title: Long-term, serial screening for intracranial aneurysms in individuals with a family history of aneurysmal subarachnoid haemorrhage: a cohort study.
abstract: BACKGROUND
  Individuals with two or more first-degree relatives who have had aneurysmal subarachnoid haemorrhage (aSAH) have an increased risk of aneurysms and aSAH. We investigated the yield of long-term serial screening for intracranial aneurysms in these individuals.
  
  
  METHODS
  In a cohort study, we reviewed the results of screening of individuals with a positive family history of aSAH (two or more first-degree relatives who had had aSAH or unruptured intracranial aneurysms) done at the University Medical Centre Utrecht (Utrecht, Netherlands) between April 1, 1993, and April 1, 2013. Magnetic resonance angiography or CT angiography was done from age 16-18 years to 65-70 years. After a negative screen, we advised individuals to contact us after 5 years, but did not actively call them for repeated screening. We recorded familial history of ruptured and unruptured intracranial aneurysms, smoking history, hypertension, previous aneurysms, screening dates, and screening results. We identified risk factors for positive initial and follow-up screens with univariable and multivariable regression analysis.
  
  
  RESULTS
  We identified aneurysms in 51 (11%, 95% CI 9-14) of 458 individuals at first screening, in 21 (8%, 5-12) of 261 at second screening, in seven (5%, 2-11) of 128 at third screening, and three (5%, 1-14) of 63 at fourth screening. Five (3%, 95% CI 1-6) of 188 individuals without a history of aneurysms and with two negative screens had a de-novo aneurysm in a follow-up screen. Smoking (odds ratio 2·7, 95% CI 1·2-5·9), history of previous aneurysms (3·9, 1·2-12·7), and familial history of aneurysms (3·5, 1·6-8·1) were significant risk factors for aneurysms at first screening in the multivariable analysis. History of previous aneurysms was the only significant risk factor for aneurysms at follow-up screening (hazard ratio 4·5, 1·1-18·7). Aneurysms were identified in six (5%, 95% CI 2-10) of 129 individuals who were screened before age 30 years. One patient developed a de-novo aneurysm that ruptured 3 years after the last negative screen.
  
  
  CONCLUSIONS
  In individuals with a family history of aSAH, the yield of long-term screening is substantial even after more than 10 years of follow-up and two initial negative screens. We advocate long-term serial screening in these individuals, although the risk of aSAH within screening intervals is not eliminated.
  
  
  BACKGROUND
  The Dutch Heart Foundation.
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: a.s.e.bor@umcutrecht.nl.
authors.forename: A Stijntje E
authors.initials: AS
authors.lastname: Bor
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Norden
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Wermer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002533:Cerebral Angiography; D015331:Cohort Studies; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis* / Q000517:prevention & control; D018810:Magnetic Resonance Angiography; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D013345:Subarachnoid Hemorrhage / Q000517:prevention & control*; D013997:Time Factors