Risk of Aneurysm Recurrence in Patients With Clipped Cerebral Aneurysms
Results of Long-Term Follow-Up Angiography
Background and Purpose—With many patients living long after microsurgical aneurysm clipping for subarachnoid hemorrhage (SAH) and with the evolution of intravascular procedures as less invasive alternatives, knowledge of the long-term results of clipping is becoming important.
Methods—Of 412 patients who underwent clipping of ruptured or unruptured cerebral aneurysms at our institution between 1976 and 1994 and who survived >3 years after surgery, 225 patients who were in good general condition and younger than 80 years were offered follow-up angiography to detect newly formed aneurysms. Of the 225, 80 patients (35.6%) agreed to undergo angiography. In addition, 32 patients underwent angiography for new medical indications other than SAH. Therefore, 112 patients underwent angiography, representing a total of 140 clipped aneurysms.
Results—The mean interval from surgery was 9.3 years for all patients and 9.0 years for the clipped aneurysms (range 3 to 21 years). Four aneurysm regrowths were detected of the 140 (2.9%) clipped aneurysms, representing 3 of 125 completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1 aneurysm not studied with postoperative angiography. De novo aneurysms were detected in 9 of 112 (8.0%) patients. The annual rate of de novo aneurysm formation was 0.89%.
Conclusions—This study shows that the annual rate of de novo aneurysm formation is relatively high (0.89%) and that the cumulative risk becomes significant after 9 years. In consideration of the fatality rate of SAH, follow-up angiography may be indicated for patients with clipped aneurysms 9 to 10 years after surgery.
The long-term results of aneurysm clipping have not been questioned since the procedure was brought into practice. With the rapid evolution of intravascular surgery as a less invasive alternate technique to protect aneurysms from bleeding, evaluation into the long-term reliability of microsurgical clipping has become important both medically and socioeconomically. Subarachnoid hemorrhage (SAH) after surgical clipping is generally considered to be a rare event, with a reported incidence of 1% to 2%.1 2 3 However, most previous studies relied on relatively short follow-up periods, rarely exceeding 4 to 5 years, which could have underestimated the risk of SAH in the long term. We recently reported that patients with completely obliterated ruptured aneurysms still carry a relatively high risk for recurrent SAH secondary to de novo aneurysm formation or regrowth of the original aneurysms.4 The median time for the recurrent SAH was ≈9 years, most likely reflecting the slow process of aneurysm growth. Furthermore, a similar risk was observed in patients with surgically treated unruptured aneurysms.5 Therefore, appropriate risk estimation of aneurysm recurrence and subsequent SAH must be made on the basis of cases with sufficiently long follow-up periods.6 Given that a small group of aneurysms should rupture and cause SAH, the rate of aneurysm recurrence may well be much higher. In the present study, we focused on the risk of aneurysm formation itself and performed angiography on 112 patients who had undergone clipping of cerebral aneurysms at our institution and investigated the incidence of de novo aneurysms and regrowth of the clipped aneurysms.
Subjects and Methods
From 1976 through 1994, 530 patients underwent clipping of ruptured or unruptured cerebral aneurysms at our institution, and 412 patients survived >3 years after surgery.4 5 Of the 412 patients, we could obtain follow-up information for 409 patients (99.3%), with only 3 patients lost to follow-up. Of the 409 patients, 87 patients were dead. The cause of death was newly developing SAH (confirmed by CT) in 7, a cause other than SAH in 73, and unknown in 7 patients. Of the 322 patients who were alive, 38 patients had undergone repeated cerebral angiography >3 years after surgery (reasons other than SAH, n=32; newly developing SAH, n=6). Of the remaining 284 patients, 59 patients were excluded because of either poor general condition or advanced age (≥80 years). All of the remaining 225 patients (56.2% of 412 total patients) were contacted and informed of the results of our previous studies through interviews or letters,4 5 and they were offered follow-up angiography. Eighty patients (35.6% of the 225 patients contacted) agreed to undergo angiography. Cerebral angiograms of the 80 patients and of the 32 patients performed for reasons other than SAH (total 112) were studied for de novo aneurysm formation and regrowth of the clipped aneurysms.
Of the 13 patients with newly developing, CT-confirmed SAH (7 dead and 6 alive), cerebral angiography was obtained after the SAH in 11 patients, but not in 2 patients who died immediately after the SAH. Aneurysms detected in these 11 patients were not included in calculation of the risk of aneurysm formation because these patients should represent all 412 patients and would lead to overestimation of the risk if included. On the other hand, exclusion of these patients would lead to underestimation of the risk. Therefore, these patients were analyzed separately.
Cerebral angiography was performed with digital subtraction angiography (DSA) or conventional angiography with manual subtraction procedures. Four-vessel studies were attempted in all cases, but in some cases, studies were limited to 3 vessels, including the originally clipped aneurysms, because of probable high risks associated with further procedures. Regrowth or de novo formation of aneurysms was examined by comparing the follow-up angiography with the previous angiography obtained before and after clipping.
Annual rates of aneurysm regrowth and of de novo formation were determined by dividing the number of positive findings (aneurysm regrowth and de novo formation, respectively) by the number of patient-years of observation for the population or particular subgroup.
Medical records of the 412 patients were reviewed for data on age, gender, number and location of aneurysms, whether the aneurysm ruptured, type of clip that was used, extent of the angiography, nature of the surgical procedure, and follow-up interval. The data were statistically analyzed by χ2 test, Fisher’s exact test, or t test. Statistical significance was set at P<0.05.
There were no complications from angiography, except for 1 instance of transient vertigo.
Of the 112 patients who were examined, 25 patients had >1 clipped aneurysm, resulting in a total of 140 clipped aneurysms. The mean interval between the surgery and the follow-up angiography was 9.3 years for all patients and 9.0 years for the clipped aneurysms (range 3 to 21 years). The examined group was younger than the nonexamined group, as expected (55.2 versus 58.4 years, P=0.0065, t test), likely because older (>80 years) patients were excluded before the follow-up angiography was offered. Other patient characteristics were similar in the 2 groups, including gender, number of aneurysms, history of SAH, and follow-up periods (Table 1⇓).
Characteristics of clipped aneurysms were also similar in the 2 groups (140 versus 343 aneurysms), including location, type of clip used, and completeness of the clipping on postoperative angiograms. Middle cerebral artery aneurysms were more frequent in the examined group, accounting for 63 of 140 aneurysms (45.0%) compared with 109 of 343 aneurysms (31.8%) of the nonexamined group (Table 2⇓).
Regrowth of clipped aneurysms was detected in 4 (2.9%) of 140 clipped aneurysms (3 of 125 completely clipped aneurysms, 1 of 14 incompletely clipped aneurysms, and 0 of 1 aneurysm that was not examined with postoperative angiography). The mean interval between the surgery and follow-up angiography was 15.5 years for the 4 aneurysm regrowths. The annual regrowth rate was 0.26% for completely clipped aneurysms (Table 3⇓). Formation of de novo aneurysms was observed in 9 of 112 patients (8.0%), and the annual risk of de novo aneurysm formation was 0.89% (Table 3⇓). Patients with multiple aneurysms at the initial study accounted for 4 of 9 (44%) patients with de novo aneurysms and 21 of 103 (20%) patients without de novo aneurysm, but there was no statistical significance (P=0.11, Fisher’s exact test). Gender was not a significant factor that affected the rate of de novo aneurysm formation. Two of 51 patients examined within 9 years of surgery and 11 of 61 patients examined >9 years after surgery had new aneurysms (regrowth or de novo) (P=0.018, Fisher’s exact test) (Table 3⇓)
Of the 11 patients with a newly developing SAH, the origin of the bleeding was regrowth of the clipped aneurysm in 5 patients and a de novo aneurysm in 4 patients (Table 4⇓). One patient had both regrowth and a de novo aneurysm, and the former was the origin of the bleeding (patient 4 in Table 4⇓). One patient had bleeding from a known but untreated aneurysm (patient 3 in Table 4⇓). Three patients developed SAH <9 years after the initial surgery from an incompletely clipped aneurysm (n=1), from an aneurysm arising in an unstudied region (n=1), and from a known but untreated aneurysm (n=1). The remaining 8 patients had bleeding >9 years after surgery.
In the study, in which we focus on aneurysm formation, we found that aneurysm recurrence, particularly the formation of de novo aneurysms, occurs at a significant rate. Interestingly, the risk of regrowth of completely clipped aneurysms (0.26% annually) was much lower than the risk of de novo aneurysm formation (0.89% annually), emphasizing the reliability of clipping.7
Although we excluded 11 patients who developed SAH during the follow-up period in calculation of the risk of regrowth or de novo aneurysm formation because these patients should represent all 412 patients, at least some of these 11 patients could have been included in the studied group if angiography was performed before the aneurysms ruptured. A rough estimation would be to consider that 2 or 3 of the 11 cases could have been included given that approximately one fourth of all patients were examined by angiography. If so, a little more than 0.89% might be the real annual risk for de novo aneurysm formation.
In our study, we did not observe a significantly higher risk of de novo aneurysm formation in multiple aneurysm patients. Similarly, gender apparently was not a factor that affected the risk of aneurysm recurrence.
Compared with the number of the aneurysms detected with follow-up angiography (13 of 112 patients), the number of SAHs (13 of 412 patients) seems to be rather high, given that the estimated risk of rupture from nongiant aneurysms ranges from 0.05% to 1% per year depending on various factors. One possible explanation is that additional aneurysms that arise in patients with a history of cerebral aneurysms may carry a higher risk of rupture.
To our knowledge, only 1 previous study described the results of late follow-up angiography in a relatively large series.8 In that study with a mean follow-up of 4.4 years, David et al8 reported a 0.52% annual regrowth rate for completely clipped aneurysms and a 1.8% annual rate of de novo aneurysm formation. The authors stated that late angiographic follow-up review would not be required for completely clipped aneurysms, although it should be indicated for incompletely obliterated aneurysms.9 10 11 However, our study, which had a follow-up period that was twice as long, showed that the cumulative risk of aneurysm recurrence reached ≈10% at 9 years. In fact, the majority of new aneurysms (11 of 13) were found in patients who undergone angiography >9 years after the initial treatment. It should also be noted that the majority of the patients (8 of 11) developed SAH after 9 years. Therefore, angiography may be necessary for patients with completely clipped aneurysms after 9 to 10 years. Patients with multiple aneurysms or female patients did not appear to be of higher risk in our study.12 13 For patients with incompletely clipped aneurysms, on the other hand, more frequent follow-up angiography (eg, every 3 years) may be indicated.
SAH is a catastrophic event,14 15 and adequately designed follow-up strategy may further improve the prognosis of patients with treated aneurysms. Whether the risk of DSA in the follow-up studies is acceptable may still be controversial, but a recent report in which meta-analysis was used estimated the risk of cerebral angiography to be 0.07%,16 which seems to justify DSA as an acceptable examination in the detection of de novo aneurysms or regrowth of original aneurysms. Unfortunately, magnetic resonance angiography or 3-dimensional CT in cerebral arteries is less likely to be feasible in patients with an aneurysm clip. On the other hand, de novo aneurysms located distant from the clip should be able to be monitored with those less-invasive methods, as well as untreated aneurysms and wrapped aneurysms.
In summary, although this follow-up angiographic study reconfirmed the long-term efficacy of complete clipping of cerebral aneurysm in terms of aneurysm recurrence, the risk of de novo aneurysm formation was significant after 9 years, and some appear to cause SAH at a significantly high rate. In consideration of the fatality rate of SAH, follow-up investigation may be indicated 9 to 10 years after surgery even for patients with completely clipped aneurysms, for whom the accumulated risk of aneurysm recurrence might exceed 10%.
- Received July 31, 2000.
- Revision received November 1, 2000.
- Accepted January 5, 2001.
- Copyright © 2001 by American Heart Association
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