Literature Review

Statement Offers Guidance for Management of Brain AVMs

A joint statement from the American Heart Association and the American Stroke Association offers clinicans guidance on the management of brain arteriovenous malformations.


 

Recent studies have helped clarify the natural history risks of intracranial hemorrhage (ICH) and seizure in patients with unruptured brain arteriovenous malformations (AVMs). In addition, researchers have completed the first randomized trial of interventional therapy versus conservative management for unruptured brain AVMs. Nevertheless, data to guide treatment decisions remain limited, and “considerable uncertainties … face physicians managing patients with ruptured and unruptured brain AVMs,” according to a scientific statement for healthcare professionals from the American Heart Association (AHA) and American Stroke Association (ASA). Optimal management of unruptured brain AVMs is a subject of debate, and discussion of treatment options should include careful consideration of natural history risks, the relative risks of intervention strategies, and patients’ life expectancy, the authors said.

The scientific statement on the management of brain AVMs was published in the August issue of Stroke. It updates the American Heart Association’s 2001 statement on this topic. The report reviews epidemiology, diagnosis, natural history, treatment, and management of ruptured and unruptured brain AVMs, as well as areas requiring more evidence. The American Academy of Neurology affirmed the value of the statement as an educational tool for neurologists. The Society of NeuroInterventional Surgery endorsed it, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Cerebrovascular Section affirmed its educational benefit.

An Uncommon Lesion

Brain AVMs are uncommon, may present with spontaneous ICH, seizures, or headache, and typically present in young adults. Neurologists may identify incidental asymptomatic AVMs when patients undergo brain imaging for other reasons. The primary goal of treatment is prevention of hemorrhagic stroke.

Colin P. Derdeyn, MD,

Colin P. Derdeyn, MD, Professor of Neurology and Radiology at the University of Iowa in Iowa City and chair of the group that wrote the scientific statement, and colleagues searched all English-language articles on brain AVMs in humans that had been published following the 2001 statement. “Advances … include the accumulation of new data related to epidemiology, biology, imaging, outcomes with treatment, and introduction of new embolic agents,” the authors said. “Most notable of these data are the results of the first randomized trial of intervention for unruptured brain AVMs, the ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations).”

ARUBA enrolled 226 adult patients with unruptured brain AVMs between 2007 and 2013. Patients were randomized to receive medical management alone or medical management with interventional therapy (eg, resection, embolization, or stereotactic radiosurgery alone or in combination).

A preplanned interim analysis found that after a mean follow-up of 33 months, the risk of stroke or death was more than three times higher in the intervention group (30.7%) than in the medical management group (10.1%). The analysis included data from 224 participants at 39 sites worldwide. On the recommendation of the ARUBA Data and Safety Monitoring Board, the National Institute of Neurological Disorders and Stroke stopped enrollment and stated that “under the experimental conditions in this trial, the interim analysis … shows that medical management is superior to intervention in patients with unruptured brain AVMs.”

Although ARUBA and an observational study by Al-Shahi Salman et al support a conservative approach to management, the studies had relatively short follow-up, considering the long duration of hemorrhage risk for patients with untreated brain AVMs. Furthermore, complication rates in the treatment arms in ARUBA were much higher than expected, the authors said. “The primary end points of ARUBA [ie, stroke or death] in the intervention group for Spetzler-Martin (SM) grade I (14.3%), II (43.3%), and III (57.1%) AVMs are higher than would have been expected in contemporary series, particularly for surgery or radiosurgery performed alone,” the authors said.

Additional studies are needed to better define long-term risks of stroke and seizure and to identify specific predictors of hemorrhagic stroke. “Long-term follow-up of participants in the ARUBA trial will be valuable for determining whether the superiority of conservative management over intervention observed in that study persists in the long term,” they said. “Further randomized controlled trials are justified to investigate the reproducibility of the findings of ARUBA and to investigate whether the balance of risk between conservative management and intervention is different in specific groups (eg, patients with SM grade I brain AVM).”

Recommendations for Management

Neurologists can inform patients about natural history risks, which are reliably quantified over approximately 10 years for ICH and approximately five years for epileptic seizure, the authors said. The annual risk of a first-ever ICH from an unruptured brain AVM is approximately 1%. The five-year risk of developing a first seizure is approximately 8%, and the five-year risk of developing epilepsy after a first seizure is approximately 58%.

Discussion of treatment options should consider natural history risks “weighed carefully against the relative risks of different intervention strategies and life expectancy,” the authors said. The SM grading scale is useful for predicting the risk of surgical resection.

For the management of patients with ruptured brain AVMs, the authors recommend that the evaluation of underlying brain AVMs and management of an initial hemorrhage follow the AHA and ASA’s 2015 spontaneous ICH management guidelines. The annual risk of recurrent ICH from a ruptured brain AVM is approximately 5%, and increasing age, deep venous drainage, arterial aneurysms, and female sex may increase the risk.

—Jake Remaly

Suggested Reading

Al-Shahi Salman R, White PM, Counsell CE, et al. Outcome after conservative management or intervention for unruptured brain arteriovenous malformations. JAMA. 2014;311(16):1661-1669.

Derdeyn CP, Zipfel GJ, Albuquerque FC, et al. Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48(8):e200-e224.

Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032-2060.

Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014;383(9917):614-621.

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