INTRODUCTION — Subarachnoid hemorrhage (SAH) is often a devastating event. Approximately 20 to 25 percent of patients die prior to reaching the hospital and, of those who make it in time, only one-third will have a "good result" after treatment [1,2].
Most SAHs are caused by ruptured saccular aneurysms. Recommendations for screening for aneurysms and methods of screening are discussed here. The epidemiology and pathogenesis of intracranial aneurysms, management of unruptured aneurysms, and screening for new aneurysms after treatment for SAH are discussed separately. (See "Unruptured intracranial aneurysms" and "Treatment of cerebral aneurysms", section on 'Early rebleeding'.)
GENERAL POPULATION SCREENING — Widespread screening for cerebral aneurysm is not warranted. This was also the conclusion in guidelines published by the American Stroke Association [3,4].
The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is approximately 0.4 to 6.0 percent [5], or between 1 and 18 million people in the United States. In adult patients without risk factors, the best estimate is that approximately 2 percent harbor asymptomatic cerebral aneurysms [6]. Aneurysmal subarachnoid hemorrhage (SAH) occurs at an estimated rate of 6 to 16 per 100,000 population [7]. In North America, this translates into approximately 30,000 affected persons per year. Thus, most aneurysms do not rupture.
The probability of rupture is related to the size of the aneurysm. Small aneurysms (<6 mm in diameter) are most commonly identified with screening, and these are at low risk for rupture (figure 1) [8]. In addition, patients with smaller aneurysms (<10 mm) that have ruptured have a better prognosis than larger aneurysm rupture [9].
Aneurysm surgery is associated with significant morbidity and mortality. In an international multicenter report of 1449 patients with unruptured intracranial aneurysms, the rate of surgery-related morbidity and mortality in those without a prior history of bleeding from a different aneurysm was 18 percent at 30 days and 16 percent at one year [8]. The one-year rates were affected by age: 6.5 percent under age 45, 14 percent between the ages of 45 and 64, and 32 percent over the age of 64. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis".)
RELATIVES OF PATIENTS WITH CEREBRAL ANEURYSM
Incidence — Family members of patients with intracranial aneurysms are at increased risk of having an aneurysm, even in the absence of a known hereditary syndrome. The mode of inheritance is variable, with autosomal dominant, recessive, and multifactorial transmission evident in different families [10,11].
The number of affected family members influences the risk. In a large population study from Scotland, the estimated 10-year prospective risk of subarachnoid hemorrhage (SAH) for relatives free of SAH at the time of the index SAH increased in an ascending manner according to the relationship to the index case as follows [12]:
●One second-degree relative, 0.3 percent (95% CI 0.0-0.6)
●One first-degree relative, 0.8 percent (95% CI 0.2-1.5)
●Two first-degree relatives, 7.1 percent (95% CI 0.2-14.0)
The wide confidence intervals around these risk estimates reflect the small numbers of SAH events that occur in relatives of index cases, even in large population studies.
The magnitude of the risk varies across studies. 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 in the general population [13]. In a second report of patients with mostly sporadic SAH, intracranial aneurysms were found in 4 percent of first-degree relatives (approximately twice the prevalence of that in the general population) [14]. In another study, the prevalence of aneurysm was 19 percent in first-degree relatives in families with two or more affected individuals [15].
Nonetheless, the risk for first-degree relatives of patients with SAH appears to be much higher than that of the general population, where the 10-year prospective risk of SAH is approximately 0.1 percent [16].
The risk of aneurysm among family members of patients with aneurysm is also influenced by those risk factors (cigarette smoking, hypertension) that affect aneurysm formation in the general population [17]. (See "Unruptured intracranial aneurysms", section on 'Risk factors for aneurysm formation'.)
Characteristics of familial aneurysms — Familial aneurysms tend to rupture at a smaller size and younger age than sporadic aneurysms [13,18,19]. Siblings often experience rupture in the same decade of life [18]. Families with intracranial aneurysms do not appear to demonstrate the phenomenon of anticipation (ie, subsequent generations are not more likely to develop SAH at younger ages than previous generations) [20].
Multiple cerebral aneurysms are also more common in the familial syndrome than among those with sporadic aneurysms [21].
Screening family members — Most cerebral aneurysms are initially discovered in families after rupture causes SAH. Thus, screening studies have predominantly looked at relatives of patients who have suffered an SAH. Recommendations for screening asymptomatic family members of patients with SAH for the presence of intracranial aneurysms depend upon the number of affected relatives.
Two or more affected first-degree relatives — Screening of asymptomatic first-degree relatives is often recommended in families that have two or more individuals with aneurysms [22]. Our usual practice is to screen relatives with magnetic resonance angiography (MRA) yearly for three years and then expand the screening interval to every five years or longer for those who had no aneurysms detected on the initial three scans.
In cohort studies, aneurysms are identified by one-time evaluation with MRA in 9 to 11 percent of individuals with two or more first-degree relatives with cerebral aneurysms [23,24].
However, not all experts agree with this approach. The American Stroke Association guidelines concluded that while people with two or more first-degree relatives with intracranial aneurysm have an increased incidence of intracranial aneurysms, the cost effectiveness of screening in these populations remains uncertain. They suggest that screening in these individuals should be considered on an individual basis [3,4,25]. Analytic models have come to different conclusions regarding the efficacy of screening, depending in part on the role of conventional angiography in screening and the choice of aneurysm treatment used in their model. One study suggested that this approach would not be effective in reducing morbidity and mortality unless aneurysm prevalence was substantially greater than 10 percent [26]. However, another study found that a screening program could reduce morbidity and mortality in this population in a cost-effective manner [27].
If the decision is made to screen, it is uncertain what screening interval is appropriate. In a study that recommended repeat screening at five-year intervals, 261 of 458 individuals had one repeat screening; 21 (8 percent) had an aneurysm [24]. Aneurysms were also identified in 7 of 128 (5 percent) at a third screening and in 3 of 63 (5 percent) at a fourth screening. Serial screening probably decreases the risk of aneurysm rupture but does not entirely prevent this, as at least two patients are described who had an SAH three years after a negative screening procedure [24,28].
All age groups may be appropriate for screening. In one series, six aneurysms were identified in individuals younger than age 30 years, suggesting against reserving screening for older patients [24,29]. Similarly, aneurysms are discovered at the same rate in older adults who have previously screened negative as they are in younger patients; thus, decisions to stop screening should instead be based on remaining life expectancy and the anticipated risks of complications with aneurysm treatment.
One affected first-degree relative — We offer, but do not recommend, one-time screening for individuals with a first-degree relative with aneurysmal SAH. Guidelines published by the American Stroke Association in 2012 state that while it might be reasonable to offer noninvasive screening, further study is needed to define the risks and benefits of this approach [25].
The lifetime risk of SAH for individuals with only one affected first-degree relative is relatively small, ranging from 1 to 4.7 percent at age 70 [12,14], although the risk of aneurysm formation may be higher [14].
While some advocate screening in this population, it is not commonly recommended [22,29]. Some studies suggest that the risks outweigh potential benefits. In one study, for example, 626 first-degree relatives of 160 patients with sporadic SAH were screened with MRA [30]. Aneurysms were found in 25 first-degree relatives (4 percent), twice the prevalence in the general population, but less than one-half the prevalence of people with two or more first-degree relatives with SAH. Eighteen underwent surgery, eleven of whom experienced a decrease in function at six months. A decision analysis model based on these data suggested that surgery increased life expectancy by 0.9 months/person screened at the expense of 19 years of decreased function per person. The number of relatives who would need to be screened to prevent one SAH during a lifetime was 149; 298 would have to be screened to prevent a fatal SAH. Other studies have also found that the quality of life and functional outcome of many patients who undergo screening followed by angiography and surgery are diminished for at least one year [31]. Furthermore, the gain in life expectancy per person screened is considerably lower than the benefits offered by other screening programs. These observations suggest that screening of patients with only one affected first-degree relative is not warranted.
Serial screening is likely to be of particularly low yield in this population. In one series, 601 individuals with one first-degree relative with aneurysmal SAH had an initial negative examination; only three had an SAH after a mean 15 years of follow-up, an incidence rate of 33.6 per 100,000 patient years [32].
Factors that may impact risk and screening recommendations — Most of the studies above have included index patients with both SAH and unruptured intracranial aneurysm, although most had SAH. Because the risk of SAH is lower in patients with unruptured aneurysms than in those with a previous SAH, we typically limit screening recommendations to those with a family history of aneurysmal SAH, although one-time screening in the setting of unruptured aneurysm might be reasonable as well [33].
We also consider other risk factors for aneurysmal SAH in shared decision-making regarding screening. Female sex, cigarette smoking, hypertension, and atherosclerotic vascular disease identify patients at high risk for SAH, particularly when these factors are present in combination [34,35]. These factors may argue for screening in patients with only one affected first-degree relative and/or for ongoing screening in patients with two or more affected family members.
HEREDITARY SYNDROMES ASSOCIATED WITH ANEURYSM FORMATION — Cerebral aneurysm formation is more common in individuals with certain hereditary syndromes, as discussed below. Despite this risk, the American Stroke Association guidelines concluded that screening is not efficacious in these populations [3,4].
Autosomal dominant polycystic kidney disease — The incidence of cerebral aneurysm in autosomal dominant polycystic kidney disease (ADPKD) is approximately 5 percent in young adults, increasing with age to as high as 10 percent in older patients [36-40]. Patients with a family history of intracranial aneurysm or subarachnoid hemorrhage (SAH) appear to be at greatest risk [36,40,41]. Patients who are aneurysm free and those who undergo aneurysm treatment remain at increased risk for de novo aneurysm formation [42].
At present, aneurysm screening is recommended for selected high-risk patients and/or in certain high-risk settings. These are discussed separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Screening'.)
Other hereditary disorders
●Glucocorticoid-remediable aldosteronism – Patients with glucocorticoid-remediable aldosteronism (GRA) appear to be at increased risk of hemorrhagic stroke due to a relatively high frequency of cerebral aneurysm rupture [43,44]. (See "Familial hyperaldosteronism", section on 'Glucocorticoid-remediable aldosteronism'.)
One case-control study identified 13 patients with hemorrhagic stroke in a group of patients with GRA, and none in age-matched controls; the case fatality rate was 61 percent. Based on this study, it was suggested that all patients with genetically proven GRA should undergo screening for cerebral aneurysm at puberty and every five years thereafter [43]. However, the benefit of such an approach has not been proven and, as in all patients, must be weighed against the risk of prophylactic surgery for small aneurysms that might not rupture.
●Connective tissue diseases – Connective tissue diseases such as Ehlers-Danlos syndrome, fibromuscular dysplasia, and pseudoxanthoma elasticum are associated with an increased risk of cerebral aneurysm formation [10,18,29,45,46], but no studies have systematically quantified the risk or addressed the issue of screening [47].
●Bicuspid aortic valve – Bicuspid aortic valve (BAV) is a congenital condition with familial clustering in some cases. A number of studies have suggested an increased risk of intracranial aneurysms [48,49]. In one case-control study, the frequency of intracranial aneurysm was higher in this population compared with a control group (9.8 versus 1.1 percent) [48].
However, the benefit of an aneurysm screening program in individuals with BAV has not been evaluated. In addition, one study suggests that aneurysms in the setting of BAV are associated with smaller size, a lower rate of rupture, and better outcomes that aneurysms in patients without BAV [50].
PATIENTS WITH PRIOR ANEURYSMAL SUBARACHNOID HEMORRHAGE — Survivors of an aneurysmal subarachnoid hemorrhage (SAH) are at risk for recurrent SAH, which may result from recurrence of the treated aneurysm, rupture of another preexisting aneurysm in a patient with multiple aneurysms, and de novo aneurysm formation. The monitoring of such patients is discussed in detail separately. (See "Late recurrence of subarachnoid hemorrhage and intracranial aneurysms".)
OTHER HIGH-RISK GROUPS — Routine screening for other high-risk subgroups is not currently recommended.
However, studies have documented high prevalence rates of aneurysm in populations with combinations of risk factors, including:
●Females who smoke and/or have hypertension – In one case-control study, unruptured intracranial aneurysms were prevalent in 19 percent of females who smoked compared with 2 percent in females who didn't smoke [51]. Hypertension also increased the risk. A follow-up multicenter case-control study documented an almost fourfold greater risk of unruptured intracranial aneurysm in females who smoked (odds ratio [OR] 3.7, 95% CI 1.61-8.50) and a seven-times-higher risk if they smoked and had hypertension (OR 6.9, 95% CI 2.49-19.24) [52]. One study suggested that one-time screening would be cost effective for females who smoke and are between the ages of 30 and 60 years [53].
●Patients with hypertension, atherosclerotic disease, and tobacco use – In one cohort study of 500 patients >35 years old with these risk factors, aneurysms were present in 5 percent; median five-year risk of aneurysm rupture was 0.9 percent [54].
CHOICE OF SCREENING TEST — If the decision is made to screen, magnetic resonance angiography (MRA) or computed tomography angiography (CTA) of the head with intravenous contrast are reasonable choices [38,40,55,56]. MRA and 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 [57-60].
●MRA can identify aneurysms 3 to 5 mm or larger (image 1) [57]. In one cohort study of 138 patients with suspected intracranial aneurysm, volume-rendering, three dimensional (3D)-time-of-flight MRA at 3 Tesla had a greater than 95 percent sensitivity and accuracy for detection of aneurysms [61].
●CTA identifies small unruptured aneurysms with high diagnostic accuracy and reader agreement [62-65]. In one retrospective cohort study of 579 patients with 711 aneurysms, CTA demonstrated a sensitivity of 95 to 97 percent and a specificity of 100 percent for detection of unruptured aneurysms measuring 3 to 5 mm. For detecting aneurysms <3 mm in diameter, sensitivity was lower (84 to 86 percent) without loss of specificity (figure 2 and figure 3) [62].
Disadvantages of CTA compared with MRA include that it requires contrast administration and exposes the patient to radiation.
●Conventional cerebral angiography is a more invasive test that is associated with a higher risk of complications and is not used for screening. While it may improve detection of very small aneurysms, such aneurysms have a low risk of bleeding, and it may not benefit the patient to identify them.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".)
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)")
SUMMARY AND RECOMMENDATIONS
●General population – Screening for asymptomatic intracranial aneurysms in the general population is not indicated. Aneurysms have a baseline prevalence of 0.2 to 6 percent in adults. These have a low risk of rupture; interventions to treat aneurysms have an associated risk of complications. (See 'General population screening' above.)
●Family members – Family members of patients with intracranial aneurysms are at increased risk of having an aneurysm. The risk increases with the degree of association and the number of family members affected. (See 'Relatives of patients with cerebral aneurysm' above.)
•For family members with two or more first-degree relatives with aneurysmal subarachnoid hemorrhage (SAH), we suggest at least one-time screening with magnetic resonance angiography (MRA) or computed tomography angiography (CTA) (Grade 2C). Follow-up imaging every three to five years will identify additional aneurysms in those who initially screen negative, but the yield declines with subsequent testing. (See 'Two or more affected first-degree relatives' above.)
•For family members with only one first-degree relative with aneurysmal SAH and those with family members with unruptured aneurysm but not SAH, we offer but do not recommend one-time screening. We generally do advise against follow-up screening in these lower-risk individuals. (See 'One affected first-degree relative' above.)
●Genetic syndromes – Genetic syndromes associated with a higher risk of cerebral aneurysm formation include autosomal dominant polycystic kidney disease (ADPKD), Ehlers-Danlos syndrome, pseudoxanthoma elasticum, glucocorticoid-remediable aldosteronism (GRA), and bicuspid aortic valve (BAV).
An approach to screening selected high-risk patients with ADPKD is discussed separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Screening'.)
For other patient groups, the risk has not been systematically quantified, and routine screening is not currently advised. (See 'Hereditary syndromes associated with aneurysm formation' above.)
●Prior aneurysmal subarachnoid hemorrhage – Survivors of an aneurysmal SAH require additional evaluation for recurrent and de novo aneurysm formation. The monitoring of such patients is discussed separately. (See "Late recurrence of subarachnoid hemorrhage and intracranial aneurysms".)
●Choice of screening test – MRA or CTA of the head with intravenous contrast are reasonable choices with comparable sensitivity and specificity. Disadvantages of CTA compared with MRA include that it requires contrast administration and that it exposes the patient to radiation. (See 'Choice of screening test' above.)
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