Author(s): Stacy M Stibb, DO, Vanessa Molina, BS
Originally published: September 14, 2015 Last updated: January 15, 2026
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Disease/Disorder

Definition

Arteriovenous malformations (AVMs) are congenital vascular lesions. They are characterized by an abnormal connection between arteries and veins that lack an intervening capillary bed, which results in direct arteriovenous shunting. AVMs are the most common of the four types of vascular malformations in the central nervous system, the other three being developmental venous anomalies (DVA), cavernous malformations (CM), and capillary telangiectasias (CTS).1-3

Etiology

In general, the etiology of AVMs is complicated and not well understood. Most theories suggest either persistence of a primitive arteriovenous connection or the development of such after the initial closure of the primitive connection.1,2 Candidate genes such as endoglin (ENG) on chromosome 9q and activin-receptor-like kinase (ALK1) on chromosome 12q have been identified as a possible genetic basis of intracranial AVMs.4,5 Despite that 95% of brain AVMs are unifocal and non-familial in etiology. The majority of cases are thought to arise from somatic genetic mutations, rather than from germ cell origin.6

In terms of etiology behind the rupture of an AVM, inflammation as well as genetic anomalies have been found to have a role. In particular, matrix metalloproteinase-9 (MMP-9) alterations can compromise vascular stability.4,5 During inflammatory events, MMP-mediated degradation of the extracellular matrix and apoptosis of vascular smooth muscle cells can lead to weakened vessels that may develop bulging walls due to pressure overload leading to rupture.6

Epidemiology

The overall incidence of AVMs is difficult to estimate as they are not commonly found unless complications arise. The prevalence of an asymptomatic (incidental) AVM is estimated to be 50 per 100,000 and the prevalence of detected AVM with symptomatic presentation is estimated to be 10-18 per 100,000.6 Capillary telangiectasis can be seen at the venous drainage territories of DVA but are typically benign. Due to their benign state, they may be found incidentally or may never be detected, which may lead to underreported cases.7

Cerebral AVMs are a common cause of intracranial hemorrhage in children representing about 30-50% of pediatric hemorrhagic strokes.1,2,8 Spinal cord AVMs comprise 20-30% of all spinal vascular malformations and are the most common cause of nontraumatic intraspinal bleeding or hematomyelia.9

It is estimated that 30-50% of individuals with hereditary hemorrhagic telangiectasia (HHT) develop AVM. The majority of HHT cases are due to HHT1 gene mutations, which lead to a pro-inflammatory state, increased angiogenesis, and decreased TGF-beta signaling. TGF-beta typically contributes to wound healing and regulation of the extra cellular matrix, therefore a decrease in this signaling pathway may contribute to the development of AVM.6 HHT carries a 10–25% lifetime risk of developing a cerebral AVM.10 Spontaneous hemorrhage of DVA is not common, thus underlying cerebral cavernous malformation, venous outflow obstruction, or flow-related shunts should be investigated.7

Patho-anatomy and physiology

There is a structural defect in the formation of the arteriolar capillary network that is normally present between arteries and veins. Due to the absence of capillary communication, shunting elevates intraluminal venous pressure and produces ectasia and muscularization that form hybrid vessels and a vascular network called a nidus (nidal-type) or mainly a direct connection between the artery and the vein (fistulous-type). Over time, the lesion enlarges due to pressure differentials. Hemorrhage is thought to be due to the non-static nature of the AVMs and the rapid expansion that can occur during times of growth, possibly related to angiogenic/vascular growth factors.1,8 Hemorrhage is often associated with increased pressure in feeding arteries and draining veins (i.e., outflow restriction).4 Hemorrhage occurs in 0.5% of cases of cranial AVMs and is more common with the fistulous type.11

In children, there is a higher incidence of AVMs in the posterior fossa, basal ganglia, and thalamus, which are more prone to bleeding and may result in catastrophic outcomes.1 In the spinal cord, the nidus-type AVM has been associated with an increased risk of bleeding, and the fistulous-type typically presents as progressive myelopathy due to its mass effect.9 Spinal AVMs are also associated with asymmetric growth in children.11

Disease progression

An AVM is the most common cause of spontaneous intracranial hemorrhage in children, with 80–85% of pediatric patients suffering a hemorrhagic event as the initial presenting symptom12Some of the other common manifestations of vascular malformations include headache, seizures, and transient ischemic attack. Depending on the location of the AVM as well as type of vascular formation, presentation can vary greatly. For instance, the vast majority (61%) of DVAs are asymptomatic. Approximately 23% of DVA present with non-specific symptoms, and the other 16% of patients experience either focal neurological deficits, seizure, or infarction.7

Risk factors for AVM hemorrhage include a previous history of hemorrhage (within 5 years), a deep-seated or infratentorial location, an exclusive deep venous drainage, nidal-type, association with an aneurysm, and diffuse morphology.1,2,13 Large, deep lesions have significant morbidity and are associated with high rates of rupture and neurologic deficits.14

Secondary conditions and complications

AVM is the most unpredictable vascular malformation. It usually remains quiescent in childhood but tends to enlarge with time and cause local destruction.11 Neurologic symptoms are dependent on location within the brain or spinal cord, presenting either as a stroke or progressive myelopathy, respectively.1,15Acute hemorrhagic events in children have been associated with up to a 25% mortality rate.1  One study found that the recurrence of AVM after surgical resection was 6/135 patients with recurrence occurring over 7 years later on average. Of these 135 patients, 17 were pediatric patients. Of the 6 patients who experienced recurrence, 5 were pediatric patients (5/17 = 29.4% recurrence in study pediatric population).16 There is typically an increased risk of recurrence if the patient’s initial presentation is hemorrhage of their vascular malformation. Recurrence is thought to be induced by hemodynamic changes and angiogenesis, as newly formed vessels are fragile and more susceptible to bursting.7 In addition young age at diagnosis has consistently emerged as a major risk factor for recurrence.17In the spinal cord, lesions with persistent perimedullary veins and those located in the cervical and upper thoracic level appear to have a higher risk of rehemorrhage.18

Essentials of Assessment

History

A detailed history that focuses on components similar to other acquired brain or spinal cord injuries including symptom timing and onset of headache, seizures, weakness, visual or swallowing abnormalities, progressive limb weakness, as well as bladder and bowel changes  is important AVMs may cause subtle learning and behavioral disorders in some children long before more obvious symptoms become evident.19,20

Physical

A comprehensive physical examination with focus on the neurological exam as one would do for a patient with a stroke or myelopathy is warranted. Assessing head circumference in an infant is important as a particularly severe type of AVM called vein of Galen malformation is associated with hydrocephalus and presents with seizures, failure to thrive and congestive heart failure.21 Presence of vascular skin lesions may be associated with hereditary/genetic abnormalities like in HHT and Sturge-Weber Syndrome, which may warrant further diagnostic work-up and genetic testing.3

Clinical functional assessment

Depending on the area of involvement and symptom presentation, one may utilize various clinical functional assessment tools. Options include the Glasgow Coma scale, Glasgow Outcome Scale, Pediatric National Institutes of Health Stroke Scale (PedNIHSS), modified Rankin scale, American Spinal Injury Association (ASIA) Impairment Scale and Functional Independence Measure for children (WeeFIM). Cognitive, speech and neuropsychological evaluation may also be needed.

Lab studies

There is no specific laboratory study to assess for AVMs. Several genetic polymorphisms have been identified that exacerbate lesion progression and increase the risk of AVM. However, these inflammatory markers are more useful to plan therapeutic strategies.22

Imaging

Early screening imaging with magnetic resonance angiography (MRA) or computed tomography (CT) has become increasingly supported in patients who have known associated conditions, such as HHT, as early detection of an AVM can help guide treatment to prevent future hemorrhage.23AVMs are usually diagnosed through a combination of magnetic resonance imaging (MRI), MRA,CT and digital subtraction angiography (DSA). These imaging studies may need to be repeated to analyze a change in the size of the AVM, presence of hemorrhage, any calcification or the appearance of new lesions.10,20 MRI with and without contrast, with MRA of the brain and/or spine helps to rule out other hemorrhagic lesions such as tumors and cavernous malformations, and can better delineate the vascular anatomy of the lesion. DSA remains the gold standard, as it provides the greatest sensitivity and detail of all the imaging types.10 DSA is also performed post-surgical resection to ensure the lesion has been fully resected.16 It has been recommended to perform ongoing imaging follow up with DSA at 6months and MRI at 1,3, and 5 years with repeat DSA if needed for high clinical concern.17

Supplemental assessment tools

Imaging studies of other areas of the body such as the lung, liver, spleen, and the gastrointestinal tract may be done to rule out other possible associated vascular anomalies.3,21

Early prediction of outcomes

There have been few studies of long-term clinical outcomes of brain AVMs in pediatric patients.

AVMs are often an incidental finding or a catastrophic presentation due to rupture/hemorrhage, making prediction of outcomes difficult. Once neurological deficit occurs, focus is on prevention of symptom worsening with secondary measures. Once rupture or hemorrhage occurs, there is an increased risk of recurrence, especially in the first year. Incidentally found AVMs have several factors that may be used to estimate the risk of hemorrhagic presentation. AVMs with associated aneurysm, a single draining vein, a single feeder, deep venous drainage, infratentorial location, deep location, diffuse morphology have a higher risk of hemorrhage.10,24 The Spetzler-Martin Grade (SMG) scale or the Spetzler-Ponce class can be used to grade AVMs according to risk.

Environment

Depending on the neurologic sequela and resultant disability, ongoing physical, occupational and speech therapy, child life services and social services may be warranted. Home and environmental modifications, along with adaptive equipment and mobility/gait aids may be needed to accommodate for resultant persistent functional impairments.

Social

Acute neurologic sequala with resultant functional impairment from an acquired brain or spinal cord injury requires good family and social support. As the child transitions back into the home, school and community, proper accommodation and assistance may be required for mobility and activities of daily living. Support, counseling, education, and developmental guidance is needed for family and other caregivers.

Professional issues

There is often a delay in diagnosis due to the low overall incidence, thus heightened clinical suspicion is necessary for prompt diagnosis. In the initial phase, when emergent symptoms are being controlled and addressed, there may be a delay in definitive treatment of the AVM. This may pose as a stressful time for patients and families with concerns about the risk of recurrence of emergent symptoms.

Rehabilitation Management and Treatments

Current treatment guidelines

Acute treatment of an AVM may be conservative or interventional depending on lesion features, clinical presentation and patient specific factors.25 Treatment options include endovascular embolization via catheter delivery of liquid embolics or coils, microsurgical resection, and stereotactic radiosurgery.1,15,26 In a recent study by Lioi et al looking at pediatric brain AVMs with 46 patients, 77.5% of the patients who completed active treatment achieved radiological cure which was defined as complete nidus obliteration on post treatment DSA and stable follow up MRI. The highest cure rate was in the microsurgery alone group with 95% cure. Endovascular treatment alone led to cure in 50%, radiosurgery alone led to cure in 33.3%, and multimodal strategies lead to a 56.2% cure rate.17

As inflammation is thought to play a role in the pathogenesis of AVM, the use of anti-inflammatory medications has been trialed as treatment. Doxycycline has shown success in some studies. Additionally, immunosuppressant drugs have been increasingly trialed.6 One study examined the use of Bleomycin Electrochemotherapy, which both induces apoptosis of targeted cells, and delivers electric pulses which further aided in targeted vascular destruction.27

At different disease stages

Acute: Observation, medical management, and emergent surgical intervention may be warranted based on AVM characteristics and clinical presentation. With acute hemorrhagic presentation, prompt life saving measures to prevent further neurologic compromise are essential. Definitive treatment may be delayed to allow for characterization, healing, or adjuvant therapy as part of a staged treatment plan due to the size, location and complexity of the lesion.15 In that same pediatric study mentioned above out of 46 patients 23 or 63% required urgent invasive management in the acute care setting including EVD placement (28.3%), craniotomy (21.7%), or ICP monitoring (13%).17

Subacute: Once medically stable depending on the location and type of vascular malformation, subsequent imaging studies are done to guide further need for surgical intervention. 54.3% of patients in the pediatric AVM study by Lioi experienced at least one clinically significant event during follow-up ranging from hydrocephalus to new onset seizures and rebleeding. 17 It is also vital to start therapy service to address functional impairments.

Chronic/stable: Long term follow-up and monitoring is necessary due to risk of recurrence and re-rupture. Despite radiological cure of AVM in over 75% of the pediatric patients studied with AVM; one third experienced clinically significant events during follow up including neuropsychological deterioration, seizures and rebleed more than 9 years from initial treatment.17 Rehabilitation strategies apply as with any other cause of acquired brain or spinal cord injury. (Please see rehabilitation care for pediatric stroke and spinal cord injury). 87% of patients in the pediatric study by Lioi et al did achieve a favorable outcome on the modified Rankin scale at 5-year post intervention. It is also vital to utilize formal neuropsychology assessment as attention, mood regulation and executive function have found to be impacted with AVM.17

Coordination of care

To date, no definitive guidelines exist for the management of brain and spinal AVMs. Multispecialty interdisciplinary care is vital given the complex nature and course of AVMs.28 This pertains to both medical/surgical management of the vascular lesion as well as in the rehabilitation management of acquired brain and spinal cord injury.

Patient and family education

Patient and family education as to the diagnosis and possible treatment options, with a good understanding of its risk and benefits, as well as the need for subsequent follow-up and rehabilitation cannot be over-emphasized.

Measurement of treatment outcomes

Outcome measures are mainly based on prevention of rebleeding and subsequent further neurologic deficits. Rates of recurrence for pediatric brain AVMs are relatively high as compared to adults, up to 13.5% even after complete obliteration.29 This underscores the importance of long term follow up with repeat imaging. Functional outcome measures such as the WeeFIM may be used for those who develop persistent neurological deficits with resultant functional impairments.

Translation into practice

AVM ruptures in children can cause debilitating neurological deficits such as dystonia, hemiparesis, spasticity, hydrocephalus, epilepsy, and ataxia.28 It can be assumed from our knowledge of stroke and spinal cord injury that rehabilitation is vital during the recovery process.

Cutting Edge and Emerging Concepts

Currently, studies are underway to better predict natural history and subsequent risk of AVM rupture. This includes utilization of beta-blockers for treatment of AVMs as well as research into specific biomarkers that can aid in risk assessment and treatment selection. Multimodality planning with a multidisciplinary team approach has been emphasized to customize the best treatment approach for each individual. The use of noninvasive radiosurgery seems to have surpassed microsurgery and has been shown to have reasonable obliteration rates.15 A longitudinal study following patients over a five-year period following stereotactic radiosurgery had a obliteration rate of 60.6% and a hemorrhage rate of 0%, suggesting it is effective and safe.25 Current studies show that the new Supplemented Spetzler-Martin (Supp-SM) grading system has superior predictive ability on surgical outcomes when compared to the Spetzler-Martin grading scale (SMS). The Supplemented Spetzler-Martin adds history of hemorrhage, age, and nidus type.30 Additionally, the use of arterial spin labeling MRI is showing some potential as a noninvasive diagnostic and follow-up study of pediatric AVMs with emerging evidence as a useful radiation- and injection-free noninvasive biomarker to objectively delineate treatment effect and aid in treatment planning.26

Gaps in Evidence-Based Knowledge

Neurovascular lesions remain a considerable cause of morbidity and mortality. While noninvasive brain imaging has led to an increase in identification of these lesions, significant gaps remain in management decisions given its poorly defined natural history and relatively low incidence, making it difficult to do prospective studies to attain more rigorous data.26

References

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  2. Novakovic RL, Lazzaro MA, Castonguay AC, et al. The diagnosis and management of brain arteriovenous malformations. Neurol Clin. 2013;31(3):749-763.
  3. Toulgoat F, Lasjaunias P. Vascular malformations of the brain. Handb Clin Neurol. 2013;112:1043-1051.
  4. Harrigan MR, Deveikis JP. Arteriovenous Malformations. Handbook of Cerebrovascular Disease & Neurointerventional Technique. 2013:571-602.
  5. Ozpinar A, Mendez G, Abla AA. Epidemiology, genetics, pathophysiology, and prognostic classifications of cerebral arteriovenous malformations. Handb Clin Neurol. 2017;143:5-13.
  6. Ricciardelli AR, Robledo A, Fish JE, Kan PT, Harris TH, Wythe JD. The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations. Biomedicines. 2023;11(11):2876-2876. doi:https://doi.org/10.3390/biomedicines11112876.
  7. Charlie Chia-Tsong Hsu, Krings T. Symptomatic Developmental Venous Anomaly: State-of-the-Art Review on Genetics, Pathophysiology, and Imaging Approach to Diagnosis. Published online March 30, 2023. doi:https://doi.org/10.3174/ajnr.a7829.
  8. O’Lynnger TM, Al-Holou WN, Gemmete JJ, et al. The effect of age on arteriovenous malformations in children and young adults undergoing magnetic resonance imaging. Childs Nerv Syst. 2011;27(8):1273-1279.
  9. 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.
  10. Lee YJ, Terbrugge KG, Saliou G, et al. Clinical features and outcomes of spinal cord arteriovenous malformations: comparison between nidus and fistulous types. Stroke. 2014;45(9):2606-2612.
  11. Boon LM, Enjolras O, Mulliken JB, et al. Vascular Malformations: Wiley-Blackwell 2011.
  12. Garcia JH, Winkler EA, Morshed RA, et al. Factors associated with seizures at initial presentation in pediatric patients with cerebral arteriovenous malformations. J Neurosurg Pediatr. 2021:1-6.
  13. Yamada S, Takagi Y, Nozaki K, et al. Risk factors for subsequent hemorrhage in patients with cerebral arteriovenous malformations. J Neurosurg. 2007;107(5):965-972.
  14. LoPresti MA, Giridharan N, Kan P, et al. Natural history of high-grade pediatric arteriovenous malformations: implications for management options. Childs Nerv Syst. 2020;36(9):2055-2061.
  15. Ajiboye N, Chalouhi N, Starke RM, et al. Cerebral arteriovenous malformations: evaluation and management. ScientificWorldJournal. 2014;2014:649036.
  16. Patrik Järvelin, Henri Pekonen, Koivisto T, Juhana Frösen. Recurrence of arteriovenous malformations of the brain after complete surgical resection. Kuopio University Hospital experience and systematic review of the literature. Neurosurgical Review. 2023;46(1). doi:https://doi.org/10.1007/s10143-023-02001-8.
  17. Lioi Francesco M.C., De Benedictis A, Luglietto D, et al. Long-term outcomes in pediatric brain AVMs: beyond radiological cure. Brain and Spine. 5(2025) 105609.
  18. Saliou G, Tej A, Theaudin M, et al. Risk factors of hematomyelia recurrence and clinical outcome in children with intradural spinal cord arteriovenous malformations. AJNR Am J Neuroradiol. 2014;35(7):1440-1446.
  19. Orme CM, Boyden LM, Choate KA, et al. Capillary malformation–arteriovenous malformation syndrome: review of the literature, proposed diagnostic criteria, and recommendations for management. Pediatr Dermatol. 2013;30(4):409-415.
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  21. Priyadarshi A, Luig M. Vein of Galen aneurysmal malformation: Pit-falls in the diagnosis. Australas J Ultrasound Med. 2016;19(4):160-163.
  22. Mouchtouris N, Jabbour PM, Starke RM, et al. Biology of cerebral arteriovenous malformations with a focus on inflammation. J Cereb Blood Flow Metab. 2015;35(2):167-175.
  23. Beslow LA, White AJ, Krings T, et al. Current Practice: Rationale for Screening Children with Hereditary Hemorrhagic Telangiectasia for Brain Vascular Malformations. AJNR American journal of neuroradiology. 2024;45(9):1177-1184. doi:https://doi.org/10.3174/ajnr.A8195.
  24. Ai X, Ye Z, Xu J, et al. The factors associated with hemorrhagic presentation in children with untreated brain arteriovenous malformation: a meta-analysis. J Neurosurg Pediatr. 2018;23(3):343-354.
  25. 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.
  26. Hak JF, Boulouis G, Kerleroux B, et al. Noninvasive Follow-up Imaging of Ruptured Pediatric Brain AVMs Using Arterial Spin-Labeling. AJNR Am J Neuroradiol. 2022.
  27. Muir T, Bertino G, Ales Groselj, et al. Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report. Radiology and oncology. 2023;57(2):141-149. doi:https://doi.org/10.2478/raon-2023-0029.
  28. Sugiyama T, Grasso G, Torregrossa F, et al. Current Concepts and Perspectives on Brain Arteriovenous Malformations: A Review of Pathogenesis and Multidisciplinary Treatment. World Neurosurg. 2022;159:314-326.
  29. Hak JF, Boulouis G, Kerleroux B, et al. Pediatric brain arteriovenous malformation recurrence: a cohort study, systematic review and meta-analysis. J Neurointerv Surg. 2022;14(6):611-617.
  30. Frisoli FA, Catapano JS, Farhadi DS, et al. Spetzler-Martin Grade III Arteriovenous Malformations: A Comparison of Modified and Supplemented Spetzler-Martin Grading Systems. Neurosurgery. 2021;88(6):1103-1110.

Original Version of the Topic

Rochelle T. Dy, MD, Catherine Schuster, MD. Vascular malformations of the brain and spine in children. 9/14/2015

Previous Revision(s) of the Topic

Catherine Schuster, MD, Michael Stoltz, BS, David Means, BS, Rochelle T. Dy, MD. Vascular malformations of the brain and spine in children. 10/8/2019

Saylee Dhamdhere, MD, Kayla Williams, MD, Nikhil Gopal, MBBS, Warona Mathuba, BS, Rajashree Srinivasan, MD, MBBS. Vascular Malformations of the Brain and Spine in Children. 1/12/2023

Author Disclosure

Stacy M Stibb, DO
Nothing to Disclose

Vanessa Molina, BS
Nothing to Disclose