title: Unruptured intracranial aneurysms in the Familial Intracranial Aneurysm and International Study of Unruptured Intracranial Aneurysms cohorts: differences in multiplicity and location.
abstract: OBJECTIVE
  Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs.
  
  
  METHODS
  The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry.
  
  
  RESULTS
  Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p<0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p=0.016).
  
  
  CONCLUSIONS
  Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.
authors.affiliation: Department of Neurology, Indiana University, Indianapolis, Indiana 46202, USA. jsmackey@iupui.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Mackey
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brown
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Moomaw
authors.forename: Laura
authors.initials: L
authors.lastname: Sauerbeck
authors.forename: Richard
authors.initials: R
authors.lastname: Hornung
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Gandhi
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Flaherty
authors.forename: Irene
authors.initials: I
authors.lastname: Meissner
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Guy
authors.initials: G
authors.lastname: Rouleau
authors.forename: David F
authors.initials: DF
authors.lastname: Kallmes
authors.forename: James
authors.initials: J
authors.lastname: Torner
authors.forename: John
authors.initials: J
authors.lastname: Huston
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D007391:International Cooperation; D002532:Intracranial Aneurysm / Q000145:classification / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000473:pathology; D010641:Phenotype; D020769:Posterior Cerebral Artery / Q000473:pathology; D012307:Risk Factors; D012737:Sex Factors