Marfan Syndrome and Intracranial Aneurysms
To the Editor:
Two brain autopsy series of patients with Marfan syndrome have now been published1 2 and, in contrast to the conclusions drawn by Conway and colleagues,2 they strongly suggest that patients with Marfan syndrome are at an increased risk of harboring an intracranial aneurysm. Combining the 2 autopsy series, incidental intracranial aneurysms were found in 2 (6.5%) of 31 patients with Marfan syndrome.1 2 This could be compared with the 0.8% to 1.3% prevalence of incidental intracranial aneurysms in the general autopsy populations at the 2 institutions.1 2 However, the mean ages of the patients in the series with Marfan syndrome at autopsy were only 281 and 392 years, respectively, and intracranial aneurysms are now well recognized to be acquired lesions. The expected prevalence of incidental intracranial aneurysms in the third and fourth decades of life would be much lower. For example, in the Johns Hopkins autopsy study used by Conway and colleagues as representative of the general autopsy population, the prevalence of incidental intracranial aneurysms was 0% in individuals less than 40 years of age.3
Conway and colleagues mention that their patient with Marfan syndrome and an intracranial aneurysm had a brother who also had Marfan syndrome, but no aneurysm was found at autopsy in the brother, although he was 5 years older at the time of his death. They then suggest that this indicates that their patient’s intracranial aneurysm was probably sporadic and not associated with the underlying arteriopathy of Marfan syndrome. This may be an overly simplistic interpretation of their data, because intracranial aneurysms are acquired lesions with multiple risk factors, both genetic and environmental. For example, Chauveau and colleagues4 described monozygotic twins with autosomal dominant polycystic kidney disease who were examined at age 47 with MR angiography. Two aneurysms were found in the twin with untreated hypertension and none in the twin with treated hypertension. Autosomal dominant polycystic kidney disease is a well-studied connective-tissue disease that is generally believed to be associated with intracranial aneurysms.
- Copyright © 1999 by American Heart Association
We appreciate Dr Schievink’s interest in our article. After careful consideration of his 3 points, however, we have to take exception to the same and reiterate our conclusion that there exists no evidence that Marfan syndrome is associated with an increased prevalence of intracranial aneurysms.
Schievink proposes that we pool the results of his autopsy studyR1 and oursR2 and change our conclusion. He reported an autopsy series of 7 Marfan patients, 2 of whom had an aneurysm. We object to a “meta-analysis” of these 2 series (which would add up to 32 patients, not 31 as Schievink calculated) for the following reason. Doing so would dilute the epidemiological strength of our series, namely, the fact that it is derived from an unselected sample of 1400 Marfan patients accumulated over 40 years, with the sampling error of a small series of 7 patients that we suspect carries an inadvertent sampling bias. As we stated in our article, it is difficult to derive any firm statistical conclusions from Dr Schievink’s series because of its small number of patients combined with the sampling bias in the cerebrovascular patient population at that hospital, which has been previously recognized, documented, and reported by a different group from the same institution.R3
Schievink goes on to state erroneously that in our previous studyR4 we reported a prevalence of aneurysms of 0% in individuals less than 40 years of age. We would like to clarify that in our autopsy series of 13 042 patients, we documented a prevalence of intracranial aneurysms of approximately 0.9% in the second decade of life, 2% in the third decade, 3% in the fourth decade, and 3.3% in the fifth decade. Moreover, the prevalence of intracranial aneurysms observed in our series in individuals younger than 40 years of age was actually higher than the overall prevalence of 1.3%, but for our statistics we chose the more conservative number of 1.3%.
Finally, Schievink states that our comment concerning the brothers in our series, one who had an aneurysm and one who did not, is “overly simplistic.” Although we are indeed aware that multiple genetic and environmental factors may contribute to aneurysm formation, we simply wanted to report this curious finding. We did not need to draw any absolute conclusions from the same, since we felt that the data presented in the paper were more than sufficient to support our conclusion.
After we submitted our paper, Dr Vincent Gott from our institution published a multi-institutional study of 675 patients with Marfan syndrome who underwent replacement of the aortic root and reported the cause of death of 86 of these patients.R5 Similar to what other investigators reported in the 5 clinical series of Marfan patients that we cite in our paper and what we noted in our own series of 710 neurosurgical patients, Gott and colleagues did not identify any Marfan patient who died from an intracranial aneurysm.
We therefore reiterate our conclusion that there exists no evidence that Marfan syndrome is associated with an increased prevalence of intracranial aneurysms, but we nevertheless thank Dr Schievink for his interest in our work.
Schievink WI, Parisi JE, Piepgras DG, Michels VV. Intracranial aneurysms in Marfan’s syndrome: an autopsy study. Neurosurgery.. 1997;41:866–871.
Conway JE, Hutchins GM, Tamargo RJ. Marfan syndrome is not associated with intracranial aneurysms. Stroke.. 1999;30:1632–1636.
de la Monte SM, Moore GW, Monk MA, Hutchins GM. Risk factors for the development and rupture of intracranial berry aneurysms. Am J Med.. 1985;78:957–964.