Intracranial aneurysms: risk factors for development and rupture

Abstract

Intracranial aneurysms occur in approximately 3% of the population. The pathogenesis of aneurysms is largely unknown, and is thought to be a complex process in which both genetic and environmental factors are involved. Aneurysms can rupture and give rise to subarachnoid haemorrhage, a devastating subtype of stroke with high morbidity and mortality. Treatment can prevent rupture, but carries a risk of major complications including death. The annual risk of rupture of an aneurysm lies around 1%, indicating that the majority of aneurysms never ruptures. Therefore, preventive treatment should be restricted to those aneurysms with high risk of rupture. However, only a limited amount of risk factors are available. Therefore, better risk factors to predict aneurysm rupture are urgently needed. In this thesis, a systematic review and meta-analysis led to the identification of irregular shape of the aneurysm as an additional risk factor for use in rupture risk prediction of aneurysms in clinical practice. This review also gives an overview of risk factors with potential for use in clinical practice, for which further research is needed. Furthermore, in a study of 624 patients with subarachnoid haemorrhage no association was found between aneurysm size and the six genetic risk loci identified in the genome wide association study on intracranial aneurysms. RNA sequencing analysis of intracranial aneurysm walls revealed the role of extracellular matrix pathways and immunoglobulins in the development of aneurysms, and immune response pathways and the lysosome pathway in rupture of aneurysms. Finally, this thesis showed that 7.0 Tesla MRI has potential for studying new risk factors for aneurysm rupture. MRI signal intensity variation reflects actual thickness variation in the aneurysm wall when using a 7.0 Tesla MRI vessel wall sequence. A method was developed to quantify and compare thickness variation between different patients, and this method can be used to study aneurysm wall thickness variation as a risk factor for growth or rupture of aneurysms. This method was also used to study the association between wall thickness variation and wall shear stress, and showed that thinner regions correlate with regions of higher wall shear stress. Pulsatility (the change in volume of the aneurysm during the cardiac cycle) is a potential risk factor for rupture, and was studied on 7.0 Tesla MRI. However, it was concluded that volume pulsation quantification is not accurate with the current imaging protocol, due to multiple imaging artefacts.