Original ArticleTreatment 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
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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Cited by (27)
Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis
2022, Journal of Stroke and Cerebrovascular DiseasesCitation Excerpt :An extension study demonstrates the durability of benefit of initial medical therapy through 50 months follow-up.5 However, several criticisms regarding trial methodology, patient selection criteria, and study conduct were put forth after study publication, indicating contention by some clinical providers to the applicability of the trial results to real-world clinical practice.6,7 Regardless of the lack of consensus, it is desirable to empirically characterize the impact of the ARUBA trial findings upon actual patient management and outcomes in clinical practice in the United States.
Brain Arteriovenous Malformations: Status of Open Surgery after A Randomized Trial of Unruptured Brain Arteriovenous Malformations
2022, Neurosurgery Clinics of North AmericaCitation Excerpt :In 2019, Pulli and colleagues28 retrospectively analyzed 142 ARUBA-eligible patients with AVM treated via a multimodal approach and again found significantly lower rates of postoperative stroke relative to the interventional arm of the ARUBA trial. Although the generalizability of these studies remains limited due to their retrospective nature and the fact that they are single-center series, their findings do consistently demonstrate better outcomes than the those of the ARUBA treatment arm, even in those patients receiving SRS alone.3–6,9 Many attributed these differences in outcome to both careful patient selection and the increased utilization of microsurgical resection as a treatment modality.
Surgical Management of Cranial and Spinal Arteriovenous Malformations
2021, Stroke: Pathophysiology, Diagnosis, and ManagementSpontaneous Regression Followed by Rupture of an Untreated Brain Arteriovenous Malformation
2020, World NeurosurgeryCitation Excerpt :Prophylactic microsurgery, radiosurgery, or endovascular obliteration aim to eliminate this risk, although the choice of the optimal approach remains a matter of debate. Despite some controversial evidence in favor of conservative management,3,4 observation is usually reserved for high-risk AVMs.5,6 Although traditionally thought to be congenital and developmental abnormalities, AVMs are dynamic lesions with cases of de novo formation and regression reported.7
A combined single-stage procedure to treat brain AVM
2020, NeurochirurgieCitation Excerpt :Since the ARUBA trial [7], indications to treat in unruptured brain AVM are under question [8,9]. However, recent studies argue that the ARUBA results cannot be applied equally for all unruptured brain AVMs and all treatment modalities [10] and that treatment of unruptured brain AVM has an acceptable safety profile when approached in a multidisciplinary manner in an experienced institution, using surgical resection as the primary treatment modality when applicable [11]. According to a recent meta-analysis of the natural history of brain AVM, unruptured AVM has a risk of rupture of 2.2% per year [12].
Changes in Clinical Presentation and Treatment Over Time in Patients with Unruptured Intracranial Arteriovenous Malformations
2020, World NeurosurgeryCitation Excerpt :Our philosophy is that unruptured AVMs should be treated if the overall risk of treatment is lower than the cumulative lifetime risk of the disease, hence the high rate of treatment in the present cohort. This approach seems to be the prevailing one in terms of management of patients with unruptured intracranial AVMs.23-30 A conservative noninterventional strategy is offered to the elderly, patients with significant comorbidities limiting their life expectancy, and those with AVMs at high risk of adverse outcome related to interventional treatment.
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.