Notch receptor expression in human brain arteriovenous malformations.

The roles of the Notch pathway proteins in normal adult vascular physiology and the pathogenesis of brain arteriovenous malformations are not well-understood. Notch 1 and 4 have been detected in human and mutant mice vascular malformations respectively. Although mutations in the human Notch 3 gene caused a genetic form of vascular stroke and dementia, its role in arteriovenous malformations development has been unknown. In this study, we performed immunohistochemistry screening on tissue microarrays containing eight surgically resected human brain arteriovenous malformations and 10 control surgical epilepsy samples. The tissue microarrays were evaluated for Notch 1-4 expression. We have found that compared to normal brain vascular tissue Notch-3 was dramatically increased in brain arteriovenous malformations. Similarly, Notch 4 labelling was also increased in vascular malformations and was confirmed by western blot analysis. Notch 2 was not detectable in any of the human vessels analysed. Using both immunohistochemistry on microarrays and western blot analysis, we have found that Notch-1 expression was detectable in control vessels, and discovered a significant decrease of Notch 1 expression in vascular malformations. We have demonstrated that Notch 3 and 4, and not Notch 1, were highly increased in human arteriovenous malformations. Our findings suggested that Notch 4, and more importantly, Notch 3, may play a role in the development and pathobiology of human arteriovenous malformations.

High fluorodeoxyglucose ((18)F)PET-uptake lymph nodes in a patient with chordoma: Tumor metastasis or sarcoidosis?

PATIENT: Male, 48 FINAL DIAGNOSIS: Chordoma Symptoms: - MEDICATION: - Clinical Procedure: - Specialty: Neurology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Fluorodeoxyglucose positron emission tomography (FDG-PET) has been used in imaging and staging of malignancies including sacral chordomas. CASE REPORT: The author's report describes the coincident pathological diagnosis of sarcoidosis in a 48-year-old male patient with a recurrent sacral chordoma. Chordoma is a low grade malignancy with frequent systemic metastases in advanced disease. Both metastases and sarcoidosis may be high FDG uptake. Unexpected PET findings need to be biopsied in order to make appropriate clinical decision in the management of chordoma. CONCLUSIONS: Lymph nodes involvement in sarcoidosis and neoplastic disease can have similar FDG-PET manifestations.