Prediction of malignant MCA infarction with DWI: pitfalls in hyperacute stroke.
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
M Sitzer
Publications and source records attributed to M Sitzer.
Expression of tissue factor in high-grade carotid artery stenosis: association with plaque destabilization.
BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.
Carotid Artery, Internal↗
[Unstable carotid stenosis--an inflammatory disease?].
Arterioarterial thromboembolism from extracranial internal carotid artery (ICA) stenosis is an important pathogenic mechanism of ischemic stroke. However, even a high-grade ICA stenosis carries a greatly variable annual risk of stroke, as high as 13% following a recent occurrence of transient or minor cerebral ischemia or as low as 1-2% in clinically asymptomatic patients. There is increasing evidence that inflammatory processes play a central role in atherosclerosis and particularly in plaque destabilization converting chronic atherosclerosis into an acute neurological disorder. In thromboendarterectomy specimens from patients with high-grade ICA stenoses, the extent of inflammatory infiltration and the expression of matrixmetalloproteinase-9 correlated to clinical and ultrasonic features of plaque destabilization such as cerebral microembolism. Inflammation might become a new therapeutic target in symptomatic carotid artery disease.
Carotid Artery, Internal↗
Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis.
BACKGROUND: Chronic Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis but whether it plays a role at an early stage in the disease is uncertain. An early estimate of atherosclerosis can be obtained by ultrasonic imaging of the carotid artery to determine intima-media thickness (IMT) and the thickness of any atheroma plaques. METHODS AND RESULTS: In 983 normal population individuals aged 30 to 70 years, we measured common carotid artery (CCA) and carotid bulb IMT, and also carotid plaque thickness and the degree of internal carotid artery (ICA) stenosis. C. pneumoniae IgA titers of >/=16 and IgG titers of >/=64 were taken as positive. There was no association between C. pneumoniae IgA or IgG seropositivity with right, left, or mean CCA or bulb IMT, or with the presence of carotid plaques. There was a significant association between IgA seropositivity and >50% mean carotid stenosis with an odds ratio of 5.24 (95% CI 1.24 to 22.21, P=0.0245) after controlling for age and sex; after controlling for other cardiovascular risk factors, this was not significant 3.96 (95% CI 0. 84 to 18.78, P=0.082). No association was found between IgA or IgG seropositivity and markers of fibrinogen, log C-reactive protein, or leukocyte count. CONCLUSIONS: We found no evidence that serological evidence of C. pneumoniae infection is associated with early atherosclerosis. It is possible that IgA seropositivity is associated with more advanced disease but this hypothesis needs to be examined in a population with a higher prevalence of advanced atherosclerosis. We found no evidence that C. pneumoniae results in a chronic systemic inflammatory state.
Adult↗
Cerebral microembolism, a disease marker for ischemic cerebrovascular events in the antiphospholipid syndrome of systemic lupus erythematosus?
OBJECTIVES: We investigated whether the detectability of microembolic Doppler signals (MES) in the intracranial circulation may help to define the individual cerebrovascular risk in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Retrospective cross-sectional study of 70 patients with SLE with or without APS, and 30 controls with a history of cerebral ischemia of unknown cause. Of all patients, 38 had a clinical history of APS and 32 did not. RESULTS: 15 patients with APS (39%) showed MES. In contrast, all patients without APS and 29 of 30 controls were microemboli-negative. MES were more strongly associated with cerebrovascular symptoms than with APS, antiphospholipid antibodies, or cardiac pathology. The time elapsed since the last ischemic cerebrovascular symptom was significantly shorter in microemboli-positive patients than in microemboli-negative patients (P<0.001). CONCLUSION: MES may be related to disease activity in patients with SLE and APS. Their detection may help to assess individual cerebrovascular risk and contribute to therapeutic decision making and therapeutic monitoring.
Adolescent↗
Reliability and validity of noninvasive imaging of internal carotid artery pseudo-occlusion.
BACKGROUND AND PURPOSE: Our study evaluated noninvasive tests for the diagnosis of atheromatous internal carotid artery (ICA) pseudo-occlusion. METHODS: Twenty patients (17 men, 3 women; mean age +/-SD, 64.3+/-11.6 years) with angiographically proven atheromatous ICA pseudo-occlusion (20 vessels) were prospectively examined with MR angiography (MRA; 2D and 3D time-of-flight techniques), color Doppler-assisted duplex imaging (CDDI) and power-flow imaging (PFI) with and without an intravenous ultrasonic contrast agent. As a control group, 13 patients (13 men; mean+/-SD age, 63.0+/-9.0 years) with angiographically proven ICA occlusion (13 vessels) were studied with the same techniques. For the determination of interobserver agreement (kappa statistics), the findings of each diagnostic technique were read by 2 blinded and independent observers who were not involved in patient recruitment and initial data acquisition. Specificity and sensitivity were calculated for all noninvasive techniques (observer consensus) in comparison to the standard of reference (intra-arterial angiography). RESULTS: Interobserver reliabilities were kappa=0.86 for intra-arterial angiography, kappa=0.90 for unenhanced CDDI, kappa=0. 93 for enhanced CDDI, kappa=0.93 for unenhanced PFI, kappa=1.0 for enhanced PFI, kappa=0.93 for 2D MRA, and kappa=0.77 for 3D MRA, respectively (P<0.0001). Specificities and sensitivities were 0.92 and 0.70 for unenhanced CDDI, 0.92 and 0.83 for enhanced CDDI, 0.92 and 0.95 for unenhanced PFI, 1.0 and 0.94 for enhanced PFI, 1.0 and 0.65 for 2D MRA, and 0.89 and 0.47 for 3D MRA, respectively. CONCLUSIONS: Advanced ultrasonographic techniques, especially PFI (with only 1 false-positive diagnosis of occlusion in the present series), can provide reliable and valid data to differentiate between ICA pseudo-occlusion and complete occlusion. In contrast, time-of-flight MRA at its present state is not capable of predicting minimal residual flow within a nearly occluded ICA.
Aged↗
[Ultrasound diagnosis in acute stroke].
Doppler- and Duplex-sonography are noninvasive methods which provide helpful insight into brain blood supply by imaging extracranial neck (extracranial Doppler/Duplex) as well the intracranial basal arteries (transcranial Doppler, transcranial color-coded Duplex). Used in combination with ultrasound contrast agents, these methods are now able to supplement and often replace conventional angiography in clinical decision making processes. In acute stroke ultrasound techniques offer bedside options to localize the underlying pathogenic process and to record the actual cerebral blood flow. In addition, the Doppler method allows both detection of cerebral microemboli and their embolic source. Although technical limitation of the Doppler/Duplex method at present impairs imaging of the distal carotid arteries and of the vertebral arteries, extracranial and intracranial Doppler has been proven to be an important clinical tool providing highly useful clinical information with excellent reliability.
Blood Flow Velocity↗
Modifiable stroke risk factors in volunteers willing to participate in a prevention program.
The current trends in stroke incidence require continued efforts to improve primary prevention. Compared to large-scale public health approaches, more limited programs targeting volunteers may offer some advantages. We invited all 12,824 members of a health insurance company program who lived within 50 km form one of two study sites to participate in a vascular screening program and aimed at reducing modifiable risk factors. 1,837 persons registered and participated (14.3%, mean age 53 +/- 12 years, 50% men). Using the Framingham stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke events can be predicted for this age group within 10 years. The majority of these 97 events will occur in those with men resting blood pressure values +/- 140mm Hg (systolic) or +/- 90 mm Hg (diastolic; 420 persons, mean age 64 +/- 7 years, 60 expected events), or with a particularly high age- and sex-adjusted risk (288 persons, mean age 68 +/- 7 years, 60 expected events). Our pilot study provides an estimate of the prevalence of modifiable vascular risk factor among volunteer participants of a prevention program. Possible benefits of this approach will be investigated in a second step using a randomized intervention.
Aged↗
Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization.
BACKGROUND AND PURPOSE: Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this study, we investigated whether the extent of inflammatory infiltration in high-grade stenoses of the internal carotid artery (ICA) correlates to clinical features of plaque destabilization. METHODS: Endarterectomy specimens from 37 consecutive patients undergoing surgery for high-grade ICA stenosis were stained immunocytochemically for macrophages (CD68) and T cells (CD3). The staining was quantified by planimetry of immunostained areas (CD68) or counting individual cells (CD3). Clinical evidence of plaque instability was provided by the preoperative assessment of recent ischemic symptoms attributable to the stenosis and of the occurrence of cerebral microembolism in transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. RESULTS: The percentage of macrophage-rich areas and number of T cells per mm2 section area were larger in recently symptomatic patients than in asymptomatic patients (macrophages: 18+/-10% versus 11+/-4%, P=0.005; T cells: 71.2+/-34.4 versus 40.5+/-31.4 mm2, P=0.005). The presence of microembolism was associated with an increase in macrophage-rich areas (P=0.011). Macrophage (19+/-10% versus 9+/-3%, P=0.0009) and T cell (71.5+/-39.0 versus 46.4+/-22 mm2, P=0.045) infiltration were more pronounced in predominantly atheromatous than in fibrous plaques, but did not correlate significantly to the presence of surface ulceration or luminal thrombosis. CONCLUSIONS: Our data suggest a role of plaque-infiltrating macrophages and T cells in the clinical destabilization of high-grade ICA stenoses. Inflammatory mechanisms may be a therapeutic target in patients with symptomatic ICA disease.
Adult↗
Cerebral microemboli in patients with antiphospholipid syndrome.
CNS involvement is one of the hallmarks underlying poor prognosis in SLE and for therapeutic strategies it is difficult to assess which patients are at risk. As detectability of cerebral microembolic signals (MES) using long-term transcranial Doppler ultrasonography (TCD) proved to be predictive of past and future thromboembolic events in patients with carotid artery stenosis, we investigated whether MES might be similarly useful in patients with antiphospholipid syndrome (APS). Our study population consisted of 46 SLE patients and five with primary APS (pAPS). Twelve of the 46 patients with SLE, 10 of them with secondary APS (sAPS), and four of five patients with pAPS had a history of cerebrovascular ischaemia (CVI). MES in the middle cerebral artery were detected in 14 of 16 patients with and in one of 35 without CVI (P < 0.001). Antiphospholipid antibodies (aPL) were positive in 12 of 15 patients with and 18 of 36 without MES, and the rate of MES correlated to the titre of aPL. MES from APS patients resembled in their energy distribution those from patients with symptomatic carotid disease and were significantly different from those associated with artificial heart valves. In conclusion, cerebral MES are detectable in APS patients and correlate with a history of CVI. Whether this innovative method may provide individual risk assessment in APS patients has to be addressed in prospective studies.
Adolescent↗
Characteristics and clinical value of an intravenous echo-enhancement agent in evaluation of high-grade internal carotid stenosis.
Although ultrasound is a highly useful tool for clinical diagnosis, it has certain limitations in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion. However, these limitations can be overcome by increasing the echogenicity of flowing arterial blood by use of echo-enhancement agents. Two phase III studies assessed the usefulness of the IV transpulmonary echo enhancer Levovist (SH U 508A) in improving characterization and quantification of severe internal carotid stenosis on ultrasound scans. In addition, Levovist-induced enhancement characteristics of the Doppler frequency spectrum have been analyzed. To be included in the study reviewed here, patients had to have a high-grade (> or = 70%) stenosis or occlusion of an internal carotid artery (ICA), as judged by conventional angiography or by standard cervical Doppler ultrasound. Patients were excluded from consideration if they were pregnant or nursing, had a history of galactosemia, or had received an ionic contrast medium within 24 hours before or after the intended administration of Levovist. Written informed consent was obtained from all patients before entry into the study. Of 32 patients (14 women, 18 men, median age 64 yr) who were included in this study, high-grade stenosis was verified in 30 ICA vessels and occlusion was verified in two vessels. After admission into the study, the carotid bifurcation was insonated in all patients using a 7.5-MHz linear array transducer for color Doppler-assisted duplex imaging and a 4-MHz pulsed-wave Doppler for velocity spectrum measurements before and after injection of the echo enhancement agent Levovist. Levovist-induced increases in carotid blood echogenicity began 11 +/- 2 seconds (mean +/- SD) after the start of injection, peaked at 21 +/- 2 dB, and had a half-life of 75 seconds. A fast Fourier transform of the original Doppler velocity spectrum demonstrated Levovist-induced enhancement throughout the entire velocity spectrum, with an increase in ICA blood flow velocity paralleling an increase in reflected ultrasound energy. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length) obtained before and during echo enhancement were highly correlated (r > 0.90). However, visualization of the entire length of the intrastenotic residual flow lumen, was significantly improved by Levovist enhancement (52% versus 83%; p = 0.01). Levovist considerably increased interpretable data by improving image quality in patients with high-grade carotid stenosis. Furthermore, the significant improvement in visualization of the residual flow lumen suggests that echo-enhancement agents may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.
Blood Flow Velocity↗
Color-flow Doppler-assisted duplex imaging fails to detect ulceration in high-grade internal carotid artery stenosis.
PURPOSE: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. METHODS: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (> or = 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. RESULTS: Interobserver reliabilities for detecting carotid plaque ulceration were kappa= 0.57 for ultrasonography and kappa = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomically defined ulceration (chi square = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). CONCLUSIONS: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions.
Adult↗
How good is intercenter agreement in the identification of embolic signals in carotid artery disease?
BACKGROUND AND PURPOSE: There has been concern regarding the reproducibility of the detection of embolic signals, particularly in patients with carotid artery stenosis in whom the signals are of low intensity. No published studies have examined inter-center agreement in reporting specific embolic signals or the factors responsible for any lack of agreement. We examined reproducibility between two centers in which widely differing proportions of embolic signals have previously been reported in patients with carotid artery stenosis. METHODS: Recordings from the middle cerebral artery of eight patients with ipsilateral carotid artery stenosis in whom embolic signals had been detected during a previously study were independently examined by three experienced observers in one center and by one experienced observer in another center. We calculated agreement within and between centers by estimating the probability that one observer would identify a specific embolic signal if other observers had identified it (a probability of 1 indicates complete agreement). The influence of different characteristics of the embolic signal on the probability of its detection as an embolic signal was determined. RESULTS: A high level of agreement in the identification of specific embolic signals was found. This was similar between all observers (.90), between the three observers in one center (.89), and between observers in the two different centers (.94). The probability of detection was independently related to the relative intensity of the embolic signal (P<.0001). It was less (although significantly) independently related to the position of the embolic signal in the cardiac cycle (P=.02), with signals in systole being more reliably detected. There was no independent relationship between the probability of detection and either the duration of the embolic signal or the velocity at the maximum intensity increase. The use of threshold intensity as a criterion for embolic signal detection increased interobserver agreement but reduced the sensitivity in detecting signals. CONCLUSIONS: The high level of interobserver agreement suggests that the technique is sufficiently reproducible for clinical use.
Blood Flow Velocity↗
Non-invasive evaluation of internal carotid stenosis with colour doppler-assisted duplex imaging.
Explore the source record for details and available documents.
Carotid Artery, Internal↗
Cerebral microembolism in patients with Sneddon's syndrome.
BACKGROUND: The pathogenesis of Sneddon's syndrome is unclear. This study addresses the question whether cerebral thromboembolism may be involved in the pathogenesis of the neurologic complications of the disorder. The study consisted of 13 patients with Sneddon's syndrome defined by both generalized livedo reticularis and a history of one or more cerebrovascular ischemic events; none had clinical or Doppler ultrasonographic evidence of atherosclerosis. METHODS: Transcranial Doppler microembolic monitoring of the middle cerebral artery; blood screening for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies). RESULTS: Five patients (38%) showed clinically silent microembolism at transcranial Doppler monitoring, with individual microembolic event rates of the middle cerebral artery between 2 per hour and 33 per hour. In this group, the time since the last ischemic symptom was significantly shorter than in the eight patients without microemboli. Antiphospholipid antibodies were detected in three patients (23%), all of whom belonged to the microemboli-positive group. CONCLUSIONS: These data suggest that the detectability of both clinically silent cerebral microembolism and antiphospholipid antibodies may provide paraclinical evidence of active disease in patients with Sneddon's syndrome. The results support the notion that an immune-mediated prothrombotic state facilitating the formation of arterial thrombi with subsequent cerebral embolization, and/or triggering in situ thrombosis of cerebral vessels, plays a pathogenetic role in the neurologic manifestations of this disorder.
Adult↗
[Contrast-enhanced color-coded duplex ultrasound of high grade carotid stenoses].
PURPOSE AND METHODS: The usefulness of SH-U-508A (Laevovist) in the quantification of high-grade internal carotid stenosis (ICA) is assessed in this study. 32 patients with high-grade ICA stenosis (> = 70%) or occlusion are examined using colour Doppler-assisted duplex imaging (CDDI) before and after injection of SH-U-508A. RESULTS: The SH-U-508A-induced increase in blood echogenicity started at 9.8 s (mean; SD: 2.2) after bolus injection and peaked at 21 dB (mean; SD: 1.9; n = 12) after 14.8 s (mean; SD: 2.9). In addition, SH-U-508A led to a significant increase in systolic peak velocity determined in the common carotid artery, by 26% (mean; SD: 9; p < 0.05). Significant differences between non-enhanced and enhanced CDDI were found for the visualisation of the entire length of the intrastenotic residual lumen (43% vs 83%; p < 0.01). Correlations between non-enhanced and enhanced CDDI were high (r > 0.9) for the determination of cross-sectional area reduction and plaque length. CONCLUSION: SH-U-508A may be useful in quantifying high-grade ICA stenoses with insufficient delineation at non-enhanced CDDI.
Aged↗
Magnetic resonance imaging of regional cerebral blood oxygenation changes under acetazolamide in carotid occlusive disease.
BACKGROUND: Gradient-echo magnetic resonance imaging can demonstrate changes in cerebral blood oxygenation with high spatiotemporal resolution. We have previously shown that this technique allows monitoring of autoregulatory responses under vasodilatory stress in the healthy human brain. Here the approach has been extended to assess impairment of the autoregulatory reserve capacity in patients with carotid occlusive disease. SUMMARY OF REPORT: We studied four patients with unilateral occlusion of the internal carotid artery on a 2.0-T clinical high-field magnetic resonance system. Oxygenation-sensitive imaging was based on long-echo-time, gradient-echo sequences (repetition time, 62.5 milliseconds; echo time, 30 milliseconds) with low flip angles (10 degrees) to emphasize changes in blood oxygenation rather than flow velocity. Dynamic recording monitored signal intensities before and after injecting 1 g of acetazolamide. In sections covering the hand area of the primary sensorimotor cortex, acetazolamide-induced magnetic resonance signal increases were attenuated in the vascular territories of occluded arteries. Lateralization of responses in the left and right hemispheric parts of the section corresponded to decreased hemodynamic reserve capacity as measured globally by transcranial Doppler ultrasonography. CONCLUSIONS: The present findings indicate that magnetic resonance imaging can demonstrate exhaustion of the autoregulatory reserve capacity when monitoring cerebral blood oxygenation changes during vasodilatory stress. We suggest that this method can help to evaluate regional cerebral hemodynamics in patients with carotid occlusive disease.
Acetazolamide↗
Cerebral microembolism and the risk of ischemia in asymptomatic high-grade internal carotid artery stenosis.
BACKGROUND AND PURPOSE: Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography distal to internal carotid artery stenosis occurs more frequently in recently symptomatic compared with asymptomatic patients. It has remained unclear whether cerebral microembolism also indicates a higher risk of future cerebral or retinal ischemia. SUMMARY OF REPORT: Sixty-four asymptomatic patients with unilateral 70% to 90% internal carotid artery stenosis were investigated prospectively (mean follow-up, 72 weeks). Five patients developed ischemic symptoms attributable to the stenosis (transient ischemic attack, 2 patients; stroke, 3 patients). A microembolic rate of > or = 2 per hour in the ipsilateral middle cerebral artery was associated with a substantially increased risk of developing ischemia of the corresponding carotid territory (odds ratio, 31; 95% confidence interval, 3 to 302; P = .005). CONCLUSIONS: This prospective pilot study suggests that cerebral microembolism detected with transcranial Doppler sonography may define a high-risk subgroup among patients with asymptomatic high-grade internal carotid artery stenosis.
Aged↗