Cerebral vein thrombosis: clinical manifestation and diagnosis

BACKGROUND: Cerebral venous thrombosis (CVT) is a disease with a wide spectrum of symptoms and severity. In this study we analysed the predictive value of clinical signs and symptoms and the contribution of D-dimer measurements for diagnosis. METHODS: We evaluated consecutive patients admitted with suspected CVT receiving non-invasive imaging. Symptoms and symptom combination as well as D-dimer levels were evaluated regarding their diagnostic value. RESULTS: 239 patients were included in this study, 170 (71%) were females. In 39 patients (16%) a CVT was found. For identifying a CVT patients underwent either a venous CT-angiography or MR-angiography or both. No combination of symptoms either alone or together with the D-dimer measurements had a sensitivity and positive predictive value as well as negative predictive value and specificity high enough to serve as red flag. D-dimer testing produced rates of 9% false positive and of 24% false negative results. For D-dimer values a Receiver Operating Characteristic curve (ROC) and the area under the curve (AUC = 0.921; CI: 0.864 - 0.977) were calculated. An increase of sensitivity above 0.9 results in a relevant decrease in specificity; a sensitivity of 0.9 matches a specificity value of 0.9. This corresponds to a D-dimer cut-off level of 0.16 μg/ml. CONCLUSION: Imaging as performed by venous CT-angiography or MR-angiography has a 1 to 2 in 10 chance to detect CVT when typical symptoms are present. D-dimer measurements are of limited clinical value because of false positive and negative results

Factors associated with shunt dynamic in patients with cryptogenic stroke and patent foramen ovale: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>As previously reported there is evidence for a reduction in right to left shunt (RLS) in stroke patients with patent foramen ovale (PFO). This occurs predominantly in patients with cryptogenic stroke (CS). We therefore analysed factors associated with a shunt reduction on follow-up in stroke patients suffering of CS.</p> <p>Methods</p> <p>On index event PFO and RLS were proven by transesophageal echocardiography and contrast-enhanced transcranial Doppler-sonography (ce-TCD). Silent PE was proved by ventilation perfusion scintigraphy (V/Q) within the stroke work-up on index event; all scans were re-evaluated in a blinded manner by two experts. The RLS was re-assessed on follow-up by ce-TCD. A reduction in shunt volume was defined as a difference of ≥20 microembolic signals (MES) or the lack of evidence of RLS on follow-up. For subsequent analyses patients with CS were considered; parameters such as deep vein thrombosis (DVT) and silent pulmonary embolism (PE) were analysed.</p> <p>Results</p> <p>In 39 PFO patients suffering of a CS the RLS was re-assessed on follow-up. In all patients (n = 39) with CS a V/Q was performed; the median age was 40 years, 24 (61.5%) patients were female. In 27 patients a reduction in RLS was evident. Silent PE was evident in 18/39 patients (46.2%). Factors such as atrial septum aneurysm, DVT or even silent PE were not associated with RLS dynamics. A greater time delay from index event to follow-up assessment was associated with a decrease in shunt volume (median 12 vs. 6 months, <it>p </it>= 0.013).</p> <p>Conclusions</p> <p>In patients with CS a reduction in RLS is not associated with the presence of a venous embolic event such as DVT or silent PE. A greater time delay between the initial and the follow-up investigation increases the likelihood for the detection of a reduction in RLS.</p

The wound inflammatory response exacerbates growth of pre-neoplastic cells and progression to cancer

There is a long‐standing association between wound healing and cancer, with cancer often described as a “wound that does not heal”. However, little is known about how wounding, such as following surgery, biopsy collection or ulceration, might impact on cancer progression. Here, we use a translucent zebrafish larval model of RasG12V‐driven neoplasia to image the interactions between inflammatory cells drawn to a wound, and to adjacent pre‐neoplastic cells. We show that neutrophils are rapidly diverted from a wound to pre‐neoplastic cells and these interactions lead to increased proliferation of the pre‐neoplastic cells. One of the wound‐inflammation‐induced trophic signals is prostaglandin E2 (PGE2). In an adult model of chronic wounding in zebrafish, we show that repeated wounding with subsequent inflammation leads to a greater incidence of local melanoma formation. Our zebrafish studies led us to investigate the innate immune cell associations in ulcerated melanomas in human patients. We find a strong correlation between neutrophil presence at sites of melanoma ulceration and cell proliferation at these sites, which is associated with poor prognostic outcome

Persistent increase in cardiac troponin I in Fabry disease: a case report

Abstract Background Hypertrophic cardiomyopathy is a frequent manifestation in Fabry disease (FD) - an X-linked lysosomal storage disorder caused by reduced activity of the enzyme α-galactosidase A. In FD an elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI) has been reported in case of clinical manifestation suggestive of myocardial ischemia. In diagnosing acute myocardial infarction cTNI is considered the most reliable parameter. Case Presentation In the referred case we present a 59 years old female patient with the diagnosis of FD presenting with persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range Conclusions Our case report demonstrates a persistent cTNI release in FD with cardiac involvement. Proving the persistence in a symptom free interval, it might be related to a direct damage of myocytes. In FD cTNI could serve as a beneficial long term parameter providing new perspectives for screening strategies.</p

Continuous cardiac troponin I release in Fabry disease.

Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD.cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI).Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: <0.01). cMRI disclosed late gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes.Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD

Cardiac troponin I: a valuable biomarker indicating the cardiac involvement in fabry disease

Objectives: Assessment of the clinical severity of Fabry disease (FD), an X-linked, rare, progressive disorder based on a genetic defect in alpha-galactosidase is challenging, especially regarding cardiac involvement. The aim of the study was to evaluate the diagnostic value of cardiac troponin I (cTnI) in discriminating FD patients with cardiac involvement in a large FD patient cohort. Methods: cTnI levels were measured with a contemporary sensitive assay in plasma samples taken routinely from FD patients. The assay was calibrated to measure cTnI levels ≥0.01 ng/ml. Elevated cTnI values (cut-off ≥0.04 ng/ml) were correlated with clinical data. Results: cTnI was assessed in 62 FD patients (median age: 47 years, males: 36%). Elevated cTnI levels were detected in 23 (37%) patients. Patients with a cTnI elevation were older (median 55 years versus 36 years, p<0.001). Elevated cTnI levels were associated with the presence of a LVH (16/23 versus 1/39; OR 65.81, CI: 6.747–641.859; p<0.001). In almost all patients with a left ventricular hypertrophy (LVH) elevated cTnI levels were detected (16/17, 94%). Absolute cTnI levels in patients with LVH were higher than in those without (median 0.23 ng/ml versus 0.02 ng/ml; p<0.001). A cTnI level <0.04ng/ml had a high negative predictive value regarding the presence of a LVH (38/39, 97%). In a control group of non-FD patients (n = 17) with LVH (due to hypertension) none showed cTnI levels ≥0.01 ng/ml. Conclusions: Elevated cTnI levels are common in FD patients, reflecting cardiac involvement. FD patients might benefit from a continuous cTnI monitoring

cTNI-values in 3 patients with Fabry disease.

<p>cTNI-values in 3 patients with Fabry disease.</p