Arterio-Venous malformations (AVMs) are congenital vascular lesions characterized by an abnormal connection between arteries and veins that lack an intervening capillary bed, resulting in direct arteriovenous shunting. It is the most common of the four types of vascular malformations in the central nervous system which also include developmental venous anomalies (DVA), cavernous malformations (CM), and capillary telangiectasias.1,2,3
In general, the etiology of AVMs is complicated and not well understood. It was originally thought that AVMs arise due to failure around the third week of embryogenesis in the differentiation of vascular channels into mature arteries, capillaries, and veins. Newer studies have shown that AVMs may arise postnatally.4 Most theories suggest either a persistence of a primitive arteriovenous connection or development of such after the initial closure of the primitive connection.1,2 It is thought to have multifactorial causes with factors including genetic manipulation and angiogenic stimulation.5
The overall incidence of AVM is difficult to estimate as they are not often found unless complications arise. It has been stated that the present-day incidence rate is 1-1.5 per 100,000 people-years. Currently, the prevalence of AVMs in the general population is unknown. The estimated prevalence could be as high as 0.2% but is only found to be 0.02% with confirmed diagnosis.6 Although its over-all prevalence is low, cerebral AVMs are a main cause of intracranial hemorrhage in children (excluding hemorrhage in prematurity and early infancy), representing about 30-50% of pediatric hemorrhagic strokes.1,2,7 Spinal cord AVMs comprise 20% to 30% of all spinal vascular malformations and are the most common cause of nontraumatic intraspinal bleeding or hematomyelia.8
In general, they occur sporadically with rare familial incidence and few reports of its association with other abnormalities like Osler-Weber-Rendu disease and Sturge-Weber Syndrome.2,3 However, cerebral AVMs can be common in individuals with hereditary hemorrhagic telangiectasia. This autosomal-dominant disease is the most common genetic cause of cerebral AVM, and it carries of 10-25% lifetime risk of developing a cerebral AVM.9
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. It is still unclear why an AVM becomes hemorrhagic in children. It is theorized that these lesions are nonstatic in nature and rapid expansion can occur during times of growth, possibly related to angiogenic/vascular growth factors.2,7
In children, there is a higher incidence of AVM occurrence in the posterior fossa, the basal ganglia and thalamus, which are more prone to bleeding and may result in catastrophic outcomes.2 In the spinal cord, the nidus-type AVM have been associated with increased risk of bleeding and the fistulous-type typically present as progressive myelopathy due to its mass effect.8
The natural history of AVMs in the pediatric population is not well understood. It 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 symptom. Overall presentation of symptoms depends on location and extent of the brain or spinal cord involved, whether due to hemorrhage or ischemia as a result of compression from venous congestion. Risk factors for AVM hemorrhage include: previous history of hemorrhage (within 5 years), deep-seated or infratentorial, having an exclusive deep venous drainage, female sex, nidal-type, with associated aneurysm and a diffuse morphology.1,2,10
Secondary conditions and complications
Cerebral AVMs may present with intracranial hemorrhage, seizures, headache and focal neurologic deficits which may result in long-term disability. Neurologic symptoms are dependent on location within the brain or spinal cord, presenting as a stroke or progressive myelopathy.2,11
Acute hemorrhagic events in children have been associated with up to 25% morality rate.2 A hemorrhagic presentation is a significant independent predictor of future hemorrhage. The annual risk of rebleeding in children is 2%-4%, but may be up to 65% when projected over the child’s lifespan.2 In the spinal cord, lesions with persistent perimedullary veins and those located in the cervical and upper thoracic level appears to have a higher risk of rehemorrhage.12
2. ESSENTIALS OF ASSESSMENT
A thorough history is important with 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 symptoms. Characteristics of headache and back pain may be non-specific, although some may report persistence in a localized area.
A complete physical examination with focus on the neurological exam as one would do for a patient with a stroke or myelopathy is warranted, keeping an eye out for asymmetries and signs/symptoms of intracranial pressure or spinal cord compromise. Neurologic findings can include limb weakness/paralysis, ataxia, sensory, visual and cranial nerve abnormalities, mental status and cognitive impairments and bladder and bowel dysfunction. Presence of vascular skin lesions may be associated with some hereditary/genetic abnormalities like Osler-Weber-Rendu disease 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 the clinical functional assessment tools such as the Glasgow Coma scale, Peds NIHHS stroke scale, ASIA Impairment Scale for spinal cord injury and Functional Independence Measure for children. Cognitive and neuropsychological evaluation may also be needed.
There is no specific laboratory study for AVM’s; however, based on its presentation and secondary medical complications, one may monitor CBC, metabolic panel, renal panel and coagulation studies.
Definitive diagnosis and characterization of AVM is accomplished by Digital Subtraction Angiography (DSA), although Computed tomography (CT) is often the initial imaging performed to show presence of hemorrhage or any calcification.9 CT angiography can further detail the vascular nature of the hemorrhage and provide an estimate of the size, location and drainage of the AVM. Magnetic resonance imaging (MRI) with and without contrast, with magnetic resonance angiography (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. (Fig 1). These imaging studies may all be used in combination to compile a clearer picture of the AVM. DSA remains the gold standard, as it provides the greatest sensitivity and detail of all the imaging types.9
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 conditions. Cardiac work-up may be needed in cases of suspected cardiovascular compromise due to the shunting phenomenon in certain types of vascular malformations which are more commonly seen in developmental vein anomalies but less commonly with AVM’s.3
Early prediction of outcomes
AVMs are often diagnosed as an incidental finding versus 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. Nidus-type spinal cord AVMs had lower complete obliteration rate that may cause delayed rebleeding and clinical progression from hemorrhage to myelopathy and long term deterioration.11 Close monitoring of these lesions are necessary. 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, and diffuse morphology, and a high Spetzler-Martin (SM) grade have a higher risk of hemorrhage. 9,13
Depending on the neurologic sequela and resultant disability, ongoing physical, occupational and speech therapy 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.
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 accommodations and assistance may be required for mobility and activities of daily living.
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, which may pose as a stressful time for the patient and family and many would want to know the risk of recurrence of emergent symptoms.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Current treatment guidelines
Treatment depends on the nature and location of the lesion and findings at presentation weighing the risks and benefits of each therapy option. Therapy may be single or multi-modal, with an ultimate goal for lesion eradication. Treatment options include endovascular embolization via catheter delivery of liquid embolics or coils, microsurgical excision, and radiosurgery (e.g. Gamma knife). Embolization alone rarely represents a curative treatment. However, a reduction in the size of the nidus or AVM flow may enable the performance of radiosurgery or facilitate surgical removal. The Spetzler-Martin (SM) grading scale is utilized as a decision tool to estimate the risk of surgical resection by evaluating the AVM size, pattern of venous drainage and eloquence of brain location, with higher grades of 4 and 5 being associated with greater surgical morbidity and mortality. 2,11
At different disease stages
Acute: observation, medical management and emergent surgical intervention may be warranted especially in cases of acute hemorrhagic presentation as life saving measures and to prevent further neurologic compromise. Definitive treatment may be delayed at a later time to allow for healing, or may need to be staged due to the size, location and complexity of the lesion.
Subacute: depending on the location and type of vascular malformation, subsequent monitoring of the lesion with symptom presentation and imaging studies are done that will guide further need for surgical intervention with a goal of lesion obliteration and prevention of re-bleeding and further neurologic sequela. In some asymptomatic AVMs that are incidentally found, clinical observation with monitoring may suffice.
Chronic/stable: Long term follow-up is warranted given the risk of rebleeding. There is no set guideline as to how long monitoring needs to be. Neurologic deficits may persist for years or indefinitely. Any new or change in symptom would warrant additional imaging/workup to ensure stability of the vascular lesion. 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).
Coordination of care
There is currently no evidence-based management guideline available for neurovascular disease conditions in children. Multispecialty and interdisciplinary care is vital given its complex nature and course, and treatment is tailored on a case to case basis.14 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 cannot be over-emphasized.
Measurement of treatment outcomes
Treatment must prevent recurrence that can worsen clinical status. Outcome measures are mainly based on prevention of rebleeding and subsequent further neurologic deficits. Serial clinical assessments and imaging studies are done to guide treatment outcomes. Functional outcome measures such as the WeeFIM (for children) may be used for those who develop persistent neurological deficits with resultant functional impairments.
Translation into practice
4. CUTTING EDGE AND EMERGING CONCEPTS
The National Institute of Neurological Disorders and Stroke (division of the NIH) has active and ongoing research in the field of AVMs and other vascular malformations. Currently, studies are underway to better predict natural history and subsequent risk of 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. In the past decade, 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.11 A recent 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 gradually effective and safe. 15 Each case should still be treated on an individual basis, although radiosurgery is indicated in AVMs with higher risk of hemorrhage.9 Additionally, the use of arterial spin labeling MRI is showing some potential as a noninvasive diagnostic and follow-up study of pediatric AVMs.16
5. GAPS IN EVIDENCE BASED KNOWLEDGE
Neurovascular lesions remain a considerable cause of morbidity and mortality. While noninvasive brain imaging has led to 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. Research should focus on measurement of risk in regard rupture, re-rupture, treatment, or medical management. 17
- R Novakovic, M Lazzaro, A Castonguay and O Zaidat. The Diagnosis and Management of Brain Arteriovenous Malformations. Neurol Clin. 21 (2013) 749-63.
- T Niazi, P Klimo Jr, R Anderson and C Raffel. Diagnosis and Management of Arteriovenous Malformation in Children. Neurosurg Clin N Am. 21 (2010) 443-456.
- F Toulgoat and P Lasjaunias. Vascular Malformations of the brain. Handbook of Clinical Neurology. 112 (3). Elsevier. (2013) 1043-1051.
- Chen, Wanqiu, Eun-Jung Choi, Cameron M. Mcdougall, and Hua Su. “Brain Arteriovenous Malformation Modeling, Pathogenesis, and Novel Therapeutic Targets.” Translational Stroke Research3 (2014): 316-29.
- Laakso, Aki. “Epidemiology and Natural History of AVMs.” Brain Arteriovenous Malformations (2017): 37-49.
- Kim, Helen, Hua Su, Shantel Weinsheimer, Ludmila Pawlikowska, and William L. Young. “Brain Arteriovenous Malformation Pathogenesis: A Response-to-Injury Paradigm.” Intracerebral Hemorrhage Research Acta Neurochirurgica Supplementum (2011): 83-92.
- TM OLynnger, WN Al-Holou, JJ Gemmete, AS Pandey, BG Thompson, HJ Garton, etal. The effect of age on arteriovenous malformations in children and young adults undergoing magnetic resonance imaging. Child Nerv Syst. 27 (2011) 1273-79.
- Derdeyn, Colin P., et al. “Management of Brain Arteriovenous Malformations: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.” Stroke, vol. 48, no. 8, 22 June 2017.
- YJ Lee, K Terbrugge, G Saliuo, T Krings. Clinical Features and Outcomes of Spinal Cord Arteriovenous Malformations. Stroke. 45 (2014) 2606-12.
- S Yamanda, Y Takagi, K Nozaki, etal. Risk Factors for Subsequent Hemorrhage in Patients with Cerebral Ateriovenous Malformations. Journal of Neurosurgery 107 (2007) 965-972.
- N Ajiboye, N Chalouhi, R Starke and R Bell. Cerebral Arteriovenous Malformations: Evaluation and management. The Scientific World Journal. 14 (2014) 1-6.
- G Saliuo, A Tej, M Theaudin, M Tardieu, A Ozanne, M Sachet, D Ducreux and K Deiva. Risk Factors of Hematomyelia Recurrence and Clinical Outcome in Children with intradural Spinal Cord Arteriovenous Malformations. Am J Neuroradiol. 35 (2014) 1440-46.
- Ai, Xiaolin, et al. “The Factors Associated with Hemorrhagic Presentation in Children with Untreated Brain Arteriovenous Malformation: a Meta-Analysis.” Journal of Neurosurgery: Pediatrics, vol. 23, no. 3, 2019, pp. 343–354.
- T Ladner, J Mahdi, A Attia, etal. A Multispecialty Pediatric Neurovascular Conference: A Model for Interdisciplinary Management of Complex Disease. Pediatric Neurology 52 (2015) 165-173.
- Mohr, J P, et al. “Medical Management with or without Interventional Therapy for Unruptured Brain Arteriovenous Malformations (ARUBA): a Multicentre, Non-Blinded, Randomised Trial.” The Lancet, vol. 383, no. 9917, 2014, pp. 614–621.
- T Blauwblomme, O Naggara, F Brunelle, D Grevent, et al. Arterial spin labeling magnetic resonance imaging:toward noninvasive diagnosis and follow-up of pediatric brain arteriovenous malformations. J Neurosurg Pediatr (2015) 1-8.
- Meling, Torstein R. “To Treat or Not to Treat Brain AVMs—that’s Still the Question.” Acta Neurochirurgica8 (2017): 1451-454.
Original Version of the Topic
Rochelle T. Dy, MD, Catherine Schuster, MD. Vascular malformations of the brain and spine in children. 9/14/2015
Catherine Schuster, MD
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Michael Stoltz, BS
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David Means, BS
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Rochelle T. Dy, MD
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