Vascular malformations of the brain and spine in children

Author(s): Rochelle T. Dy, MD, Catherine Schuster, MD

Originally published:09/14/2015

Last updated:09/14/2015

1. DISEASE/DISORDER

Definition

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

Etiology

AVMs are thought to arise due to failure around the third week of embryogenesis, in the differentiation of vascular channels into mature arteries, capillaries and veins. 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

Epidemiology

The overall incidence of AVM is unknown as they are not often found unless complications arise. The estimated prevalence varies from 10-18 per 100,000. Despite the congenital nature of the disease, cerebral AVMs are less commonly discovered in children than in adults, with children composing only 3% to 19% of AVM patients.

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.1,2,4

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 Spinal cord AVMs comprise 20% to 30% of all spinal vascular malformations, and is the most common cause of nontraumatic intraspinal bleeding or hematomyelia.5

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.2,4

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.5

Disease progression

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.1,2,8

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.2,7

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.6

2. ESSENTIALS OF ASSESSMENT

History

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.

Physical

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.

Lab studies

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.

Imaging

Computed tomography (CT) is often the initial imaging performed, which may show presence of hemorrhage or any calcification. 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 or spinal 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). Conventional 4-vessel angiography remain the gold standard, so as not to miss very small AVMs not seen in MRAs, and is commonly used for treatment planning.1,6

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.7 Close monitoring of these lesions are necessary.

Environment

Depending on the neurologic sequela and resultant disability, ongoing physical, occupational and speech therapy may be warranted. Home and environmental modifications, along with adaptive equipments 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 accommodations and assistance may be required for mobility and activities of daily living.

Professional

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 grading system is utilized as a decision tool for microsurgical approach to estimate the risk of surgical resection of an AVM.2,7

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.9 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

Not applicable

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. 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 has surpassed microsurgery and has been shown to have reasonable obliteration rates.7 Additionally, the use of arterial spin labeling MRI is showing some potential as a noninvasive diagnostic and follow-up study of pediatric AVMs.10

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.

REFERENCES

  1. R Novakovic, M Lazzaro, A Castonguay and O Zaidat. The Diagnosis and Management of Brain Arteriovenous Malformations. Neurol Clin. 21 (2013) 749-63.
  2. 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.
  3. F Toulgoat and P Lasjaunias. Vascular Malformations of the brain. Handbook of Clinical Neurology. 112 (3). Elsevier. (2013) 1043-1051.
  4. 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.
  5. YJ Lee, K Terbrugge, G Saliuo, T Krings. Clinical Features and Outcomes of Spinal Cord Arteriovenous Malformations. Stroke. 45 (2014) 2606-12.
  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.
  7. N Ajiboye, N Chalouhi, R Starke and R Bell. Cerebral Arteriovenous Malformations: Evaluation and management. The Scientific World Journal. 14 (2014) 1-6.
  8. 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.
  9. 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.
  10. 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.

Author Disclosure

Rochelle T. Dy, MD
Nothing to Disclose

Catherine Schuster, MD
Nothing to Disclose

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