; 95% confidence interval (CI): 1.5-140.8]. Symptom knowledge and action knowledge were not found to be significantly associated with shorter pre-hospital times, whereas the correct diagnosis of stroke by the manager (OR: 0.2; 95% CI: 0.1-0.4) and calling the emergency medical system (OR: 0.3; 95% CI: 0.1-0.7) independently led to a higher likelihood to arrive at a hospital within 2 hours. CONCLUSION: Our study underscores that good theoretical knowledge about stroke does not imply appropriate management in the emergency situation. Educational efforts need to incorporate more practical aspects in order to translate theoretical knowledge into concrete action.

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.

Platelets in patients with acute ischemic stroke are exhausted and refractory to thrombin, due to cleavage of the seven-transmembrane thrombin receptor (PAR-1).

Platelet 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<0.001) and failed to respond to thrombin in vitro. Enhanced surface expression of CD62P, CD63, TSP-1 and less mepacrine uptake showed platelet degranulation during stroke. Platelets from patients with acute cerebral ischemia are exhausted and desensitized to thrombin through cleavage of PAR-1, indicating that high concentrations of thrombin occur with acute cerebrovascular ischemic events in vivo.

Carotid artery auscultation--anachronism or useful screening procedure?

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.

Seizures after cerebrovascular events: risk factors and clinical features.

BACKGROUND: Epileptic seizures are well known sequelae of patients with stroke but only little is known about the different risk factors and about the influence of the different types of stroke including sinus thrombosis and bleedings on developing such seizures. Further, the association of post-stroke seizures and conventional vascular risk factors has not been evaluated to date. METHODS: We performed a cohort study on a sample of 593 consecutive patients with different types of cerebrovascular events. In 421 patients, sufficient data were obtained in a personal interview over a mean observation period of 30 months. Data regarding the clinical history were recorded from the patients' charts. RESULTS: The total prevalence of epileptic seizures was 11.6%, the total annual risk was 4.6%. We detected the following significant risk factors: younger age at stroke; higher NIH stroke scale score; any coagulopathy. TIA was found significantly less frequent as a cause of seizures as compared to infarction, bleeding, and sinus thrombosis. Patients with bleeding (14.3%) and with sinus thrombosis (16.3%) were significantly more frequent in the seizure group than in the non-seizure group (6.7% and 1.6%, respectively). The location of stroke, including cortical versus subcortical, did not influence the risk of seizures. The majority of patients developed secondary generalized seizures (57.1%). In adjusted analyses, the two major risk factors for post-stroke epilepsy were a higher NIH stroke scale and a sinus thrombosis as the initial cerebrovascular event. Common lifestyle, vascular, and metabolic risk factors of stroke and for dementia were not associated with the development of seizures. CONCLUSIONS: In conclusion, our data show that epileptic seizures occur in particular after major strokes and in sinus thrombosis. Interestingly, conventional vascular risk factors were not associated with the occurrence of post-stroke seizures. Considering the risk for seizures after certain types of cerebrovascular events might help to early identify patients for anticonvulsive treatment. In the future, it should be investigated whether these patients might benefit from pre-emptive anticonvulsant treatment.