Pathogenesis oF Intracranial Aneurysms
Intracranial aneurysms (IA) are a common neurological problem, the rupture of which
frequently constitutes a catastrophic neurological event. While the pathogenesis is largely
unknown, it is believed that both genetic and environmental factors work in concert to
some degree within patients. Our goal was to take a comprehensive approach to
understanding the pathogenesis of IA by identifying factors leading to the formation,
growth and rupture of IA.
Since 1994, we have recruited patients and families with IA into the Yale Brain
Aneurysm Database. Information regarding aneurysm characteristics (size, location,
number), patient characteristics (age, medical, and social history), and family history
were recorded. We analyzed this database for environmental factors associated with
aneurysmal rupture. Within the same database, we identified and analyzed kindreds with
a high IA incidence and penetrance using genome-wide linkage analysis. Collaborations
with other centers provided additional kindreds to analyze and confirm our results.
Analysis of our database revealed hypertensive patients with IA ¡Ü 7mm were 2.6 times
more likely to rupture (p = .01, 95% CI: 1.21, 5.53) than normotensive patients. Posterior
circulation aneurysms were 3.5 times more likely to rupture than anterior circulation
aneurysms (p = .048, 95% CI: 0.95, 19.4). Further, genome-wide linkage analysis
revealed significant linkage to a single locus, with a lod score of 4.2 at 1p34-36.
We identified hypertension, young age, and posterior circulation as significant risk
factors for rupture among patients with small aneurysms (¡Ü 7mm). Additionally, we are
the first to map the gene responsible for IA to chromosome 1p34-26.
Advisor:Murat Gunel MD
School Location:USA - Connecticut
Source Type:Master's Thesis
Keywords:map ruptured hemorrhages gene mortality genetics aneurysm intracranial brain pathology pathogenesis
Date of Publication:12/23/2005