Correspondence

The ARUBA Study: What Is the evidence? LETTER: malformations (AVMs) of the brain are very A rteriovenous complex and fascinating pathologies affecting the central

nervous system (CNS). They came into clinical attention more than a century ago, and since that time, they have been recognized as lesions that can cause serious neurological deficits or death. Over the last decade, there has been a growing interest in gaining more knowledge about the incidence, frequency, and clinical course of these vascular lesions, and both retrospective and prospective-based studies offering new insights have accumulated. Recently, the findings of the randomized trial of unruptured brain arteriovenous malformations (ARUBA) study (1) have opened new avenues in the understanding of such pathology. The study showed that medical management alone was superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain AVMs who were followed up for 33 months. Given the results observed, some points warrant emphasis and clarification.

The ARUBA study is the first randomized controlled clinical trial assessing the outcomes of 2 management strategies (i.e., medical management with interventional therapy or medical management alone) in patients diagnosed with an unruptured brain AVM, and its results are in line with population-based data (2) that previously suggested a significantly increased risk of stroke and focal neurological deficits for unruptured brain AVM in patients undergoing an intervention. We remain cautious, however, and critical of the conclusion, and believe that this study has not effectively answered the question of what is the preferred mode of therapy. The study should reveal data from each therapeutic modality, especially for the so-called “interventional” therapy, a combined therapeutic treatment made up of different strategies (i.e., surgery, embolization, and stereotactic radiotherapy, alone or in combination). There is no evidence of clinical outcomes comparing different interventional treatments

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against each other. It is well known that each of the so-called interventional modalities presents specific indications and a different rate of success. Management decisions are made in light of the lifetime risk of hemorrhage versus the risk of treatment. The risk of AVM rupture is reduced only by complete exclusion of the AVM from the intracranial circulation. Treatment is therefore highly individualized and dependent on the angioarchitecture, location of the AVM itself, age and comorbidity of the patient, and the relative risks of different treatment modalities for that particular treating center. To extrapolate the early results of this study to all patients with unruptured AVM would be a misinterpretation of the ARUBA data and a serious disservice to our patients and our profession. Although the ARUBA report is an important step in defining the treatment of unruptured AVM, optimum management of the entire group of patients with AVM is still far from clear. We hope the 5-year follow-up results will be able to provide further insights into the best long-term management. Giovanni Grasso Section of Neurosurgery, Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo, Palermo, Italy To whom correspondence should be addressed: Giovanni Grasso, M.D., Ph.D. [E-mail: [email protected]] Published online 13 April 2014; http://dx.doi.org/10.1016/j.wneu.2014.04.057.

REFERENCES 1. 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 ARUBA Investigators: Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 383:614-621, 2014.

2. Wedderburn CJ, van Beijnum J, Bhattacharya JJ, Counsell CE, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Al-Shahi Salman R, SIVMS Collaborators: Outcome after interventional or conservative management of unruptured brain arteriovenous malformations: a prospective, population-based cohort study. Lancet Neurol 7:223-230, 2008.

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The ARUBA study: what is the evidence?

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