Elsevier

World Neurosurgery

Volume 120, December 2018, Pages e1156-e1162
World Neurosurgery

Original Article
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

Portions of this work were presented in electronic poster form at the 2018 meeting of the American Association of Neurological Surgeons.
https://doi.org/10.1016/j.wneu.2018.09.025Get rights and content

Highlights

  • The ARUBA trial has received fierce criticism.

  • We evaluated 86 cases of treated unruptured brain AVMs at our institution.

  • The results were 8.3% symptomatic stroke/death, 4.5% long-term clinical impairment, and 92.4% cure.

  • In total, 65.1% underwent microsurgical resection, compared with only 15.8% in ARUBA.

  • A better trial design with realistic clinical practices is warranted.

Objective

The A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial has received fierce criticism, including considerable selection bias, poor generalizability, questionable clinical practices (only 15.8% underwent surgical resection, the gold standard for arteriovenous malformation [AVM] treatment), and short follow-up (33 months) for a disease process that carries a life-long risk. In this study, we sought to present our own experience treating unruptured brain AVMs to provide supporting evidence of the ARUBA trial criticism.

Methods

All cases of treated brain AVMs from 2004 to 2017 at our institution were retrospectively reviewed and included in the analysis if they met ARUBA trial inclusion criteria. The primary outcome was symptomatic stroke or death. Secondary outcomes included AVM obliteration, long-term clinical impairment (modified Rankin Scale score >1), and new major or minor postoperative deficit.

Results

Of the 245 reviewed cases, 86 met the ARUBA trial criteria. Treatment included microsurgical resection alone (2.3%), preoperative embolization followed by microsurgical resection (62.8%), stereotactic radiosurgery alone (10.5%), embolization followed by stereotactic radiosurgery (15.1%), and embolization alone (9.3%). The primary outcome was met in 8.3%, new perioperative major and minor complications occurred in 5.8% and 12.8%, and long-term clinical impairment in 4.5%. AVM obliteration was observed in 92.4% overall and in 100% of patients who underwent surgical resection.

Conclusions

The criticism of the ARUBA trial is warranted, as our study found that treatment of unruptured brain AVMs has an acceptable safety profile when approached in a multidisciplinary manner at an experienced institution, using surgical resection as the primary treatment modality when applicable.

Introduction

Treatment of unruptured brain arteriovenous malformations (AVMs) presents a complex challenge to neurosurgeons. Brain AVMs are relatively uncommon findings, with an estimated prevalence of 1 in every 2000 adults, but they account for approximately 2% of all hemorrhagic strokes.1, 2, 3, 4 Despite a relatively low annual hemorrhage rate of 1.3%–4.12% per year, mortality after the first hemorrhage is approximately 10%.2, 5, 6 Of the patients who survive, after 3 months there is an additional 20% mortality, and one third remain moderately disabled.7 The decision as to whether to treat an unruptured AVM is therefore difficult and must be weighed carefully against the risks of intervention.

In an attempt to address this question, the authors of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) compared 114 patients treated with intervention with 109 patients treated conservatively with medical management.8 The trial was halted early due to a significant difference in outcomes, with 30.7% of patients in the intervention group meeting the primary outcome of symptomatic stroke or death versus 10.1% of patients in the medical management group at a median follow-up of 33.2 months.8 Furthermore, 46.2% of patients in the intervention group were clinically impaired (modified Rankin Scale score [mRS] of 2 or greater) compared with 15.1% of patients in the medical management group at 30 months.8 The rate of spontaneous AVM rupture was found to be 2.2% per year.

These results have been met with fierce criticism for several reasons. Of the 1740 patients initially screened, only 226 (13%) were randomized, which introduces considerable selection bias.9 Excluding patients with radiographic evidence of previous hemorrhage or previous intervention compromises the generalizability of the study.10 Despite the fact that 76 (68%) of the 114 patients in the intervention group had low-grade (Spetzler–Martin [SM] grade I or II) AVMs, only 18 (15.8%) underwent surgical resection with or without preoperative embolization, the gold standard treatment modality. The majority of patients received only partial treatment with embolization and/or radiosurgery, and 30 (26.3%) even received embolization alone despite evidence that this may even increase the risk of hemorrhage.9, 10, 11, 12 Finally, a follow-up time of 33 months for a disease process that presents a life-long risk of hemorrhage is insufficient, and the conclusions drawn about long-term risk of hemorrhage with conservative management are limited.9, 10, 11, 12

In support of this criticism, several groups have published their own experiences with treating unruptured brain AVMs in ARUBA-eligible patients with significantly better outcomes. Unlike the ARUBA trial, most of these studies used surgical resection in a majority of cases, as is standard clinical practice, and found rates of symptomatic stroke or death of 12.2%–16.1% and clinical impairment in 6%–13.8% of treated patients.11, 13, 14, 15, 16 Additional studies evaluating outcomes of ARUBA-eligible patients treated with stereotactic radiosurgery (SRS) reported symptomatic stroke or death in 10.3%–11.5%, and long-term clinical impairment in 4%–12%.17, 18 To this end, we present our own experience of unruptured brain AVMs treated with intervention using a multidisciplinary approach between 2004 and 2017, consistent with our view of best clinical practice.

Section snippets

Patient Selection and Evaluation

The cases of 245 patients within the institutional review board–approved Neurological Surgery Patient Registry who underwent treatment of an unruptured brain AVM at our institution between 2004 and 2017 were retrospectively reviewed. These cases were screened and only included in the analysis if they met the inclusion/exclusion criteria of the ARUBA trial. Cases were included if they were patients aged 18 years or older, with a diagnosis of unruptured brain AVM without previous hemorrhage or

Clinical and Radiographic Characteristics

Of the 245 reviewed cases, 86 met the ARUBA trial criteria. Table 1 summarizes the clinical and radiographic baseline characteristics of all 86 patients. The average age was 43.6 ± 14.6 years, and 45 (52.3%) were male. Forty (46.5%) had no medical comorbidities, 30 (34.9%) had minor comorbidities, and 16 (18.6%) had major comorbidities.

Nine (10.5%) patients were asymptomatic at diagnosis (incidental), whereas 44 (51.2%) presented with headaches, 35 (40.7%) with seizures, and 44 (51.2%) with

Discussion

In this study, the cases of 86 patients with unruptured brain AVMs who met the inclusion/exclusion criteria of the ARUBA trial and underwent treatment at our institution from 2004 to 2017 were retrospectively reviewed. Although the baseline clinical and radiographic characteristics of our patients were similar to those in the ARUBA trial, our outcomes were significantly better. Of the 86 patients in our study, 7 (8.3%) met the primary outcome of symptomatic stroke or death, compared with 30.7%

Conclusions

In this study, we present the cases of 86 patients with ARUBA-eligible unruptured brain AVMs treated with intervention at a single institution. The primary outcome of symptomatic stroke or death was met in 8.3%, long-term clinical impairment was found in 4.5%, and complete nidus obliteration was achieved in 92.4% overall and 100% in patients who underwent microsurgical resection. These results, along with the results of numerous other similar studies summarized previously, compare favorably to

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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