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1. Clinical Review Asymptomatic unruptured intracranial aneurysms Approach to screening and treatment John T. Lysack MD FRCPC Annalee Coakley MD CCFP ABSTRACT…
  • 1. Clinical Review Asymptomatic unruptured intracranial aneurysms Approach to screening and treatment John T. Lysack MD FRCPC Annalee Coakley MD CCFP ABSTRACT OBJECTIVE  To review the current knowledge of screening and treatment of asymptomatic unruptured  intracranial aneurysms (AUIAs) using a case-based approach. SOURCES OF INFORMATION  PubMed was searched from January 1995 to January 2008 using the phrase  unruptured intracranial aneurysm. Scientific statements of the Stroke Council of the American Heart  Association pertaining to intracranial aneurysms were also reviewed. MAIN MESSAGE  Most small AUIAs (≤ 5 mm) do not rupture, and the risks of treatment are substantial.  Most small AUIAs can therefore be managed conservatively. Endovascular coiling or surgical clipping of  larger aneurysms (> 5 mm) should be considered on a case-by-case basis. CONCLUSION  There is currently a lack of sound scientific evidence to support treatment of unruptured  intracranial aneurysms. A prospective randomized controlled trial—Trial on Endovascular Aneurysm  Management—is now under way to address this issue. It is expected to conclude in 2021. RÉSUMÉ OBJECTIF  Revoir les données actuelles sur le dépistage et le traitement des anévrysmes intracrâniens non  rompus asymptomatiques (AINA) en utilisant une méthode de cas par cas. SOURCES DE L’INFORMATION  On a consulté PubMed entre janvier 1995 et janvier 2008 à l’aide de  l’expression unruptured intracranial aneurysm. On a aussi relevé les déclarations scientifiques du Stroke Council de l’American Heart Association à propos des anévrysmes intracrâniens.  PRINCIPAL MESSAGE  La plupart des petits AINA (≤ 5 mm) ne se rompent pas tandis que les risques de  traiter sont importants. La plupart des petits AINA peuvent donc être traités de façon conservatrice. Dans  le cas des anévrysmes plus importants (> 5 mm), l’insertion d’un coil endovasculaire ou le clampage  chirurgical devraient être envisagés en fonction de chaque cas. CONCLUSION  À l’heure actuelle, il n’y a pas de preuve scientifique solide justifiant de traiter un anévrysme  intracrânien non rompu. Cette question fait présentement l’objet d’un essai randomisé prospectif  (Trial  on Endovascular Aneurysm Management), qui doit se terminer en 2021.   This article has been peer reviewed. Cet article a fait l’objet d’une révision par des pairs. Can Fam Physician 2008;54:1535-8  FOR PRESCRIBING INFORMATION SEE PAGE 1603 Vol 54: noVember • noVembre 2008  Canadian Family Physician • Le Médecin de famille canadien 1535
  • 2. Clinical Review Asymptomatic unruptured intracranial aneurysms B rain imaging, for a variety of reasons, is being per- Sources of information formed more frequently in Canada. As a result, an  PubMed  was  searched  using  the  phrase  unruptured increasing  number  of  asymptomatic  unruptured  intracranial aneurysm.  Results  were  limited  to  human  intracranial  aneurysms  (AUIAs)  are  being  discovered,  studies  published  in  the  English  language  from  January  either  on  purpose  (ie,  via  screening)  or  as  an  inciden- 1995 to January 2008. Relevant papers were selected for  tal  finding  (ie,  incidentaloma).  As  more  aneurysms  are  review. Additional articles were identified from the refer- discovered,  family  physicians  can  expect  to  be  further  ence lists of relevant papers. Scientific statements of the  involved in their management. Stroke  Council  of  the  American  Heart  Association  that  For  screening  to  be  considered  effective,  the  pertained to intracranial aneurysms were also reviewed.  screened  population  must  have  a  better  outcome  than  the  unscreened  population.  Differences  in  outcome  Main message between screened and unscreened populations are pri- When intracranial aneurysms rupture the results are dev- marily a reflection of the risks related to diagnosis and  astating; half of patients die and up to half of those who  treatment  versus  the  natural  history  of  the  condition.  survive  are  disabled.1  Fortunately,  although  the  preva- Similarly, differences in outcome between patients with  lence  of  intracranial  aneurysms  in  the  general  popula- treated  and  conservatively  managed  incidentalomas  tion is relatively high (2%),2 the incidence of subarachnoid  are a reflection of the risks related to treatment versus  hemorrhage (SAH) in the general population is relatively  the natural history of the condition. In other words, the  low (6 to 9 cases per 100 000 person-years).3,4 This implies  natural  history  of  a  lesion  must  be  sufficiently  poor  to  that most intracranial aneurysms never rupture. justify the risks of intervention. The  best  estimate  of  the  rupture  risk  of  intracranial  aneurysms  is  arguably  from  a  recent  meta-analysis,5  Case 1 which  yielded  an  annual  rupture  risk  of  0.6%  to  1.3%.  Ms  A.  is  a  45-year-old  woman  who  has  recently  Subgroup  analyses  showed  that  asymptomatic  aneu- moved  to  the  city  and  presents  to  her  new  fam- rysms were 4 to 5 times less likely to rupture than symp- ily physician for an initial visit. She is in good health,  tomatic aneurysms; small aneurysms (≤ 5 mm) were 2 to  but during a routine review of her family history it is  3 times less likely to rupture than larger (> 5 mm) aneu- revealed that her father died of a ruptured intracranial  rysms;  and  anterior  circulation  aneurysms  were  2  to  3  aneurysm. She is unaware of any other family history  times  less  likely  to  rupture  than  posterior  circulation  of intracranial aneurysm. She is asymptomatic and in  aneurysms  (those  involving  the  vertebrobasilar  system  good  health.  Should  Ms  A.  be  screened  for  an  intra- or  posterior  cerebral  arteries). 5  An  earlier  study  sug- cranial aneurysm? gested that the annual rupture risk for small aneurysms  (< 10 mm) might be as low as 0.05%, although this claim  Case 2 is controversial.6 Ms  B.  is  a  45-year-old  woman  who  was  struck  in  Patients with a family history of aneurysmal SAH are  the  face  by  a  softball  during  a  recreational  game.  at increased risk of harbouring an intracranial aneurysm  She reported to the local emergency department for  compared  with  the  general  population.  Epidemiologic  management  of  a  laceration.  In  case  of  underlying  studies  have  shown  that  patients  with  a  single  first- injury,  a  computed  tomography  scan  of  the  head  degree  relative  with  aneurysmal  SAH  have  a  3%  to  6%  and  facial  bones  was  performed.  There  was  no  risk of harbouring AUIAs (twice the baseline risk of the  fracture or intracranial hemorrhage; however, focal  general population),7,8 while patients with 2 or more first- prominence of the left middle cerebral artery (MCA)  degree  relatives  with  aneurysmal  SAH  have  an  8%  to  raised  the  possibility  of  an  incidental  unruptured  10% risk of harbouring AUIAs (4 to 5 times the baseline  intracranial  aneurysm.  A  computed  tomography  risk of the general population).8,9  angiogram  was  performed,  which  confirmed  the  In  deciding  whether  or  not  to  intervene,  the  risk  of  presence  of  a  3-mm  saccular  aneurysm  at  the  left  intervention  (ie,  treatment-related  mortality  and  mor- MCA  bifurcation.  Does  this  aneurysm  require  treat- bidity)  must  be  weighed  against  the  risk  of  noninter- ment? vention  (ie,  risk  of  rupture).  Treatment-related  risks  are  substantial.  In  a  recent,  large  retrospective  study  (2535  Case 3 cases  from  18  American  states),  11.5%  of  patients  had  Ms C. is a 45-year-old woman who comes to her fam- an  adverse  outcome  following  elective  treatment  of  ily  physician  for  follow-up  of  an  incidentally  discov- their  unruptured  intracranial  aneurysm  and  53  patients  ered  3-mm  left  MCA  bifurcation  aneurysm.  Although  (2.1%)  died.10  A  prospective  study  of  the  risks  and  ben- she remains asymptomatic, she has been researching  efits  of  screening  for  intracranial  aneurysms  in  first- her condition on the Internet and is now considering  degree  relatives  of  patients  with  sporadic  SAH  showed  prophylactic  treatment.  She  has  heard  that  coiling  is  that  although  screening  resulted  in  a  small  increase  in  better than clipping. Is that true? life expectancy (4 weeks per person screened), this was  1536 Canadian Family Physician • Le Médecin de famille canadien  Vol 54: noVember • noVembre 2008
  • 3. Asymptomatic unruptured intracranial aneurysms Clinical Review overshadowed by a substantial decrease in quality of life  EDITOR’S KEY POINTS (19  years  of  decreased  function  per  person  screened).7  • Brain imaging is being performed more frequently The  study  also  showed  that  in  order  to  prevent  1  SAH,  in Canada and, as a result, an increasing number of 149  first-degree  relatives  would  need  to  be  screened;  asymptomatic unruptured intracranial aneurysms to prevent 1 fatal SAH, 298 would need to be screened.  (AUIAs) are being discovered. How should such From  a  societal  perspective,  the  cost-effectiveness  of  AUIAs be managed? various  management  strategies  is  also  of  interest.  In  • While ruptured intracranial aneurysms are devas- a  recent  comprehensive  cost-effectiveness  analysis,11  tating—half of patients die and up to half of those conservative  management  (no  treatment)  was  the  only  who survive are disabled—most intracranial aneu- cost-effective  strategy  for  small  (< 7  mm)  intracranial  rysms never rupture. Management decisions are cur- aneurysms (using an incremental cost-effectiveness ratio  rently made based on estimations of natural history threshold of $100 000 per quality-adjusted life-year). versus expected treatment outcomes. Treatment- Given  the  relatively  high  risks  of  treatment  and  the  related risks are substantial, and there is currently comparatively  modest  anticipated  benefits,  the  Stroke  insufficient evidence to support surgical or endovas- Council of the American Heart Association has concluded  cular treatment of AUIAs in most cases. that screening for AUIAs in the general population is not  • Should the natural history of a lesion be estimated indicated.12  Despite  increased  risk  of  harboured  AUIAs,  to be sufficiently poor to justify the risks of inter- screening patients with a single first-degree relative with  vention, some evidence suggests that endovascular aneurysmal  SAH  is  also  not  generally  recommended.12  coiling of unruptured intracranial aneurysms might Screening  patients  with  2  or  more  first-degree  relatives  improve outcomes compared with surgical clipping. with  aneurysmal  SAH  is  controversial—although  this  Because coiling is a relatively new technique, how- population  is  at  a  substantially  greater  risk  of  harbour- ever, its long-term outcomes are not yet known and ing  AUIAs,  the  effectiveness  of  screening  has  not  been  questions remain about the durability of endovas- studied  and  therefore  remains  unknown.12  Treatment  is  cular repair. not generally advocated in patients with small (< 10 mm)  asymptomatic intracranial aneurysms in patients without  POINTS DE REPèRE DU RÉDACTEUR a personal history of SAH.12 • Comme l’imagerie cérébrale est utilisée de plus en T h e   p r o s p e c t i v e,   r a n d o m i z e d   I n t e r n a t i o n a l  plus souvent au Canada, un nombre croissant d’ané- Subarachnoid  Aneurysm  Trial  (ISAT) 13  showed  that  vrysmes intra-crâniens non rompus asymptoma- endovascular coiling of ruptured intracranial aneurysms  tiques (AINA) sont découverts. Comment doit-on was  associated  with  improved  outcomes  when  com- traiter ces AINA? pared  with  surgical  clipping  (24%  versus  31%  morbidity  • Alors que la rupture d’un anévrysme intracrânien or  severe  disability  at  1  year).  Although  not  as  rigor- est désastreuse—la moitié des patients meurent et ously  studied,  coiling  of  unruptured  intracranial  aneu- plus de la moitié des survivants sont handicapés— rysms  might  improve  short-term  outcomes  as  well.  In  la plupart de ces lésions ne se rompent jamais. À a  recent  nonrandomized  retrospective  study,10  adverse  l’heure actuelle, la décision de traiter tient compte outcomes  at  discharge  following  endovascular  treat- de l’évolution naturelle prévue de l’anévrysme par ment  of  unruptured  intracranial  aneurysms  were  less  rapport aux résultats escomptés du traitement. Les frequent  than  those  following  surgical  treatment  (7%  traitements comportent des risques importants et il versus  13%),  and  in-hospital  mortality  rates  were  lower  n’y a actuellement pas de preuves suffisantes pour (0.9% versus 2.5%). justifier un traitement chirurgical ou endovasculaire Because  coiling  is  a  relatively  new  technique,  how- dans la majorité des cas d’AINA. ever,  its  long-term  outcomes  are  not  yet  known.  • Pour les anévrysmes dont l’évolution naturelle est Questions  remain  about  the  durability  of  endovascu- suffisamment inquiétante pour justifier le risque lar  repair.  For  example,  follow-up  with  the  ISAT13  study  d’une intervention, certaines données suggèrent que population  has  shown  that  retreatment  occurs  almost  l’insertion d’un coil dans un anévrysme intracrânien 7  times  more  frequently  for  coiled  aneurysms  than  for  non rompu pourrait avoir une meilleure issue qu’un clipped aneurysms.14 clampage chirurgical. Toutefois, comme l’insertion du coil est une technique relativement nouvelle, ses Case resolutions résultats à long terme ne sont pas encore connus, et Based  on  the  evidence  presented,  the  cases  should  be  on ignore toujours la durabilité de cette intervention. resolved as follows: Case 1.  Ms  A.  does  not  need  to  be  screened  for  an  for  AUIAs  in  patients  with  a  single  first-degree  relative  intracranial aneurysm. Given the relatively high risks of  with  a  ruptured  intracranial  aneurysm  is  not  generally  treatment and the modest anticipated benefits, screening  recommended (level II evidence). Vol 54: noVember • noVembre 2008  Canadian Family Physician • Le Médecin de famille canadien 1537
  • 4. Clinical Review Asymptomatic unruptured intracranial aneurysms Case 2.  Ms B.’s aneurysm does not need to be treated.  Contributors Drs Lysack  and  Coakley  contributed  to  the  concept  of  the  article,  the  litera- The risks of treatment might be greater than the risk of  ture  search,  the  review  of  selected  articles,  and  preparing  the  manuscript  for  rupture  for  her  small  (≤ 5  mm)  AUIA  (level  II  evidence).  submission. Endovascular coiling or surgical clipping of larger aneu- Competing interests None declared rysms  should  be  considered  on  a  case-by-case  basis.  Correspondence Consultation  with  an  interventional  neuroradiologist  or  Dr John T. Lysack, Diagnostic Imaging, Foothills Medical Centre, 1403-29 St  neurosurgeon  should  be  considered  for  patients  with  NW, Calgary AB T2N 2T9; e-mail [email protected] AUIAs larger than 5 mm (level III evidence). references 1. Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional  outcome after subarachnoid hemorrhage: a systematic review. Stroke  Case 3.  Ms  C.  might  be  correct  that  coiling  is  better  1997;28(3):660-4. 2. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of  than  clipping.  There  is  some  evidence  that  short-term  intracranial aneurysms: a systematic review. Stroke 1998;29(1):251-6. outcomes  are  better  with  coiling  than  with  clipping  3. De Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ. Incidence of sub- arachnoid haemorrhage: a systematic review with emphasis on region, age,  (level  II  evidence),  but  whether  or  not  long-term  out- gender and time trends. J Neurol Neurosurg Psychiatry 2007;78(12):1365-72. comes are similar has yet to be determined. 4. Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of subarachnoid  hemorrhage: role of region, year, and rate of computed tomography: a  meta-analysis. Stroke 1996;27(4):625-9. Conclusion 5. Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ. Risk of rupture of  unruptured intracranial aneurysms in relation to patient and aneurysm  The optimal management of patients with AUIAs is con- characteristics: an updated meta-analysis. Stroke 2007;38(4):1404-10. 6. International Study of Unruptured Intracranial Aneurysms Investigators.  troversial. There is currently a lack of good scientific evi- Unruptured intracranial aneurysms—risk of rupture and risks of surgical  dence  to  support  surgical  or  endovascular  treatment  of  intervention. N Engl J Med 1998;339(24):1725-33. 7. Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid  unruptured intracranial aneurysms.15 Screening is there- Hemorrhage Study Group. Risks and benefits of screening for intracranial  fore difficult to justify at the present time. In the absence  aneurysms in first-degree relatives of patients with sporadic subarachnoid  hemorrhage. N Engl J Med 1999;341(18):1344-50. of  a  randomized  controlled  trial  of  intervention  versus  8. Ronkainen A, Miettinen H, Karkola K, Papinaho S, Vanninen R, Puranen  observation, management decisions are currently made  M, et al. Risk of harboring an unruptured intracranial aneurysm. Stroke  1998;29(2):359-62. based on estimations of natural history versus expected  9. Raaymakers TW, Rinkel GJ, Ramos LM. Initial and follow-up screening for  treatment  outcomes  (level III evidence).  A  prospec- aneurysms in families with familial subarachnoid hemorrhage. Neurology  1998;51(4):1125-30. tive  randomized  controlled  trial  (Trial  on  Endovascular  10. Higashida RT, Lahue BJ, Torbey MT, Hopkins LN, Leip E, Hanley DF.  Aneurysm Management, known as the TEAM study)16 is  Treatment of unruptured intracranial aneurysms: a nationwide assessment of  effectiveness. AJNR Am J Neuroradiol 2007;28(1):146-51. now  under  way  to  address  this  issue.  It  is  expected  to  11. Takao H, Nojo T. Treatment of unruptured intracranial aneurysms: decision  conclude in 2021.  and cost-effectiveness analysis. Radiology 2007;244(3):755-66. 12. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC Jr, Brott T, et al.  Recommendations for the management of patients with unruptured intra- Levels of evidence cranial aneurysms: a statement for healthcare professionals from the Stroke  Council of the American Heart Association. Stroke 2000;31(11):2742-50. 13. Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al.  Level I: At least one properly conducted randomized  International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clip- ping versus endovascular coiling in 2143 patients with ruptured intracranial  controlled trial, systematic review, or meta-analysis aneurysms: a randomised comparison of effects on survival, depen- Level II: Other comparison trials, non-randomized,  dency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet  2005;366(9488):809-17. cohort, case-control, or epidemiologic studies, and  14. Campi A, Ramzi N, Molyneux AJ, Summers PE, Kerr RS, Sneade M, et al.  Retreatment of ruptured cerebral aneurysms in patients randomized by coil- preferably more than one study ing or clipping in the International Subarachnoid Aneurysm Trial (ISAT).  Level III: Expert opinion or consensus statements Stroke 2007;38(5):1538-44. Epub 2007 Mar 29. 15. Raymond J, Meder JF, Molyneux AJ, Fox AJ, Johnston SC, Collet JP, et al.  Unruptured intracranial aneurysms: the unreliability of clinical judgment, the  necessity for evidence, and reasons to participate in a randomized trial. J Dr Lysack is an Assistant Professor of Radiology an
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