NORD gratefully acknowledges William L. Young, MD, Departments of Anesthesia and Perioperative Care, Neurological Surgery, and Neurology, University of California, San Francisco, for assistance in the preparation of this report.
Arteriovenous malformation (AVM) is a vascular lesion that is a tangle of vessels of varying sizes in which there is one or more direct connections between the arterial and venous circulations. In the lesion there is no capillary bed, which is part of normal tissue. Brain AVMs are often presumed to be congenital, but there is no direct evidence that they form in utero. The distribution of age at detection for brain AVMs is normally-distributed with the mean age in the mid-30’s. Although a small number of AVMs manifest themselves at or shortly after birth, most of them present later in life, and just as likely, form and progress during the later years of life. The lack of capillaries allows blood traveling through the abnormal fistulous connections to flow rapidly. The low resistance of the direct A-V connections, termed fistulas, results in very high flow rates in the vessels leading to and within the AVM. These high flow rates can lower the pressure in the arteries leading to the AVM and to surrounding relatively normal brain tissue. Further, because of the direct A-V connections, the pressure in the arteries, even if somewhat reduced, are transmitted to the veins draining the AVM and surrounding brain, which normally operate at very low pressures. AVM can occur in many different parts of the body, but those located in the central nervous system (brain and spinal cord) can cause problems that affect the brain like other forms of stroke.
Symptoms of AVM occur only after a highly variable amount of damage to the brain or spinal cord has occurred: this ranges from minor symptoms such as headache to devastating rupture with hemorrhagic stroke. A small percentage of AVMs are detected incidentally during investigation of unrelated medical problems and are completely asymptomatic. AVMs cause damage to the brain or spinal cord by several mechanisms: directly reducing oxygen to neurological tissues through (a) a change in vascular pressures; (b) compression of adjacent neural tissue by the abnormal vascular structures of the AVM; (c) bleeding (hemorrhage) into surrounding tissues. Bleeding has several adverse effects including exerting pressure on adjacent neural tissue and also by leaving toxic blood products in contact with neural tissue.
Seizures are the presenting symptom in 15-40% of individuals with AVM. Cerebral hemorrhage can occur when an AVM ruptures and a large amount of blood is released into the brain. Brain hemorrhage causes the presenting symptoms in roughly half of patients with a brain AVM. The risk for cerebral hemorrhage in individuals with AVM is approximately 2-4% per year, but there is a very wide range of bleeding risks depending on the anatomic and physiologic characteristics of the AVM. The annualized rates vary from below 1% to as high as 30%. Seizures are the second most important presentation of AVMs. Headache occurs in 10-50% of those with AVM and may be the presenting symptom. There is no tell-tale (pathognomonic) pattern for seizure or headache.
Not all of the headaches that bring AVMs to clinical attention are due to the lesion. It is often difficult to know if the headaches are related to the AVM. Other neurological symptoms sometimes occur depending on the location of the AVM. These symptoms can include muscle weakness or paralysis in one area of the body; Symptoms also include, but are not limited to, loss of coordination (ataxia) sometimes leading to difficulty walking; difficulty planning tasks (apraxia); dizziness; vision problems; difficulty speaking or understanding others (aphasia); numbness, tingling or pain; memory problems; mental confusion, hallucinations or dementia. One retrospective study demonstrated that approximately two-thirds of individuals with AVM have a history of mild learning disabilities in childhood or adolescence.
Spinal AVMs can present in a number of ways, including sudden and severe back pain that can cause sensory loss, muscle weakness, localized paralysis, or a more gradual onset of neurological problems in sensation or motor function in the extremities.
AVM are often attributed to result from an error in embryonic or fetal development, but there is no direct evidence of this assertion. No environmental risk factors have been identified for neurological AVM. AVM does not usually run in families, but somewhere on the order of 5% of AVMs may be due to autosomal dominant inheritance of a genetic mutation, most commonly hereditary hemorrhagic telangiectasia or the capillary malformation-AVM syndrome. AVM can rarely be associated with certain syndromes such as Wyburn-Mason syndrome.
AVM affects males and females in equal numbers. There does not appear to be an increased risk for particular ethnic and racial groups. The best estimates for new detection of an AVM are 1 per 100,000 population per year (about 3000 new cases detected per year in the U.S.) The population prevalence is about 10 per 100,000, i.e., there are probably about 30,000 individuals in the U.S. who harbor an AVM or have had an AVM that was treated. They occur throughout life, but the peak onset of symptoms is 35-40 years of age.
A variety of imaging studies are used to diagnose AVM. Noninvasive imaging technologies that are used to diagnose AVM are computed axial tomography (CT) and magnetic resonance imaging (MRI). CT is particularly useful in identifying a hemorrhage but can identify only large AVM. MRI is necessary for the initial diagnosis of AVM. Magnetic resonance angiography (MRA) can be used to determine the pattern and speed of blood flow through AVM but can miss small lesions.
The current gold standard for diagnosis is X-ray angiography. This test is usually performed by placing a small tube (catheter) in the femoral artery, a large artery in the groin. A contrast agent that highlights blood vessels is injected into the blood vessels that supply the brain, then X-rays can reveal the structure of blood vessels in and around the lesion. The results of the angiogram help to determine the most appropriate treatment. An angiogram is often needed for treatment planning.
There is no specific medical therapy currently available, but this is an area of active research. There are some promising medical therapies for AVMs outside of the brain that might one day be adapted for use to treat brain AVMs. Medications can be used to control the headaches, pain or seizures associated with AVM. Surgery may or may not be recommended on a case-by-case basis based on the estimated risks and benefits. Surgery is often necessary because if an AVM is left untreated there is a risk for hemorrhage. Three types of surgery are used for AVM, either alone or in combination. Conventional surgery (microsurgical resection) to remove the AVM is appropriate if the lesion is located in an accessible area that does not involve critically important functional areas and is relatively small in size. Endovascular embolization is a surgical technique in which the AVM is blocked off so that blood can no longer flow through it. This technique is sometimes all that is necessary to cure the AVM but often it is used as a first step prior to other types of surgery. Most North American practitioners do not use embolization as a sole therapy. Radiosurgery is a procedure in which a high dose of radiation is focused on the AVM, which sets off a gradual process that eventually closes the vessels in the lesion. Patients are not protected from spontaneous bleeding during the period of several years that it takes for closure.
Researchers at Columbia University are conducting a study to determine if medical management is better than invasive therapy for improving the long-term outcome of patients with unruptured brain arteriovenous malformations. A Randomized Trial of Unruptured Brain AVMs (ARUBA) is currently recruiting patients. For more information about this study, Protocol Number: NCT00389181, visit http://clinicaltrials.gov/ct2/show/NCT00389181?term=arteriovenous+malformation&rank=5, or contact J. P. Mohr, MS, MD (212-305-8033 firstname.lastname@example.org) or Alan J. Moskowitz, MD (212-659-9567 Alan.Moskowitz@MSSM.EDU)
The UCSF Center for Cerebrovascular Research undertakes a variety of studies related to the epidemiology, genetics, development of biomarkers, treatment outcomes and vascular biology. For more information contact Helen Kim, PhD, or William L. Young, MD, Center for Cerebrovascular Research, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Ave, Box 1363, San Francisco, CA 94110.
A genetic study of people with occult vascular malformations of the brain is currently being conducted at Yale University. An occult AVM is one that is not obvious on an angiogram but may be seen upon MRI scan. For more information on this study, contact:
Murat Gunel, M.D.
Yale University School of Medicine
Section of Neurosurgery
333 Cedar St.
New Haven, CT 06510
A genetic study of individuals affected by certain types of vascular malformation (e.g., AVMs, CCMs, hemangiomas, etc.) is being conducted at Duke University. Participants must have 3 or more members of their family affected by a vascular malformation. For more information on this study, contact:
Douglas Marchuk, PhD
Department of Molecular Genetics and Microbiology
Durham, NC 27710
A genetic study of people with both sporadic brain AVMs and brain AVMs due to HHT is being conducted by the Brain Vascular Malformation Consortium, which is part of the Office of Rare Disease Research (NIH) program, “Rare Disease Clinical Research Network.”
For more information on this study, contact:
William L. Young, MD
University of California, San Francisco
San Francisco General Hospital
1001 Potrero Ave, Room, Box 1363
San Francisco, CA 94110
tel: 415.206.8906 fax: 415.206.8907
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Kim H, Pawlikowska L, Young WL. Genetics and vascular biology of brain vascular malformations (Chapter 12). In: Mohr JP, Wolf PA, Grotta JC, Moskowitz MA, Mayberg MR, von Kummer R, editors. Stroke: Pathophysiology, Diagnosis, and Management. 5th ed. Philadelphia: Churchill Livingstone Elsevier; 2011. p. 169-186.
van Beijnum J, van der Worp HB, Buis DR, Al-Shahi Salman R, Kappelle LJ, Rinkel GJ, van der Sprenkel JW, Vandertop WP, Algra A, Klijn CJ. Treatment of brain arteriovenous malformations: a systematic review and meta-analysis. JAMA. 2011 Nov 9;306(18):2011-2019.
Hernesniemi J, Romani R, Lehecka M, Isarakul P, Dashti R, Celik O, Navratil O, Niemela M, Laakso A. Present state of microneurosurgery of cerebral arteriovenous malformations. Acta Neurochir Suppl. 2010;107:71-76.
Laakso A, Dashti R, Juvela S, Niemela M, Hernesniemi J. Natural history of arteriovenous malformations: presentation, risk of hemorrhage and mortality. Acta Neurochir Suppl. 2010;107:65-69.
van Beijnum J, Lovelock CE, Cordonnier C, Rothwell PM, Klijn CJ, Salman RA. Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies. Brain. 2009 Feb;132(Pt 2):537-543.
Wedderburn CJ, van Beijnum J, Bhattacharya JJ, Counsell CE, Papanastassiou V, Ritchie V, Roberts RC, Sellar RJ, Warlow CP, Al-Shahi Salman R. Outcome after interventional or conservative management of unruptured brain arteriovenous malformations: a prospective, population-based cohort study. Lancet Neurol. 2008 Mar;7(3):223-230.
Kim H, Sidney S, McCulloch CE, Poon KY, Singh V, Johnston SC, Ko NU, Achrol AS, Lawton MT, Higashida RT, Young WL. Racial/ethnic differences in longitudinal risk of intracranial hemorrhage in brain arteriovenous malformation patients. Stroke. 2007 Sep;38(9):2430-2437.
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 May 9;66(9):1350-1355.
Arteriovenous Malformation Study Group. Arteriovenous malformations of the brain in adults. N Engl J Med. 1999 Jun 10;340(23):1812-1818.
Sen, S; Arteriovenous Malformations; eMedicine; http://emedicine.medscape.com/article/1160167-overview Last Update:January 18, 2013, Accessed:January 22, 2013.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100