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(Stroke. 2001;32:1933.)
© 2001 American Heart Association, Inc.

Letters to the Editor

Risk of Subarachnoid Hemorrhage From a De Novo Aneurysm

Seppo Juvela, MD, PhD

Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland

To the Editor:

I read with interest a recent article¹ concerning risk of de novo aneurysm formation and recommendations for future screening for these aneurysms after successful clipping of an intracranial aneurysm. Although the results of the study are reliable, the conclusions are not based on the data of this and previous studies. The patients whose aneurysms have been treated successfully should not unnecessarily be made anxious and fearful for decades because of a very low risk for subarachnoid hemorrhage (SAH) from a potential de novo aneurysm.

In our first angiographic follow-up study (published in 1993²), of 31 patients with a mean follow-up of 9 years (range 0.8 to 23.0 years; total follow-up of 279 person-years), formation rate of a de novo aneurysm cases was 2.2%/y, which was similar to that in a recent study (1.8%/y).³ In both of these studies, the formation rate of new aneurysms was likely too high, because new SAH cases were overrepresented in these study populations. Interestingly, in the study of Tsutsumi and colleagues,¹ the formation rate of a de novo aneurysm was lower and similar (0.89% per year) to that in our recent study (0.84%/y), obtained among 89 patients with a mean follow-up time of 20.1 years per patient (range 1.2 to 38.9 years; total follow-up time 1789 person-years),⁴ which suggests that aneurysm formation rate is lower if the follow-up is not restricted to a high-risk population. In our study, there were 15 de novo aneurysm cases, and female gender and cigarette smoking increased this risk. De novo aneurysms developed during a mean follow-up time of 18.8±7.7 years, a period not differing significantly from that of those without de novo aneurysms. In cases in which a de novo aneurysm caused SAH, the follow-up time was somewhat shorter (14.7±8.1 years, range 3.4 to 28.4 years).

When the aneurysm formation rate of our study is adjusted to the population, with an equal sex ratio and a smoking prevalence of 25% as in the general population, the aneurysm formation rate is 0.56%/y.⁴ It was somewhat surprising that female gender was not associated with aneurysm formation in the study of Tsutsumi and colleagues,¹ likely because of too few de novo aneurysm cases or overrepresentation of men among those with angiographic follow-up. It is well known that women have a higher risk for SAH.⁴ Because female gender does not increase either risk for rupture of a verified unruptured aneurysm^2,5,6 or risk for growth of an intact aneurysm,⁴ women very likely have an increased risk for aneurysm formation.

Diagnosis of de novo aneurysm is rare, since these are almost always diagnosed after a rupture. Assuming, on the basis of our previous study,^4,6 that the risk of rupture of an unruptured aneurysm is approximately 1.3%/y and that the rate of formation of an aneurysm is 0.84%/y, patients whose aneurysms have been treated successfully seem to have a risk for SAH from a de novo aneurysm of 11/100 000 per year. When the aneurysm formation rate is 0.56%/y, the approximate SAH incidence is 7.3/100 000 per year. These incidences of SAH are even lower than those of the general adult population (30 to 60/100 000 per year). Alternatively, risk of SAH from a de novo aneurysm can be calculated directly from data. In the study of Tsutsumi and colleagues,¹ it seemed to be 100/100 000 per year or 0.1%/y (4 de novo aneurysm SAH cases per approximately 3980 follow-up years in 412 patients). In our study,^4,6 this rate was 78/100 000 per year (95% CI 9 to 276/100 000 per year; 2 de novo aneurysm SAH cases per 2575 follow-up years in 142 patients). Thus, treated SAH patients may have at most a 2- to 3-fold increase of subsequent SAH from a de novo aneurysm. It seems that future screening of new aneurysms is not justified, particularly as it is now controversial whether unruptured aneurysm should even be operated on.^5,6 Rupture risk of an unruptured aneurysm is clearly higher than that of a potential de novo aneurysm. In our study,⁶ 33 (currently 34) of 142 patients with unruptured aneurysms suffered SAH from their untreated aneurysm whereas only 2 had SAH from a de novo aneurysm.

In 2 of our 89 patients with aneurysm follow-up,⁴ an aneurysm had developed in the neck of an aneurysm that had ruptured and been clipped. In 4 other patients whose ruptured aneurysms were not totally clipped, the size of the aneurysm increased during follow-up: 2 of the patients suffered a rebleed from that aneurysm (1 rebleed was fatal). These were not considered de novo aneurysms. It seems that clipping of a ruptured aneurysm was relatively efficient from the 1950s to 1970s. Screening of aneurysms may be justified only among patients with a "heavy" family history for these lesions, eg, with 3D CT angiography, which is as reliable as conventional angiography in detecting de novo aneurysms.⁴

References

1. Tsutsumi K, Ueki K, Morita A, Usui M, Kirino T. Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results of long-term follow-up angiography. Stroke. 2001; 32: 1191–1194.[Abstract/Free Full Text]
2. Juvela S, Porras M, Heiskanen O. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. J Neurosurg. 1993; 79: 174–182.[Medline] [Order article via Infotrieve]
3. David CA, Vishteh AG, Spetzler RF, Lemole M, Lawton MT, Partovi S. Late angiographic follow-up review of surgically treated aneurysms. J Neurosurg. 1999; 91: 396–401.[Medline] [Order article via Infotrieve]
4. 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.[Abstract/Free Full Text]
5. The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms: risk of rupture and risks of surgical intervention. N Engl J Med. 1998; 339: 1725–1733.[Abstract/Free Full Text]
6. Juvela S, Porras M, Poussa K. Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg. 2000; 93: 379–387.[Medline] [Order article via Infotrieve]

Response

Kazuo Tsutsumi, MD; Keisuke Ueki, MD Takaaki Kirino, MD

Department of Neurosurgery, Aizu Chuou Hospital, and Department of Neurosurgery, University of Tokyo Hospital, Tokyo, Japan

We appreciate Dr Juvela’s comments on our article, and we also would like to take this opportunity to express our full respect for his numerous important studies that have contributed to the body of knowledge in this specific field.^1,2

As Dr Juvela pointed out, whether screening for new aneurysm formation is to be recommended or not can be a difficult issue. However, as we described in our article,³ we did observe 4 cases of SAH from de novo aneurysms in our series of 412 patients, which, as Dr Juvela noted, exceeded his estimation of 11/100 000 person-years. Furthermore, shortly after we submitted our paper, 2 of the 145 patients who did not undergo follow-up angiography in our study developed SAH from a do novo aneurysm at 7 and 11 years, respectively, after surgery; 1 died and the other became bedridden. Therefore, current statistics seems to indicate an even higher risk (0.15%/y) of SAH from de novo aneurysms. We wish to make it clear that we are not proposing to screen patients every year after the treatment, thus causing them decades of unnecessary anxiety or fear about fatal SAH. However, the risk is cumulative in each patient, and our study shows that the cumulative risk of SAH, from both de novo and regrowth, is 2% and 9% after 10 and 20 years, respectively.⁴ Importantly, most of the SAH from a de novo aneurysm (5 of 6, including the 2 additional cases) developed >10 years after surgery. Therefore, we believe that patients who have been fortunate to live >10 years after surgery in good health should benefit from being notified of the risk and being offered screening for aneurysm recurrence at that point. Although there still is controversy, Dr Juvela apparently shares with us the view that unruptured aneurysms, once detected, are better be treated surgically.

We did not observe any increased risk of de novo aneurysm formation in females, which did not surprise us. De novo aneurysm formation in patients with verified aneurysms, which is already highly selected, should be considered separately from that in the general population. It seems reasonable to us that women with verified aneurysm did not have increased risk of de novo aneurysm formation compared with men, just as they did not have increased risk of growth or rupture of intact aneurysms.

Compared with our unselected series,³ including 20% with multiple aneurysms, the series of Juvela et al^1,2 relied heavily on patients with unruptured aneurysms accompanying a ruptured and clipped aneurysm, which is reflected in the very high ratio (90%) of multiple aneurysm cases. Bearing that in mind, we were somewhat surprised by the similar risk of de novo aneurysm formation in our series and theirs (0.89% and 0.81%, respectively). When we include the 11 cases with newly developing SAH, de novo aneurysms were found more frequently in multiple aneurysm cases (8/31 vs 8/92; P=0.014, ² test). Therefore, we felt that the risk of de novo aneurysm formation in the series of Juvela et al was a little lower than we expected from our data. Before referring to the possible "racial difference," we should continue to collect more information. Meanwhile, how to interpret the data currently available and how to reflect these data in clinical decisions to benefit patients still seems to be open to discussion and also could change with time, considering the rapid progress in medical technology.

References

1. Juvela S, Porras M, Poussa K. Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg. 2000; 93: 379–387.
2. Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: long-term follow-up study. Stroke. 2001; 32: 485–491.
3. Tsutsumi K, Ueki K, Morita A, Usui M, Kirino T. Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results of long-term follow-up angiography. Stroke. 2001; 32: 1191–1194.
4. Tsutsumi K, Ueki K, Usui M, Kwak S, Kirino T. Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms. Stroke. 1998; 29: 2511–2513.[Abstract/Free Full Text]

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