Intracranial dural arteriovenous fistulae (DAVF) are rare and poorly understood vascular malformations. They consist of a direct connection between arteries and veins, with the nidus located within the dura. DAVFs present as a potentially disabling intracranial hemorrhage in onethird of the patients. Although their pathogenesis is unknown, disordered angiogenesis and thrombosis may have an important role. Several hypotheses will be tested in this project. We will determine whether the presence of cortical venous drainage is a predictor of intracranial hemorrhage (ICH). Further, we will test whether low natural history risk patients have a better outcome after attempted therapy. To assess possible causal factors, we will test whether pro-thrombotic genetic polymorphisms and oral contraceptive use are associated with the occurrence of DAVF.
The Specific Aims will be as follows: 1) To determine clinical characteristics of DAVF patients who present with ICH, 2) to document the treatment response and longterm outcome in DAVF patients, 3) to determine the frequency of pro-thrombotic genetic polymorphism in DAVF patients compared with controls, and 4) to determine the influence of environmental factors in DAVF formation. This research should provide useful new information about the natural history of DAVF, their optimal management and role of genetic and hormonal factors in their development. In addition the proposed project will combine didactic teaching, mentoring, and clinical research to build upon Dr. Singh's training in neurovascular neurology, thereby allowing her to develop as an independent clinical investigator in neurovascular neurology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23NS042072-01
Application #
6365619
Study Section
NST-2 Subcommittee (NST)
Program Officer
Marler, John R
Project Start
2001-09-25
Project End
2006-08-31
Budget Start
2001-09-25
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$135,697
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
LaHue, Sara C; Kim, Helen; Pawlikowska, Ludmila et al. (2018) Frequency and characteristics associated with inherited thrombophilia in patients with intracranial dural arteriovenous fistula. J Neurosurg :1-5
Singh, Vineeta; Smith, W S; Lawton, Michael T et al. (2008) Risk factors for hemorrhagic presentation in patients with dural arteriovenous fistulae. Neurosurgery 62:628-35;discussion 628-35
Flint, Alexander C; Roebken, Ashley; Singh, Vineeta (2008) Primary intraventricular hemorrhage: yield of diagnostic angiography and clinical outcome. Neurocrit Care 8:330-6
Singh, Vineeta; Carman, Melissa; Roeper, Jochen et al. (2007) Brief ischemia causes long-term depression in midbrain dopamine neurons. Eur J Neurosci 26:1489-99
Schilstrom, Bjorn; Yaka, Rami; Argilli, Emanuela et al. (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci 26:8549-58
Halim, Alexander X; Johnston, S Claiborne; Singh, Vineeta et al. (2004) Longitudinal risk of intracranial hemorrhage in patients with arteriovenous malformation of the brain within a defined population. Stroke 35:1697-702
Ungless, Mark A; Singh, Vineeta; Crowder, Tara L et al. (2003) Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. Neuron 39:401-7