A multidisciplinary, inter-institutional group of investigators with long-standing interest in brain vascular malformations proposes to establish a RDCRC. The diseases of study are common Hispanic mutation familial Cavernous Malformations (CCM), Sturge-Weber Syndrome (SWS) and Brain Arteriovenous Malformation (BAVM) in Hereditary Hemorrhagic Telangectasia (HHT). The three projects will focus on (a) establishment of scalable, relational databases to facilitate observational studies and clinical trials, working with the RDCRN DMCC;and (b) development of markers for disease progression with near-term potential for aiding prognostication and clinical trial development.
The aims for CCM include identification of genetic markers for disease progression in cross-sectional and longitudinal study designs using a Genome-Wide Association approach.
The aims for SWS are to use urinary excretion of angiogenic mediators as markers for disease progression. Further, we will establish somatic mutations as an underlying disease mechanism with an eye towards adapting such knowledge into a biomarker strategy.
The aims for HHT include quantitative estimation of intracranial hemorrhage (ICH) risk in cross-sectional and longitudinal study designs, using both angioarchitectural features and genetic variation in inflammatory genes. Pilot projects will evaluate novel treatment strategies for the diseases, including the use of aspirin in SWS and tetracycline-class agents in hemorrhagic vascular malformations. We will utilize CTSAs or GCRCs at UCSF, Duke, New Mexico, Kennedy Krieger and Univ. Toronto, with a detailed program for training new investigators in clinical research on rare diseases. Three international Patient Support Organizations (PSOs)-Angioma Alliance, Sturge Weber Foundation, HHT Foundation International-will actively participate. With the DMCC, we will develop a website as a portal for web-based data entry and include a wide range of information for patients, families and professionals. We will utilize a network of established Centers of Excellence in SWS and HHT to identify patients. This RDCRC will provide a much-needed and valuable resource for the clinical neurovascular community for the study of these three disorders.

Public Health Relevance

Brain vascular malformations are resource-intensive to manage effectively, and have high probability of serious neurological morbidity. Specific medical therapies for these diseases are lacking. The identification of markers for progression would improve patient surveillance and optimize management, and treatment trials will require risk stratification for selection and surrogate outcomes for trial development.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y (50))
Program Officer
Jacobs, Tom P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Meybodi, Ali Tayebi; Kim, Helen; Nelson, Jeffrey et al. (2018) Surgical Treatment vs Nonsurgical Treatment for Brain Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia: A Retrospective Multicenter Consortium Study. Neurosurgery 82:35-47
Wellman, Rebecca J; Cho, Su Bin; Singh, Pratibha et al. (2018) G?q and hyper-phosphorylated ERK expression in Sturge-Weber syndrome leptomeningeal blood vessel endothelial cells. Vasc Med :1358863X18786068
Morrison, Melanie A; Payabvash, Seyedmehdi; Chen, Yicheng et al. (2018) A user-guided tool for semi-automated cerebral microbleed detection and volume segmentation: Evaluating vascular injury and data labelling for machine learning. Neuroimage Clin 20:498-505
Walcott, Brian P; Winkler, Ethan A; Zhou, Sirui et al. (2018) Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing. Hum Genome Var 5:18001
Pawlikowska, Ludmila; Nelson, Jeffrey; Guo, Diana E et al. (2018) Association of common candidate variants with vascular malformations and intracranial hemorrhage in hereditary hemorrhagic telangiectasia. Mol Genet Genomic Med 6:350-356
De la Torre, Alejandro J; Luat, Aimee F; Juhász, Csaba et al. (2018) A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome. Pediatr Neurol 84:11-20
Kasthuri, Raj S; Montifar, Megan; Nelson, Jeffrey et al. (2017) Prevalence and predictors of anemia in hereditary hemorrhagic telangiectasia. Am J Hematol :
Zou, Xiaowei; Hart, Blaine L; Mabray, Marc et al. (2017) Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Neuroradiology 59:685-690
Tang, Alan T; Choi, Jaesung P; Kotzin, Jonathan J et al. (2017) Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature 545:305-310
Strickland, Corinne D; Eberhardt, Steven C; Bartlett, Mary R et al. (2017) Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology 284:443-450

Showing the most recent 10 out of 49 publications