Abstract
Purpose
The first randomized controlled study on unruptured brain arteriovenous malformations (bAVM), the ARUBA trial, demonstrate the superiority of medical management; however, it failed to completely rule out the efficacy of therapeutic interventions due to several limitations. This study aimed to examine the outcomes of multimodal interventional treatment for bAVM in terms of safety and efficacy.
Methods
We reviewed 226 consecutive patients with unruptured bAVM admitted to our institute between 2002 and 2022. Treatment methods were divided into medical management and therapeutic intervention, including microsurgery, stereotactic surgery, and endovascular intervention. First, the choice of therapeutic modalities was assessed in the pre-ARUBA (before February 2014) and post-ARUBA (after March 2014) eras. Second, the incidence of symptomatic stroke or death and functional prognosis with a modified Rankin scale (mRS) score of ≥2 at 5 years was compared between the medical management and therapeutic intervention.
Results
In the pre- and post-ARUBA groups, 73% and 84% of patients underwent therapeutic interventions, respectively (p = 0.053). The rate of symptomatic stroke or death was lower in patients who underwent interventional therapies than in those who underwent medical management (9.7% vs. 22%, p = 0.022); however, the opposite was observed in the ARUBA trial (31% vs. 10%). The annual incidence of stroke or death was also lower in the interventional therapy group (4.3%/y vs. 1.8%/year, hazard ratio = 0.45, 95% confidence interval: 0.18–1.08, p = 0.032). The rate of mRS score of ≥2 after a 5-year follow-up was 18% and 6% in the medical treatment and intervention groups (p = 0.14).
Conclusions
The therapeutic intervention rate did not decrease, even after the publication of the ARUBA trial. The rate of stroke or death was lower in the intervention group, indicating that a tailored choice of multimodality is safe and effective for managing unruptured bAVM.
Similar content being viewed by others
References
Cenzato M, Boccardi E, Beghi E, Vajkoczy P, Szikora I, Motti E, Regli L, Raabe A, Eliava S, Gruber A, Meling TR, Niemela M, Pasqualin A, Golanov A, Karlsson B, Kemeny A, Liscak R, Lippitz B, Radatz M et al (2017) European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH). Acta Neurochir 159:1059–1064. https://doi.org/10.1007/s00701-017-3154-8
Grasso G (2014) The ARUBA study: what is the evidence? World Neurosurg 82:e576. https://doi.org/10.1016/j.wneu.2014.04.057
Ilyas A, Chen CJ, Abecassis IJ, Al-Saiegh F, Ironside N, Jabbour PM, Tjoumakaris S, Gooch MR, Lee CC, Sheehan JP, Ding D (2022) Stereotactic radiosurgery for a randomized trial of unruptured brain arteriovenous malformations-eligible patients: a meta-analysis. Neurosurgery 91:684–692. https://doi.org/10.1227/neu.0000000000002115
Izumo T, Okamura K, Takahira R, Matsunaga Y, Sadakata E, Maeda H, Yamaguchi S, Baba S, Morofuji Y, Hiu T, Horie N, Anda T, Kitagawa N, Tokunaga Y, Hayashi K, Matsumoto Y, Nagata I, Matsuo T (2022) Impact of pre-operative embolization with onyx for brain arteriovenous malformation surgery. Front Neurol 13:875260. https://doi.org/10.3389/fneur.2022.875260
Javadpour M, Al-Mahfoudh R, Mitchell PS, Kirollos R (2016) Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients. Br J Neurosurg 30:619–622. https://doi.org/10.1080/02688697.2016.1181153
Kano H, Kondziolka D, Flickinger JC, Park KJ, Parry PV, Yang HC, Sirin S, Niranjan A, Novotny J Jr, Lunsford LD (2013) Multistaged volumetric management of large arteriovenous malformations. Prog Neurol Surg 27:73–80. https://doi.org/10.1159/000341629
Link TW, Winston G, Schwarz JT, Lin N, Patsalides A, Gobin P, Pannullo S, Stieg PE, Knopman J (2018) 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 120:e1156–e1162. https://doi.org/10.1016/j.wneu.2018.09.025
Luther E, McCarthy DJ, Burks J, Govindarajan V, Lu VM, Silva M, Lang M, Gross BA, Starke RM (2022) National reduction in cerebral arteriovenous malformation treatment correlated with increased rupture incidence. J Neurointerv Surg. https://doi.org/10.1136/jnis-2022-019110
Magro E, Gentric JC, Darsaut TE, Ziegler D, Msi BMW, Raymond J (2017) Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials. J Neurosurg 126:486–494. https://doi.org/10.3171/2015.6.JNS15619
Maruyama D, Satow T, Kataoka H, Mori H, Hamano E, Orita Y, Eguchi S, Takahashi JC (2018) Multimodal interventional treatment and outcomes for unruptured arteriovenous malformations. Acta Neurochir Suppl 129:115–120. https://doi.org/10.1007/978-3-319-73739-3_17
Meling TR, Proust F, Gruber A, Niemela M, Regli L, Roche PH, Vajkoczy P (2014) On apples, oranges, and ARUBA. Acta Neurochir 156:1775–1779. https://doi.org/10.1007/s00701-014-2140-7
Mohr JP, Overbey JR, Hartmann A, Kummer RV, Al-Shahi Salman R, Kim H, van der Worp HB, Parides MK, Stefani MA, Houdart E, Libman R, Pile-Spellman J, Harkness K, Cordonnier C, Moquete E, Biondi A, Klijn CJM, Stapf C, Moskowitz AJ, ARUBA co-investigators (2020) Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial. Lancet Neurol 19:573–581. https://doi.org/10.1016/S1474-4422(20)30181-2
Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, Al-Shahi Salman R, Vicaut E, Young WL, Houdart E, Cordonnier C, Stefani MA, Hartmann A, von Kummer R, Biondi A, Berkefeld J, Klijn CJ, Harkness K, Libman R, Barreau X, Moskowitz AJ, international Ai (2014) Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614-621. https://doi.org/10.1016/S0140-6736(13)62302-8
Molina CA, Selim MH (2014) Unruptured brain arteriovenous malformations: keep calm or dance in a minefield. Stroke 45:1543–1544. https://doi.org/10.1161/STROKEAHA.113.004244
Patel SD, Saber H, Desai N, Otite FO, Kaneko N, Mehta TV, Hinman J, Hassan AE, Jadhav A, Liebeskind DS, Saver JL (2022) Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: a national sample analysis. J Stroke Cerebrovasc Dis 31:106807. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106807
Pulli B, Chapman PH, Ogilvy CS, Patel AB, Stapleton CJ, Leslie-Mazwi TM, Hirsch JA, Carter BS, Rabinov JD (2019) Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA. J Neurosurg:1–10. https://doi.org/10.3171/2019.8.JNS19998
Rutledge WC, Abla AA, Nelson J, Halbach VV, Kim H, Lawton MT (2014) Treatment and outcomes of ARUBA-eligible patients with unruptured brain arteriovenous malformations at a single institution. Neurosurg Focus 37:E8. https://doi.org/10.3171/2014.7.FOCUS14242
Saatci I, Geyik S, Yavuz K, Cekirge HS (2011) 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. https://doi.org/10.3171/2011.2.JNS09830
Sasagasako T, Mori H, Hattori EY, Ikedo T, Hamano E, Shimonaga K, Kushi Y, Iihara K, Kataoka H (2023) Radiation-induced changes associated with obliteration of brain AVMs after repeat radiosurgery. AJNR Am J Neuroradiol 44:143–149. https://doi.org/10.3174/ajnr.A7772
Schramm J, Schaller K, Esche J, Bostrom A (2017) Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases. J Neurosurg 126:1056–1063. https://doi.org/10.3171/2016.4.JNS153017
Snyder MH, Chen CJ, Farzad F, Ironside N, Kellogg RT, Southerland AM, Park MS, Sheehan JP, Ding D (2021) Interventional outcomes for patients eligible for entry into the ARUBA clinical trial: a systematic review and meta-analysis. J Neurosurg:1–13. https://doi.org/10.3171/2021.7.JNS211186
Tonetti DA, Gross BA, Atcheson KM, Jankowitz BT, Kano H, Monaco EA, Niranjan A, Flickinger JC, Lunsford LD (2018) The benefit of radiosurgery for ARUBA-eligible arteriovenous malformations: a practical analysis over an appropriate follow-up period. J Neurosurg 128:1850–1854. https://doi.org/10.3171/2017.1.JNS162962
van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ (2011) Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA 306:2011–2019. https://doi.org/10.1001/jama.2011.1632
Volovici V, Schouten JW, Vajkoczy P, Dammers R, Meling TR (2021) Unruptured arteriovenous malformations: do we have an answer after the final follow-up of ARUBA? A Bayesian viewpoint. Stroke 52:1143–1146. https://doi.org/10.1161/STROKEAHA.120.032429
Wang A, Mandigo GK, Feldstein NA, Sisti MB, Connolly ES, Solomon RA, Lavine SD, Meyers PM (2020) Curative treatment for low-grade arteriovenous malformations. J Neurointerv Surg 12:48–54. https://doi.org/10.1136/neurintsurg-2019-015115
Weber W, Kis B, Siekmann R, Jans P, Laumer R, Kuhne D (2007) Preoperative embolization of intracranial arteriovenous malformations with Onyx. Neurosurgery 61:244–252; discussion 252-244. https://doi.org/10.1227/01.NEU.0000255473.60505.84
Wong J, Slomovic A, Ibrahim G, Radovanovic I, Tymianski M (2017) Microsurgery for ARUBA trial (a randomized trial of unruptured brain arteriovenous malformation)-eligible unruptured brain arteriovenous malformations. Stroke 48:136–144. https://doi.org/10.1161/STROKEAHA.116.014660
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ikedo, T., Yamamoto, E.H., Mori, H. et al. Impact of tailored multimodal treatment for unruptured brain arteriovenous malformation: comparison with a randomized trial of unruptured brain arteriovenous malformations. Acta Neurochir 165, 3779–3785 (2023). https://doi.org/10.1007/s00701-023-05815-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00701-023-05815-z