Abstract 63: Mutation of Platelet-Derived Growth Factor Receptor B Causes Cerebrovascular Malformation and Enhances Brain Arteriovenous Malformation Severity in Mice

Background and Purpose: Deletion of Endoglin (Eng), an arteriovenous malformation (AVM) causative gene causes AVM in the brain angiogenic region. Reduction of pericytes is correlate with brain AVM hemorrhage. The platelet-derived growth factor B and its receptor β (PDGF-B/PDGFRβ) play important roles in regulating pericyte recruitment during angiogenesis. We hypothesize that mutation of PDGFRβ causes cerebrovascular malformation and enhances bAVM severity in Eng mutant mice. Methods: Three mouse models were used: (1) Pdgfrβ F7 (F7) mice that have mutations disrupting Pdgfrβ signaling, (2) Pdgfb -icreER; Eng f /f mice that have Pdgfb promoter driving, tamoxifen (TM) inducible cre expression in ECs and an floxed Eng gene; and (3) Pdgfb -icreER; Eng f /f ;F7 +/- mice. Brain angiogenesis was induced by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF). Brain AVMs were induced in Pdgfb -icreER; Eng f /f and Pdgfb -icreER; Eng f /f ;F7 mice by TM induced EC Eng deletion and intra-brain AAV-VEGF injection. Brain AVM phenotypes were analyzed 8-weeks after model induction by latex vascular cast to detect arteriovenous shunts and macroscopic level of AVMs, immunostaining and Prussian blue staining to quantify dysplasia vessels and hemorrhage. Results: Compared to WT mice, F7 +/- and F7 +/+ mice have more dysplastic vessels and fewer vascular pericyte before and after AAV-VEGF injection. F7 +/- and F7 +/+ mice showed hemorrhage on the AAV-VEGF injection sites and AVM like vessels (a few arteriovenous shunts) in 16% F7 +/- and 66% of F7 +/+ mice. Pdgfb -icreER; Eng f /f mice showed dysplastic vessels and hemorrhage at AAV-VEGF injection sites. Compared to Pdgfb -icreER; Eng f /f mice, Pdgfb -icreER; Eng f /f ;F7 +/- had a higher penetrance of bAVM (71% vs 50%) and more dysplastic vessels. Conclusion: F7 mutation cause AVM like structure in mouse brain and exacerbates bAVM phenotype in Eng mutant mice.

Neurofibromatosis type-1 with seizures and cerebrovascular malformation: a case study

Neurofibromatosis type 1 (NF1) is the most common autosomal dominant neurocutaneous among humans. Epilepsy is more prevalent in NF1 patients than in the general population. NF1 vasculopathy is also a significant but underrecognized complication of the disease, affecting both arterial and venous blood vessels. Herein, we report a 2 year old female child with seizures and multiple cafe-au-lait spots on the body. The patient was diagnosed with NF1 based on clinical findings and family history. MRI Brain revealed middle cerebral artery dysplasia. Here we discuss diagnostic and treatment challenges and briefly reviews the existing literature.

Sturge-Weber Syndrome and Related Cerebrovascular Malformation Syndromes

Sturge-Weber syndrome is a rare disorder presenting with a capillary malformation, better known as a port-wine birthmark, on the upper face, glaucoma, and a leptomeningeal angioma. Most children develop seizures and strokes, with variable degrees of neurodevelopmental impairments including hemiparesis, visual field deficits, cognitive deficits, epilepsy, and migraines. In 2013, a somatic activating mutation in GNAQ was identified in the capillary malformations and leptomeningeal angiomas of Sturge-Weber patients. In the diagnosis of Sturge-Weber syndrome, contrast-enhanced imaging is essential to the diagnosis of brain involvement. Functional imaging has demonstrated impaired venous drainage and a role for seizures in exacerbating perfusion deficits. Aggressive seizure management is fundamental to treatment. Some data supports the use of low-dose aspirin to reduce the occurrence of strokelike episodes and seizures.

What the Neurosurgeon needs to know about Cerebral Developmental Venous anomalies

Venous Angiomas or Developmental venous anomalies (DVA) are extreme variations of normal transmedullary veins that are necessary for the drainage of white and gray matter, also are one type of cerebrovascular malformation (CVM), sharing category with capillary telangiectesias, cavernous malformations (CM), and arteriovenous malformations (AVM), each of which may also be associated with a DVA. DVA are the most commonly encountered CVM, accounting for up to 60% of all CVM. We present a review of the literatura

Auditory Dysfunction in Patients with Cerebrovascular Disease

Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.