Arterio-venous_Malformations

Introduction

Arteriovenous malformations of the brain - often just called AVMs, for short - are abnormal tangles of blood vessels. No-one knows why they occur, except in the genetic condition called Hereditary Haemorrhagic Telangiectasia. Many think that people are born with AVMs, but whether they actually arise later or not, they probably lie dormant for many years. Studies in which people without any neurological symptoms have undergone brain MRI scanning have shown that one in every 2,000 people has an AVM that hasn't caused any symptoms.

Prognosis

The most feared consequence of an AVM is brain haemorrhage. This appears tobe less fatal than so-called 'primary intracerebral haemorrhage', which mainly affects older people. The risk of bleeding from an AVM is still being studied: two population-based studies are underway, the Scottish Audit of Intracranial Vascular Malformations (www.saivms.scot.nhs.uk), and the New York Islands AVM Study.

The best hospital-based study of AVM prognosis hasfound that three main factors increase someone's future risk of bleeding from an AVM: if they presented with a brain haemorrhage, if the AVM islocated deep within the brain, and if the AVM's veins drain exclusively intothe deep system of veins [1]. The yearly risk of bleeding varies from 1% to 34%.

Treatment

There are three main treatments, used either alone or in combination, to tryand obliterate an AVM: (a) cutting out the abnormal blood vessels (neurosurgery), (b) glueing up the abnormal vessels (endovascular embolisation), or (c) focussed beams of radiation (stereotactic radiotherapy/radiosurgery).

Because of the high risk of bleeding of some AVMs (such as those that have already bled, are located deep in the brain, and those that drain into the deep veins),sometimes there is no doubt that interventional treatment should be undertaken. However, recent work from the Scottish population-based audit has shown that treatment of AVMs that have never bled appears to worsen short-term outcome in comparison to no treatment [2].

ARUBA Trial

ARUBA stands for: A Randomised Trial of Unruptured Brain Arteriovenous Malformations.

So far, no-one has ever done a randomised controlled trial (which is the 'acid test' for any treatment) to demonstrate that it is beneficial to treat any sort of brain AVM [3]. Because the treatment of unruptured AVMs is most controversial, ARUBA is studying adults with an unruptured brain AVM. If specialists decide that it is technically possible to treat a brain AVM, anyone who agrees to participate in ARUBA would be randomly allocated to one of two groups:

(1) a policy of interventional treatment of the brain AVM, or

(2) no immediate interventional treatment of the brain AVM. By interventional treatment, ARUBA is referring to neurosurgery, endovascular embolisation, or stereotactic radiotherapy. The intention is to compare thelong-term outcome for these 2 groups of people, over at least 5 years. ARUBA is funded by the National Institute of Neurological Disorders and Stroke(NINDS) in the USA, but it is taking place in Europe and Australia as well.

Aims of the ARUBA study

1. To determine whether medical management is superior to invasivetreatment of unruptured brain AVMs.

2. If medical management is not superior to invasive treatment, todetermine if medical management is not inferior to invasive therapies forpreventing death or stroke in the treatment of unruptured brain AVMs.

3. To determine whether medical management of brain AVMs decreases the risk of death or disability compared to invasive treatments.A number of secondary aims will look at differences in quality of life,death, quality-adjusted survival, adverse effects, and costs. The study will also look into the relative benefits of invasive treatments as opposed to medical management depending on size, location, venous drainage pattern or age.

References

1. Stapf C, Mast H, Sciacca RR, Choi JH, Khaw AV, Connolly ES, Pile-Spellman J, Mohr JP. Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology 2006;66(9):1350-5.

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 2008;7(3):223-30.

3. Al-Shahi R, Warlow CP. Interventions for treating brain arteriovenous malformations in adults. Cochrane Database Syst Rev 2006;(1):CD003436.

Author: Rustam Al-Shahi Salman

Reviewers: Paul Brennan, Andrew Robson

Updated: September 27 2008.