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Unruptured Intracranial Aneurysms
Unruptured Intracranial Aneurysms
Authors:
Robert J Singer, MD
Christopher S Ogilvy, MD
Guy Rordorf, MD
Section Editor:
Jose Biller, MD, FACP, FAAN, FAHA
Deputy Editor:
Janet L Wilterdink, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Jul 2017. | This topic last updated: Sep 26, 2013.
Rupture of an intracranial aneurysm is believed to account for 0.4 to 0.6 percent of all
deaths. Approximately 10 percent of patients die prior to reaching the hospital, and only
one-third has a "good result" after treatment. (See "Treatment of aneurysmal
subarachnoid hemorrhage".)
RISK FACTORS
Genetic factors The role for genetic factors in the pathogenesis of intracranial
aneurysm formation is supported by studies that have found an increased risk in patients
with some known hereditary syndromes and by the occurrence of aneurysms in families.
A systematic review and meta-analysis confirmed a substantial genetic contribution to
the occurrence of intracranial aneurysms that involve multiple pathophysiologic
pathways, while noting that large-scale replication studies in a full spectrum of
populations are needed with investigation on how specific genetic factors related to
aneurysm size, location and risk of rupture [6].
Familial aneurysms tend to rupture at a smaller size and younger age than sporadic
aneurysms [12,21,22]. Siblings often experience rupture in the same decade of life [21].
Aneurysms tend to occur at similar locations within families, suggesting that a specific
anatomic vulnerability may be inherited [23].
Other factors Because intracranial aneurysms are the major etiology of SAH, risk
factors for SAH may also be risk factors for intracranial aneurysms. Risk factors for SAH
include hypertension, cigarette smoking, and alcohol consumption [24-26]. (See "Clinical
manifestations and diagnosis of aneurysmal subarachnoid hemorrhage".)
Coarctation of the aorta Patients with coarctation of the aorta are at increased risk
for aneurysm formation [33,34]. This may result secondary hypertension of from shared
morphological or genetic risk factors. (See "Clinical manifestations and diagnosis of
coarctation of the aorta".)
Saccular aneurysms are thin-walled protrusions from the intracranial arteries that are
composed of a very thin or absent tunica media, and an absent or severely fragmented
internal elastic lamina [35].
Fusiform aneurysms consist of enlargement or dilatation of the entire circumference of
the involved vessel that may in part be formed due to atherosclerosis.
Mycotic aneurysms usually result from infected emboli due to infective endocarditis [36].
Endothelialized wall with linearly organized smooth muscle cells (Type A); 7 of 17 (41
percent) ruptured.
Thickened wall with disorganized smooth muscle cells (Type B); 11 of 20 (55 percent)
ruptured.
Hypocellular wall with either intimal hyperplasia or organizing luminal thrombosis (Type
C); 9 of 14 (64 percent) ruptured.
Extremely thin thrombosis-lined hypocellular wall (Type D); all 15 (100 percent) ruptured.
Lack of elastic lamina was a common feature of both ruptured and unruptured
aneurysms. Ruptured aneurysm walls were more likely to have complete absence of
endothelial lining and evidence of inflammation, characterized by T cell and macrophage
infiltration, compared with unruptured walls.
Treatment of the aneurysm may lead to resolution of symptoms [43]. (See "Treatment of
aneurysmal subarachnoid hemorrhage".)
Pretest probability should affect the interpretations of CTA results: in the presence of
SAH, an aneurysm is likely, and a positive CTA finding of any size can generally be
trusted, while a negative result should lead to further testing; in the absence of SAH, a
CTA finding of a large aneurysm (>7 mm) can be trusted, but findings of small or
medium aneurysms have a higher likelihood of being false positives and may require
confirmation, if felt to be clinically important [47].
Size The ISUIA and UCAS confirmed results from previous studies showing that the
rates of aneurysmal rupture were lower in smaller aneurysms [50-54]. The size cutpoint
in both studies for defining low risk of rupture was 7 mm [50,51]. With increasing size
over 7 mm, the risk of aneurysmal SAH increases correspondingly. In the ISUIA, for
anterior circulation aneurysms 5-year rates of rupture for those 7 to 12mm was 2.6
percent; for those 13 to 24 mm, 14.5 percent; and for those > 25 mm, 40 percent.
Another prospective cohort study followed 374 patients with 448 aneurysms that were
<5 mm in size; the average annual rupture rate was 0.54 percent overall; 0.34 percent
for single aneurysms and 0.95 for multiple aneurysms [55]. In this group, aneurysm
rupture risk was also somewhat higher in those <50 years of age and those with
aneurysms >4 mm in size. Hazard ratios reported in the UCAS, using aneurysms 3 to 4
mm as the reference, were 3.3 for aneurysms 7 to 9 mm, 9.1 for aneurysms 10 to 24
mm and 76.3 for aneurysms 25 mm [51].
Aneurysm growth is more likely to occur in larger than smaller aneurysm [56,57]. Among
165 patients with 191 unruptured aneurysms, the frequency of enlargement over 47
months was 7, 25, and 83 percent for aneurysms <8 mm, 8 to 12 mm, and >13 mm,
respectively [57]. One study also found that internal carotid and basilar artery aneurysms
were more likely to grow than those located in other regions [56].
The results of one study suggest that risks of rupture in smaller, <5mm aneurysms can
be further stratified by the aneurysm-to-vessel size ratio; a ratio of 3.1 was the threshold
identified for a higher risk of rupture (OR 9.10) [58]. This finding requires independent
verification.
Hypothesis of growth and rupture There are some concerns about the data
reported from studies of unruptured intracranial aneurysms showing a low rate of rupture
for aneurysms 7 mm and smaller [50,52-54] because a large percentage of patients that
present with SAH appear to have had rupture of aneurysms that were smaller than 10
mm in diameter [59], and a majority appear smaller than 7 mm in diameter [60]. Based
on available clinical and natural history data, as well as pathophysiology, the following
hypothesis of aneurysmal growth and rupture has been proposed as the explanation for
this apparent discrepancy [37,54,61]:
If this hypothesis is correct, it follows that the critical size for aneurysmal rupture is
smaller for aneurysms that rupture soon after formation, as would appear to be true for
the vast majority of small aneurysms that rupture [37,61]. This hypothesis is based on
data derived from patients with unruptured aneurysms and no history of prior SAH, and it
is probably not applicable to patients who have an unruptured aneurysm and prior SAH
from another aneurysm.
Site Both the ISUIA and the UCAS, as well as other studies, have found that the risk
of aneurysm rupture varied according to its location [50,51,62].
In the ISUIA, three aneurysm site groupings were associated with different rates of
rupture [50]. The three groupings of aneurysm site were based on the parent artery:
The cumulative five-year rate of rupture according to aneurysm site and size at
diagnosis were as follows:
For 7 to 12 mm aneurysms, rupture rates for cavernous carotid, anterior circulation, and
posterior circulation aneurysms were 0, 2.6, and 14.5 percent.
For 13 to 24 mm aneurysms, rupture rates for cavernous carotid, anterior circulation,
and posterior circulation aneurysms were 3.0, 14.5, and 18.4 percent.
For 25 mm or larger aneurysms, rupture rates for cavernous carotid, anterior circulation,
and posterior circulation aneurysms were 6.4, 40, and 50 percent.
In the UCAS, aneurysms in the anterior and posterior communicating arteries were more
likely to rupture than those in the middle cerebral artery [51]. Using the latter group as a
reference, the hazard ratios associated with rupture in the posterior and anterior
communicating arteries were 1.9 and 2.0, respectively.
Prior hemorrhage If an individual has had a previous aneurysmal SAH, the risk of
rupture of a separate aneurysm is probably higher than if the individual did not have that
history. In the ISUIA, unruptured aneurysms less than 7 mm in a patient with a history of
aneurysmal SAH ruptured at a rate of 0.5 percent per year compared 0.1 percent per
year in those with no prior aneurysmal SAH [50]. A higher risk for those with prior SAH
was not noted for larger aneurysm categories in the ISUIA, but the number of patients
with large unruptured aneurysms and prior SAH were relatively small.
Family history Familial aneurysms tend to rupture at a smaller size and younger age
than sporadic aneurysms [12,21,22]. In one study, the observed rupture rate of 1.2
percent per year was almost 17 times higher than the rupture rate of aneurysms
matched for size and location in the ISUIA [22].
Others In the UCAS, the presence of a daughter sac (an irregular protrusion of the
aneurysm wall) was associated with an increased risk of rupture (HR = 1.6), while the
presence of thrombus or calcification did not appear to influence the risk of rupture [51].
One study found that multiple aneurysms were more likely to grow than single lesions
[62]. Studies of advanced imaging techniques hold the promise that new technologies
will be able to identify other characteristics of aneurysms at high risk of rupture, such as
inflammation within the aneurysm wall [67].
In both the ISUIA and UCAS, the effect of patient's age, gender, hypertension and
tobacco smoking were not significant predictors of SAH in a multivariate analysis [50,51].
In contrast, a case control study comparing patients with ruptured and unruptured
cerebral aneurysm, found that smoking and a migraine history appeared to increase the
risk of rupture, while hypercholesterolemia (or possibly its treatment with statins)
appeared to be protective [68]. In this study, the prevalence of hypertension, age,
gender, were not different between the groups.
Risk factors for poor outcomes include advanced age, larger aneurysm size, and
location in the posterior circulation; these are more consistently observed in surgically
rather than endovascularly treated patients [50,72].
The investigators also point to specific groups from their data that appear to have the
largest benefit from intervention, such as open surgery for patients younger than 50
years with aneurysms of the posterior communicating artery that are 7 to 24 mm.
Although it may be appropriate to take these subgroup data into account when making
recommendations for individual patients, it is important to recognize that such subgroup
analyses are vulnerable to statistical problems and need to be confirmed prospectively.
A later decision and cost-effectiveness analysis used the 2003 ISUIA data and
compared surgical or endovascular treatment with no treatment for unruptured
intracranial aneurysms [74]. The following observations were reported:
For 50 year old patients, treatment was ineffective or not cost effective for aneurysms
with the following characteristics:
Small (<7 mm), due to the low risk of rupture
Located in the cavernous carotid artery
Large (>25 mm) and located in the posterior circulation, due to the high risk of
complications from treatment
For 40 year old patients, treatment was ineffective or not cost effective for aneurysms
with the following characteristics:
Small (<12 mm) or large (>25 mm) and located in the cavernous carotid artery
Small (<7 mm) and located in the anterior circulation
Special situations
Carotid stenosis One study found that intracranial aneurysms appeared to be more
common than expected in a population of patients with symptomatic carotid artery
disease, perhaps because of shared risk factors [76]. Aneurysms distal to a symptomatic
cervical internal carotid artery stenosis may be susceptible to sudden hemodynamic
changes with carotid endarterectomy (CEA) that could lead to aneurysmal rupture [37].
On the other hand, surgical clipping of an aneurysm distal to a severe internal carotid
stenosis may increase the risk of ischemic stroke.
Unfortunately, data for this situation are too sparse to allow firm conclusions as to which
problem should be tackled first. However, caution is advised if CEA is performed in this
setting, especially if the unruptured ipsilateral aneurysm is 7 mm or larger in diameter or
if there is a history of SAH from another aneurysm.
However, anticoagulant therapy does appear to increase the severity of rupture should it
occur. (See "Anticoagulant and antiplatelet therapy in patients with an unruptured
intracranial aneurysm".)
RECOMMENDATIONS The available studies emphasize the need to examine each
case individually, considering factors such as comorbid medical illness, patient age,
aneurysm size and location, and risks of treatment. The sum of these data support
expectant management of very small saccular aneurysms, particularly when such
aneurysms are located in the anterior circulation or when they are detected in older
patients.
Whom to treat A task force of the Stroke Council of the American Heart Association
published recommendations (also prior to the 2003 ISUIA data) for the management of
patients with an unruptured intracranial aneurysm that are similar to the above
recommendations [78]:
Monitoring For patients with unruptured intracranial aneurysms that are not treated
with open surgery or endovascular methods, the following recommendations are made
for monitoring [37]:
Patients whose aneurysm is treated are at risk for recurrent aneurysm formation and
require monitoring. This is discussed in detail separately. (See "Late recurrence of
subarachnoid hemorrhage and intracranial aneurysms".)
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