A prospective cohort study on patients treated with anticoagulants for cerebral vein thrombosis.

OBJECTIVES: Cerebral vein thrombosis (CVT) is a potentially fatal disorder for which treatment guidelines are scanty. To assess the short- and long-term benefit of anticoagulant therapy, we performed a prospective cohort study on CVT patients. METHODS: Forty-four consecutive CVT patients received conventional anticoagulation with heparin followed by warfarin for at least 3 months. Patients presenting with symptoms suggestive of pulmonary embolism (PE) underwent confirmatory objective tests. Acquired or inherited risk factors for thrombosis were investigated in all patients. Thrombotic and hemorrhagic events occurring during treatment, and the long-term outcome using the modified Rankin Scale (mRS) were recorded. RESULTS: Congenital and/or acquired conditions predisposing to thrombosis were detected in 37 patients (84.1%), with a high prevalence of oral contraceptive use (66.7% of females) and thrombophilia (31.8%); more than one risk factor was seen in 31.8% of cases. At referral, six patients (13.6%) presented with symptoms of PE, which was confirmed in all. During the initial treatment period, two patients (4.5%) developed symptomatic progression of CVT, which was fatal in 1, and 2 (4.5%) developed major bleeding complications. A favorable outcome (mRS 0-2) at 6-12 months was recorded in 37 of the 43 patients who survived the acute phase (86%). CONCLUSIONS: The outcome of CVT patients managed with conventional anticoagulation who survive the initial phase is favorable in the vast majority. The prevalence of concomitant PE is considerably high, supporting the need of anticoagulant therapy.

Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Olfactory cortexes and the olfactory tracts are involved in sporadic Creutzfeldt-Jakob disease. We examined peripheral regions of the olfactory sensory pathway, including the olfactory mucosa, to assess whether pathologic infectious prion protein (PrPSc) is deposited in the epithelium lining the nasal cavity. METHODS: We studied nine patients with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease. We obtained the brain, the cribriform plate with the attached olfactory mucosa, and the surrounding respiratory epithelium at autopsy. Control samples of nasal mucosa were obtained post mortem or at biopsy from age-matched control subjects and from control patients with other neurodegenerative diseases. The olfactory and respiratory mucosa and the intracranial olfactory system were analyzed by light microscopy, immunohistochemistry, and Western blotting for pathological changes and for deposition of PrPSc. RESULTS: In all nine patients with sporadic Creutzfeldt-Jakob disease, PrPSc was found in the olfactory cilia and central olfactory pathway but not in the respiratory mucosa. No PrPSc was detected in any of the tissue samples from the 11 controls. CONCLUSIONS: Our pathological and biochemical studies show that PrPSc is deposited in the neuroepithelium of the olfactory mucosa in patients with sporadic Creutzfeldt-Jakob disease, indicating that olfactory biopsy may provide diagnostic information in living patients. The olfactory pathway may represent a route of infection and a means of spreading prions.

Beta amyloid angiogenic activity in vitro and in vivo.

Angiogenesis has been suggested as a direct contributor to Alzheimer's disease (AD) pathology. The major pathological hallmarks of AD are the presence of neurofibrillary tangles and, beta-amyloid plaques associated with activated microglia, astrocytes, degenerating neurons and vascular toxicity. In this study, Abeta1-40 and Abeta1-42 peptides, both components of the senile plaques in AD, were used to study their angiogenic activity in vitro, by using normal human cerebral endothelial cells (HCECs), and in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. Results showed that both peptides stimulate in vitro endothelial cell proliferation, chemotaxis and morphogenesis in Matrigel. Moreover, by using the aorta ring assay, both peptides stimulated the formation of capillary-like structures. An angiogenic response was induced in the CAM assay, similar to that induced by fibroblast growth factor-2 (FGF-2), a well-known angiogenic cytokine. Overall, these data support the hypothesis that Abeta peptides may contribute to angiogenesis occurring in AD and suggest that limiting the pro-angiogenic activity of Abeta peptides may therefore provide a useful target to control angiogenesis associated to AD and therefore limit the disease progression.

Double vena cava filter insertion in congenital duplicated inferior vena cava: a case report and literature review.

The complex embryogenesis of the inferior vena cava (IVC) may result in several anomalies, often presenting as an incidental radiological finding. In addition to the differential diagnosis with pathological lesions, recognizing IVC defects is crucial for invasive procedures. This report describes a patient with a right femoral vein thrombosis who could not be given anticoagulant therapy due to a concomitant acute cerebral hemorrhage. He was found to have an asymptomatic duplicated IVC with interiliac communication. A filter had to be inserted in each vena cava to prevent pulmonary embolism. A review of the literature dealing with the few reported cases of filter insertion in congenital duplicated IVC is presented.

Endothelial cells from human cerebral aneurysm and arteriovenous malformation release ET-1 in response to vessel rupture.

Cerebral aneurysms and arteriovenous malformations (AVM) are a common cause of stroke and cerebral hemorrage. Both are often discovered when they rupture, causing subarachnoid hemorrhage (SAH). SAH-induced vasospasm is mediated by enhanced vasoconstriction due to endothelin-1 (ET-1). We investigated whether endothelial cells (ECs) obtained from aneurysm and AVM express phenotypic and genotypic alterations contributing to the development of vasospasm after SAH. We isolated ECs from human AVM and aneurysm and then confirmed their EC origin by polymerase chain reaction and immunocytochemistry with endothelial markers. Experiments were also carried out with human cerebral microvascular and umbilical vein ECs (HCECs and HUVECs respectively) for comparison. We tested EC proliferation ability and microtubule formation in Matrigel at different cell passages. Five aneurysm (3 ruptured, 2 unruptured) and 3 AVM (2 ruptured, 1 unruptured) ECs were tested for ET-1 release in the culture medium. Aneurysm and AVM ECs expressed von Willebrand factor, Adrenomedullin, and exhibited a progressive reduction of proliferation and in vitro angiogenic ability after the V passage. Significantly higher levels of ET-1 have been detected in ECs from ruptured aneurysms and AVMs. We report the first successful isolation and characterization of primary EC lines from human cerebral vascular lesions. Augmented release of ET-1 is correlated with the rupture of the abnormal vessel confirming its role in vasospasm after SAH. Furthermore, ECs obtained from these vascular malformations can be used as an experimental model to study SAH-induced vasoconstriction.