Correspondence

Risks and Benefits of Screening for Intracranial Aneurysms

N Engl J Med 2000; 342:739-740March 9, 2000

Article

To the Editor:

Determining the risk of rupture of an intracranial aneurysm solely on the basis of a single radiologic measurement of an aneurysm in a first-degree relative of a patient with spontaneous subarachnoid hemorrhage and the statistical annual rate of rupture for aneurysms of that size, as proposed by the Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group (Oct. 28 issue),1 is faulty. Aneurysms do not remain one size, nor do they grow at annual rates, but rather in unpredictable spurts.2

The cause of the initial formation of an aneurysm is unknown. With regard to the much-studied issue of expansion and rupture, a viable hypothesis suggests that, as aneurysms are subjected to low-frequency pulsatile blood pressure, areas of weakness develop in their walls, some as radiologically discernible daughter lobules. Rupture may occur well after the events that originally caused the areas of weakness. The risk of rupture does not depend on size, but rather on the presence of these areas of weakness or lobules.

Accordingly, assessments of risk and benefit must be based on the cumulative lifetime risk of rupture (reportedly, 30 percent of sporadic aneurysms rupture in young persons3) and must take into account the frequent increases in size and the development of lobules that precede rupture.

The study group could also have considered other benefits of screening. For example, screening studies could help answer questions about the poorly defined natural history of aneurysms, leading to the development of more useful screening procedures and tools.4 In addition, as many as 40 percent or more5 of those with aneurysmal rupture have preliminary symptoms or signs before rupture — notably, a new headache, or one of different character. Screening with magnetic resonance angiography should not be used only to identify candidates for surgery. The identification of patients with aneurysms allows new symptoms to receive proper assessment, and new aneurysmal growth or development of lobules can be monitored. Currently, patients with new symptoms often are not referred to neurologists and receive an incorrect diagnosis, such as migraine or tension headache.

Claus P. Speth, M.D.
501 Princeton Blvd., Wenonah, NJ 08090

5 References

1. 1

   The Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group. Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage. N Engl J Med 1999;341:1344-1350
   Full Text | Web of Science | Medline

2. 2

   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) 1999;141:153-159
   CrossRef | Web of Science | Medline

3. 3

   Juvela S, Porras M, Heiskanen O. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. J Neurosurg 1993;79:174-182
   CrossRef | Web of Science | Medline

4. 4

   Alterman RL, Drucker E. Cost-effective screening for cerebral aneurysms. Neurosurg Clin N Am 1998;9:497-507
   Web of Science | Medline

5. 5

   Mayer PL, Awad IA, Todor R, et al. Misdiagnosis of symptomatic cerebral aneurysm: prevalence and correlation with outcome at four institutions. Stroke 1996;27:1558-1563
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The purpose of our study was to determine the benefits and risks of screening for and treatment of unruptured intracranial aneurysms in the first-degree relatives of patients with subarachnoid hemorrhage. Dr. Speth suggests that we missed a chance to answer questions about the natural history of aneurysms and comments on our estimation of the risk of rupture. Although the process of aneurysm formation, growth, and rupture is still not understood, screening for aneurysms and then studying their natural history was not the aim of our study.

We based our estimations on a systematic review of the data from all available studies of the risk of rupture of unruptured aneurysms (for a total of 3907 patient-years) rather than on data from a single study (with less than 200 patient-years). In none of these studies nor in the recently published data from the International Study of Unruptured Intracranial Aneurysms1 is the presence of daughter lobules mentioned as a clinically important prognostic factor with regard to rupture. On the other hand, size is a well-validated risk factor for rupture. Moreover, further information about prognostic factors that could be used to identify aneurysms prone to rupture would add detail to our analysis but is unlikely to alter our main conclusions. In the absence of factors that can be used to identify persons with such aneurysms before diagnostic imaging, screening of family members is not warranted at this time. If future research results in more knowledge about factors determining the risk of rupture, new estimations can be used in our calculations of the benefits of screening.

Dr. Speth also suggests that surgery for relatives with unruptured aneurysms should be postponed until preliminary symptoms or signs occur that could predict rupture of the aneurysm. However, there is prospective evidence that such symptoms or signs are seldom present in patients with subarachnoid hemorrhage.2 The initial episode of headache represents not a minor leakage but a genuine subarachnoid hemorrhage with an outcome similar to that of a hospital-based series of patients with subarachnoid hemorrhage. Moreover, it is questionable whether screening is justified without there being any subsequent treatment options for relatives with unruptured aneurysms.

Theodora W.M. Raaymakers, M.D.
Gabriel J.E. Rinkel, M.D.
University Hospital Utrecht, 3584 CX Utrecht, the Netherlands

Patrick M.M. Bossuyt, Ph.D.
Academic Medical Center, 1105 AZ Amsterdam, the Netherlands

for the Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group

2 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   Linn FHH, Rinkel GJE, Algra A, van Gijn J. The notion of “warning leaks” in subarachnoid haemorrhage: are such patients in fact submitted with a rebleed? J Neurol Neurosurg Psychiatry (in press).