Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

[Transient global amnesia and Tako-Tsubo cardiomyopathy--coincidence or corollary?]. / Transiente globale Amnesie und Tako-Tsubo-Kardiomyopathie - Zufall oder logische Folge?

HISTORY: A 69-year-old female patient who had been physically and mentally healthy was admitted to our emergency department because of acute onset of amnesia. INVESTIGATIONS: Inconspicuous diagnostic findings led to the diagnosis of transient global amnesia (TGA). Furthermore bradycardia and elevated troponins were detected. Because of these findings a cardiologic workup was performed resulting in the diagnosis of Tako-Tsubo cardiomyopathy. TREATMENT AND COURSE: The patient recovered completely from TGA as well as from the slight reduction of the left-ventricular ejection fraction as part of the Tako-Tsubo cardiomyopathy. CONCLUSION: There are similarities of the two diseases Tako-Tsubo cardiomyopathy and TGA concerning triggers as well as reversibility. Patients presenting with symptoms suggestive for TGA should be considered to undergo additional cardiologic evaluation.

Lack of increase of cerebrovascular events during German World Cup soccer games in 2006.

An association of passively watching a soccer game with an incidence of cardiovascular events was previously reported. With access to the stroke database of the Federal State of Hesse, Germany, we examined whether the incidence of cerebrovascular events was elevated during the Federation Internationale de Football Association (FIFA) World Cup in Germany from 9 June to 9 July 2006 on days of matches involving the German team and whether particular characteristics were noted in stroke patients on these days. We analyzed a prospective stroke registry and calculated incidence ratios for the 7 days of matches played by the German team as compared with the control period ranging from May 2006 to July 2006 using a Poisson regression with a log link to model the number of cerebrovascular events per day for all patients and for subgroups of patients, grouped according to sex, severity of stroke, type of stroke and risk factors. About 2,918 patients with ischemic stroke or intracerebral hemorrhage were included. The regression model did not disclose a higher incidence of cerebrovascular events on days of matches played by the German team. Onset admission time on these days was significantly reduced. In contrast to recent observations regarding cardiac events, we found no effect of passively watching soccer games on incidence of stroke or intracerebral hemorrhage, probably because of the different underlying pathophysiologies of stroke and cardiac events. Onset admission time was slightly reduced on days when a German match was played, probably since more strokes occurred under observation of potential support persons, reflecting the tendency of German people to gather to watch matches played by the national team.

Treatment of symptomatic high-grade intracranial stenoses with the balloon-expandable Pharos stent: initial experience.

INTRODUCTION: We report our first clinical experience with a CE-marked flexible monorail balloon-expandable stent for treatment of high-grade intracranial stenoses. METHODS: Between April 2006 and November 2007 21 patients with symptomatic intracranial stenoses (>70%) were treated with the PHAROS stent. In seven patients, the procedure was performed during acute stroke intervention. Procedural success, clinical complication rates and mid-term follow-up data were prospectively recorded. RESULTS: During a median follow-up period of 7.3 months one additional patient died of an unknown cause 3 months after the intervention. A patient with a significant residual stenosis presented with a new stroke after further progression of the residual stenosis. None of the successfully treated patients experienced ipsilateral stroke. CONCLUSION: Recanalization of intracranial stenoses with the balloon-expandable Pharos stent is technically feasible. The periprocedural complication rate and mid-term follow-up results were in the range of previously reported case series. This pilot study was limited by the small sample size and severe morbidity of the included patients. Final evaluation of the efficacy of Pharos stent treatment demands further investigation.

Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis.

OBJECTIVE: There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors. DESIGN: A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls. METHODS: We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT. RESULTS: The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p<0.0001) or 0.044 mm [0.021-0.066 mm] (p=0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5-29.4%] or 0.250 mm [0.198-0.303 mm] higher in HIV patients (p<0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART). CONCLUSIONS: HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4-14% greater and the "vascular age" 4-5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.

Serum GFAP is a diagnostic marker for glioblastoma multiforme.

A serum marker for malignant cerebral astrocytomas could improve both differential diagnosis and clinical management of brain tumour patients. To evaluate whether the serum concentration of glial fibrillary acidic protein (GFAP) may indicate glioblastoma multiforme (GBM) in patients with single supratentorial space-occupying lesions, we prospectively examined 50 consecutive patients with histologically proven GBM, World Health Organization (WHO) grade IV, 14 patients with anaplastic astrocytoma (WHO grade III), 4 patients with anaplastic oligodendroglioma, 13 patients with diffuse astrocytoma (WHO grade II), 17 patients with a single cerebral metastasis and 50 healthy controls. Serum was taken from the patients before tumour resection or stereotactic biopsy. Serum GFAP levels were determined using a commercially available ELISA test and were detectable in 40 out of the 50 GBM patients (median: 0.18 microg/l; range: 0-5.6 microg/l). The levels were significantly elevated compared with those of the non-GBM tumour patients and healthy controls (median: 0 mug/l; range: 0-0.024 microg/l; P < 0.0001, respectively). Non-GBM tumour patients and all healthy subjects showed zero serum GFAP levels. There was a significant correlation between tumour volume (Spearman Rho, CC = 0.47; 95% confidence interval, 0.2-0.67; P < 0.001), tumour necrosis volume (CC = 0.49; 95% confidence interval, 0.2-0.72; P = 0.004), the amount of necrotic GFAP positive cells (CC = 0.61; 95% confidence interval, 0.29-0.81; P = 0.007) and serum GFAP level among the GBM patients. A serum GFAP level of >0.05 microg/l was 76% sensitive and 100% specific for the diagnosis of GBM in patients with a single supratentorial mass lesion in this series. Therefore, it can be concluded that serum GFAP constitutes a diagnostic biomarker for GBM. Future studies should investigate whether serum GFAP could also be used to monitor therapeutic effects and whether it may have a prognostic value.

Anthropometric approximation of body weight in unresponsive stroke patients.

BACKGROUND AND PURPOSE: Thrombolysis of acute ischaemic stroke is based strictly on body weight to ensure efficacy and to prevent bleeding complications. Many candidate stroke patients are unable to communicate their body weight, and there is often neither the means nor the time to weigh the patient. Instead, weight is estimated visually by the attending physician, but this is known to be inaccurate. METHODS: Based on a large general population sample of nearly 7000 subjects, we constructed approximation formulae for estimating body weight from simple anthropometric measurements (body height, and waist and hip circumference). These formulae were validated in a sample of 178 consecutive inpatients admitted to our stroke unit, and their accuracy was compared with the best visual estimation of two experienced physicians. RESULTS: The simplest formula gave the most accurate approximation (mean absolute difference 3.1 (2.6) kg), which was considerably better than the best visual estimation (physician 1: 6.5 (5.2) kg; physician 2: 7.4 (5.7) kg). It reduced the proportion of weight approximations mismatched by >10% from 31.5% and 40.4% (physicians 1 and 2, respectively) to 6.2% (anthropometric approximation). Only the patient's own estimation was more accurate (mean absolute difference 2.7 (2.4) kg). CONCLUSIONS: By using an approximation formula based on simple anthropometric measurements (body height, and waist and hip circumference), it is possible to obtain a quick and accurate approximation of body weight. In situations where the exact weight of unresponsive patients cannot be ascertained quickly, we recommend using this approximation method rather than visual estimation.

[Neurosyphilis: important differential diagnosis of herpes simplex encephalitis]. / Neurosyphilis: Wichtige Differenzialdiagnose einer Herpesenzephalitis.

Diagnosis of herpes simplex encephalitis in the acute stage is based on clinical symptoms (nonspecific prodromi, neuropsychological deficits, epileptic seizures) in combination with typical CSF abnormalities (lymphomonozytic pleocytosis) and MR imaging abnormalities assumed to be typical for herpes simplex encephalitis (increased fluid-attenuated inversion recovery and T2 hyperintensities in the mesiotemporal lobe region). Definite diagnosis of herpes simplex encephalitis is based on positive polymerase chain reaction in the CSF, usually available some days after hospital admission. Suspected herpes simplex encephalitis requires immediate treatment with acyclovir. Bacterial encephalitis caused by spirochetes may present with similar features but requires different treatment. This should therefore be considered in the differential diagnosis of herpes simplex encephalitis. We report a young patient with neurosyphilis whose correct diagnosis could be made only several days after beginning specific treatment.

Increased endothelial cell apoptosis in symptomatic high-grade carotid artery stenosis: preliminary data.

OBJECTIVE: Endothelial cell (EC) apoptosis has been associated with thrombus formation on an eroded atherosclerotic plaque surface. Alongside plaque rupture, it may constitute another mechanism of plaque destabilisation. We investigated whether EC apoptosis also may be involved in plaque destabilisation in high-grade internal carotid artery (ICA) stenosis. METHODS: We compared the degree of EC apoptosis in carotid endarterectomy specimens from n=38 patients undergoing surgery for high-grade ICA stenosis (> or =70%; n=19 clinically asymptomatic; n=19 symptomatic). The total number of endothelial cells (ECs) and apoptotic cells were determined using CD31 immunohistochemistry and the TdT dUTP nick end-labeling (TUNEL) method respectively. RESULTS: Overall, EC apoptosis was a rare finding. The median percentage of apoptotic ECs was 0.0% (0.0-0.7%) in asymptomatic and 0.5% (0.0-7.3%) in symptomatic plaques (p=0.015, Mann-Whitney U test). No difference was observed between ruptured and unruptured plaque (0.0% [0.0-6.0%] vs 0.0% [0.0-5.7%]; p=0.446). CONCLUSIONS: Our results indicate that TUNEL-detected EC apoptosis is rare in carotid plaque from patients with >70% stenosis.

Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006.

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

[Endovascular treatment for intracranial stenoses. A common statement by neurologists and neuroradiologists]. / Endovaskuläre Behandlung intrakranieller Stenosen. Eine gemeinsame Stellungnahme von Neurologen und Neuroradiologen.

Intracranial stenoses cause 5-10% of all strokes and are increasingly detected by means of modern imaging methods. The stroke danger of high-grade symptomatic stenoses is relatively high, with an annual risk of approximately 10% under medical treatment. Coumadin increases the risk of hemorrhage, and after risk/benefit considerations, antiplatelets should be preferred for antithrombotic therapy. Despite optimized medical treatment, a small group of patients with recurrent symptoms or symptomatic stenoses without adequate collateral supply probably carry higher spontaneous stroke risk and may be considered for intracranial stenting, which itself is associated with procedural risks of up to 10%. Currently published case series show relatively high complication rates as a major drawback of endovascular treatment, mainly strokes after occlusion of perforating branches extending from the stenotic vessel segment or hemorrhagic complications. According to data from smaller feasibility studies, stroke rates in follow-up after successful stenting seem to be low. The average rate of high-grade restenosis with possible indication for reintervention is 10%. Improvements in endovascular treatment aim at reducing vessel wall trauma during balloon angioplasty by underdilatation or the use of self-expanding stents. Until complication rates are dependably reduced to values of 5-6%, indication for endovascular treatment should be restricted to patients without therapeutic alternatives. According to limited data with large variation between different studies, a prospective multicentric registry is proposed for systematic evaluation and further development of the method.

[Evaluation of different protocols for the leg cuff technique for measurement of dynamic cerebral autoregulation]. / Evaluierung verschiedener Messprotokolle für die Leg-cuff-Methode zur Messung der dynamischen zerebralen Autoregulation.

AIM: Aaslid's leg cuff method is a well validated technique to measure dynamic cerebral autoregulation. In the literature different protocols to choose cuff pressure have been described. The aim of this study is to find a technique as accurate as possible without un-necessary inconvenience for the patient. METHOD: The leg cuff test with bilateral cuffs was performed on 10 young healthy volunteers with three different protocols (cuff pressure at systolic level, doppler controlled and 30 mmHg above systolic level). For each examination the autoregulation index invented by Tiecks and Mahony was calculated. Statistical modelling of correlated data was done with Generalized Estimating Equations. RESULTS: The choice of the protocol influences the quality of the actual autoregulation test. The most reliable protocol is also the most inconvenient one for the patient. We found no systematic bias of the protocol on the autoregulation index, but the relation between induced blood pressure drop and resulting autoregulation index was close to statistical significance. CONCLUSION: For the leg cuff test with bilateral cuffs in awake patients we recommend to apply the protocol proposed by Tiecks. Additional report of the magnitude of induced blood pressure drop would be helpful to improve the results' comparability.

[Post-stroke-depression. Algorithm for a standardized diagnostic approach in clinical routine]. / Post-Stroke-Depression. Algorithmus für ein standardisiertes diagnostisches Vorgehen in der klinischen Routine.

Depression is a frequent and important complication after stroke. The occurrence of a post-stroke-depression (PSD) has a significant impact on the functional and cognitive deficit, on mortality and on quality of life after stroke. In contrast to the clinical importance, PSD is often ignored in routine management of stroke patients and remains often untreated if diagnosed. The diagnostic uncertainty is aggravated by the lack of appropriate diagnostic criteria for PSD in the International Classification of Diseases (ICD-10) used in Germany. For the first time, we present an algorithm, which allows for a standardized examination of stroke patients on the presence of PSD. All stroke patients should be examined initially by a short and simple screening tool and are subjected to more extensive procedures only if PSD is assumed based on the screening result. Furthermore potentials and limitations to convert the diagnosis of PSD into a diagnostic related group (DRG) that is used to calculate the hospital's reimbursement are highlighted. Finally pharmacological treatment options for PSD are discussed.

Diffusion-weighted MR imaging lesions after filter-protected stenting of high-grade symptomatic carotid artery stenoses.

BACKGROUND AND PURPOSE: The clinical efficacy of filter devices in internal carotid artery (ICA) stent placement has been a matter of controversy. The aim of this retrospective study was to assess the number and extent of cerebral emboli, as represented by new lesions on diffusion-weighted MR imaging (DWI), in patients treated with filter-protected carotid stent placement. METHODS: Standard DWI (B0 = 1000) was performed within 48 hours before and 48 hours after filter-protected carotid stent placement in 50 patients with symptomatic, high grade (>70%), atherosclerotic ICA stenosis. Number, extent, and vascular territory of new DWI lesions after stent placement were assessed by consensus of 2 experienced neuroradiologists. Multifactorial statistical analysis was performed to determine risk factors associated with DWI lesions. RESULTS: New punctate DWI lesions with a median diameter of 2 mm were detected in 14 of 50 cases in the territory of the stented ICA and in 7 of 50 cases in other vascular territories. Median lesion load was 1 lesion (range, 1-15) per positive case in the stented ICA and 1 lesion (range, 1-7) in other vascular territories. All DWI lesions were clinically asymptomatic. Because of 1 hyperperfusion syndrome with temporary brain swelling, the 30-day stroke and death rate was 2%. Age >or =70 years was the only significant predictor for new DWI lesions, whereas sex, degree and site of stenosis, vascular risk factors, and stent and filter type showed no significant correlation. CONCLUSIONS: New DWI lesions after filter-protected carotid stent placement are substantially more frequent in the ipsilateral ICA territory compared with other vascular territories. Therefore, intraluminal filters cannot completely protect the brain from procedure-related embolization. However, individual lesion load and the risk of clinically relevant ischemia is low.

[Long term follow-up after intracranial vertebro-basilar artery stenting]. / Langzeitergebnisse nach Behandlung intrakranieller vertebrobasilärer Stenosen mit Stents.

PURPOSE: Recurrent ischemic symptoms attributable to intracranial high-grade vertebrobasilar artery stenoses are associated with a high risk of ischemic stroke, particularly if these occur in spite of aggressive medical treatment. Long term efficacy data for endovascular stent angioplasty of symptomatic intracranial stenoses are lacking. The purpose of this prospective study is to determine the rates of deaths, of ischemic events and of restenosis during long-term follow-up. MATERIALS AND METHODS: Between June 2001 and February 2004 twelve patients (11 male, 1 female; median 63 yrs; range, 46 - 75 yrs) with recurrent ischemic symptoms attributed to > or = 70 % intracranial vertebro-basilar artery stenoses, who had failed aggressive medical treatment, were included. Median follow-up was 24 months (range: 6 to 36 months). Intracranial stenoses were measured using 3D rotation angiography data sets and treated with balloon expandable stents. All patients were scheduled for follow-up including clinical (Barthel Index) and transcranial Doppler examinations and intraarterial angiography at 6 months after intervention. Clinical outcome was defined as the rate of stroke in any vascular territory or death during follow-up. Vascular outcome was determined by the rate of in-stent restenosis 50 % on follow-up as examined by intraarterial angiography at 6 months or by transcranial color-coded duplex sonography. RESULTS: Stent placement was technically successful in all patients. No patient had further cerebral ischemic symptoms; two patients died (1 myocardial infarct, 1 sudden death) during follow-up of median 24 months. The degree of stenoses was reduced from median 81 % (range 69 - 94 %) to 19 % (range 10 - 36 %) immediately after stent placement and to 32 % (range 22 - 48 %) after 6 months. No restenosis > or = 50 % occurred during follow-up. CONCLUSION: Based on this limited series, we believe that in patients, with recurrent symptoms despite aggressive medical treatment, endovascular stent placement in intracranial high-grade vertebrobasilar artery stenoses can be an effective and safe treatment option.

Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke.

BACKGROUND: Biomarkers of stroke are an evolving field of clinical research. A serum marker which can differentiate between haemorrhagic and ischaemic stroke in the very early phase would help to optimise acute stroke management. OBJECTIVE: To examine whether serum glial fibrillary acidic protein (GFAP) identifies intracerebral haemorrhage (ICH) in acute stroke patients. METHODS: A pilot study assessing 135 stroke patients admitted within six hours after symptom onset. Diagnosis of ICH (n = 42) or ischaemic stroke (n = 93) was based on brain imaging. GFAP was determined from venous blood samples obtained immediately after admission, using a research immunoassay. RESULTS: GFAP was detectable in the serum of 39 patients (34 of 42 (81%) with ICH, and five of 93 (5%) with ischaemic stroke). Serum GFAP was substantially raised in patients with ICH (median 11 ng/l, range 0 to 3096 ng/l) compared with patients with ischaemic stroke (median 0 ng/l, range 0 to 14 ng/l, p<0.001). Using receiver operating characteristic curve analysis, a cut off point of 2.9 ng/l provided a sensitivity of 0.79 and a specificity of 0.98 for the identification of ICH in acute stroke (positive predictive value 0.94, negative predictive value 0.91; p<0.001). CONCLUSIONS: Serum GFAP can reliably detect ICH in the acute phase of stroke. Further evaluation of the usefulness of GFAP as an early diagnostic marker of ICH is now required, with the aim of optimising cause specific emergency management.

Phosphatidylserine IgG and beta-2-glycoprotein I IgA antibodies may be a risk factor for ischaemic stroke.

OBJECTIVE: Antiphospholipid antibodies (APLA) are established risk factors for venous thrombosis but their role in the pathogenesis of cerebral ischaemia is unclear. The purpose of the present study was to evaluate the relevance of various APLA in patients with cryptogenic stroke (group A, n = 21) and determined causes of stroke (group B, n = 104) according to the TOAST classification in comparison with healthy volunteers without any thrombotic or ischaemic event in their history (group C, n = 84). METHODS: Median ages were 52 yr (A), 60 yr (B) and 51 yr (C). Blood samples were tested for lupus anticoagulant (LA) using phospholipid-dependent coagulation tests (activated partial thromboplastin time, diluted Russell viper venom time). Confirmatory tests were performed if necessary. Furthermore, we assessed the presence of specific APLA and their antibody subclasses against cardiolipin (AclA), phosphatidylserine (ApsA), phosphatidylinositol (ApiA) and beta-2-glycoprotein I (Abeta2A) using enzyme-linked immunosorbent assay. RESULTS: For ApsA IgG we found a significantly higher prevalence in stroke patients (57.7%) compared with normal subjects (4.8%; P < 0.001). Similarly, Abeta2A IgA was significantly more prevalent in stroke patients (20.8%) in comparison with normals (3.6%; P < 0.001). For all other APLAs tested, no significant differences emerged after adjustment for multiple comparisons. We did not find significant differences between stroke subtypes for any APLA. CONCLUSION: The results of this study suggest a relevant role for antiphosphatidylserine IgG and anti-beta2-glycoprotein I IgA in stroke aetiology.

Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid artery stenosis.

OBJECTIVE: There is growing evidence that, in high-grade internal carotid artery (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque rupture and symptom development. The possibility that smooth muscle cell (SMC) apoptosis is involved in loss of fibrous cap volume has only been examined in a limited number of patients with high grade carotid artery stenosis. METHODS: Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm intervals. Plaque instability was defined clinically, by a history of recent ischemic symptoms (< 60 days before surgery; n = 19) attributable to the stenosis, or histopathologically by the presence of plaque rupture (n = 14). Detailed morphometric analyses of the fibrous cap was based on routine stains; for DNA in situ end labeling the TUNEL technique was used. SMCs were identified by immunostaining for SMC actin. RESULTS: We found no significant difference between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to various morphometric measures of the fibrous cap (i.e. mean area, number of plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/- 77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs. 30.1 +/- 60.9; P=0.117). CONCLUSIONS: These data suggest that continuous thinning of the fibrous cap is not an essential prerequisite for plaque rupture in ICA stenosis. Symptomatic, but not ruptured plaque, were associated with the highest number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes plaque rupture by fibrous cap thinning.