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.

INTRODUCTION Most subarachnoid hemorrhages (SAH) are caused by ruptured

intracranial saccular (berry) aneurysms. The epidemiology and pathogenesis of
intracranial aneurysms and the management of unruptured aneurysms are discussed
here. The epidemiology, etiology, clinical manifestations, diagnosis, and treatment of
SAH, and issues related to screening for aneurysms are discussed separately.
(See "Clinical manifestations and diagnosis of aneurysmal subarachnoid
hemorrhage" and "Treatment of aneurysmal subarachnoid hemorrhage" and "Screening
for intracranial aneurysm".)

EPIDEMIOLOGY The prevalence of intracranial saccular aneurysms by radiographic

and autopsy series is estimated to be 3.2 percent in a population without comorbidity, a
mean age of 50 years, and a 1:1 gender ratio [1,2],. Of patients with cerebral
aneurysms, 20 to 30 percent have multiple aneurysms [3]. Aneurysmal SAH occurs at
an estimated rate of 6 to 16 per 100,000 population [4]. In North America, this translates
into approximately 30,000 affected persons per year. Thus, most aneurysms, particularly
small aneurysms, do not rupture (see 'Risk of aneurysm rupture' below).

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".)

Most intracranial aneurysms (approximately 85 percent) are located in the anterior

circulation, predominantly on the circle of Willis. Common sites include the junction of
the anterior communicating artery with the anterior cerebral artery, the junction of the
posterior communicating artery with the internal carotid artery, and the bifurcation of the
middle cerebral artery. Posterior circulation sites often include the top of the basilar
artery, the junction of the basilar artery and the superior or anterior inferior cerebellar
arteries, and the junction of the vertebral artery and the posterior inferior cerebellar
artery [5].
 There is a female preponderance for aneurysms ranging from 54 to 61 percent [2,4]. In
populations older than 50 years, the increased prevalence in women may approach a 2
to 1 ratio or greater. (See 'Estrogen deficiency' below.)

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].

Hereditary syndromes A known hereditary syndrome is often present when

aneurysms are diagnosed in more than one family member. Heritable disorders
associated with the presence of intracranial aneurysm include:

Connective tissue diseases such as Ehlers-Danlos syndrome and pseudoxanthoma

elasticum are associated with intracranial aneurysms [7,8], but probably not Marfan
syndrome [9]. The mechanism by which connective tissue diseases predispose to
aneurysm formation presumably involves an inherent weakness of the arterial wall
exposed to the non-laminar flow pattern of blood, which is then exposed to shear
stresses. Aneurysm formation in glucocorticoid-remediable hyperaldosteronism may
result in part from congenital hypertension during the early stages of cerebrovascular
development [10]. Concurrent hypertension also may contribute in polycystic kidney
disease, although the precise mechanism is unclear.
Autosomal dominant polycystic kidney disease (PKD) is associated with a 6.9 times
higher risk of intracranial aneurysm [2]. Autosomal recessive PKD may also be a risk
factor [11]. (see "Extrarenal manifestations of autosomal dominant polycystic kidney
disease")
Glucocorticoid-remediable aldosteronism (familial aldosteronism type I)
(see "Familial hyperaldosteronism")
Moyamoya syndrome is also associated with an increased frequency of intracranial
aneurysms. Although most cases of moyamoya are sporadic, there is probably a
genetic susceptibility underlying the disease, and familial occurrence is known to
occur. (See "Moyamoya disease: Etiology, clinical features, and diagnosis".)

Familial aneurysms Family members of patients with intracranial aneurysms are at

increased risk of having an aneurysm, even in the absence of a known hereditary
syndrome. In one study, for example, the age-adjusted prevalence of incidental
aneurysms in first-degree relatives of patients with an aneurysm was 9 percent, a
number significantly higher than the general population [12]. Only a small proportion of
these families had an identifiable hereditary syndrome known to be associated with
aneurysms. In a second report of patients with mostly sporadic SAH, intracranial
aneurysms were found in 4 percent of first-degree relatives (approximately twice that of
the general population) [13]. Other studies have estimated that a family history of
aneurysm or subarachnoid hemorrhage confers a 3.6 times greater risk [2].

The mode of inheritance is variable, with autosomal dominant, recessive, and

multifactorial transmission evident in different families [14,15]. Familial aneurysms have
been linked to multiple chromosomal loci [15-20].

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".)

Hypercholesterolemia and regular physical exercise appear to decrease the risk of

aneurysm formation; there is some speculation that the former effect is mediated
through statin therapy [27].

Known and possible risk factors for aneurysm formation include:

Cigarette smoking The importance of cigarette smoking was illustrated in a case-

control analysis of 45 men and 70 women with SAH between the ages of 35 and 64 [28].
Cigarette smokers had a significantly increased risk of SAH compared with a control
population; the relative risk for men and women was 3.0 and 4.7, respectively, and the
risk increased with the number of cigarettes smoked. Those who both smoked and had
hypertension had an almost 15-fold increase in risk of SAH compared with normotensive
nonsmokers; this additive effect of hypertension and smoking on aneurysm formation
has been noticed in other studies as well [27] In a study of familial intracranial
aneurysms, the risk of intracranial aneurysm within affected families was increased by
cigarette smoking [19].

The mechanism by which cigarette smoking predisposes to aneurysm formation may

involve decreasing the effectiveness of alpha-1 antitrypsin, an important inhibitor of
proteases such as elastase [5]. Support for this hypothesis is derived from studies,
which suggest that patients with alpha-1 antitrypsin deficiency are at increased risk of
aneurysm formation [21].
 Hypertension The association between hypertension and aneurysm formation and
rupture has been controversial, although the balance of evidence suggests that
hypertension is a risk factor [27]. One report, for example, compared 113 patients with
SAH and angiographically verified aneurysms to 63 patients with SAH but no aneurysm
[29]. Blood pressure greater than 160/95 was present in 62 percent of patients with
aneurysms compared with 37 percent without. In another study in which over 20,000
Medicare patients were followed, there was an increased prevalence of hypertension in
patients with aneurysms compared with a control population (43 versus 35 percent) [30].

Estrogen deficiency There is a female preponderance for aneurysms ranging from

54 to 61 percent [4]. The estrogen deficiency of menopause causes a reduction in the
collagen content of tissues. (See "Clinical manifestations and diagnosis of menopause".)

This collagen wasting may contribute to aneurysm development in postmenopausal

women, analogous to the situation in patients with connective tissue diseases. In one
case-control study, premenopausal women without a history of smoking or hypertension
were at reduced risk of SAH compared with age-matched postmenopausal women (odds
ratio 0.24) [31]. Furthermore, the use of estrogen replacement therapy was associated
with a reduced risk of SAH in postmenopausal women (odds ratio 0.47). This protective
effect of estrogen replacement therapy has been seen in other studies as well [32].

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".)

PATHOGENESIS OF ANEURYSM FORMATION Saccular aneurysms are

responsible for most SAHs, although fusiform and mycotic aneurysms can be identified
in selected patients.

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].

The pathogenesis of saccular aneurysm formation is multifactorial [37]. Hemodynamic

stress causes excessive wear and tear and breakdown of the internal elastic lamina.
Turbulent blood flow produces vibrations that may coincide with the resonant frequency
of the vessel wall, resulting in structural fatigue. Patients with hyperdynamic flow
patterns as a result of anomalous collateral pathways or other high-flow states are
predisposed to accelerated degenerative changes in the vessel wall and subsequent
aneurysm development. Hypertension, cigarette smoking, and connective tissue disease
 probably play a contributory rather than causal role in this process (see 'Other
factors' above). There is some evidence that inflammation plays a role in the
pathogenesis and growth of intracranial aneurysms [38-40].

In a study that examined 66 saccular aneurysm samples (42 ruptured and 24

unruptured), four histological types of aneurysm walls were identified that may reflect
consecutive stages of degeneration leading to rupture [41]:

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.

CLINICAL MANIFESTATIONS Most intracranial aneurysms are asymptomatic unless

they rupture, and so they are usually found either incidentally or when a patient presents
with SAH. (See "Clinical manifestations and diagnosis of aneurysmal subarachnoid
hemorrhage".)

Some unruptured aneurysms can become symptomatic [42,43]. Symptoms include

headache (which may be severe and comparable to the headache of SAH [42]), visual
acuity loss, cranial neuropathies (particularly third nerve palsy), pyramidal tract
dysfunction, and facial pain; they are felt to be due to the mass effect of the aneurysm.
(See "Third cranial nerve (oculomotor nerve) palsy in adults".) Ischemia can occur as a
result of emboli originating from within an aneurysm.

Treatment of the aneurysm may lead to resolution of symptoms [43]. (See "Treatment of
aneurysmal subarachnoid hemorrhage".)

DIAGNOSIS Most intracranial aneurysms present as SAH or are found incidentally or

on screening. (See "Screening for intracranial aneurysm".) Because symptomatic
unruptured aneurysms are unusual, there are little data on the best diagnostic strategy in
the presence of symptoms that could be due to an aneurysm.

Magnetic resonance angiography (MRA) and CT angiography (CTA) appear to be able

to detect aneurysms 5 mm or larger; smaller aneurysms (down to 2 mm) are less reliably
detected or may be seen in retrospect when compared with cerebral angiography [44-
47]. A systematic review of studies of CTA concluded that the sensitivity of CTA ranged
from 53 percent for 2 mm aneurysms to 95 percent for 7 mm aneurysms, and that
specificity was also higher for larger aneurysms (figure 1A-B) [47]. As technology
improves, the sensitivity and specificity of noninvasive imaging is also likely to improve.
A 2011 meta-analysis of CTA diagnosis of intracranial aneurysms found that, compared
with single-detector CTA, use of multidetector CTA was associated with an overall
improved sensitivity and specificity for aneurysm detection (both >97 percent) as well as
improved detection of smaller aneurysms 4 mm in diameter [48]. Another study
examining 307 aneurysm in 246 patients found that three-dimensional time-of-flight MRA
with volume rendering at 3.0 Tesla had a sensitivity and specificity of 99 and 97 percent
that was irrespective of aneurysm size (range <3 mm to >10 mm) [49].

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].

Angiography is a more invasive test that is associated with a higher risk of

complications, and it should only be performed if there is a high clinical suspicion for an
aneurysm despite negative noninvasive studies. Very small aneurysms (below the
practical limit of detection of MRA and CTA) can occasionally present with symptoms
such as third nerve palsy [43].

RISK OF ANEURYSM RUPTURE Two large prospective studies have reported on

the natural history of unruptured intracranial aneurysms, the International Study of
Unruptured Intracranial Aneurysms (ISUIA), which prospectively assessed 1692 patients
with 2686 unruptured, untreated aneurysms (6544 patient-years) in the United States,
Canada, and Europe [50], and the Unruptured Cerebral Aneurysms Study (UCAS), a
Japanese cohort which followed 6697 aneurysms in 5720 patients (11,660 aneurysm-
years) [51]. Both of these studies noted that aneurysm size and location were associated
with the risk of rupture.

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]:

Intracranial saccular aneurysms are acquired lesions, not congenital.

Most intracranial aneurysms develop over a short period of hours, days, or weeks,
attaining a size allowed by the elasticity limits of the aneurysmal wall; at this point, the
aneurysm either ruptures or undergoes stabilization and hardening.
Those aneurysms that do not rupture gain significant tensile strength due to
compensatory hardening with formation of excessive collagen. Therefore, the likelihood
of rupture decreases unless the size of the aneurysm is fairly large at the time of initial
stabilization.
Aneurysms 1 cm or larger at initial stabilization are considerably more likely to undergo
subsequent growth and rupture because wall stress increases with the square of the
diameter (Laplace's law).

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:

Cavernous carotid artery aneurysms had the lowest rates of rupture.

Anterior circulation aneurysms, involving the anterior communicating, anterior cerebral or
internal carotid arteries, had intermediate rates of rupture.
Posterior circulation aneurysms, involving the vertebrobasilar, posterior cerebral arterial
system, or posterior communicating arteries, had the highest rates of rupture.

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.

Racial differences It is unclear whether racial or genetic background has a

substantial impact upon the natural history of unruptured intracranial aneurysms. The
prospective ISUIA data were obtained primarily from white populations in North America
and Europe, but no similar large prospective study has been published in other
populations. However, predisposition to aneurysm formation is clearly influenced by
genetic makeup (see 'Genetic factors' above), and there is epidemiologic evidence of
wide variations in the rate of SAH worldwide [63].

Although not directly comparable, data from a systematic review of 13 retrospective

studies of unruptured intracranial aneurysms in Japan [64] found a much higher overall
rupture rate than that reported in the ISUIA study [50]. Similar to the ISUIA data, the risk
of rupture in Japan was significantly increased for large, posterior circulation, and
symptomatic aneurysms [64]. Most of the studies in the Japanese review included a mix
of patients with and without prior SAH, populations that appear to have different risks in
the prospective ISUIA study. Prospective studies underway in Japan may address these
issues [65,66].
Precipitating events An acute trigger event such as physical exertion appears to
occur in some case of aneurysm rupture but not all. Emotionally stressful life events
have not been convincingly shown to be a trigger for aneurysm rupture.
(See "Aneurysmal subarachnoid hemorrhage: Epidemiology, risk factors, and
pathogenesis", section on 'Pathogenesis'.)

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.

MANAGEMENT OF UNRUPTURED ANEURYSMS The management of unruptured

intracranial aneurysms is controversial [69]. There are no randomized trials on which to
base recommendations. Decisions about therapy need to weigh the natural history of the
aneurysm, the risks of intervention, and patient preferences.

Risk of intervention A systematic review and meta-analysis of the available

observational studies included 60 studies, 9845 patients and 10,845 aneurysms. The
overall mortality associated with surgical clipping of unruptured aneurysms was 1.7
percent, unfavorable outcomes occurred in 6.7 percent [70].
 Observational studies that compared the risks of surgical versus endovascular repair in
general found lower rates of poor outcomes in patients treated with endovascular repair.
In the ISUIA, rates of poor neurologic outcome at one year were 12.6 percent and 9.8
percent for those treated surgically and endovascularly respectively [50]. In another
cohort study, endovascular repair was associated with lower mortality (0.6 versus 1.6
percent) and lower rates of stroke (4.3 versus 9.0 percent) [71].

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].

Age is a crucial element in deciding whether to treat an unruptured aneurysm [37].

Morbidity and mortality are increased with open surgery in patients 50 years and older
and with endovascular procedures in patients 70 years and older. However, age has
relatively little effect on the natural history of unruptured aneurysms.

Benefit of intervention The ISUIA investigators concluded that in patients without a

history of previous SAH, it is unlikely that any therapy would be able to improve upon the
untreated natural history of aneurysms that are smaller than 7 mm, and they also
suggested that in patients with larger asymptomatic unruptured aneurysms, patient
preference for immediate risk versus risk over time might determine the appropriate
course of action.

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.

The management of unruptured intracranial aneurysms has also been evaluated by

studies performing cost-effectiveness analyses. One such study, published prior to the
prospective 2003 ISUIA report [50], found that treatment of asymptomatic aneurysms
<10 mm in diameter in patients with no history of SAH from another aneurysm worsened
clinical outcomes; treatment of unruptured aneurysms that were larger, symptomatic, or
in patients with a history of SAH was cost-effective [73]. Aneurysm location was not
considered in this analysis.

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

With AVM Rare patients have an intracranial aneurysm associated with an

intracranial arteriovenous malformations (AVM). These aneurysms are more likely to be
associated with growth and rupture than aneurysms in general [75]. Therefore, repairing
the aneurysm prior to treating the AVM is recommended.

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.

Use of antithrombotic therapy Patients with intracranial aneurysms may require

antithrombotic therapy for the management of other conditions such as atrial fibrillation.
The available data are limited, somewhat conflicting, and not sufficient to determine
whether anticoagulant (eg, warfarin) or antiplatelet therapy increases the risk of
aneurysm rupture. While other studies have suggested a higher associated risk, a trend
of a protective effect of aspirin use (3 times weekly) for the risk of aneurysm rupture
was noted in a nested case-control study using the untreated cohort of patients in the
ISUIA study (adjusted OR = 0.27; 95% CI 0.11 0.67) [77]. This finding requires
confirmation in other studies.

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]:

The treatment of small incidental intracavernous internal carotid artery aneurysms is

generally not indicated. For large symptomatic intracavernous aneurysms, treatment
decisions should be individualized on the basis of patient age, severity and progression
of symptoms, and treatment alternatives. The higher risk of treatment and shorter life
expectancy in older individuals must be considered in all patients, and it favors
observation in older patients with asymptomatic aneurysms.
Symptomatic intradural aneurysms of all sizes should be considered for treatment with
relative urgency.
Coexisting or remaining aneurysms of all sizes in patients with a SAH due to another
treated aneurysm warrant consideration for treatment. Aneurysms located at the basilar
apex carry a relatively high risk of rupture. Treatment decisions must take into account
the patient's age, existing medical and neurologic condition, and relative risks of repair. If
a decision is made for observation, reevaluation on a periodic basis with CTA/MRA or
selective contrast angiography should be considered, with changes in aneurysmal size
sought, although careful attention to technical factors will be required to optimize the
reliability of these measures.
Given the apparent low risk of hemorrhage from incidental, small (<7 mm) aneurysms in
patients without previous SAH, observation rather than intervention is generally
advocated. However, special consideration for treatment should be given to young (<50
years) patients in this group.
Asymptomatic aneurysms 7 to 10 mm in diameter warrant strong consideration for
treatment, taking into account patient age, existing medical and neurologic conditions,
and relative risks for treatment [79].

Choice of procedure Surgical treatment of unruptured aneurysms has been the

most common procedure used in patients who undergo definitive therapy. In clinical
studies, which are typically in centers with high case volumes, endovascular techniques
appear to be associated with lower morbidity and mortality than surgical clipping and are
playing an increasing role in the treatment of unruptured aneurysms [80-84].
(See "Treatment of cerebral aneurysms", section on 'Unruptured aneurysms'.)
 New technologies, such as flow diversion, may advance the safety of endovascular
treatment and allow aneurysms, previously considered to be inaccessible or
technologically difficult for such treatment. [85]

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]:

We suggest that unruptured intracranial aneurysms be monitored with CTA or MRA

annually for two to three years, and every two to five years thereafter if the aneurysm is
clinically and radiographically stable [37]. However, it is not unreasonable to obtain the
first reimaging study of newly detected small aneurysms at six months, since there is
evidence that newly formed small aneurysms may be at higher risk of rupture than older
more stable aneurysms (see 'Hypothesis of growth and rupture'above). Longer
reimaging intervals are certainly appropriate if the six-month study shows no significant
change.
Patients should be instructed to avoid smoking, heavy alcohol consumption, stimulant
medications, illicit drugs, and excessive straining and Valsalva maneuvers.

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".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education

materials, The Basics and Beyond the Basics. The Basics patient education pieces
are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on patient info and the keyword(s) of
interest.)

Basics topic (see "Patient education: Brain aneurysm (The Basics)")

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Vernooij MW, Ikram MA, Tanghe HL, et al. Incidental findings on brain MRI in the
general population. N Engl J Med 2007; 357:1821.
2. Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial
aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a
systematic review and meta-analysis. Lancet Neurol 2011; 10:626.
3. STEHBENS WE. ANEURYSMS AND ANATOMICAL VARIATION OF CEREBRAL
ARTERIES. Arch Pathol 1963; 75:45.
4. Sarti C, Tuomilehto J, Salomaa V, et al. Epidemiology of subarachnoid hemorrhage in
Finland from 1983 to 1985. Stroke 1991; 22:848.
5. Schievink WI. Intracranial aneurysms. N Engl J Med 1997; 336:28.
6. Alg VS, Sofat R, Houlden H, Werring DJ. Genetic risk factors for intracranial aneurysms:
a meta-analysis in more than 116,000 individuals. Neurology 2013; 80:2154.
7. Neil-Dwyer G, Bartlett JR, Nicholls AC, et al. Collagen deficiency and ruptured cerebral
aneurysms. A clinical and biochemical study. J Neurosurg 1983; 59:16.