(Verbatim from applicant?s abstract) This competing continuation application represents a logical continuation of the plan based on the results of the present RO1. NS34949 was submitted in 1995 and renewed in 1998. The PI changed institutions in January 2000. The new project expands the scope of the current ROl by emphasizing a longitudinal population-based component to brain arteriovenous malformation (BAVM) basic epidemiology and natural history.
In Specific Aim I we will re-examine the natural history of BAVM using a hybrid referral and population-based approach. enabling us to resolve the contradictory hypotheses on whether initial presentation determines future natural history. More importantly, we will more accurately estimate rates of subsequent hemorrhage from which to construct clinical trials.
In Specific Aim II we will determine the influence of genetic factors known to influence the incidence and outcome from other intracranial hemorrhage (ICH) syndromes (Apolipoprotein Epsilon 2 and Epsilon 4 alleles: APOE2 and 4).
In Specific Aim III we use a population-based registry (KPNC) to clarify the ascertainment and distribution of BAVM cases by race-ethnic group. The methods consist using our well-established case ascertainment and database registry of BAVM cases in the San Francisco Bay Area. New case material derives from the referral population at UCSF and, after correcting for overlap, a population-based approach in conjunction with Kaiser Permanente Northern California (KPNC: about 3 million covered lives). The general hypotheses are that there are at least two biologic clinical behaviors of BAVMs. We propose to identify risk factors for spontaneous BAVM hemorrhage and treatment outcome. Although the primary reason to treat BAVMs is prophylaxis against intracranial hemorrhage (ICH) treatment decisions must account for both treatment and natural history risk. However, data on these two distinct risks are currently insufficient, which greatly hamper the formulation of randomized clinical trials of BAVM treatment comparing different treatment modalities. The significance of this work is that by clearly documenting natural history risks, a risk-based strategy for treatment will serve as the basis for one or more multicenter (possibly multinational) clinical trials. Such trials may include some combination of surgical, endovascular, radiosurgical or medical treatment and can specifically weigh treatment against natural history risk. The accomplishment of these aims could bring to treating physicians and surgeons the means to further decrease morbidity from BAVMs and a basis for more rational and cost-effective decision-making as regards interventional therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034949-11
Application #
6844681
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Moy, Claudia S
Project Start
1995-09-30
Project End
2006-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
11
Fiscal Year
2005
Total Cost
$335,975
Indirect Cost
Name
University of California San Francisco
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Alexander, Matthew D; Hippe, Daniel S; Cooke, Daniel L et al. (2018) Targeted Embolization of Aneurysms Associated With Brain Arteriovenous Malformations at High Risk for Surgical Resection: A Case-Control Study. Neurosurgery 82:343-349
Yu, Jay F; Nicholson, Andrew D; Nelson, Jeffrey et al. (2018) Predictors of intracranial hemorrhage volume and distribution in brain arteriovenous malformation. Interv Neuroradiol 24:183-188
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
Winkler, Ethan A; Birk, Harjus; Burkhardt, Jan-Karl et al. (2018) Reductions in brain pericytes are associated with arteriovenous malformation vascular instability. J Neurosurg 129:1464-1474
Chen, Xiaolin; Cooke, Daniel L; Saloner, David et al. (2017) Higher Flow Is Present in Unruptured Arteriovenous Malformations With Silent Intralesional Microhemorrhages. Stroke 48:2881-2884
Ma, Li; Kim, Helen; Chen, Xiao-Lin et al. (2017) Morbidity after Hemorrhage in Children with Untreated Brain Arteriovenous Malformation. Cerebrovasc Dis 43:231-241
Alexander, Matthew D; Cooke, Daniel L; Hallam, Danial K et al. (2016) Less can be more: Targeted embolization of aneurysms associated with arteriovenous malformations unsuitable for surgical resection. Interv Neuroradiol 22:445-51
Pekmezci, Melike; Nelson, Jeffrey; Su, Hua et al. (2016) Morphometric characterization of brain arteriovenous malformations for clinical and radiological studies to identify silent intralesional microhemorrhages. Clin Neuropathol 35:114-21
Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey et al. (2016) Genome-wide association study of sporadic brain arteriovenous malformations. J Neurol Neurosurg Psychiatry 87:916-23
Potts, Matthew B; Lau, Darryl; Abla, Adib A et al. (2015) Current surgical results with low-grade brain arteriovenous malformations. J Neurosurg 122:912-20

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