Neurointervention.  2023 Jun;18(2):80-89. 10.5469/neuroint.2023.00171.

Management of Adult Unruptured Brain Arteriovenous Malformations: An Updated Network Meta-Analysis

• Dmytriw AA
• Ku J
• Ghozy S
• Grewal S
• Cancelliere NM
• Azzam AY
• Regenhardt RW
• Rabinov JD
• Stapleton CJ
• Patel K
• Patel AB
• Pereira VM
• Tymianski M

• KMID: 2543363
• DOI: http://doi.org/10.5469/neuroint.2023.00171

Abstract

The management of unruptured brain arteriovenous malformations (ubAVMs) is a complex challenge to neurovascular practitioners. This meta-analysis aimed to identify the optimal management of ubAVMs comparing conservative management, embolization, radiosurgery, microsurgical resection, and multimodality. The search strategy was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Ovid Medline, Embase, Web of Science, and Cochrane Library databases to identify relevant papers. Using R version 4.1.1., a frequentist network meta-analysis was conducted to compare different management modalities for the ubAVMs. Overall, the conservative group had the lowest risk of rupture (P-score=0.77), and the lowest rate of complications was found in the conservative group (P-score=1). Among different interventions, the multimodality group had the highest rupture risk (P-score=0.34), the lowest overall complications (P-score=0.75), the best functional improvement (P-score=0.65), and the lowest overall mortality (P-score=0.8). However, multimodality treatment showed a significantly higher risk of rupture (odds ratio [OR]=2.13; 95% confidence interval [95% CI]=1.18–3.86) and overall complication rate (OR=5.56; 95% CI=3.37–9.15) compared to conservative management; nevertheless, there were no significant differences in overall mortality or functional independence when considered independently. Conservative management is associated with the lowest rupture risk and complication rate overall. A multimodal approach is the best option when considering mortality rates and functional improvement in the context of existing morbidity/symptoms. Microsurgery, embolization, and radiosurgery alone are similar to the natural history in terms of functional improvement and mortality, but have higher complication rates.

Keyword

Arteriovenous malformation; A Randomized Trial of Unruptured Brain Arteriovenous Malformations; Neurosurgery

Figure

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  Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.

Reference

1. Morris Z, Whiteley WN, Longstreth WT Jr, Weber F, Lee YC, Tsushima Y, et al. Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2009; 339:b3016.

2. Flores BC, Klinger DR, Rickert KL, Barnett SL, Welch BG, White JA, et al. Management of intracranial aneurysms associated with arteriovenous malformations. Neurosurg Focus. 2014; 37:E11.

3. Rangel-Castilla L, Russin JJ, Martinez-Del-Campo E, Soriano-Baron H, Spetzler RF, Nakaji P. Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment. Neurosurg Focus. 2014; 37:E1.

4. Abecassis IJ, Xu DS, Batjer HH, Bendok BR. Natural history of brain arteriovenous malformations: a systematic review. Neurosurg Focus. 2014; 37:E7.

5. Kim H, Al-Shahi Salman R, McCulloch CE, Stapf C, Young WL; MARS Coinvestigators. Untreated brain arteriovenous malformation: patient-level meta-analysis of hemorrhage predictors. Neurology. 2014; 83:590–597.

6. Gross BA, Du R. Natural history of cerebral arteriovenous malformations: a meta-analysis. J Neurosurg. 2013; 118:437–443.

7. Fukuda K, Majumdar M, Masoud H, Nguyen T, Honarmand A, Shaibani A, et al. Multicenter assessment of morbidity associated with cerebral arteriovenous malformation hemorrhages. J Neurointerv Surg. 2017; 9:664–668.

8. Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, International ARUBA Investigators, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014; 383:614–621.

9. Bambakidis NC, Cockroft KM, Hirsch JA, Connolly ES, Amin-Hanjani S, Meyers PM, et al. The case against a randomized trial of unruptured brain arteriovenous malformations: misinterpretation of a flawed study. Stroke. 2014; 45:2808–2810.

10. Knopman J, Stieg PE. Management of unruptured brain arteriovenous malformations. Lancet. 2014; 383:581–583.

11. Rutledge WC, Abla AA, Nelson J, Halbach VV, Kim H, Lawton MT. Treatment and outcomes of ARUBA-eligible patients with unruptured brain arteriovenous malformations at a single institution. Neurosurg Focus. 2014; 37:E8.

12. Gross BA, Scott RM, Smith ER. Management of brain arteriovenous malformations. Lancet. 2014; 383:1635.

13. Link TW, Winston G, Schwarz JT, Lin N, Patsalides A, Gobin P, et al. Treatment of unruptured brain arteriovenous malformations: a single-center experience of 86 patients and a critique of the a randomized trial of unruptured brain arteriovenous malformations (ARUBA) trial. World Neurosurg. 2018; 120:e1156–e1162.

14. Ding D, Starke RM, Kano H, Mathieu D, Huang P, Kondziolka D, et al. Radiosurgery for cerebral arteriovenous malformations in a randomized trial of unruptured brain arteriovenous malformations (ARUBA)-eligible patients: a multicenter study. Stroke. 2016; 47:342–349.

15. Pollock BE, Link MJ, Brown RD. The risk of stroke or clinical impairment after stereotactic radiosurgery for ARUBA-eligible patients. Stroke. 2013; 44:437–441.

16. Tsuji A, Nozaki K. A prospective and retrospective study of cerebral AVM treatment strategies 1990-2014. Acta Neurochir Suppl. 2016; 123:135–139.

17. Javadpour M, Al-Mahfoudh R, Mitchell PS, Kirollos R. Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients. Br J Neurosurg. 2016; 30:619–622.

18. Wong J, Slomovic A, Ibrahim G, Radovanovic I, Tymianski M. Microsurgery for ARUBA trial (a randomized trial of unruptured brain arteriovenous malformation)-eligible unruptured brain arteriovenous malformations. Stroke. 2017; 48:136–144.

19. Brandecker S, Hadjiathanasiou A, Kern T, Schuss P, Vatter H, Güresir E. Primary decompressive craniectomy in poor-grade aneurysmal subarachnoid hemorrhage: long-term outcome in a single-center study and systematic review of literature. Neurosurg Rev. 2021; 44:2153–2162.

20. Howard J, Trevick S, Younger DS. Epidemiology of multiple sclerosis. Neurol Clin. 2016; 34:919–939.

21. Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP. Evaluating the quality of evidence from a network meta-analysis. PLoS One. 2014; 9:e99682.

22. Rücker G, Schwarzer G. Ranking treatments in frequentist network meta-analysis works without resampling methods. BMC Med Res Methodol. 2015; 15:58.

23. Hashan MR, Ghozy S, El-Qushayri AE, Pial RH, Hossain MA, Al Kibria GM. Association of dengue disease severity and blood group: a systematic review and meta-analysis. Rev Med Virol. 2021; 31:1–9.

24. Afify MA, Ahmed IGG, Alkahtani TA, Altulayhi RI, Alrowili ASM, Ghozy S, et al. Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. Environ Sci Pollut Res Int. 2021; 28:10576–10588.

25. Rücker G, Schwarzer G. Resolve conflicting rankings of outcomes in network meta-analysis: partial ordering of treatments. Res Synth Methods. 2017; 8:526–536.

26. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355:i4919.

27. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898.

28. Potts MB, Lau D, Abla AA, Kim H, Young WL, Lawton MT; UCSF Brain AVM Study Project. Current surgical results with low-grade brain arteriovenous malformations. J Neurosurg. 2015; 122:912–920.

29. Lv X, Wu Z, Li Y, Yang X, Jiang C. Hemorrhage risk after partial endovascular NBCA and ONYX embolization for brain arteriovenous malformation. Neurol Res. 2012; 34:552–556.

30. Pulli B, Stapleton CJ, Walcott BP, Koch MJ, Raymond SB, Leslie-Mazwi TM, et al. Comparison of predictive grading systems for procedural risk in endovascular treatment of brain arteriovenous malformations: analysis of 104 consecutive patients. J Neurosurg. 2019; 133:342–350.

31. Pulli B, Chapman PH, Ogilvy CS, Patel AB, Stapleton CJ, Leslie-Mazwi TM, et al. Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA. J Neurosurg. 2019; 133:1792–1801.

32. Schramm J, Schaller K, Esche J, Boström A. Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases. J Neurosurg. 2017; 126:1056–1063.

33. Lawton MT; UCSF Brain Arteriovenous Malformation Study Project. Spetzler-Martin Grade III arteriovenous malformations: surgical results and a modification of the grading scale. Neurosurgery. 2003; 52:740–748. discussion 748-749.

34. Abecassis IJ, Nerva JD, Feroze A, Barber J, Ghodke BV, Kim LJ, et al. Multimodality management of Spetzler-Martin grade 3 brain arteriovenous malformations with subgroup analysis. World Neurosurg. 2017; 102:263–274.

35. Ding D, Starke RM, Kano H, Lee JY, Mathieu D, Pierce J, et al. Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations: an international multicenter study. J Neurosurg. 2017; 126:859–871.

36. Awad A, Essuman K, Regenhardt RW, Leslie-Mazwi TM, Patel AB, Stapleton CJ. Extensive cerebral arteriovenous malformation-associated intraventricular hemorrhage. Neurohospitalist. 2022; 12:418–419.

37. Chang TC, Shirato H, Aoyama H, Ushikoshi S, Kato N, Kuroda S, et al. Stereotactic irradiation for intracranial arteriovenous malformation using stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 2004; 60:861–870.

38. Mathis JA, Barr JD, Horton JA, Jungreis CA, Lunsford LD, Kondziolka DS, et al. The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain. AJNR Am J Neuroradiol. 1995; 16:299–306.

39. Dawson RC 3rd, Tarr RW, Hecht ST, Jungreis CA, Lunsford LD, Coffey R, et al. Treatment of arteriovenous malformations of the brain with combined embolization and stereotactic radiosurgery: results after 1 and 2 years. AJNR Am J Neuroradiol. 1990; 11:857–864.

40. Miyachi S, Negoro M, Okamoto T, Kobayashi T, Kida Y, Tanaka T, et al. Embolisation of cerebral arteriovenous malformations to assure successful subsequent radiosurgery. J Clin Neurosci. 2000; 7 Suppl 1:82–85.

41. Chen JC, Mariscal L, Girvigian MR, Vanefsky MA, Glousman BN, Miller MJ, et al. Hypofractionated stereotactic radiosurgery for treatment of cerebral arteriovenous malformations: outcome analysis with use of the modified arteriovenous malformation scoring system. J Clin Neurosci. 2016; 29:155–161.

42. Wang HC, Chang RJ, Xiao F. Hypofractionated stereotactic radiotherapy for large arteriovenous malformations. Surg Neurol Int. 2012; 3(Suppl 2):S105–S110.

43. Boström JP, Bruckermann R, Pintea B, Boström A, Surber G, Hamm K. Treatment of cerebral arteriovenous malformations with radiosurgery or hypofractionated stereotactic radiotherapy in a consecutive pooled linear accelerator series. World Neurosurg. 2016; 94:328–338.

44. Potts MB, Zumofen DW, Raz E, Nelson PK, Riina HA. Curing arteriovenous malformations using embolization. Neurosurg Focus. 2014; 37:E19.

45. Abla AA, Nelson J, Kim H, Hess CP, Tihan T, Lawton MT. Silent arteriovenous malformation hemorrhage and the recognition of “unruptured” arteriovenous malformation patients who benefit from surgical intervention. Neurosurgery. 2015; 76:592–600. discussion 600.

46. Moon K, Levitt MR, Almefty RO, Nakaji P, Albuquerque FC, Zabramski JM, et al. Safety and efficacy of surgical resection of unruptured low-grade arteriovenous malformations from the modern decade. Neurosurgery. 2015; 77:948–952. discussion 952-953.

47. Hernesniemi JA, Dashti R, Juvela S, Väärt K, Niemelä M, Laakso A. Natural history of brain arteriovenous malformations: a longterm follow-up study of risk of hemorrhage in 238 patients. Neurosurgery. 2008; 63:823–829. discussion 829-831.

48. Stapf C, Mast H, Sciacca RR, Choi JH, Khaw AV, Connolly ES, et al. Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology. 2006; 66:1350–1355.

49. D’Aliberti G, Talamonti G, Piparo M, Debernardi A, Zella S, Boccardi E, et al. Venous flow rearrangement after treatment of cerebral arteriovenous malformations: a novel approach to evaluate the risks of treatment. World Neurosurg. 2014; 82:160–169.

50. Derdeyn CP, Zipfel GJ, Albuquerque FC, Cooke DL, Feldmann E, Sheehan JP, American Heart Association Stroke Council, et al. Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017; 48:e200–e224.

51. Singfer U, Hemelsoet D, Vanlangenhove P, Martens F, Verbeke L, Van Roost D, et al. Unruptured brain arteriovenous malformations: primary ONYX embolization in ARUBA (a randomized trial of unruptured brain arteriovenous malformations)-eligible patients. Stroke. 2017; 48:3393–3396.