Physical Factors Effecting Cerebral Aneurysm Pathophysiology

Abstract

Many factors that are either blood-, wall-, or hemodynamics-borne have been associated with the initiation, growth, and rupture of intracranial aneurysms. The distribution of cerebral aneurysms around the bifurcations of the circle of Willis has provided the impetus for numerous studies trying to link hemodynamic factors (flow impingement, pressure, and/or wall shear stress) to aneurysm pathophysiology. The focus of this review is to provide a broad overview of such hemodynamic associations as well as the subsumed aspects of vascular anatomy and wall structure. Hemodynamic factors seem to be correlated to the distribution of aneurysms on the intracranial arterial tree and complex, slow flow patterns seem to be associated with aneurysm growth and rupture. However, both the prevalence of aneurysms in the general population and the incidence of ruptures in the aneurysm population are extremely low. This suggests that hemodynamic factors and purely mechanical explanations by themselves may serve as necessary, but never as necessary and sufficient conditions of this disease’s causation. The ultimate cause is not yet known, but it is likely an additive or multiplicative effect of a handful of biochemical and biomechanical factors.

Alternative Splicing of Endothelial Fibronectin Is Induced by Disturbed Hemodynamics and Protects Against Hemorrhage of the Vessel Wall

“…However, even given pre-existing genetic defects, not all blood vessels develop aneurysms; hemodynamics are a critical determinant of the location of aneurysms. For example intracranial aneurysms are more likely to grow and rupture in regions of the vasculature with disturbed flow 4-6 . The frictional force of flow, or shear stress, is sensed by the endothelium, which plays a critical role in regulating the vessels' response to these flows 7 .…”

Prognostic value of premorbid hypertension and neurological status in aneurysmal subarachnoid hemorrhage: pooled analyses of individual patient data in the SAHIT repository

“…14,27,37 Survivors are largely left with prolonged functional impairments requiring their dependence on others to meet daily needs. 1 It is now recognized that aneurysmal SAH is the end result of a chronic disorder of cerebral arteries 3,33 and that the formation, growth, and eventual rupture of aneurysms is facilitated by preexisting hypertension. 5,23 Hypertension has been identified as the most common comorbid disease, with reported prevalence estimates exceeding 40% in some studies.…”

“…11,17,19,21,29,30,32,40 While older studies focused on mortality outcomes and did not fully account for the influence of confounding factors such as patient age, 17,19,29,40 more contemporary studies with better risk adjustment have also offered contradictory findings. 11,22,31,33 Patient neurological status is the single most important indicator of the severity of brain injury soon after SAH and is critical to treatment decisions and prediction of outcome. 14,31,43 However, accurate estimation of the prognostic strength of neurological status has been challenging as investigators have usually focused on prognostic associations only in the context of patients who were enrolled into randomized clinical trials (RCTs) 11,32 or singlehospital cohorts, 21,24 with risk adjustment for a variable set of confounders.…”

Effect of Disturbed Blood Flow on Endothelial Cell Gene Expression

“…Disturbed flow also promotes cerebral aneurysm formation, such as in the context of preexisting genetic defects, although molecular mechanisms have not been elucidated. 3 The effects of disturbed flow on endothelial cell biology have been studied extensively in the inner (lesser) curvature of the aortic arch (Figure). The hemodynamics of this region have been evaluated and modeled extensively, especially in the mouse.…”