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.

Morphological and Hemodynamic Risk Factors for Middle Cerebral Artery Aneurysm: a Case-Control Study of 190 Patients.

This study analyzed morphometric and hemodynamic parameters of aneurysmal and non-aneurysmal middle cerebral artery (MCA) bifurcations and their relationship with optimal values derived from the principle of minimum work (PMW). The study included 96 patients with MCA aneurysm and 94 controls. Aneurysm patients presented with significantly higher values of the radius and cross-sectional area of the MCA trunk, angle between the post-bifurcation branches (α angle) and volume flow rate (VFR) and had significantly lower values of junction exponent and pulsatility index than the controls. The Φ1 and Φ2 angles (angles between the MCA trunk axis and the larger and smaller branch, respectively) and α angle in all groups were significantly larger than the optimal PMW-derived angles. The most important independent predictors of MCA aneurysm were junction exponent (odds ratio, OR = 0.42), α angle (OR = 1.07) and VFR (OR = 2.36). Development of cerebral aneurysms might be an independent effect of abnormalities in hemodynamic and morphometric factors. The risk of aneurysm increased proportionally to the deviation of morphometric parameters of the bifurcation from their optimal PMW-derived values. The role of bifurcation angle in aneurysm development needs to be explained in future research as the values of this parameter in both aneurysm patients and non-aneurysmal controls in were scattered considerably around the PMW-derived optimum.