In gratitude of the loyal support of our members, the CNS is offering complimentary 2021 Annual Meeting registration to all members! Learn more.

  • Outcomes of Ruptured Intracranial Arteriovenous Malformations Treated with Gamma Knife Radiosurgery

    Final Number:

    Dale Ding MD; Chun-Po Yen MD; Robert M. Starke MD MSc; Zhiyuan Xu MD; Jason P. Sheehan MD PhD FACS

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: Ruptured intracranial arteriovenous malformations (AVM) are at a significantly greater risk for future hemorrhage than unruptured lesions thereby necessitating treatment in the majority of cases. We describe the radiosurgical outcomes for a large cohort of ruptured AVMs.

    Methods: From an institutional AVM radiosurgery database, we identified all patients with a history of AVM rupture. Those with less than 2 years radiologic follow-up were excluded except those with obliteration resulting in 565 ruptured AVM patients for analysis with a median radiologic follow-up of 57 months. The patients’ median age was 29 years, and 21% underwent pre-radiosurgery embolization. The median volume and prescription dose were 2.1 cc and 22 Gy, respectively. The Spetzler-Martin grade was III or higher in 56% of patients, the median radiosurgery-based AVM score was 1.08, and the Virginia Radiosurgery AVM Scale (RAS) was 3 to 4 points in 44%.

    Results: The cumulative obliteration rate was 76%, and the actuarial obliteration rates were 41% and 64% at 3 and 5 years, respectively. Multivariate analysis identified no pre-radiosurgery embolization (P<0.001), increased prescription dose (P=0.001), single draining vein (P=0.046), no post-radiosurgery hemorrhage (P=0.007), and lower Virginia RAS (P=0.020) as independent predictors of obliteration. The annual risk of latency period hemorrhage was 2.0% with a 1.6% rate of hemorrhage-related morbidity and mortality. Decreased prescription dose (P<0.001) and multiple draining veins (P=0.003) were independent predictors of post-radiosurgery hemorrhage based on multivariate analysis. The rates of symptomatic and permanent radiation-induced changes (RIC) were 8% and 2.7%, respectively. From multivariate analysis, single draining vein (P<0.001) and higher Virginia RAS (P=0.005) were independent predictors of RIC following radiosurgery.

    Conclusions: Radiosurgery effectively treats ruptured AVMs with an acceptably low risk to benefit ratio. For ruptured AVMs, favorable outcomes are more likely when pre-radiosurgical embolization is avoided and a higher prescription dose can be delivered.

    Patient Care: AVM rupture is the most devastating and feared and complication associated with this cerebrovascular pathology. Our retrospective analysis demonstrates that Gamma Knife radiosurgery affords a favorable risk to benefit profile for ruptured AVMs and identifies independent predictors of successful outcomes and complications.

    Learning Objectives: By the conclusion of this session, participants should be able to 1) Describe the outcomes of Gamma Knife radiosurgery as a treatment approach for ruptured intracranial arteriovenous malformations, 2) Discuss, in small groups the patient, arteriovenous malformation and treatment characteristics which predict obliteration and radiation-induced changes following radiosurgery, and 3) Identify an effective treatment for ruptured arteriovenous malformations.

    References: 1. Achrol AS, Guzman R, Varga M, Adler JR, Steinberg GK, and Chang SD: Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course. Neurosurg Focus 26: E9, 2009. 2. Andrade-Souza YM, Ramani M, Scora D, Tsao MN, terBrugge K, and Schwartz ML: Embolization before radiosurgery reduces the obliteration rate of arteriovenous malformations. Neurosurgery 60: 443-51; discussion 451-2, 2007. 3. Bing F, Doucet R, Lacroix F, Bahary JP, Darsaut T, Roy D, Guilbert F, Raymond J, and Weill A: Liquid embolization material reduces the delivered radiation dose: clinical myth or reality? AJNR Am J Neuroradiol 33: 320-2, 2012. 4. Chang SD, Shuster DL, Steinberg GK, Levy RP, and Frankel K: Stereotactic radiosurgery of arteriovenous malformations: pathologic changes in resected tissue. Clin Neuropathol 16: 111-6, 1997. 5. Choi JH and Mohr JP: Brain arteriovenous malformations in adults. Lancet Neurol 4: 299-308, 2005. 6. Choi JH, Mast H, Sciacca RR, Hartmann A, Khaw AV, Mohr JP, Sacco RL, and Stapf C: Clinical outcome after first and recurrent hemorrhage in patients with untreated brain arteriovenous malformation. Stroke 37: 1243-7, 2006. 7. Cockroft KM: Unruptured brain arteriovenous malformations should be treated conservatively: no. Stroke 38: 3310-1, 2007. 8. da Costa L, Wallace MC, Ter Brugge KG, O'Kelly C, Willinsky RA, and Tymianski M: The natural history and predictive features of hemorrhage from brain arteriovenous malformations. Stroke 40: 100-5, 2009. 9. Davis SM and Donnan GA: Unruptured brain arteriovenous malformations: another asymptomatic conundrum. Stroke 38: 3312, 2007. 10. Ding D, Yen CP, Xu Z, Starke RM, and Sheehan JP: Radiosurgery for patients with unruptured intracranial arteriovenous malformations. J Neurosurg 2013. 11. Fiehler J and Stapf C: ARUBA--beating natural history in unruptured brain AVMs by intervention. Neuroradiology 50: 465-7, 2008. 12. Graf CJ, Perret GE, and Torner JC: Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 58: 331-7, 1983. 13. Gross BA and Du R: Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg 118: 437-43, 2013. 14. Hamilton MG and Spetzler RF: The prospective application of a grading system for arteriovenous malformations. Neurosurgery 34: 2-6; discussion 6-7, 1994. 15. Han PP, Ponce FA, and Spetzler RF: Intention-to-treat analysis of Spetzler-Martin grades IV and V arteriovenous malformations: natural history and treatment paradigm. J Neurosurg 98: 3-7, 2003. 16. Hartmann A, Mast H, Mohr JP, Koennecke HC, Osipov A, Pile-Spellman J, Duong DH, and Young WL: Morbidity of intracranial hemorrhage in patients with cerebral arteriovenous malformation. Stroke 29: 931-4, 1998. 17. Heros RC, Korosue K, and Diebold PM: Surgical excision of cerebral arteriovenous malformations: late results. Neurosurgery 26: 570-7; discussion 577-8, 1990. 18. Kano H, Kondziolka D, Flickinger JC, Park KJ, Parry PV, Yang HC, Sirin S, Niranjan A, Novotny J, Jr., and Lunsford LD: Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations. J Neurosurg 116: 54-65, 2012. 19. Kano H, Kondziolka D, Flickinger JC, Park KJ, Iyer A, Yang HC, Liu X, Monaco EA, 3rd, Niranjan A, and Lunsford LD: Stereotactic radiosurgery after embolization for arteriovenous malformations. Prog Neurol Surg 27: 89-96, 2013. 20. Kano H, Kondziolka D, Flickinger JC, Yang HC, Flannery TJ, Niranjan A, Novotny J, Jr., and Lunsford LD: Stereotactic radiosurgery for arteriovenous malformations, Part 5: management of brainstem arteriovenous malformations. J Neurosurg 116: 44-53, 2012. 21. Kano H, Kondziolka D, Flickinger JC, Yang HC, Flannery TJ, Niranjan A, Novotny J, Jr., and Lunsford LD: Stereotactic radiosurgery for arteriovenous malformations, Part 4: management of basal ganglia and thalamus arteriovenous malformations. J Neurosurg 116: 33-43, 2012. 22. Kano H, Kondziolka D, Flickinger JC, Yang HC, Flannery TJ, Awan NR, Niranjan A, Novotny J, and Lunsford LD: Stereotactic radiosurgery for arteriovenous malformations, part 2: management of pediatric patients. J Neurosurg Pediatr 9: 1-10, 2012. 23. Kano H, Lunsford LD, Flickinger JC, Yang HC, Flannery TJ, Awan NR, Niranjan A, Novotny J, Jr., and Kondziolka D: Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations. J Neurosurg 116: 11-20, 2012. 24. Kano H, Kondziolka D, Flickinger JC, Yang HC, Flannery TJ, Awan NR, Niranjan A, Novotny J, Jr., and Lunsford LD: Stereotactic radiosurgery for arteriovenous malformations, Part 3: outcome predictors and risks after repeat radiosurgery. J Neurosurg 116: 21-32, 2012. 25. Katsaridis V, Papagiannaki C, and Aimar E: Curative embolization of cerebral arteriovenous malformations (AVMs) with Onyx in 101 patients. Neuroradiology 50: 589-97, 2008. 26. Kilic K, Konya D, Kurtkaya O, Sav A, Pamir MN, and Kilic T: Inhibition of angiogenesis induced by cerebral arteriovenous malformations using gamma knife irradiation. J Neurosurg 106: 463-9, 2007. 27. Lawton MT, Du R, Tran MN, Achrol AS, McCulloch CE, Johnston SC, Quinnine NJ, and Young WL: Effect of presenting hemorrhage on outcome after microsurgical resection of brain arteriovenous malformations. Neurosurgery 56: 485-93; discussion 485-93, 2005. 28. Lawton MT, Kim H, McCulloch CE, Mikhak B, and Young WL: A supplementary grading scale for selecting patients with brain arteriovenous malformations for surgery. Neurosurgery 66: 702-13; discussion 713, 2010. 29. Mast H, Young WL, Koennecke HC, Sciacca RR, Osipov A, Pile-Spellman J, Hacein-Bey L, Duong H, Stein BM, and Mohr JP: Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 350: 1065-8, 1997. 30. Miller RA and Jankowitz B: Endovascular embolization in combination with radiosurgery for treatment of arteriovenous malformations. Prog Neurol Surg 27: 81-8, 2013. 31. Mohr JP, Moskowitz AJ, Stapf C, Hartmann A, Lord K, Marshall SM, Mast H, Moquete E, Moy CS, Parides M, Pile-Spellman J, Al-Shahi Salman R, Weinberg A, Young WL, Estevez A, Kureshi I, and Brisman JL: The ARUBA trial: current status, future hopes. Stroke 41: e537-40, 2010. 32. Morgenstern LB, Hemphill JC, 3rd, Anderson C, Becker K, Broderick JP, Connolly ES, Jr., Greenberg SM, Huang JN, MacDonald RL, Messe SR, Mitchell PH, Selim M, and Tamargo RJ: Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 41: 2108-29, 2010. 33. Mounayer C, Hammami N, Piotin M, Spelle L, Benndorf G, Kessler I, and Moret J: Nidal embolization of brain arteriovenous malformations using Onyx in 94 patients. AJNR Am J Neuroradiol 28: 518-23, 2007. 34. Natarajan SK, Ghodke B, Britz GW, Born DE, and Sekhar LN: Multimodality treatment of brain arteriovenous malformations with microsurgery after embolization with onyx: single-center experience and technical nuances. Neurosurgery 62: 1213-25; discussion 1225-6, 2008. 35. Ondra SL, Troupp H, George ED, and Schwab K: The natural history of symptomatic arteriovenous malformations of the brain: a 24-year follow-up assessment. J Neurosurg 73: 387-91, 1990. 36. Panagiotopoulos V, Gizewski E, Asgari S, Regel J, Forsting M, and Wanke I: Embolization of intracranial arteriovenous malformations with ethylene-vinyl alcohol copolymer (Onyx). AJNR Am J Neuroradiol 30: 99-106, 2009. 37. Pandey P, Marks MP, Harraher CD, Westbroek EM, Chang SD, Do HM, Levy RP, Dodd RL, and Steinberg GK: Multimodality management of Spetzler-Martin Grade III arteriovenous malformations. J Neurosurg 116: 1279-88, 2012. 38. Pollock BE, Flickinger JC, Lunsford LD, Maitz A, and Kondziolka D: Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 42: 1239-44; discussion 1244-7, 1998. 39. Pollock BE, Flickinger JC, Lunsford LD, Bissonette DJ, and Kondziolka D: Factors that predict the bleeding risk of cerebral arteriovenous malformations. Stroke 27: 1-6, 1996. 40. Pollock BE, Kondziolka D, Flickinger JC, Patel AK, Bissonette DJ, and Lunsford LD: Magnetic resonance imaging: an accurate method to evaluate arteriovenous malformations after stereotactic radiosurgery. J Neurosurg 85: 1044-9, 1996. 41. Saatci I, Geyik S, Yavuz K, and Cekirge HS: Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg 115: 78-88, 2011. 42. Schneider BF, Eberhard DA, and Steiner LE: Histopathology of arteriovenous malformations after gamma knife radiosurgery. J Neurosurg 87: 352-7, 1997. 43. Schwyzer L, Yen CP, Evans A, Zavoian S, and Steiner L: Long-term Results of Gamma Knife Surgery for Partially Embolized Arteriovenous Malformations. Neurosurgery 71: 1139-48, 2012. 44. Spetzler RF and Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 65: 476-83, 1986. 45. St George EJ, Perks J, and Plowman PN: Stereotactic radiosurgery XIV: The role of the haemosiderin 'ring' in the development of adverse reactions following radiosurgery for intracranial cavernous malformations: a sustainable hypothesis. Br J Neurosurg 16: 385-91, 2002. 46. Stapf C and Mohr JP: Unruptured brain arteriovenous malformations should be treated conservatively: yes. Stroke 38: 3308-9, 2007. 47. Stapf C, Mohr JP, Choi JH, Hartmann A, and Mast H: Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy. Curr Opin Neurol 19: 63-8, 2006. 48. Stapf C, Mast H, Sciacca RR, Choi JH, Khaw AV, Connolly ES, Pile-Spellman J, and Mohr JP: Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology 66: 1350-5, 2006. 49. Starke RM, Yen CP, Ding D, and Sheehan JP: A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients. J Neurosurg 2013. 50. Starke RM, Yen CP, Ding D, and Sheehan JP: A Practical Grading Scale to Predict Radiosurgery Outcome in Arteriovenous Malformations: Analysis of 1,012 Treated Patients. J Neurosurg In press: 2013. 51. Steiner L, Lindquist C, Adler JR, Torner JC, Alves W, and Steiner M: Clinical outcome of radiosurgery for cerebral arteriovenous malformations. J Neurosurg 77: 1-8, 1992. 52. Stemer AB, Bank WO, Armonda RA, Liu AH, Herzig DW, and Bell RS: Acute embolization of ruptured brain arteriovenous malformations. J Neurointerv Surg 5: 196-200, 2013. 53. Sure U, Battenberg E, Dempfle A, Tirakotai W, Bien S, and Bertalanffy H: Hypoxia-inducible factor and vascular endothelial growth factor are expressed more frequently in embolized than in nonembolized cerebral arteriovenous malformations. Neurosurgery 55: 663-9; discussion 669-70, 2004. 54. Valle RD, Zenteno M, Jaramillo J, Lee A, and De Anda S: Definition of the key target volume in radiosurgical management of arteriovenous malformations: a new dynamic concept based on angiographic circulation time. J Neurosurg 109 Suppl: 41-50, 2008. 55. van Rooij WJ, Sluzewski M, and Beute GN: Brain AVM embolization with Onyx. AJNR Am J Neuroradiol 28: 172-7; discussion 178, 2007. 56. Wegner RE, Oysul K, Pollock BE, Sirin S, Kondziolka D, Niranjan A, Lunsford LD, and Flickinger JC: A modified radiosurgery-based arteriovenous malformation grading scale and its correlation with outcomes. Int J Radiat Oncol Biol Phys 79: 1147-50, 2011. 57. Yen CP, Monteith SJ, Nguyen JH, Rainey J, Schlesinger DJ, and Sheehan JP: Gamma Knife surgery for arteriovenous malformations in children. J Neurosurg Pediatr 6: 426-34, 2010.

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy