A Review of Von Hippel-Lindau Syndrome.

Von Hippel-Lindau syndrome (VHL) is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40-52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.

Dynamic Contrast-Enhanced MRI in Low-Grade Versus Anaplastic Oligodendrogliomas.

BACKGROUND AND PURPOSE: Low-grade and anaplastic oligodendrogliomas are often difficult to differentiate on the basis of conventional MR imaging characteristics. Dynamic contrast-enhanced (DCE) MRI can assess tumor microvasculature and has demonstrated utility for predicting glioma grade and prognosis in primary brain tumors. The aim of our study was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K(trans) ) derived from DCE MRI in differentiating between grade II and grade III oligodendrogliomas. MATERIALS AND METHODS: Twenty-four consecutive patients with pathologically confirmed oligodendroglioma (World Health Organization grade II, n = 14 and grade III, n = 10) were retrospectively assessed. Pretreatment DCE MRI was performed and regions of interest were manually drawn around the entire tumor volume to calculate Vp and K(trans) . The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were performed to compare pharmacokinetic parameters between the 2 groups. RESULTS: The Vpmean values for grade III oligodendrogliomas were significantly higher (P = .03) than those for grade II oligodendrogliomas. The K(trans) mean values were higher in grade III lesions, but the difference between the 2 groups was not statistically significant (P > .05). Based on ROC analysis, the Vpmean (area under curve = .757, SD = .1) cut-off value that provided the best combination of high sensitivity and specificity to distinguish between grade II and III oligodendrogliomas was 2.35 (P < .03). CONCLUSION: The results of our study suggest the DCE MRI parameter Vpmean can noninvasively differentiate between grade II and grade III oligodendrogliomas.

Pericytes are required for blood-brain barrier integrity during embryogenesis.

Vascular endothelial cells in the central nervous system (CNS) form a barrier that restricts the movement of molecules and ions between the blood and the brain. This blood-brain barrier (BBB) is crucial to ensure proper neuronal function and protect the CNS from injury and disease. Transplantation studies have demonstrated that the BBB is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells. Owing to the close spatial relationship between astrocytes and endothelial cells, it has been hypothesized that astrocytes induce this critical barrier postnatally, but the timing of BBB formation has been controversial. Here we demonstrate that the barrier is formed during embryogenesis as endothelial cells invade the CNS and pericytes are recruited to the nascent vessels, over a week before astrocyte generation. Analysing mice with null and hypomorphic alleles of Pdgfrb, which have defects in pericyte generation, we demonstrate that pericytes are necessary for the formation of the BBB, and that absolute pericyte coverage determines relative vascular permeability. We demonstrate that pericytes regulate functional aspects of the BBB, including the formation of tight junctions and vesicle trafficking in CNS endothelial cells. Pericytes do not induce BBB-specific gene expression in CNS endothelial cells, but inhibit the expression of molecules that increase vascular permeability and CNS immune cell infiltration. These data indicate that pericyte-endothelial cell interactions are critical to regulate the BBB during development, and disruption of these interactions may lead to BBB dysfunction and neuroinflammation during CNS injury and disease.