Integrin β8 Deletion Enhances Vascular Dysplasia and Hemorrhage in the Brain of Adult Alk1 Heterozygous Mice.

Brain arteriovenous malformation (bAVM), characterized by tangled dysplastic vessels, is an important cause of intracranial hemorrhage in young adults, and its pathogenesis and progression are not fully understood. Patients with haploinsufficiency of transforming growth factor-β (TGF-β) receptors, activin receptor-like kinase 1 (ALK1) or endoglin (ENG) have a higher incidence of bAVM than the general population. However, bAVM does not develop effectively in mice with the same haploinsufficiency.

Morphometric characterization of brain arteriovenous malformations for clinical and radiological studies to identify silent intralesional microhemorrhages.

Brain arteriovenous malformations (bAVMs) are vascular lesions that can cause significant morbidity and mortality, particularly when they bleed, i.e., rupture.

Genome-wide association study of sporadic brain arteriovenous malformations.

Background: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium.

Methods: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays.

Hemorrhage rates from brain arteriovenous malformation in patients with hereditary hemorrhagic telangiectasia.

Background And Purpose: Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs).

The ACVRL1 c.314-35A>G polymorphism is associated with organ vascular malformations in hereditary hemorrhagic telangiectasia patients with ENG mutations, but not in patients with ACVRL1 mutations.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vascular malformations (VMs) and caused by mutations in TGFβ/BMP9 pathway genes, most commonly ENG or ACVRL1. Patients with HHT have diverse manifestations related to skin and mucosal telangiectases and organ VMs, including arteriovenous malformations (AVM). The clinical heterogeneity of HHT suggests a role for genetic modifiers.

Current surgical results with low-grade brain arteriovenous malformations.

Object: Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process.

Methods: A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period.

Adult mouse venous hypertension model: common carotid artery to external jugular vein anastomosis.

The understanding of the pathophysiology of brain arteriovenous malformations and arteriovenous fistulas has improved thanks to animal models. A rat model creating an artificial fistula between the common carotid artery (CCA) and the external jugular vein (EJV) has been widely described and proved technically feasible. This construct provokes a consistent cerebral venous hypertension (CVH), and therefore has helped studying the contribution of venous hypertension to formation, clinical symptoms, and prognosis of brain AVMs and dural AVFs.

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation.

Aim: To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation (bAVM) is not associated with iron deposition (indicator of microhemorrhage).

Methods: Sections of unruptured, previously untreated bAVM specimens (n=19) were stained immunohistochemically for T-lymphocytes (CD3), B-lymphocytes (CD20), plasma cells (CD138) and macrophages (CD68). Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains.

The natural history of AVM hemorrhage in the posterior fossa: comparison of hematoma volumes and neurological outcomes in patients with ruptured infra- and supratentorial AVMs.

Object: Patients with posterior fossa arteriovenous malformations (AVMs) are more likely to present with hemorrhage than those with supratentorial AVMs. Observed patients subject to the AVM natural history should be informed of the individualized effects of AVM characteristics on the clinical course following a new, first-time hemorrhage. The authors hypothesize that the debilitating effects of first-time bleeding from an AVM in a previously intact patient with an unruptured AVM are more pronounced when AVMs are located in the posterior fossa.

Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress.

Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1) and oxidative stress.

Untreated brain arteriovenous malformation: patient-level meta-analysis of hemorrhage predictors.

Objective: To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts.

Methods: We harmonized data from Kaiser Permanente of Northern California (n = 856), University of California San Francisco (n = 787), Columbia University (n = 672), and the Scottish Intracranial Vascular Malformation Study (n = 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of time-to-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors.

Endoglin deficiency impairs stroke recovery.

Background And Purpose: Endoglin deficiency causes hereditary hemorrhagic telangiectasia-1 and impairs myocardial repair. Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia-1 are associated with a high incidence of paradoxical embolism in the cerebral circulation and ischemic brain injury. We hypothesized that endoglin deficiency impairs stroke recovery.

Common variants on 9p21.3 are associated with brain arteriovenous malformations with accompanying arterial aneurysms.

Objective: To investigate whether previously reported 9p21.3 single nucleotide polymorphisms (SNPs) are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying arterial aneurysms. Common variants in the 9p21.

Stereotactic radiosurgery at a low marginal dose for the treatment of pediatric arteriovenous malformations: obliteration, complications, and functional outcomes.

Unlabelled: OBJECT.: Stereotactic radiosurgery (SRS) is an established treatment modality for brain arteriovenous malformations (AVMs) in children, but the optimal treatment parameters and associated treatment-related complications are not fully understood. The authors present their single-institution experience of using SRS, at a relatively low marginal dose, to treat AVMs in children for nearly 20 years; they report angiographic outcomes, posttreatment hemorrhage rates, adverse treatment-related events, and functional outcomes.

Deep arteriovenous malformations in the basal ganglia, thalamus, and insula: multimodality management, patient selection, and results.

Objective: This study sought to describe a single institution's experience treating arteriovenous malformations (AVMs) of the basal ganglia, thalamus, and insula in a multimodal fashion.

Methods: We conducted a retrospective review of all deep AVMs treated at our institution between 1997 and 2011 with attention to patient selection, treatment strategies, and radiographic and functional outcomes.

Results: A total of 97 patients underwent initial treatment at our institution.

Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia.

Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have a higher prevalence of brain arteriovenous malformation (AVM) than the general population and patients with other HHT subtypes. The pathogenesis of brain AVM in HHT1 patients is currently unknown and no specific medical therapy is available to treat patients.

Induction of brain arteriovenous malformation in the adult mouse.

Brain arteriovenous malformations (bAVM) are tangles of abnormal, dilated vessels that directly shunt blood between the arteries and veins. The pathogenesis of bAVM is currently unknown. Patients with hereditary hemorrhagic telangiectasia (HHT) have a higher prevalence of bAVM than the general population.

De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation.

Background And Purpose: In humans, activin receptor-like kinase 1 (Alk1) deficiency causes arteriovenous malformations (AVMs) in multiple organs, including the brain. Focal Alk1 pan-cellular deletion plus vascular endothelial growth factor stimulation induces brain AVMs in the adult mouse. We hypothesized that deletion of Alk1 in endothelial cell (EC) alone plus focal vascular endothelial growth factor stimulation is sufficient to induce brain AVM in the adult mouse.

Endovascular biopsy: evaluating the feasibility of harvesting endothelial cells using detachable coils.

The absence of safe and reliable methods to harvest vascular tissue in situ limits the discovery of the underlying genetic and pathophysiological mechanisms of many vascular disorders such as aneurysms. We investigated the feasibility and comparable efficacy of endothelial cell collection using a spectrum of endovascular coils. Nine detachable coils ranging in k coefficient (0.

MRI blood-brain barrier permeability measurements to predict hemorrhagic transformation in a rat model of ischemic stroke.

Permeability imaging might add valuable information in the risk assessment of hemorrhagic transformation. This study evaluates the predictive value of blood-brain barrier permeability (BBBP) measurements extracted from dynamic contrast-enhanced MRI for hemorrhagic transformation in ischemic stroke. Spontaneously hypertensive and Wistar rats with 2 h filament occlusion of the right MCA underwent MRI during occlusion, at 4 and 24 h post reperfusion.

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.

Background: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy.

Methods: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries.

A genome-wide investigation of copy number variation in patients with sporadic brain arteriovenous malformation.

Background: Brain arteriovenous malformations (BAVM) are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGFβ) signaling pathway.

Methods: To investigate whether copy number variations (CNVs) contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian.

Angiographic features help predict outcome after stereotactic radiosurgery for the treatment of pediatric arteriovenous malformations.

Purpose: Arteriovenous malformations (AVMs) are a frequent cause of hemorrhagic stroke in children. Stereotactic radiosurgery (SRS) is an established treatment for these lesions, particularly those that are surgically inaccessible. Because only complete AVM obliteration is believed to protect against the future risk of hemorrhage, identifying lesion characteristics that predict response to therapy is an important objective.

Temporal lobe arteriovenous malformations: anatomical subtypes, surgical strategy, and outcomes.

Object: Descriptions of temporal lobe arteriovenous malformations (AVMs) are inconsistent. To standardize reporting, the authors blended existing descriptions in the literature into an intuitive classification with 5 anatomical subtypes: lateral, medial, basal, sylvian, and ventricular. The authors' surgical experience with temporal lobe AVMs was reviewed according to these subtypes.