Biology, Physics, and Genetics of Intracranial Aneurysm Formation: A Review

Intracranial aneurysms (IAs) are persistent, localized dilatations of the arterial wall that are found in ∼3% of the general population. The most severe complication of IAs is rupture, which results in devastating consequences such as subarachnoid hemorrhage and brain damage with serious neurologic sequelae. Numerous studies have characterized the mechanisms underlying IA development and growth and identified several environmental modifiable (smoking, hypertension) and nonmodifiable risk factors (related to the histology of cerebral arteries and genetic factors) in its pathogenesis. Hemodynamic stress also likely plays a crucial role in the formation of IAs and is conditioned by the geometry and morphology of the vessel tree, but its role in the natural history of unruptured IAs remains poorly understood; it is believed that changes in blood flow might generate the hemodynamic forces that are responsible for damage to the vascular wall and vessel remodeling that lead to IA formation. This review summarizes the most relevant data on the current theories on the formation of IAs, with particular emphasis on the roles of special conditions resulting from the microscopic anatomy of intracranial arteries, hemodynamic factors, bifurcation morphometry, inflammatory pathways, and the genetic factors involved in IA formation.