Results of ARUBA Are Applicable to Most Patients With Nonruptured Arteriovenous Malformations
2014; Lippincott Williams & Wilkins; Volume: 45; Issue: 5 Linguagem: Inglês
10.1161/strokeaha.113.002698
ISSN1524-4628
Autores Tópico(s)Intracerebral and Subarachnoid Hemorrhage Research
ResumoHomeStrokeVol. 45, No. 5Results of ARUBA Are Applicable to Most Patients With Nonruptured Arteriovenous Malformations Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBResults of ARUBA Are Applicable to Most Patients With Nonruptured Arteriovenous Malformations J.P. Mohr, MD, MS J.P. MohrJ.P. Mohr From the Doris & Stanley Tananbaum Stroke Center, NY. Originally published11 Mar 2014https://doi.org/10.1161/STROKEAHA.113.002698Stroke. 2014;45:1541–1542Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2014: Previous Version 1 2006 (Kissimmee, FL) was the last such controversy session on brain arteriovenous malformations (AVMs) at an International Stroke Conference. The patient then was somewhat older but raised similar management issues. Intervention had produced a major stroke. A dissatisfied interventionalist in the audience was overheard to murmur, "I want some answers." A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial had just been funded by National Institutes of Neurological Diseases and Stroke (NINDS) but had not begun.Some additional information would help hemorrhage risk assessment for the current case. Evidence of previous hemorrhage, symptomatic or not, raises the risk of further hemorrhage; based on current practice, it would argue for intervention with a goal of lesion eradication. Recent onset headaches could mean she is developing venous stenosis or dilatation, thought by some a risk factor for hemorrhage, albeit not easily treated. If the AVM site straddles the arterial borderzones, risk of first hemorrhage would be lower than for sites elsewhere. To be characterized as Spetzler–Martin Grading System (SMGS) 3 presumably means the 3 points are the sum of 2 points for the 4 cm (medium) size, the third point from eloquent site (superficial parietal location), not deep venous drainage. The score could be improved using the expanded scale proposed by the Center for Cerebrovascular Research, University of California, San Francisco.The questions posed might make some readers assume the patient is expected to be referred for interventional therapy (a radiosurgery option not cited). We suggest she might be as well or better managed by medical therapy alone, treating the headache. Often-quoted annual hemorrhage risks of 4% and death of 1% have seemed to justify intervention. But modern reports for those not having bled have values as low as 1% to 2% for hemorrhage, and less for death.1 By contrast, adverse events for interventions have proved far higher than formerly assumed; for those both bled and no-bled, a recent meta-analysis cited point estimates for surgery 29% (range 1.5–54), embolization 25% (range 7.6–55), and radiotherapy 13% (range 0–63).2And no surprise: AVMs being embedded in brain, eradication efforts risk disturbing healthy tissue (adjacent to, possibly within the AVM), generating syndromes of varying degrees of severity. Intervention efforts have been sustained by hopes that some compensatory mechanisms may shorten the course or eventually yield an acceptable residual syndrome. Those favoring conservative management separately hope that hemorrhage will be long delayed, confined mainly to the nidus with minor syndrome effects, thereafter justifying subsequent eradication efforts for the expected. The dilemma has been posed as sleeping dogs or unexploded bombs?The recently published data from the ARUBA trial,3 applicable for those never having bled, corroborates outcomes from both the recent meta-analysis2 and population-based reports.4 (Considering that the ARUBA cohort comes from 39 centers worldwide, the results serve to confirm both external and internal validity of the trial.) The majority (62%) of those randomized to ARUBA were of the smaller size and more superficial locations thought most favorable for attempted eradication: SMGS I 30%, II 32%, III 28%, and IV 10%. Begun in 2007, the randomization phase of the trial was ended in April 2013 by a NINDS-appointed data and safety monitoring board. Although strongly recommending long-term follow-up, their action was based on a >3-fold incidence of stroke (confirmed by imaging) and death in the interventional arm compared with the medical. There was a clear increase in stroke/death outcomes with intervention those whose with SMGS II-III (too few cases were in SMGS IV for suitable statistical analysis), but no similar indication of increased stroke events by SMGS in the medical arm. Follow-up for the 223 participants was at a mean of 3.3 years. The distribution of disability scores (≥2 as rated by the modified Rankin Scale) was also persistently and significantly worse for those having events in the interventional arm compared with the medical. These results disappointed hopes for substantial early syndrome improvement. (Longer-term follow-up can assess whether these disparities in event rates and functional status will persist.)Available data justify a recommendation that she defer intervention: the frequency of headaches or seizures documented in ARUBA is the same whether or not patients undergo intervention to eradicate the AVM. However, if treated now, her likelihood of having symptomatic stroke or death is >3 times higher as compared with being simply managed medically for headaches. There is reasonable hope that she may be spared hemorrhage in her lifetime, which any such event would prove clinically mild, and that improved methods of management will have evolved. We recommend she live a normal life and proceed with her eventual career and family plans.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 2 of a 3-part article. Parts 1 and 3 appear on pages 1539 and 1543, respectively.Correspondence to J.P. Mohr, MD, MS, Columbia University College of Physicians and Surgeons, Director of Doris & Stanley Tananbaum Stroke Center, Neurological Institute, 710 West 168th Street, New York, NY 10032–2603. E-mail [email protected]References1. Mohr JP, Moskowitz AJ, Parides M, Stapf C, Young WL. Hull down on the horizon: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial.Stroke. 2012; 43:1744–1745.LinkGoogle Scholar2. van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, et al. Treatment of brain arteriovenous malformations: a systematic review and meta-analysis.JAMA. 2011; 306:2011–2019.CrossrefMedlineGoogle Scholar3. Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbe JR, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. November 20, 2013. doi:10.1016/S0140-6736(13)62302-8.: http//www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62302-8/abstract. Accessed November 20, 2013.Google Scholar4. van Beijnum J, Lovelock CE, Cordonnier C, Rothwell PM, Klijn CJ, Al-Shahi Salman R; SIVMS Steering Committee and the Oxford Vascular Study. Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies.Brain. 2009; 132(pt 2):537–543.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Catapano J, Frisoli F, Nguyen C, Labib M, Cole T, Baranoski J, Kim H, Spetzler R and Lawton M Intermediate-grade brain arteriovenous malformations and the boundary of operability using the supplemented Spetzler-Martin grading system, Journal of Neurosurgery, 10.3171/2020.11.JNS203298, 136:1, (125-133) Magro E and Gentric J (2020) Brain AVM management: Anything new under the sun?, Journal of Neuroradiology, 10.1016/j.neurad.2019.11.003, 47:1, (3-4), Online publication date: 1-Feb-2020. Kassiri J, Rajapakse T, Wheatley M and Sinclair D (2019) Neurovascular Lesions in Pediatric Epilepsy, Journal of Child Neurology, 10.1177/0883073819838445, 34:10, (549-555), Online publication date: 1-Sep-2019. Shakur S, Brunozzi D, Hussein A, Linninger A, Hsu C, Charbel F and Alaraj A (2017) Validation of cerebral arteriovenous malformation hemodynamics assessed by DSA using quantitative magnetic resonance angiography: preliminary study, Journal of NeuroInterventional Surgery, 10.1136/neurintsurg-2017-012991, 10:2, (156-161), Online publication date: 1-Feb-2018. Joyce C and Gomez C (2018) Reimagining ARUBA: Theoretical Optimization of the Treatment of Unruptured Brain Arteriovenous Malformations, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2018.07.007, 27:11, (3100-3107), Online publication date: 1-Nov-2018. Wong J, Slomovic A, Ibrahim G, Radovanovic I and Tymianski M (2016) Microsurgery for ARUBA Trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformation)–Eligible Unruptured Brain Arteriovenous Malformations, Stroke, 48:1, (136-144), Online publication date: 1-Jan-2017. Badakhshi H (2017) Arteriovenöse Malformation des zentralen Nervensystems Bildgeführte stereotaktische Radiochirurgie, 10.1007/978-3-662-54724-3_3, (45-59), . Javadpour M, Al-Mahfoudh R, Mitchell P and Kirollos R (2016) Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients, British Journal of Neurosurgery, 10.1080/02688697.2016.1181153, 30:6, (619-622), Online publication date: 1-Nov-2016. Magro E, Gentric J, Darsaut T, Batista A, Chaalala C, Roberge D, Weill A, Roy D, Bojanowski M and Raymond J (2016) Le traitement des MAVS cérébrales (TOBAS) : une étude randomisée controlée avec registre, Neurochirurgie, 10.1016/j.neuchi.2015.12.008, 62:4, (197-202), Online publication date: 1-Aug-2016. Badakhshi H (2016) Arteriovenous Malformations of the Central Nervous System Image-Guided Stereotactic Radiosurgery, 10.1007/978-3-319-39189-2_8, (107-120), . Wong J, Radovanovic I and Tymianski M (2015) The Impact of ARUBA on the Management of Unruptured Brain Arteriovenous Malformations : Review of Literature, Japanese Journal of Neurosurgery, 10.7887/jcns.24.605, 24:9, (605-613), . Mohr J and Yaghi S (2015) Management of Unbled Brain Arteriovenous Malformation Study, Neurologic Clinics, 10.1016/j.ncl.2014.12.006, 33:2, (347-359), Online publication date: 1-May-2015. Hartmann A and Mohr J (2015) Acute Management of Brain Arteriovenous Malformations, Current Treatment Options in Neurology, 10.1007/s11940-015-0346-5, 17:5, Online publication date: 1-May-2015. Ellis J and Lavine S (2014) Role of Embolization for Cerebral Arteriovenous Malformations, Methodist DeBakey Cardiovascular Journal, 10.14797/mdcj-10-4-234, 10:4, (234) May 2014Vol 45, Issue 5 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.113.002698PMID: 24619392 Manuscript receivedNovember 22, 2013Manuscript acceptedJanuary 6, 2014Originally publishedMarch 11, 2014 Keywordshemorrhagearteriovenous malformationheadachePDF download Advertisement SubjectsTreatment
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