7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Screening for intracranial aneurysm : Robert J Singer, MD, Christopher S Ogilvy, MD, Guy Rordorf, MD : Jos Biller, MD, FACP, FAAN, FAHA : Janet L Wilterdink, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 11, 2020. INTRODUCTION Subarachnoid hemorrhage (SAH) is often a devastating event. Approximately 10 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]. 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 and 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'.) RATIONALE The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is approximately 0.4 to 6.0 percent [2], or between 1 to 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 [3]. Of patients with cerebral aneurysms, 20 to 30 percent have multiple aneurysms [4]. Aneurysmal subarachnoid hemorrhage (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 do not rupture. The probability of rupture is related to the size of the aneurysm. Small aneurysms (less than 6 mm in diameter) are most commonly identified with screening, and these are at low risk for https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 1/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate rupture ( figure 1) [5]. In addition, patients with smaller aneurysms (<10 mm) that have ruptured have a better prognosis than larger aneurysm rupture [6]. 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 [5]. 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".) These findings suggest that widespread screening for cerebral aneurysm is not warranted. This was also the conclusion in guidelines published by the American Stroke Association [7,8]. However, screening may be considered in some populations at relatively high risk of cerebral aneurysm formation: First-degree relatives of patients with cerebral aneurysm, when two or more family members have been affected. Patients with a heritable disorder associated with the presence of intracranial aneurysm, such as autosomal dominant polycystic kidney disease (ADPKD), glucocorticoid-remediable aldosteronism (GRA), and connective tissue diseases such as Ehlers-Danlos syndrome IV and pseudoxanthoma elasticum [9,10]. RELATIVES OF PATIENTS WITH CEREBRAL ANEURYSM Family members of patients with intracranial aneurysms are at increased risk of having an aneurysm. 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 [11]. 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 subarachnoid hemorrhage (SAH), intracranial aneurysms were found in 4 percent of first-degree relatives (approximately twice that of the general population) [12]. The mode of inheritance is variable, with autosomal dominant, recessive, and multifactorial transmission evident in different families [13]. In a large population study from Scotland, the estimated 10-year prospective risk of SAH for relatives free of SAH at the time of the index SAH increased in an ascending manner according to https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 2/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate the relationship to the index case as follows [14]: 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. 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 [15]. 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 [16]. (See "Unruptured intracranial aneurysms", section on 'Aneurysm formation'.) Familial aneurysms tend to rupture at a smaller size and younger age than sporadic aneurysms [11,17,18]. Siblings often experience rupture in the same decade of life [17]. 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) [19]. Multiple cerebral aneurysms are also more common in the familial syndrome than among those with sporadic aneurysms [20]. 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 generally recommended in families that have two or more individuals with aneurysms [21]. One study that employed this approach found aneurysms by magnetic resonance angiography (MRA) in 37 of 400 (9 percent) asymptomatic individuals among 68 families with a history of aneurysmal SAH [22]. 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 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 3/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate greater than 10 percent [23]. However, another study found that a screening program could reduce morbidity and mortality in this population in a cost-effective manner [24]. 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, 74 patients had one repeat screening and 28 patients had a second repeat screening [25]. Ten new aneurysms were detected in nine patients; two patients had an SAH three years after a negative screening procedure. 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 has not been evaluated. They suggest that screening in these individuals should be considered on an individual basis [7,8,26]. Our usual practice is to screen relatives with MRA yearly for three years and then expand the screening interval to every five years for those who had no aneurysms detected on the initial three scans. One affected first-degree relative 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 [12]. Some advocate screening in this population as well, but this approach is not generally recommended [21]. In one study, for example, 626 first-degree relatives of 160 patients with sporadic SAH were screened with MRA, followed by conventional angiography in those thought to have aneurysms [27]. 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: five with medium-sized aneurysms (5 to 11 mm in diameter), 11 with small aneurysm (less than 5 mm), and two with both small and medium-sized aneurysms. Outcome was assessed at six months after surgery and was combined with a decision analysis model to estimate the effectiveness of screening: Eleven patients who underwent surgery experienced a decrease in function at six months. 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. https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 4/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate 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 [28]. 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. 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 [26]. 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 [7,8]. 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 [29-33]. Patients with a family history of intracranial aneurysm or subarachnoid hemorrhage (SAH) appear to be at greatest risk [29,33,34]. In one study, for example, asymptomatic intracranial aneurysms were found in 6 of 27 patients (22 percent) with, and only 3 of 56 patients (5 percent) without, a positive family history [33]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".) It has been estimated that aneurysm rupture occurs in 65 to 75 percent of affected patients with ADPKD, a value higher than that of non-ADPKD patients with an intracerebral aneurysm [32]. Aneurysm rupture in ADPKD most often occurs before the age of 50 and in patients with poorly controlled hypertension [32]. In addition, patients who have already had one aneurysm clipped following a cerebral bleed may be at increased risk of new aneurysm formation for as long as 15 years after the initial surgery [35]. Nevertheless, the role for radiologic screening of asymptomatic patients with ADPKD is unsettled. As mentioned above, the decision is based upon weighing the risks of aneurysm surgery versus the benefits of possibly preventing aneurysm rupture; the risk-benefit ratio in asymptomatic patients with ADPKD is uncertain. At present, routine screening is recommended only for high-risk patients, such as those with a previous rupture, a positive family history of an intracerebral bleed, warning symptoms, a high-risk occupation in which loss of consciousness would place the patient or others at extreme risk, and prior to surgery that is likely to be https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 5/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate associated with hemodynamic instability with hypertension [29,34]. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations", section on 'Screening'.) Other hereditary disorders Patients with glucocorticoid-remediable aldosteronism (GRA) are at increased risk of hemorrhagic stroke, in part due to a relatively high frequency of cerebral aneurysm rupture [36] (see "Familial hyperaldosteronism"). It has been suggested that all patients with genetically proven GRA should undergo screening for cerebral aneurysm at puberty and every five years thereafter [36]. 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 such as Ehlers-Danlos syndrome and pseudoxanthoma elasticum are associated with an increased risk of cerebral aneurysm formation [13,17], but no studies have specifically addressed the issue of screening. Bicuspid aortic valve is a congenital condition with familial clustering in some cases. 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) [37]. However, the benefit of an aneurysm screening program in individuals with bicuspid aortic valve has not been evaluated. 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".) 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 [31,33,38,39]. MRA can identify aneurysms 3 to 5 mm or larger [40]. In one cohort study of 138 patients with suspected intracranial aneurysm, volume-rendering, 3D-time-of-flight MRA at 3 Tesla had a greater than 95 percent sensitivity and accuracy for detection of aneurysms [41]. https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 6/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate CTA identifies small unruptured aneurysms with high diagnostic accuracy and reader agreement [42,43]. 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 2A-B) [42]. Conventional cerebral angiography is a more invasive test that is associated with a higher risk of complications. Furthermore, the benefits of finding smaller aneurysms with angiography are unlikely to be of benefit for screening purposes. 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." th th The Basics patient education pieces are written in plain language, at the 5 to 6 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 th th sophisticated, and more detailed. These articles are written at the 10 to 12 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 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 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 7/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate low risk of rupture; interventions to treat aneurysms have an associated risk of complications. (See 'Rationale' above.) 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.) 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. (See 'Hereditary syndromes associated with aneurysm formation' above.) In populations with two or more first-degree relatives with intracranial aneurysm, screening programs have demonstrated an increased incidence of intracranial aneurysms, but the cost effectiveness of screening in these populations has not been evaluated. Screening in these individuals should be considered on an individual basis. Our usual practice is to screen relatives with magnetic resonance yearly for three years and then expand the screening interval to every five years for those who had no aneurysms detected on the initial three scans. (See 'Two or more affected first-degree relatives' above.) Theoretical modeling suggests that screening is not efficacious in populations with genetic syndromes associated with cerebral aneurysm formation or in family members with a single first-degree relative with aneurysmal subarachnoid hemorrhage (SAH) or an intracranial aneurysm. (See 'One affected first-degree relative' above and 'Hereditary syndromes associated with aneurysm formation' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Tidswell P, Dias PS, Sagar HJ, et al. Cognitive outcome after aneurysm rupture: relationship to aneurysm site and perioperative complications. Neurology 1995; 45:875. 2. Rinkel GJ, Djibuti M, Algra A, van Gijn J. 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Intracranial aneurysms in autosomal dominant polycystic kidney disease. Kidney Int 1994; 45:1140. 35. Chauveau D, Sirieix ME, Schillinger F, et al. Recurrent rupture of intracranial aneurysms in autosomal dominant polycystic kidney disease. BMJ 1990; 301:966. 36. Litchfield WR, Anderson BF, Weiss RJ, et al. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 1998; 31:445. 37. Schievink WI, Raissi SS, Maya MM, Velebir A. Screening for intracranial aneurysms in patients with bicuspid aortic valve. Neurology 2010; 74:1430. 38. Raaymakers TW, Buys PC, Verbeeten B Jr, et al. MR angiography as a screening tool for intracranial aneurysms: feasibility, test characteristics, and interobserver agreement. AJR Am J Roentgenol 1999; 173:1469. 39. Wiebers DO, Torres VE. Screening for unruptured intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med 1992; 327:953. 40. Huston J 3rd, Nichols DA, Luetmer PH, et al. 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Topic 1135 Version 16.0 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 11/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate GRAPHICS Graph showing risk of rupture of intracranial aneurysms among patients with and without history of prior subarachnoid hemorrhage Retrospective analysis of the probability of subarachnoid hemorrhage (SAH) over time in patients with an unruptured intracranial aneurysm: 446 without (top panel) and 438 with (bottom panel) a history of SAH from a different aneurysm. The results are shown according to the size of the aneurysm. The risk is clearly related to the size of the aneurysm in patients with no prior history of SAH, with aneurysms <10 mm in size having a very low incidence of rupture. Such a relationship was not apparent in those with a prior history of SAH; the values are not shown for aneurysms 25 mm in this group because of the small number of patients. Data from: The International Study of Unruptured Intracranial Aneurysms Investigators, N Engl J Med 1998; 339:1725. Graphic 63534 Version 4.0 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 12/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate Sensitivity of CTA for intracranial aneurysms The graph shows the increasing sensitivity of CTA with increasing aneurysm size. Points represent the median, and error bars represent the 95 percent confidence limits. Aneurysms greater than 10 mm have been pooled. Data from: van Gelder, JM. Computed tomographic angiography for detecting cerebral aneurysms: implications of aneurysm size distribution for the sensitivity, speci city, and likelihood ratios. Neurosurgery 2003; 53:597. Graphic 81565 Version 2.0 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 13/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate False-positive intracranial aneurysms reported by CTA Bars represent the number of reported aneurysms of each size from 199 false-positive reports of aneurysms. Data from: van Gelder, JM. Computed tomographic angiography for detecting cerebral aneurysms: implications of aneurysm size distribution for the sensitivity, speci city, and likelihood ratios. Neurosurgery 2003; 53:597. Graphic 69728 Version 1.0 https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 14/15 7/7/23, 11:35 AM Screening for intracranial aneurysm - UpToDate Contributor Disclosures Robert J Singer, MD No relevant financial relationship(s) with ineligible companies to disclose. Christopher S Ogilvy, MD Consultant/Advisory Boards: Cerevasc [Hydrocephalus]; Contour [Aneurysms]; Medtronic [Chronic subdural hematoma]. All of the relevant financial relationships listed have been mitigated. Guy Rordorf, MD No relevant financial relationship(s) with ineligible companies to disclose. Jos Biller, MD, FACP, FAAN, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Janet L Wilterdink, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/screening-for-intracranial-aneurysm/print 15/15