Unruptured cerebral aneurysms are identified more

Transcription

1 J Neurosurg 117:20 25, 2012 Annual rupture risk of growing unruptured cerebral aneurysms detected by magnetic resonance angiography Clinical article Takashi Inoue, M.D., Ph.D., 1 Hiroaki Shimizu, M.D., Ph.D., 1 Miki Fujimura, M.D., Ph.D., 2 Atsushi Saito, M.D., Ph.D., 1 and Teiji Tominaga, M.D., Ph.D. 3 1 Department of Neurosurgery, Kohnan Hospital; 2 Department of Neurosurgery, Sendai Medical Center; and 3 Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan Object. In this paper, the authors goals were to clarify the characteristics of growing unruptured cerebral aneurysms detected by serial MR angiography and to establish the recommended follow-up interval. Methods. A total of 1002 patients with 1325 unruptured cerebral aneurysms were retrospectively identified. These patients had undergone follow-up evaluation at least twice. Aneurysm growth was defined as an increase in maximum aneurysm diameter by 1.5 times or the appearance of a bleb. Results. Aneurysm growth was observed in 18 patients during the period of this study (1.8%/person-year). The annual rupture risk after growth was 18.5%/person-year. The proportion of females among patients with growing aneurysms was significantly larger than those without growing aneurysms (p = ). The aneurysm wall was reddish, thin, and fragile on intraoperative findings. Frequent follow-up examination is recommended to detect aneurysm growth before rupture. Conclusions. Despite the relatively short period, the annual rupture risk of growing unruptured cerebral aneurysms detected by MR angiography was not as low as previously reported. Surgical or endovascular treatment can be considered if aneurysm growth is detected during the follow-up period. ( Key Words cerebral aneurysm magnetic resonance angiography rupture vascular disorders Abbreviations used in this paper: ACoA = anterior communicating artery; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = magnetic resonance angiography; SAH = subarachnoid hemorrhage. Unruptured cerebral aneurysms are identified more frequently since imaging techniques have improved. The cumulative rupture rate of unruptured cerebral aneurysms in patients with no history of SAH is quite low, 3,7,21 so many patients have been observed without surgical intervention. However, the bleeding rate of unruptured cerebral aneurysms depends on the study design and population. 2,9,10,19,23 The apparent paradox of natural history data suggesting a low rupture risk for small unruptured cerebral aneurysms and the low median size of ruptured cerebral aneurysms remains unexplained and perplexing. 17,22 Aneurysm growth is probably associated with rupture, but this relationship has not been well characterized. 5 Follow-up imaging to screen for growth or change in the morphology of unruptured cerebral aneurysms remains controversial. 1,4,6,8,11 13,15 17,20,24 Therefore, an important question to answer is whether close follow-up will help to establish or disprove a relationship between rupture risk and aneurysm growth. The present study investigated the characteristics of growing unruptured cerebral aneurysms detected by serial MRA and calculated the recommended follow-up interval. Methods Patient Population We retrospectively identified eligible patients with unruptured cerebral aneurysms who underwent aneurysm evaluation at least twice between January 1, 2008, and December 31, 2009, from the neuroimaging database 20 J Neurosurg / Volume 117 / July 2012

2 Growing aneurysms of our hospital. A total of 1002 patients with 1325 aneurysms were selected (640 women and 362 men, age range years [median 65.0 years]), of whom 275 patients had multiple aneurysms (maximum 5 aneurysms). The median follow-up period was 10.1 months, and the total follow-up period was 997 person-years. The percentages of patients followed up every 6 and 12 months were both approximately 45%. Patients with symptomatic aneurysms were included in this study only if SAH was excluded by lumbar puncture within a few days after onset of symptoms. We did not include patients younger than 18 years old or those with mycotic cerebral aneurysms, traumatic aneurysms, or aneurysms as part of a genetic syndrome, for example, Ehlers-Danlos syndrome or polycystic kidney disease. The treatment strategy of our hospital for unruptured cerebral aneurysms was to recommend intervention or observation for aneurysms larger or smaller than 5 mm, respectively, if the patient was younger than 70 years old. Any medical condition, such as malignant neoplasm, cardiac heart failure, or renal failure, was also considered in the decision to treat or not. We also recommended intervention for aneurysms with documented growth. The final selection of treatment was made by the patients. The study protocol was approved by the local ethics committee. Magnetic Resonance Angiography Magnetic resonance angiography was performed using a whole-body 1.5-T MRI scanner (General Electric Medical Systems) and a parallel imaging head coil. All patients underwent 3D time-of-flight MRA using the following parameters: repetition time 29 msec, echo time 6.9 msec, matrix , FOV 160 mm, and 1.2 mm thickness 40 slices 2 slabs (overwrap 8 slices). The data were transferred to a workstation connected to the scanner and were then processed using a 3D volume rendering algorithm. The 3D volume rendering setting was selected, assuming that the parent arteries were the same diameter. The aneurysm size was measured using the workstation tool by the same author (T.I.). The maximum size was decided in the monitor by viewing the 3D volume rendering images from multiple directions. The maximum size was defined as the aneurysm size. The morphological change was estimated visually. All authors discussed the cases of growing aneurysms. Definition of Aneurysm Growth We defined aneurysm growth as 2 patterns on the basis of the MRA findings: maximum aneurysm diameter increase by 1.5 times; and obvious morphological change, such as appearance of bleb. Statistical Analysis Data are expressed as the median and range. The difference between values was analyzed by the chi-square test. Statistical significance was set at a level of p < The annual rupture risk after growth was expressed using the person-year method. Results Aneurysm growth was observed in 18 patients during J Neurosurg / Volume 117 / July 2012 the study period (1.8%/person-year). The annual rupture risk after growth was 18.5%/person-year. The characteristics of the patients with growing aneurysms are shown in Table 1. The 16 women and 2 men ranged in age from 36 to 86 years (median 68.5 years). The proportion of females with growing aneurysms was significantly larger than those without growing aneurysms (88.9% vs 63.9%, p = ). The aneurysms were located on the ACoA in 8 patients, ICA in 4 (1 ophthalmic and 3 posterior communicating arteries), MCA in 4, basilar artery anterior inferior cerebellar artery in 1, and basilar artery superior cerebellar artery in 1. Four patients had another aneurysm, located on the ICA and MCA in 2 cases each. Both patients with contralateral ICA aneurysms had previously suffered an SAH. There was no significant difference in aneurysm location and multiplicity between patients with and without aneurysm growth. Six patients had undergone clipping or coiling before aneurysm rupture (3 cases each). Eight patients preferred continuous observation and did not suffer an SAH during this period. Aneurysm rupture was observed 1 23 months after aneurysm growth in 4 of these 18 patients. The annual rupture risk of growing aneurysms was 18.5%/person-year. Based on this result, the percentages to detect aneurysm growth before rupture with evaluations every 12 and 6 months were calculated by the following formulas, respectively: X = (1 - M/100) = ( ) 100 = 81.5%, and X = (1 - M/100) = 90.3%, where X 12 is the percentage to detect aneurysm growth before rupture with evaluation every 12 months (%), M is the calculated rupture risk of growing aneurysms per month (%), and X 6 is the percentage to detect aneurysm growth before rupture with evaluation every 6 months (%). This formula is based on the following: 1) The aneurysm does not need to rupture before follow-up. 2) The probability of the aneurysm not rupturing during 12 months is (1 - M/100) 12, and this value could be determined by the present study ( ). 3) M is calculated for solving the equation of (1 - M/100) 12 = 81.5%. 4) Finally, a probability of not rupturing during 6 months is calculated. Illustrative Cases Case 11 This 74-year-old woman presented with a right ICA aneurysm detected by MRA at examination for her headache. She opted to undergo sequential follow-up MRA. The aneurysm grew in 2 years from 5.0 to 8.0 mm (Fig. 1). Case 14 This 63-year-old woman presented with bilateral MCA aneurysms detected by MRA at examination for her headache. The patient underwent MRA every 6 months. The final MRA documented obvious aneurysm growth, but she did not again visit our hospital, and the aneurysm ruptured 1 month later (Fig. 2). Case 7 This 74-year-old woman presented with a small 21

3 T. Inoue et al. TABLE 1: Characteristics of patients with growing aneurysms* Case No. Age (yrs), Sex Aneurysm Location Outcome ACoA aneurysm (1.6 mm in diameter) detected by MRA at examination for her memory disturbance. Nine months later, the aneurysm had grown to 3.8 mm in diameter. She underwent clipping surgery. The aneurysm had a thin and reddish wall intraoperatively, and it ruptured during manipulation before clipping (Fig. 3). This case was not counted as a rupture case. Duration Until Rupture (mos) Other Aneurysms On Admission Size (mm) After Growth 1 44, F ACoA observation NA none , F ACoA clipping NA none , F ACoA observation NA none , F ACoA clipping NA none , M ACoA coiling NA none , M ACoA observation NA none , F ACoA clipping NA none , F ACoA rupture 23 none , F ICA observation NA contralat ICA (previously ruptured) , F ICA rupture 21 contralat ICA (previously ruptured) , F ICA observation NA none , F ICA observation NA none , F MCA observation NA contralat MCA (unruptured) , F MCA rupture 1 contralat MCA (unruptured) , F MCA coiling NA none , F MCA coiling NA none , F BA-AICA rupture 23 none , F BA-SCA observation NA none * AICA = anterior inferior cerebellar artery; BA = basilar artery; NA = not applicable; SCA = superior cerebellar artery. Discussion The main finding of this study was that the annual rupture risk of growing unruptured cerebral aneurysms detected by MRA was 18.5%/person-year, which was higher than that previously reported. 13,16,17 Understanding the natural history of unruptured cerebral aneurysms is critical to patient management. The appropriate management of unruptured cerebral aneurysms has not yet been established. The International Study of Unruptured Intracranial Aneurysms suggested a drastically lower risk of SAH for aneurysms smaller than 10 mm, 7,21 and the investigators concluded that the size of cerebral aneurysms is the key factor in determining the risk of rupture. The risk factors for aneurysm growth are female sex, larger size, and location on the MCA, and the growth risk is about 5% 10%. 13,15 17,24 Computational fluid dynamics studies have suggested that flow in aneurysms is related to aneurysm growth. 18 The growth region of the aneurysm could be exposed to either greater than the wall sheer stress at the inflow zone or lower wall sheer stress and higher oscillatory sheer in the aneurysm sac. Computational fluid dynamics may have the potential to predict not only aneurysm growth but also the features of Fig. 1. Case 11. Magnetic resonance angiograms. A: A 5.0-mmdiameter right ICA aneurysm is seen on admission. B and C: Slight growth of the aneurysm is seen 3 (B) and 9 (C) months later. D: Fifteen months later, the aneurysm diameter was 8.0 mm, which was defined as a growing aneurysm. 22 J Neurosurg / Volume 117 / July 2012

4 Growing aneurysms Fig. 3. Case 7. A and B: Magnetic resonance angiograms showing a 1.6-mm-diameter ACoA aneurysm on admission (A). The aneurysm had grown to 3.8 mm in diameter 9 months later (B). C and D: Intraoperative photographs showing the thin and reddish aneurysm wall (arrow) and bleeding due to rupture (arrowhead) (C) and clipping of the aneurysm (D). Fig. 2. Case 14. Magnetic resonance angiograms showing a small right MCA aneurysm on admission (upper), and obvious growth of the aneurysm 6 months later (lower, arrow). the aneurysm wall (thin and reddish or thick and yellow). Therefore, computational fluid dynamics may help to determine the therapeutic methods for patients with aneurysms, given that whether intervention or observation is preferable remains very uncertain. On the other hand, the rupture risk after growth has not been accurately estimated, as no patient with growing aneurysms has been reported to suffer SAH,13,16,17 or because only fast-growing aneurysms ruptured during the observation period.11 The main difference between the present and previous studies was the definition of aneurysm growth. All previous reports defined growth as an J Neurosurg / Volume 117 / July 2012 increase of 1 or 2 mm in diameter, or just an increase on source images. The specific resolution of MRA in our present study was mm, and the scan time was approximately 4 minutes. These parameters were not specific to clinical practice. An increase of 1 or 2 mm in diameter is equivalent to an increase of 1 or 2 pixels on the source images. We think that detection of aneurysm growth is too difficult with this method. We could obtain MRA studies with higher resolution if there was more time for each patient or if a higher magnetic field scanner (3.0 T) is used, but such parameters would conflict with daily clinical practice. Therefore, we accepted only a 1.5-times increase in diameter or obvious bleb formation to indicate growth. This requirement partly explains why our growth risk (1.8%/person-year) and rupture risk (18.5%/person-year) were lower and higher, respectively, than those of previous reports. The only significant risk factor in the present study for growth was female sex. Location and multiplicity were not significant risk factors. Female sex was previously reported to be a risk factor of growth. Location and multiplicity are controversial as risk factors for aneurysm growth.4,8,15,17 The size of the aneurysms is also one of the key factors associated with rupture. In the present study, 8 growing aneurysms (44%) were smaller than 3 mm. This result suggests that small aneurysms are not always safe from rupture. In our present study, we mainly estimated the risks after rather than before aneurysm growth. Additionally, our neuroimaging database had not recorded other useful patient characteristics, such as smoking status, hypertension, prior SAH, or statin administration. Therefore, our study could not adequately assess the risk factors for the aneurysm growth. 23

5 T. Inoue et al. It was reported that some aneurysms might bleed very shortly after formation or growth. 14,22 However, in the present study, 3 of 4 aneurysms ruptured more than 20 months after growth. Only 1 patient suffered SAH 1 month after the aneurysm growth. Therefore, aneurysm rupture may not always occur soon after formation or growth. We selected neurosurgical clipping or endovascular coiling for the treatment of 6 patients. As shown in the intraoperative findings in Fig. 3, the aneurysm wall was reddish, thin, and fragile. We need to confirm whether the walls of growing aneurysms are more fragile than those of stable aneurysms. Although many factors should be considered to determine the management of patients with unruptured cerebral aneurysms, surgical or endovascular treatment should be considered if aneurysm growth is observed during the follow-up period. A randomized control study is required to definitively answer this question. We performed the clipping or coiling surgeries in 6 patients. If these patients had not undergone the treatment and if none of the aneurysms ruptured, the annual rupture risk after growth was calculated at 15.6%/person-year. On the other hand, if all of the treated aneurysms ruptured 1 month later without treatment, the annual rupture risk after growth was 45.2%/person-year. The true annual rupture risk after growth may be between 15.6% and 45.2%. The detection rates of aneurysm growth were 90.3% and 81.5% with follow-up intervals of 6 and 12 months, respectively. Aneurysm rupture is a life-threatening event for patients. More than 10% of patients who suffer an SAH will die before admission. Severe vasospasm may also occur after SAH even if successful intervention has been performed. The number of patients with disabled status or those who die is certainly not small after aneurysm rupture. Although there are many important issues controlling whether to treat even if the aneurysm is growing, establishing whether the aneurysm is still stable or growing is very important. Therefore, we recommend followup examinations every 6 months to recognize aneurysm growth before rupture, as the detection rate is 90.3%. This study has some limitations. As mentioned above, we determined the characteristics after, not before, aneurysm growth and did not have adequate information for all patients with or without aneurysm growth. Second, our measurement of aneurysm diameter by MRA was somewhat inaccurate, especially using volume rendering. The measurement remained subjective despite standardization of the parameters of MRA and volume rendering settings. We should develop a more objective method using workstations as previously reported. 6 The objective method measured the change in aneurysm volume with 3D MRA using contrast medium. We determined the growth or bleb formation with discussion by authors, so inter- or intraobserver variability was not performed. Third, we retrospectively examined the patients with aneurysms for 2 years. A prospective study with longer follow-up period is needed to obtain more conclusive evidence. Conclusions Although this study covered a relatively short period, the annual rupture risk of growing cerebral aneurysms detected by MRA was 18.5%/person-year. The aneurysm wall tended to appear reddish, thin, and fragile. Surgical or endovascular treatment can be considered if aneurysm growth is detected during the follow-up period. Frequent follow-up examination is recommended to detect aneurysm growth before rupture. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Inoue. Acquisition of data: Fujimura. Analysis and interpretation of data: Inoue. Drafting the article: Inoue. Critically revising the article: all authors. Re viewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Inoue. Sta tis tical analysis: Shimizu. Study supervision: Tominaga. References 1. Allcock JM, Canham PB: Angiographic study of the growth of intracranial aneurysms. J Neurosurg 45: , Asari S, Ohmoto T: Natural history and risk factors of unruptured cerebral aneurysms. Clin Neurol Neurosurg 95: , Bromberg JE, Rinkel GJ, Algra A, Greebe P, van Duyn CM, Hasan D, et al: Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage. BMJ 311: , Burns JD, Huston J III, Layton KF, Piepgras DG, Brown RD Jr: Intracranial aneurysm enlargement on serial magnetic resonance angiography: frequency and risk factors. Stroke 40: , Chmayssani M, Rebeiz JG, Rebeiz TJ, Batjer HH, Bendok BR: Relationship of growth to aneurysm rupture in asymptomatic aneurysms 7 mm: a systematic analysis of the literature. Neu rosurgery 68: , Dispensa BP, Saloner DA, Acevedo-Bolton G, Achrol AS, Jou LD, McCulloch CE, et al: Estimation of fusiform intracranial aneurysm growth by serial magnetic resonance imaging. J Magn Reson Imaging 26: , International Study of Unruptured Intracranial Aneurysms Investigators: Unruptured intracranial aneurysms risk of rupture and risks of surgical intervention. N Engl J Med 339: , 1998 (Erratum in N Engl J Med 340:744, 1999) 8. Juvela S: Natural history of unruptured intracranial aneurysms: risks for aneurysm formation, growth, and rupture. Acta Neurochir Suppl 82:27 30, Juvela S, Porras M, Heiskanen O: Natural history of unruptured intracranial aneurysms: a long-term follow-up study. J Neu rosurg 79: , Juvela S, Porras M, Poussa K: Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 93: , Kamitani H, Masuzawa H, Kanazawa I, Kubo T: Bleeding risk in unruptured and residual cerebral aneurysms angiographic annual growth rate in nineteen patients. Acta Neurochir (Wien) 141: , Koffijberg H, Buskens E, Algra A, Wermer MJ, Rinkel GJ: Growth rates of intracranial aneurysms: exploring constancy. J Neurosurg 109: , Matsubara S, Hadeishi H, Suzuki A, Yasui N, Nishimura H: Incidence and risk factors for the growth of unruptured ce- 24 J Neurosurg / Volume 117 / July 2012

6 Growing aneurysms rebral aneurysms: observation using serial computerized tomography angiography. J Neurosurg 101: , Mitchell P, Jakubowski J: Estimate of the maximum time interval between formation of cerebral aneurysm and rupture. J Neurol Neurosurg Psychiatry 69: , Miyazawa N, Akiyama I, Yamagata Z: Risk factors for growth of unruptured intracranial aneurysms: follow-up study by serial 0.5-T magnetic resonance angiography. Neurosurgery 58: , Phan TG, Huston J III, Brown RD Jr, Wiebers DO, Piepgras DG: Intracranial saccular aneurysm enlargement determined using serial magnetic resonance angiography. J Neurosurg 97: , Sonobe M, Yamazaki T, Yonekura M, Kikuchi H: Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke 41: , Sugiyama SI, Meng H, Funamoto K, Inoue T, Fujimura M, Nakayama T, et al: Hemodynamic analysis of growing intracranial aneurysms arising from a posterior inferior cerebellar artery. World Neurosurg [epub ahead of print], Tsutsumi K, Ueki K, Morita A, Kirino T: Risk of rupture from incidental cerebral aneurysms. J Neurosurg 93: , Wermer MJ, van der Schaaf IC, Velthuis BK, Majoie CB, Albrecht KW, Rinkel GJ: Yield of short-term follow-up CT/ MR angiography for small aneurysms detected at screening. Stroke 37: , Wiebers DO, Whisnant JP, Huston J III, Meissner I, Brown RD Jr, Piepgras DG, et al: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362: , Wiebers DO, Whisnant JP, Sundt TM Jr, O Fallon WM: The significance of unruptured intracranial saccular aneurysms. J Neurosurg 66:23 29, Yasui N, Suzuki A, Nishimura H, Suzuki K, Abe T: Longterm follow-up study of unruptured intracranial aneurysms. Neu rosurgery 40: , Yonekura M: Small unruptured aneurysm verification (SUAVe Study, Japan) interim report. Neurol Med Chir (Tokyo) 44: , 2004 Manuscript submitted December 7, Accepted April 3, Please include this information when citing this paper: published online April 27, 2012; DOI: / JNS Address correspondence to: Takashi Inoue, M.D., Department of Neurosurgery, Kohnan Hospital, Nagamachiminami, Taihaku-ku, Sendai, Miyagi , Japan. tainoue@ kohnan-sendai.or.jp. J Neurosurg / Volume 117 / July