Diagnosis and Treatment of Arteriovenous Malformations

  • J. P. MohrEmail author
  • J. Kejda-Scharler
  • J. Pile-Spellman
Part of the following topical collections:
  1. Topical Collection on Stroke


Brain arteriovenous malformations (bAVMs) are among the least common of causes of brain hemorrhage, seizures, or headaches. Embedded in the brain, their widely varying size, arterial feeders draining venous pattern and nidus complexity make them among the most challenging of disorders for attempted eradication. The low prevalence has created a literature long dominated by anecdote, only recently and slowly being clarified by epidemiological, pathophysiological, and imaging data. A first-ever randomized clinical trial seeks to determine if invasive intervention to eradicate the lesion—and its attendant risks of complications—offers a better prognosis than awaiting a hemorrhage before undertaking such efforts.


Diagnosis Treatment bAVM Arteriovenous malformation ARUBA Seizures Headache Hemorrhage 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Al-Shahi R, Warlow C. A systematic review of the frequency and prognosis of arteriovenous malformations of the brain in adults. Brain. 2001;124:1900–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Brown Jr RD, Wiebers DO, Torner JC, O'Fallon WM. Incidence and prevalence of intracranial vascular malformations in Olmsted County, Minnesota, 1965 to 1992. Neurology. 1996;46:949–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Al-Shahi R, Bhattacharya JJ, Currie DG, et al. Scottish Intracranial Vascular Malformation Study (SIVMS): evaluation of methods, ICD-10 coding, and potential sources of bias in a prospective, population-based cohort. Stroke. 2003;34:1156–62.PubMedCrossRefGoogle Scholar
  4. 4.
    Mohr JP, Wolf PA, Grotta J, et al. Stroke: pathophysiology, diagnosis, and management, 3 ed, Elsevier Saunders. 2011.Google Scholar
  5. 5.
    Yue NC, Longstreth Jr WT, Elster AD, et al. Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. Radiology. 1997;202:41–6.PubMedGoogle Scholar
  6. 6.
    Katzman GL, Dagher AP, Patronas NJ. Incidental findings on brain magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA. 1999;282:36–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Berman MF, Sciacca RR, Pile-Spellman J, et al. The epidemiology of brain arteriovenous malformations. Neurosurgery. 2000; 47:389–96; discussion 97.Google Scholar
  8. 8.
    Willinsky RA, Lasjaunias P, Terbrugge K, Burrows P. Multiple cerebral arteriovenous malformations (AVMs). Review of our experience from 203 patients with cerebral vascular lesions. Neuroradiology. 1990;32:207–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Leblanc GG, Golanov E, Awad IA, Young WL. Biology of vascular malformations of the brain. Stroke. 2009;40:e694–702.PubMedCrossRefGoogle Scholar
  10. 10.
    Marks MP, Lane B, Steinberg GK, Chang PJ. Hemorrhage in intracerebral arteriovenous malformations: angiographic determinants. Radiology. 1990;176:807–13.PubMedGoogle Scholar
  11. 11.
    • Stefani MA, Porter PJ, terBrugge KG, et al. Angioarchitectural factors present in brain arteriovenous malformations associated with hemorrhagic presentation. Stroke. 2002;33:920–4. Detailed description of the may variations in arterial feeders and venous drainage. Google Scholar
  12. 12.
    •• Duong DH, Young WL, Vang MC, et al. Feeding artery pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral arteriovenous malformations. Stroke. 1998;29:1167–76. Evidence that feeding artery pressure accounts for the major risk of rupture. Google Scholar
  13. 13.
    Josephson CB, Bhattacharya JJ, Counsell CE, et al. Seizure risk with AVM treatment or conservative management: prospective, population-based study. Neurology. 2012;79:500–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Garcin B, Houdart E, Porcher R, et al. Epileptic seizures at initial presentation in patients with brain arteriovenous malformation. Neurology. 2012;78:626–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Hofmeister C, Stapf C, Hartmann A, et al. Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation. Stroke. 2000;31:1307–10.PubMedCrossRefGoogle Scholar
  16. 16.
    Osipov A, Koennecke HC, Hartmann A, et al. Seizures in cerebral arteriovenous malformations: type, clinical course, and medical management. Interventional Neuroradiology. 1997;3:37–41.PubMedGoogle Scholar
  17. 17.
    Ennoksson P, Bynke H. Visual field defects in arteriovenous aneurysma of the brain. Acta Ophtalmol. 1958;36:586.CrossRefGoogle Scholar
  18. 18.
    Troost BT, Newton TH. Occipital lobe arteriovenous malformations: clinical and radiologic features in 26 cases with comments on differentiation from migraine. Arch Ophthalmol. 1975;93:250–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Englot DJ, Young WL, Han SJ, et al. Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients. Neurosurgery. 2012;71:572–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Mackenzie I. The clinical presentation of the cerebral angioma: a review of 50 cases. Brain. 1953;76:184–214.PubMedCrossRefGoogle Scholar
  21. 21.
    Northfield DWC. Angiomatous malformations of the brain. Guys Hosp Rep. 1940;90:149.Google Scholar
  22. 22.
    Evans RW. Diagnostic testing for the evaluation of headaches. Neurologic Clin. 1996;14:1–26.CrossRefGoogle Scholar
  23. 23.
    Jeng JS, Tang SC, Yip PK. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis. 2004;18:290–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Lazar RM, Connaire K, Marshall RS, et al. Developmental deficits in adult patients with arteriovenous malformations. Arch Neurol. 1999;56:103–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Hai J, Wan JF, Lin Q, et al. Cognitive dysfunction induced by chronic cerebral hypoperfusion in a rat model associated with arteriovenous malformations. Brain Res. 2009;1301:80–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Hai J, Su SH, Lin Q, et al. Cognitive impairment and changes of neuronal plasticity in rats of chronic cerebral hypoperfusion associated with cerebral arteriovenous malformations. Acta Neurologica Belgica. 2010;110:180–5.PubMedGoogle Scholar
  27. 27.
    McKissock W, Paterson JH. A clinical survey of intracranial angiomas with special reference to their mode of progression and surgical treatment: a report of 110 cases. Brain. 1956;79:233–66.PubMedCrossRefGoogle Scholar
  28. 28.
    McCormick WF, Nofzinger JD. "Cryptic" vascular malformations of the central nervous system. J Neurosurg. 1966;24:865–75.PubMedCrossRefGoogle Scholar
  29. 29.
    Guidetti B, Delitala A. Intracranial arteriovenous malformations. Conservative and surgical treatment. J Neurosurg. 1980;53:149–52.PubMedCrossRefGoogle Scholar
  30. 30.
    •• Choi JH, Mast H, Sciacca RR, et al. Clinical outcome after first and recurrent hemorrhage in patients with untreated brain arteriovenous malformation. Stroke. 2006;37:1243–7. The clinical outcomes are far more mild from bAVMs than from other forms of primary brain hemorrhage. Google Scholar
  31. 31.
    •• van Beijnum J, Lovelock CE, Cordonnier C, et al. Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies. Brain. 2009;132:537–43. Population-based study. Google Scholar
  32. 32.
    • Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65:476–83. Widely-used grading system for predicting outcome from surgery: size, location and 'eloquence' are the major variables. Google Scholar
  33. 33.
    Du R, Dowd CF, Johnston SC. et al. Interobserver variability in grading of brain arteriovenous malformations using the Spetzler-Martin system. Neurosurgery. 2005;57:668–75; discussion 75.Google Scholar
  34. 34.
    Ogilvy CS, Stieg PE, Awad I, et al. AHA Scientific Statement: recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the Stroke Council. American Stroke Association. Stroke. 2001;32:1458–71.PubMedCrossRefGoogle Scholar
  35. 35.
    • Hartmann A, Mast H, Mohr JP, et al. Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations. Stroke. 2005;36:2431–5. Outcomes vary by treatment modality. Google Scholar
  36. 36.
    • Lawton MT, Du R, Tran MN, et al. Effect of presenting hemorrhage on outcome after microsurgical resection of brain arteriovenous malformations. Neurosurgery. 2005;56:485–93; discussion −93. Outcomes worse for those who had not bled. Google Scholar
  37. 37.
    • Maruyama K, Kawahara N, Shin M, et al. The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations. N Engl J Med. 2005;352:146–53. Those not having bled prior to therapy have more frequent hemorrhage from radiotherapy. Google Scholar
  38. 38.
    Parkhutik V, Lago A, Tembl JI, et al. Postradiosurgery hemorrhage rates of arteriovenous malformations of the brain: influencing factors and evolution with time. Stroke. 2012;43:1247–52.PubMedCrossRefGoogle Scholar
  39. 39.
    •• van Beijnum J, van der Worp HB, Buis DR. et al. Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA. 2011;306:2011–9. Major review article justifying a clinical trial. Google Scholar
  40. 40.
    Ondra SL, Troupp H, George ED, Schwab K. The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg. 1990;73:387–91.PubMedCrossRefGoogle Scholar
  41. 41.
    Mast H, Young WL, Koennecke HC, et al. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet. 1997;350:1065–8.PubMedCrossRefGoogle Scholar
  42. 42.
    • Mohr JP, Moskowitz AJ, Parides M. et al. Hull down on the horizon: a Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) Trial. Stroke. 2012;43:1744–5. Rebuttal to the latest criticisms of the ARUBA trial. Google Scholar
  43. 43.
    Hernesniemi JA, Dashti R, Juvela S, et al. Natural history of brain arteriovenous malformations: a long-term follow-up study of risk of hemorrhage in 238 patients. Neurosurgery. 2008;63:823–9; discussion 9–31.Google Scholar
  44. 44.
    Laakso A, Dashti R, Juvela S, et al. Risk of hemorrhage in patients with untreated Spetzler-Martin grade IV and V arteriovenous malformations: a long-term follow-up study in 63 patients. Neurosurgery. 2011;68:372–7; discussion–8.Google Scholar
  45. 45.
    Berman MF, Hartmann A, Mast H, et al. Determinants of resource utilization in the treatment of brain arteriovenous malformations. AJNR. 1999;20:2004–8.PubMedGoogle Scholar
  46. 46.
    Brown Jr RD. Unruptured brain AVMs: to treat or not to treat. Lancet Neurol. 2008;7:195–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Kim H, Pourmohamad T, McCulloch CE, et al. Multicenter study of predictors for intracranial haemorrhage risk in the natural history of brain arteriovenous malformations (bAVM). 1st World AVM Congress. Edinburgh; 2012.Google Scholar
  48. 48.
    •• Stapf C, Mast H, Sciacca RR, et al. Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology. 2006;66:1350–5. Lowest risk for those with no deep bAVM location or deep venous drainage. Google Scholar
  49. 49.
    Stapf C, Mohr JP, Choi JH, et al. Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol. 2006;19:63–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Stapf C, Mohr JP. Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke. 2007;38:3308–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Cockroft KM. Unruptured brain arteriovenous malformations should be treated conservatively: no. Stroke. 2007;38:3310–1.PubMedCrossRefGoogle Scholar
  52. 52.
    Mohr JP, Moskowitz AJ, Stapf C, et al. The ARUBA trial: current status, future hopes. Stroke. 2010;41:e537–40.PubMedCrossRefGoogle Scholar
  53. 53.
    Ross J, Al-Shahi Salman R. Interventions for treating brain arteriovenous malformations in adults. Cochrane Database Syst Rev. 2010:CD003436.Google Scholar
  54. 54.
    Frenzel T, Lee CZ, Kim H, et al. Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance. Cerebrovasc Dis. 2008;25:157–63.PubMedCrossRefGoogle Scholar
  55. 55.
    Fiehler J, Stapf C. ARUBA–beating natural history in unruptured brain AVMs by intervention. Neuroradiology. 2008;50:465–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Mathiesen T. Arguments against the proposed randomised trial (ARUBA). Neuroradiology. 2008;50:469–71.PubMedCrossRefGoogle Scholar
  57. 57.
    Cockroft KM, Jayaraman MV, Amin-Hanjani S, et al. A perfect storm: how a randomized trial of unruptured brain arteriovenous malformations' (ARUBA's) trial design challenges notions of external validity. Stroke. 2012;43:1979–81.PubMedCrossRefGoogle Scholar
  58. 58.
    Raymond J, Naggara O, Guilbert F, Altman DG. Assessing prognosis from nonrandomized studies: an example from brain arteriovenous malformations. AJNR. 2011;32:809–12.PubMedCrossRefGoogle Scholar
  59. 59.
    Houdart E. The need for new regulations on randomized clinical trials in surgical treatments. Neuroradiology. 2010;52:1061–2.PubMedCrossRefGoogle Scholar
  60. 60.
    •• Kim H, McCulloch CE, Johnston SC. et al. Comparison of 2 approaches for determining the natural history risk of brain arteriovenous malformation rupture. Am J Epidemiol. 2010;171:1317–22. Calculations of risk for hemorrhage based on date of discovery vs, assumption of presence since birth. Google Scholar
  61. 61.
    Ovalle F, Shay SD, Mericle RA. Delayed intracerebral hemorrhage after uneventful embolization of brain arteriovenous malformations is related to volume of embolic agent administered: multivariate analysis of 13 predictive factors. Neurosurgery. 2012;70:313–20.PubMedCrossRefGoogle Scholar
  62. 62.
    Mohr JP, Mast H, Kejda-Scharler J, et al. Proposal for an AVM Registry. 1st World AVM Congress. Edinburgh; 2012.Google Scholar
  63. 63.
    Lazar RM, Marshall RS, Pile-Spellman J, et al. Anterior translocation of language in patients with left cerebral arteriovenous malformation. Neurology. 1997;49:802–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Lepski G, Honegger J, Liebsch M, et al. Safe resection of arteriovenous malformations in eloquent motor areas aided by functional imaging and intraoperative monitoring. Neurosurgery. 2012;70:276–88; discussion 88–9.Google Scholar
  65. 65.
    Koga T, Maruyama K, Kamada K, et al. Outcomes of diffusion tensor tractography-integrated stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012;82:799–802.PubMedCrossRefGoogle Scholar
  66. 66.
    Ichikawa T, Suzuki K, Sasaki T, et al. Utility and the limit of motor evoked potential monitoring for preventing complications in surgery for cerebral arteriovenous malformation. Neurosurgery. 2010;67:ons222–8; discussion 8.Google Scholar
  67. 67.
    Kejda-Scharler J, DeLaPaz R, Mohr JP. Use of MRI, fMRI, and DTI for interventional decision after minimal AVM haemorrhage 1st World AVM Congress. Edinburgh; 2012.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • J. P. Mohr
    • 1
    Email author
  • J. Kejda-Scharler
    • 1
  • J. Pile-Spellman
    • 2
  1. 1.Neurological Institute, Doris and Stanley Tananbaum Stroke CenterColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Radiology and department of Neurosciences at WinthropUniversity HospitalMineolaUSA

Personalised recommendations