What causes brain aneurysms?

What Causes Brain Aneurysms?

Brain aneurysms develop from a combination of acquired hemodynamic stress at arterial branch points and underlying vessel wall weakness, with modifiable risk factors like smoking and hypertension playing critical roles in their formation and rupture.

Anatomical and Structural Factors

Most brain aneurysms are saccular lesions that form at branch points of major intracranial arteries, particularly within the Circle of Willis 1, 2. The structural vulnerability at these bifurcation points results from:

• Hemodynamic stress concentrated at arterial branch points where blood flow creates mechanical forces on vessel walls 3
• Microscopic anatomy of intracranial arteries that differs from extracranial vessels, with thinner media and less elastic tissue making them more susceptible to aneurysm formation 3
• Vessel wall remodeling in response to chronic hemodynamic forces and inflammatory processes 3, 4

Children show different patterns than adults, with more posterior circulation involvement and giant aneurysms, and less frequent involvement of anterior and posterior communicating arteries 1.

Modifiable Risk Factors

Smoking

Cigarette smoking is the most important modifiable risk factor for aneurysm formation, with studies showing dramatically increased risk 1. One case-control study demonstrated an odds ratio of 9.1 for patients with >10 pack-years of smoking history 5. The American Heart Association/American Stroke Association guidelines strongly recommend smoking cessation counseling for all patients with unruptured aneurysms 1.

Hypertension

Hypertension contributes to both aneurysm formation and rupture through increased hemodynamic stress and activation of inflammatory pathways 1. Blood pressure control is recommended as a Class I intervention for patients with unruptured aneurysms 1. Hypertension was identified as a significant independent predictor of rupture in prospective studies 1.

Alcohol Consumption

Excessive alcohol use increases risk of aneurysm development and rupture 1, 4, 6. The mechanism likely involves both direct vascular effects and associated hypertension.

Genetic and Hereditary Conditions

Several inherited conditions substantially increase aneurysm risk 1:

• Autosomal dominant polycystic kidney disease: Approximately 8% of affected individuals develop intracranial aneurysms 1
• Ehlers-Danlos syndrome type IV: Associated with aneurysms affecting the intracranial portion of the internal carotid artery 1
• Fibromuscular dysplasia: About 7% of patients develop intracranial aneurysms 1
• Coarctation of the aorta: Increases risk, with average age of aneurysm rupture at 25 years 1
• Marfan syndrome and pseudoxanthoma elasticum: Also associated with increased risk 1

Familial clustering occurs even without identified genetic syndromes, with first-degree relatives of aneurysm patients having a 4-fold increased prevalence 1. However, there is no clear mendelian inheritance pattern, and familial aneurysms have been linked to different chromosomes (19q13.3 and 7q11) in different families 1.

Inflammatory and Molecular Mechanisms

Inflammation plays a crucial role in aneurysm pathogenesis and growth 1, 3:

• Reactive oxygen species induce endothelial dysfunction through Nuclear Factor Kappa-B activation, a key regulator of proinflammatory genes 4
• Chronic inflammation combined with hemodynamic stress leads to vessel wall degradation 3, 4
• Inadequate dietary antioxidants may increase risk through oxidative stress mechanisms 4

Infectious Causes

Mycotic (infectious) aneurysms result from arterial damage caused by infective emboli, most commonly in children with infective endocarditis from congenital or rheumatic heart disease 1. These aneurysms:

• Develop more distally in the cerebral vasculature than saccular aneurysms 1
• Are often multiple 1
• Can result from bacterial or fungal infections 1
• May resolve with treatment of the underlying infection 1

Demographic Factors

Women have increased susceptibility to aneurysm formation 1, 6. The protective effect of estrogen on arterial wall components and inflammatory molecules may explain why aneurysm incidence increases after menopause 6. The role of oral contraceptives remains controversial, with some data suggesting high-dose estrogen formulations may increase risk 1.

Age influences risk, with aneurysm prevalence increasing with age, though aneurysms are thought to be acquired rather than congenital 1.

Clinical Pitfalls

• Hypertension is NOT a common cause of brain hemorrhage in children, unlike adults—only 1 of 26 pediatric patients with brain hemorrhage had systemic hypertension in autopsy series 1
• Multiple aneurysms occur in 15-30% of patients, with risk factors including female sex, smoking, hypertension, and family history 1
• Aneurysm growth increases rupture risk, making surveillance imaging important for conservatively managed cases 1