Brain aneurysm is a localized bulge in the wall of an artery, normally filled with blood. It could have different shapes.
The radiological and autoptic prevalence of aneurysms is 3,2% (in people without comorbidity) with a mean age of 50y and 1:1 ratio between male and female.
Note than in population older than 50y, gender ratio is 2:1 for women because of estrogenic deficiency.
Aneurysmal subarachnoid hemorrhage (SAH) occurs in 6-16 cases/100.000 people.
85% of the aneurysm are located in the anterior circulation, on the circle of Willis.
In patients with aneurysms, 20-30% have multiple ones.
- Junction between AComA (anterior communicating artery) with ACA (anterior cerebral artery)
- Junction between PComA (posterior communicating artery) with ICA (internal carotid artery)
- Bifurcation of MCA (middle cerebral artery)
- Localization in the posterior circulation includes:
- Tip of the basilar artery
- Junction between the basilar artery and AICA (Anterior Inferior Cerebellar Artery) or SCA (Superior Cerebellar Artery)
- Junction between the vertebral artery and the PICA (Posterior Inferior Cerebellar Artery)
- Genetic Factors: some studies revealed the importance of this type of factors on the development of the aneurysms.
- Hereditary Syndromes: it has to be suspected if more than one family member develops intracranial aneurysms
- Familial aneurysm: even in absence of hereditary syndrome.
Hereditary Syndromes (details):
- Connective tissue disease (Ehlers-Danlos disease, pseudoxanthoma elasticum)
- Autosomal dominant polycystic kidney disease (PKD) but also autosomal recessive form
- Familiar aldosteronism type I
- Moyamoya syndrome
The age-adjusted prevalence in first-degree relatives of patient with aneurysm is 9%.
Note that familial aneurysms tend to rupture even if they are smaller than sporadic aneurysms and the rupture occurs at younger age. The localization of the aneurysm tends to be similar in a family, too.
Intracranial aneurysms are the major cause of SAH and in fact these pathologies have in common several risk factors.
- Cigarette smoking
- Alcohol consumption
Others factors not directly correlated to aneurysm's pathogenesis:
- Estrogen deficiency: cause a reduction of collagen content of tissues
- Coarctation of aorta: this condition causes secondary hypertension
Note that physical activity and hypercholesterolemia can reduce the risk of aneurysm formation.
There are three type of intracranial aneurysm:
- Saccular aneurysm: thin-walled protrusion of the artery with absence or reduction of both the tunica media and the internal elastic lamina
- Fusiform aneurysm: dilatation of the entire wall of the artery usually due to atherosclerosis
- Mycotic aneurysm: caused by mycotic emboli (for example in the setting of an infective endocarditis)
Note that saccular aneurysms are responsible of most cases of SAH (subarachnoid hemorrhage).
The pathogenesis is thought to be multifactorial.
Some risk factors and hemodynamic patterns contribute to the development of the aneurysm.
- Hemodynamic stress: due to hypertension, cigarette smoke, etc. This stress causes a damage of the internal elastic lamina with a probably breakdown of it.
- Turbulent blood flow: associated with high-flow states. The vibration of the vessels can cause a stress-response that damage the wall of the artery.
The pathogenesis reflects the histology of the arterial wall of the aneurysm: this is a characteristic that is important to evaluate the risk of rupture.
There are four type of aneurysm according to the histology of the artery’s wall:
- Type A: Endothelialized wall with linearly organized smooth muscle cells
- Type B: Thickened wall with disorganized smooth muscle cells
- Type C: Hypocellular wall with either intimal hyperplasia or organizing luminal thrombosis
- Type D: extremely thin thrombosis-lined hypocellular wall
From type A to type D the risk of rupture increases.
Note that the internal elastic lamina is absent in all types of aneurysm.
Most of the aneurysms are asymptomatic and so they can be found:
- In the setting of aneurysmal SAH
If aneurysms are symptomatic, the fundamental symptoms and signs are (depending on the site):
- Headache (comparable to SAH’s headaches)
- Facial pain
- Pyramidal dysfunction
- Cranial nerves neuropathies (for example III nerve palsy)
- Visual acuity loss
- Cerebral ischemia due to formation of emboli in aneurysms
The major complication is the rupture of the aneurysm.
The risk factors for the rupture of aneurysms are:
- Size: the cut-off value in aneurysm diameter to define a lower risk of rupture is 7mm. With higher diameter, the risk of rupture increase progressively. Note that biggest aneurysm grows faster, too.
There is some concern about this cut-off value because a lot of patients presented with SAH seems to have had a rupture of an aneurysm <10mm. So, a hypothesis of growth and rupture of the aneurysm was developed:
- The aneurysm developed in few time (hours, days or week) acquiring a diameter that reflect the elastic properties of the arterial wall. The aneurysm can either rupture or stabilized itself.
- An aneurysm stabilizes itself in diameter through a thickening in the collagen matrix gaining a significative tensile strength.
- Because of Laplace’s law (wall stress increase with the square of the diameter), aneurysm >1cm at initial stabilization are considered at major risk of rupture.
So: for aneurysm that ruptures after their formation the cut-off value is smaller than in other aneurysm.
- Cavernous carotid artery aneurysms: lower risk of rupture
- Anterior circulation aneurysms (including ICA’s aneurysm): intermediate risk of rupture
- Posterior circulation aneurysms: highest rates of rupture
- Racial differences: in Japan there is a higher risk of rupture than in Europe and North America
- Precipitating event: acute physical exercises and emotional stress can increase the risk of aneurysm rupture
- Prior hemorrhage
- Family history
- Daughter sac (protrusion of the wall): increase the risk of rupture
- Calcification and thrombus: don’t change the risk of rupture
- Multiple aneurysm are more prone to rupture
If there is a suspect of aneurysm because of the presence of both the risk factors and the symptoms, there are two different strumental tests:
- Magnetic resonance angiography (MRA)
- CT angiography (CTA)
- Cerebral Angiography
Note that these tests can detect aneurysms with a diameter >5mm. Aneurysm <2mm can’t be detected or can be detected in retrospective studies.
Schievink WI. Intracranial aneurysms. N Engl J Med 1997; 336:28.
Alg VS, et.al. Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals. Neurology 2013; 80:2154.
Ronkainen A, et al. Familial intracranial aneurysms. Lancet 1997; 349:380.
Teunissen LL, et.al. Risk factors for subarachnoid hemorrhage: a systematic review. Stroke 1996; 27:544.
Wiebers DO, et al. Pathogenesis, natural history, and treatment of unruptured intracranial aneurysms. Mayo Clin Proc 2004; 79:1572.
Raps EC, et al. The clinical spectrum of unruptured intracranial aneurysms. Arch Neurol 1993; 50:265.
Friedman JA, et al. Small cerebral aneurysms presenting with symptoms other than rupture. Neurology 2001; 57:1212.
Wiebers DO, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362:103.
Wiebers DO, et.al. The significance of unruptured intracranial saccular aneurysms. J Neurosurg 1987; 66:23.
Forget TR Jr, et al. A review of size and location of ruptured intracranial aneurysms. Neurosurgery 2001; 49:1322.
Kashiwazaki D, et.al. Size ratio can highly predict rupture risk in intracranial small (<5 mm) aneurysms. Stroke 2013; 44:2169.
Johnston SC, et al. Endovascular and surgical treatment of unruptured cerebral aneurysms: comparison of risks. Ann Neurol 2000; 48:11.
Etminan N, et.al. Unruptured intracranial aneurysms: development, rupture and preventive management. Nat Rev Neurol. 2016 Dec;12(12):699-713.
Kim ST, et.al. Neurovascular manifestations of connective-tissue diseases: A review. Interv Neuroradiol. 2016 Dec;22(6)
Mohan D, et.al. Genetic factors involves in intracranial aneurysms--actualities. J Med Life. 2015 Jul-Sep;8(3)
Findlay JM, et.al. Cerebral Vasospasm: A Review. Can J Neurol Sci. 2016 Jan;43(1)
Backes D, et.al. Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis. Stroke. 2016 Apr;47(4)
Chalouhi N, et.al. Review of cerebral aneurysm formation, growth, and rupture. Stroke. 2013 Dec;44(12):3613-22
Mark S. Greenberg, Handbook of Neurosurgery, Thieme.
Giorgio Saraceno, MS
University of Brescia (Italy)
Federico Nicolosi, MD
University of Milan