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

Intracranial aneurysms (IAs) are persistent, localised dilatations of the arterial wall that are found in approximately 3% of the general population. The most severe complication of IAs is rupture, which results in devastating consequences such as subarachnoid haemorrhage and brain damage with serious neurological sequelae. Numerous studies have characterised the mechanisms underlying IA development and growth and identified a number of environmental modifiable (smoking, hypertension) and nonmodifiable risk factors (related to the histology of cerebral arteries and genetic factors) in its pathogenesis. Haemodynamic 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 haemodynamic forces that are responsible for damage to the vascular wall and vessel remodelling that lead to IA formation. This review summarises 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, haemodynamic factors, bifurcation morphometry, inflammatory pathways, and the genetic factors involved in IA formation.