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on February 19, 2009

Stroke. 2009
Published online before print February 19, 2009, doi: 10.1161/STROKEAHA.108.542571
A more recent version of this article appeared on June 1, 2009
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Submitted on November 11, 2008
Revised on December 20, 2008
Accepted on January 6, 2009

Greater Rupture Risk for Familial as Compared to Sporadic Unruptured Intracranial Aneurysms

Joseph P. Broderick MD*; Robert D. Brown Jr MD; Laura Sauerbeck MS; Richard Hornung DrPH; John Huston III MD; Daniel Woo MD; Craig Anderson MD; Guy Rouleau MD, PhD; Dawn Kleindorfer MD; Matthew L. Flaherty MD; Irene Meissner MD; Tatiana Foroud PhD; E. Charles J. Moomaw PhD; E. Sander Connolly MD; for the FIA Study Investigators

From the University of Cincinnati College of Medicine (J.P.B., L.S., D.W., D.K., M.L.F., C.J.M.), Cincinnati, Ohio; the Mayo Clinic (R.D.B., J.H., I.M.), Rochester, Minn; the Cincinnati Children's Hospital Medical Center (R.H.), Cincinnati, Ohio; The George Institute for International Health (C.A.), University of Sydney, Sydney, Australia; Notre Dame Hospital (G.R.), Montreal, Canada; Indiana University School of Medicine (T.F.), Indianapolis, Ind; and Columbia University (E.S.C.), New York, NY.

* To whom correspondence should be addressed. E-mail: joseph.broderick{at}uc.edu.

Background and Purpose—The risk of intracranial aneurysm (IA) rupture in asymptomatic members of families who have multiple affected individuals is not known.

Methods—First-degree unaffected relatives of those with a familial history of IA who had a history of smoking or hypertension but no known IA were offered cerebral MR angiography (MRA) and followed yearly as part of a National Institute of Neurological Diseases and Stroke-funded study of familial IA (Familial Intracranial Aneurysm [FIA] Study).

Results—A total of 2874 subjects from 542 FIA Study families were enrolled. After study enrollment, MRAs were performed in 548 FIA Study family members with no known history of IA. Of these 548 subjects, 113 subjects (20.6%) had 148 IAs by MRA of whom 5 subjects had IA ≥7 mm. Two subjects with an unruptured IA by MRA/CT angiography (3-mm and 4-mm anterior communicating artery subsequently had rupture of their IA. This represents an annual rate of 1.2 ruptures per 100 subjects (1.2% per year; 95% CI, 0.14% to 4.3% per year). None of the 435 subjects with a negative MRA have had a ruptured IA. Survival curves between the MRA-positive and -negative cohorts were significantly different (P=0.004). This rupture rate of unruptured IA in the FIA Study cohort of 1.2% per year is approximately 17 times higher than the rupture rate for subjects with an unruptured IA in the International Study of Unruptured Aneurysm Study with a matched distribution of IA size and location 0.069% per year.

Conclusions—Small unruptured IAs in patients from FIA Study families may have a higher risk of rupture than sporadic unruptured IAs of similar size, which should be considered in the management of these patients.


Key words: intracranial aneurysm • familial • magnetic resonance angiography • risk of rupture • smoking


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Stroke, June 1, 2009; 40(6): 1947 - 1947.
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