Yield of Short-Term Follow-up CT/MR Angiography for Small Aneurysms Detected at Screening
Background and Purpose— Patients with a history of subarachnoid hemorrhage (SAH) or familial intracranial aneurysms (FIA) are at increased risk for aneurysm formation and rupture. Small aneurysms detected at screening may be left untreated and followed over time. The yield of follow-up CT/MR angiography (CTA/MRA) 1 or 2 years after detection to evaluate growth of these aneurysms is unknown.
Methods— We prospectively followed patients with small aneurysms detected at screening at a 1-year interval using CTA or MRA. We assessed size, site, and number of the aneurysms and risk factors such as smoking, alcohol use, and hypertension. We evaluated the short-term growth and rupture rate and possible risk factors for growth and rupture.
Results— Ninety-three patients (67 with a history of SAH, 16 with FIA, and 10 with a history of both SAH and FIA) with 125 aneurysms underwent CTA/MRA follow-up. Sixty-five patients were followed up once, and 28 patients were followed up twice (median follow-up time, 1.3 years). In 3 of the 93 patients (3.2%), an aneurysm enlarged slightly (0.5 to 1.5 mm). Two patients (2.2%) had a SAH: 1 from an aneurysm at the clip-site from a previous operation that ruptured without enlargement and the other from a newly developed dissecting aneurysm. The only statistically significant risk factor for growth and rupture was a history of both SAH and FIA (relative risk, 10.1; 95% CI, 1.3 to 81.9).
Conclusions— The yield of early follow-up of small aneurysms in patients with a history of SAH or FIA is small and does not eliminate the risk of rupture. Whether follow-up at intervals >1 year is useful requires further study.
Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm has a poor prognosis.1 Screening is often recommended in people with an increased risk of aneurysm formation and rupture, such as persons with familial intracranial aneurysms (FIA) (≥2 relatives with SAH or unruptured aneurysms).2 The risk of new aneurysms and recurrent SAH is also increased in patients with a history of SAH. Screening these patients has a high yield, with an aneurysm detected in 16% of the patients.3
If a very small aneurysm is found with screening, it is not always treated. Small aneurysms, however, can increase in size over several years. Enlarging aneurysms have a relatively high risk of rupture because size is an important determinant of the risk of rupture and possibly also because enlarging aneurysms are unstable.4,5 Small aneurysms that are left untreated may be followed over time by noninvasive methods such as CT or MR angiography (CTA/MRA). Because the growth rate of aneurysms is largely unknown, it is unclear how frequently CTA or MRA should be performed. Frequent follow-up might increase the detection of growing aneurysms, and subsequent treatment may prevent SAH. Conversely, frequent follow-up is also costly, has psychosocial consequences, and in case of CTA might be harmful because of radiation effects or contrast allergic reactions.6,7
We studied the yield of short-term serial follow-up by means of CTA or MRA for small aneurysms detected at screening in persons with FIA and patients with a history of SAH. We assessed the frequency and rate of growth and tried to identify risk factors for growth and rupture.
We prospectively performed short-term clinical and radiological follow-up in patients with a history of SAH and persons with FIA in whom an aneurysm <5 mm was detected at screening but not treated. We identified patients with a history of SAH from a database of patients from the University Medical Center Utrecht (UMCU) and the Academic Medical Center Amsterdam (AMC) who had participated in a study on screening for new aneurysms after SAH (the ASTRA study). In this study 610 patients who had been admitted between 1985 and 2001 for SAH to the AMC or UMCU and in whom the ruptured aneurysm was treated by means of clipping were screened with CTA between 2002 and 2004. All patients were between 18 and 70 years of age at the time of the first screening. The persons with FIA (defined as ≥2 first-degree relatives with SAH or unruptured intracranial aneurysms) were retrieved from a hospital-based screening register on familial SAH in the UMCU. In the UMCU, screening with MRA is performed every 5 years in asymptomatic relatives with FIA. All patients with small aneurysms <5 mm detected at familial screening that were left untreated were included. Excluded from the study were patients who had untreated fusiform aneurysms.
At baseline we recorded risk factors such as size, site, and number of the aneurysms that were detected, history of hypertension, smoking and alcohol use, and number of first-degree relatives with intracranial aneurysms. In patients with a history of SAH, the small aneurysm detected at screening was first classified as (1) aneurysm located at the clip from the previous operation (regrowth) or (2) aneurysm at a new location remote from the clip-site. For the aneurysms at a new location, the initial CTA or conventional intra-arterial angiography (digital subtraction angiography [DSA]) at the time of the SAH was reviewed, when available, to evaluate whether the aneurysm was in retrospect visible. If the aneurysm was not present at the time of the SAH, it was classified as “de novo,” and if the aneurysm was present in retrospect, it was classified as “additional.” For the additional aneurysms, growth in the time between the SAH and the detection at screening was assessed. This classification (de novo or enlarged additional aneurysms as opposed to stable additional aneurysms) was evaluated as a potential risk factor for growth or rupture at the short-term follow-up in patients with a history of SAH.
For the additional aneurysms, not only “prospective” follow-up time (time from detection of the aneurysm at screening to the time of the follow-up CTA or MRA) but also “retrospective” follow-up time (time from the SAH to detection of the aneurysm) is available. Because the purpose of the study was to assess the yield of short-term CTA or MRA after detection of the aneurysm, the follow-up time reported is the time from detection of the aneurysm at screening to the time of the follow-up CTA or MRA.
Follow-up CTA or MRA was scheduled at a 1-year interval. In patients with a history of SAH, CTA was performed because MRA is associated with more artifacts in patients with ruptured aneurysms treated by means of clipping. In the AMC, CTA was performed on a 4-detector multislice CT (Philips Picker Mx8000); in the UMCU, CTA was performed on a 16-detector multislice CT (Philips Mx8000 LDT). The CT scans were performed with a field of view of 160 and a slice thickness of 1 mm reconstructed at 0.5 mm, resulting in a voxel size of 0.3×0.3×0.5 mm. In persons with FIA, a 1.5-T MRA was performed (Philips Medical Systems). Both CTA and MRA have a high sensitivity in the evaluation of small intracranial aneurysms.8–10 Aneurysm size was measured in 2 directions (maximum length [neck to fundus] and maximum width). Enlargement was defined as increase in size of ≥0.5 mm in at least 1 direction. To avoid interobserver variation, the size of the aneurysm at follow-up CTA/MRA was assessed by the same neuroradiologist who measured the size of the aneurysm at detection. If patients did not show up for the follow-up CTA/MRA, we tried to contact the patient or the general practitioner to ensure that the patient was still alive and had not had a SAH.
We assessed the frequency of growth and rupture including corresponding 95% CIs. We evaluated possible risk factors for growth and rupture of aneurysms at follow-up combined by comparing the characteristics of the patients with growth or rupture at short-term follow-up with those of the patients with stable aneurysms at short-term follow-up. Continuous variables were compared by t tests, and categorical variables were compared by χ2 tests.
We found 104 patients with an aneurysm <5 mm detected at screening. The aneurysm was treated in 7 of the 104 patients (7%). Treatment in these patients was performed at their own request or was advised because rupture of aneurysms <5 mm within 2 years of formation had occurred in the family. Four patients declined further follow-up. In total we performed follow-up CTA or MRA in 93 patients: 67 patients with a history of SAH, 16 patients with FIA, and 10 patients with a history of both SAH and FIA, with a total of 125 aneurysms. Eight (6%) of the 125 aneurysms were located at the clip-site from previous surgery for a ruptured aneurysm; the other aneurysms were located at different sites. The mean age of the patients was 51 years (range, 20 to 69 years), and 75% of them were women (Table). The mean size of the aneurysms was 3 mm. Sixty-five patients were followed up once after detection of the aneurysm (median interval between detection and follow-up, 1.1 years; range, 0.7 to 2.2 years), and 28 patients were followed up twice (median interval between detection and second follow-up, 2.2 years; range, 1.4 to 3.8 years). The median follow-up time of the 93 patients was 1.3 years (range, 0.7 to 3.8 years).
Enlargement of the aneurysm on the follow-up CTA occurred in 3 of the 93 patients (3.2%; 95% CI, 0.8% to 9.8%). All 3 patients had a history of SAH, and 2 of them also had FIA. Enlargement did not occur in any of the 16 patients who were screened for FIA but had no history of SAH themselves. None of the 8 regrowth aneurysms enlarged. Enlargement was found in 2 of the 3 patients at the first follow-up and in 1 at the second follow-up.
The first patient, a 56-year-old woman, had been treated in 1996 for a ruptured aneurysm of the left middle cerebral artery (MCA). Screening in 2003 revealed 3 new right MCA aneurysms that were not visible in retrospect on the DSA of 1996 and were classified as de novo. On the follow-up CTA 1 year later, 1 of these aneurysms had enlarged from 2.8×2 to 3.5×2 mm.
The second patient, a 38-year-old woman, had been treated in 1993 after SAH from a left MCA aneurysm. Screening at the patient’s request in 1999 showed no new aneurysms. Screening in 2003 showed a right MCA aneurysm that could in retrospect be identified on the CTA of 1999. The DSA of 1993 was no longer available for review in 2003. In retrospect, the aneurysm had enlarged in size between 1999 and 2003 from 2×1 to 2×3 mm. A prospective follow-up CTA was performed in 2004, and the aneurysm had marginally enlarged from 2×3 to 2.5×3 mm.
The third patient, a 58-year-old woman, had been treated for a SAH in 1996. A 2.5×3-mm aneurysm of the anterior communicating artery was detected on screening in 2003. The second follow-up CTA in 2005 showed an increase in size of this aneurysm to 4×4 mm (Figure 1).
Because the enlargement was only modest in all 3 patients, no treatment was performed.
Rupture occurred in 2 of the 93 patients (2.2%; 95% CI, 0.4% to 8.3%). One patient had a recurrent SAH from an aneurysm at the clip-site from a previous operation that ruptured without enlargement (Figure 2). The other had a SAH from a newly developed dissecting aneurysm of the A1 segment of the right anterior cerebral artery (Figure 3). Both patients had a history of SAH, and 1 also had FIA. Rupture did not occur in any of the 16 patients who were screened for FIA but had no history of SAH themselves.
Risk Factors for Growth and Rupture
Because 1 patient had a SAH from a newly developed aneurysm instead of from an aneurysm that was followed over time, she was not included in the risk factor analyses. The 4 remaining patients with growth or rupture of an aneurysm were all women (P=0.57, Fisher exact test), were on average younger (difference of means, 4 years; 95% CI, −6.1 to 14.1), more often had multiple aneurysms at the time of the detection of the aneurysm (relative risk [RR], 3.0; 95% CI, 0.4 to 22.9) and aneurysms located at the MCA (RR, 3.5; 95% CI, 0.7 to 9.6), more often were current smokers (RR, 2.0; 95% CI, 0.2 to 19.9), and had a de novo aneurysm or an additional aneurysm that had enlarged between the time of the SAH and detection at the first screening (RR, 4.5; 95% CI, 0.5 to 40.5), but these risk factors did not reach statistical significance. The only risk factor that was statistically significant was a history of both SAH and FIA (RR, 10.1; 95% CI, 1.3 to 81.9).
We found that the yield of early follow-up of small untreated aneurysms in patients with a history of SAH or FIA is very small. Only a few aneurysms enlarged, and this enlargement was very small without consequences for treatment. The low rate of growth suggests that follow-up CTA 1 year after detection in patients with a high risk of SAH is not useful. This study also once again showed that rupture of small aneurysms remains unpredictable, and enlargement is only 1 factor that is involved in the process of rupture. Despite absence of growth, a SAH occurred in 1 patient with a small stable regrowth aneurysm and in 1 other patient from a newly developed dissecting aneurysm. The only risk factor we found for growth or rupture at short-term follow-up was a history of both SAH and FIA.
Two other studies have addressed the short-term radiological follow-up of unruptured aneurysms.11,12 Neither specifically addressed small aneurysms, both included different categories of patients, and both had a wide range of follow-up. In a Japanese study, 166 aneurysms in 140 patients were monitored by means of CTA over a mean period of 17.7 months (range, 3 to 84 months).11 Enlargement was found overall in 10 aneurysms (6.4%) and in 3 of 125 aneurysms (2.4%) <5 mm. Another, retrospective study that used serial MRA found that in 4 of 57 patients (7%) with 62 unruptured aneurysms, an aneurysm had enlarged during a mean follow-up time of 50 months (range, 17 to 90 months). The median aneurysm size in this study was 5 mm. However, none of the aneurysms that enlarged were <9 mm in diameter, and no enlargement occurred in the first 23 months of follow-up.12 In both studies no aneurysm ruptured during the follow-up period. The results of our study cannot be compared easily with the other 2 studies because of differences in patient populations. Only 7 (3.5%) of the total 197 patients investigated in the other 2 studies had a history of SAH, and 34 (17%) had a positive family history. In addition, the mean age of our patients was 10 years younger. Because we included only aneurysms of patients with a history of SAH or a positive family history, our results cannot be extrapolated to small aneurysms that are detected incidentally in persons without a history of SAH or a family history. However, because the rupture risk of incidental aneurysms is smaller than in patients with a history of SAH or a positive family history, it is likely that for these aneurysms short-term follow-up is also not useful.5
In our study all patients had aneurysms <5 mm. In our clinic, patients with a history of SAH or FIA with aneurysms ≥5 mm are usually treated. The advantage of our study is that the proportion of treated patients with an aneurysm <5 mm was known. Only a small number of patients were treated, and therefore selection bias because of treatment of more aggressive or larger aneurysms is likely to be low. In most other studies on rupture risk or growth rate of aneurysms, these data are unknown.5,11,12
Because only 3 of the aneurysms followed over time enlarged and 1 ruptured, the sample size for the univariate analysis was small, and multivariate analysis for risk factors could not be performed. The risk factor we found should therefore be interpreted with some caution because it might be confounded with other risk factors. In addition, in our study some risk factors might not have become evident because of the small number of aneurysms with growth or rupture.
If, for whatever reason, it is decided not to treat an unruptured aneurysm, radiographic follow-up is an option. Our study shows that short-term follow-up by CTA or MRA of aneurysms <5 mm is not helpful. The yield in terms of growing aneurysms is small, and it does not eliminate the risk of rupture. These data should be discussed on an individual basis in patients with small aneurysms when decisions on management are made. Given the lack of efficiency and safety, some patients might therefore choose treatment of the aneurysm. It remains unclear whether follow-up at longer intervals is useful. Long-term prospective follow-up data on large cohorts of patients with unruptured aneurysms who undergo frequent serial CTA or MRA are needed to study the effectiveness of such a follow-up and to provide more information on the mechanism and risk factors of aneurysm growth and rupture.
This study was supported by a grant from the Netherlands Organization for Scientific Research/ZonMw (grant 945-02 to 007).
- Received October 7, 2005.
- Accepted October 26, 2005.
Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke. 1997; 28: 660–664.
Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC Jr, Brott T, Hademenos G, Chyatte D, Rosenwasser R, Caroselli C. Recommendations for the management of patients with unruptured intracranial aneurysms: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 2000; 31: 2742–2750.
Wermer MJ, van der Schaaf IC, Velthuis BK, Algra A, Buskens E, Rinkel GJ. Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain. 2005; 128 (pt 10): 2421–2429.
Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001; 32: 485–491.
Wiebers DO, Whisnant JP, Huston J III, Meissner I, Brown RD Jr, Piepgras DG, Forbes GS, Thielen K, Nichols D, O’Fallon WM, Peacock J, Jaeger L, Kassell NF, Kongable-Beckman GL, Torner JC. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003; 362: 103–110.
Wermer MJ, van der Schaaf IC, Van Nunen P, Bossuyt PM, Anderson CS, Rinkel GJ. Psychosocial impact of screening for intracranial aneurysms in relatives with familial subarachnoid hemorrhage. Stroke. 2005; 36: 836–840.
Prokop M, Galanski M. Computed Tomography of the Body. Stuttgart, Germany: Georg Thieme Verlag; 2003: 46–48.