OVERVIEW: What every practitioner needs to know

Are you sure your patient has a vascular malformation? What are the typical findings for this disease?

Cerebral arteriovenous malformations (AVMs) are congenital lesions of direct shunts between arteries and veins without intervening capillary beds. Based on their anatomy, AVMs are categorized as: (1) high-flow with few arterial feeders and draining veins; (2) diffuse, low-flow with multiple arterial feeders and draining veins; and (3) linear with multiple arterial feeders draining into a single vein.

Approximately 80% of pediatric patients with AVMs present initially with an intracranial hemorrhagic event. Fifteen percent of patients initially present with a chronic seizure disturbance.

Infants with AVMs may present with symptoms caused by mass effect from a large draining vein or hydrocephalus resulting from poor cerebrospinal fluid absorption secondary to high venous pressures. Other signs and symptoms include: ischemia, bruit, and macrocephaly (secondary to hydrocephalus).

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Would imaging studies be helpful? If so, which ones?

Computed tomography (CT) is typically the initial study performed, as most pediatric patients with AVMs present emergently with intracranial hemorrhage. CT angiography provides further anatomical detail, size, and location of the AVM, and is particularly useful when further imaging must be delayed for emergent surgical intervention.

Magnetic resonance imaging (MRI) with angiography (MRA) is often obtained to better localize and define the anatomy of the lesion, and rule out other possible hemorrhagic lesions (such as tumors or cavernous malformations).

Cerebral angiography remains the gold standard for diagnosing AVMs. Angiography reveals the anatomical characteristics of the lesion clearly, including visualization of the feeding arterials, draining veins, location and size of the nidus, presence of aneurysms, and venous anomalies like ectasia, varices, and stenosis. Angiography also allows assessment of blood flow through the AVM.

If you are able to confirm that the patient has a vascular malformation, what treatment should be initiated?

The primary goal of immediate therapy is to stabilize the child with respect to airway management and hemodynamic resuscitation. The clinical status of the patient will determine if emergent neurosurgical intervention is needed to address increased intracranial pressure (ICP).

If the patient is deemed stable, the primary goal of management is to control ICP and prevent re-hemorrhaging via strict blood pressure control and antiepileptic drug use, if needed. An urgent ventriculostomy may be required when there is hydrocephalus associated with the hemorrhage.

Definitive treatment for AVMs is encouraged to prevent recurrent hemorrhage and to restore neurologic function. The goal of treatment is to completely obliterate or resect the entire vascular lesion. To achieve this, a combination of microsurgical resection, endovascular embolization, and/or stereotactic radiosurgery may be employed. At this time, the optimal management among these three treatment modalities remains controversial and further prospective studies are needed. Currently, treatment planning is best determined on a case-by-case basis with a multidisciplinary team.

Surgical resection is typically the primary treatment in most patients as it offers an immediate cure and allows access to remove a hematoma. However, surgical resection may be associated with a high perioperative risk in the case of young infants, AVMs in deep-seated locations, or in higher-grade AVMs.

Recent technological advances have led to an increased use of endovascular treatment modalities for pediatric AVMs. Currently, embolization serves as a powerful adjunctive treatment to surgery and/or radiosurgery, but rarely provides a cure alone.

Stereotactic radiosurgery has been shown in several retrospective studies to achieve excellent obliteration rates and is a good treatment option when surgery is not possible. However, the long-term effects of radiation on the developing nervous system are not well known, and several studies have shown some perioperative complications and a few cases of radiation-induced malignancy.

What are the possible outcomes of vascular malformations?

AVM is the most common cause of spontaneous intraparenchymal hemorrhage in children. The annual rate of hemorrhage in children with AVMs is approximately 2%-4%. Given the higher incidence of posterior fossa AVMsand deep-seated AVMs in the pediatric population, a hemorrhagic event carries a 25% mortality risk and up to a 50% morbidity risk. Given the likelihood of eventual hemorrhage and the associated significant sequelae, treating even asymptomatic AVMs in children should be considered.

A previous history of hemorrhage and deep-seated or infratentorial AVM location have been consistently shown be risk factors for re-hemorrhage. Other possible risk factors include: female sex, associated aneurysms, diffuse AVM morphology type, and exclusive deep venous drainage.

What causes this disease and how frequent is it?

The prevalence of cerebral AVMs is less than 1% in the overall population. Children account for 3%-19% of patients treated for AVMs. While most AVMs occur sporadically, some studies have documented familial patterns and associations with other vascular syndromes. Compared with adult patients with AVMs, pediatric patients are more likely to have multiple AVMs with a predilection for the posterior fossa.

How do these pathogens/genes/exposures cause the disease?

The precise mechanism for AVM development is unknown; however, it is hypothesized that most malformations occur during the third week of embryogenesis. There is a defect in the formation of the capillaries between the arteries and veins, which results in elevated intraluminal venous pressures that produce ectasia and muscularization. Hybrid vessels with arterial and venous characteristics are formed.

It is believed that these lesions are dynamic and involved in angiogenesis and remodeling. Over time they enlarge and become symptomatic in childhood. Supporting this theory, some studies have shown an association between vascular endothelial growth factor and an increased risk of recurrent AVMs (Sonstein et al, 1996).

Despite AVMs traditionally being classified as congenital lesions, there are a growing number of case reports in the literature of acquired or “de novo” AVMs (Akimoto et al, 2003). This underscores our limited knowledge of AVM pathogenesis.

What is the evidence?

For further reading:

Rubin, D, Santillan, A, Greenfield, JP. “Surgical management of pediatric cerebral arteriovenous malformations”. Childs Nerv Syst. vol. 26. 2010. pp. 1337-44. (This review paper details the management options available for pediatric AVMs: preoperative embolization, stereotactic radiosurgery, and surgery; and discusses the complications and outcomes that can be expected with each option.)

Niazi, TN, Klimo, P, Anderson, RC, Raffel, C. “Diagnosis and management of arteriovenous malformations in children”. Neurosurg Clin N Am. vol. 21. 2010. pp. 443-56. (This review paper details the incidence, natural history, pathophysiology of pediatric AVMs. Of note, there is a section on relevant imaging studies that may be useful in diagnosing AVMs.)

Sonstein, WJ, Kader, A, Michelsen, WJ. “Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study”. J Neurosurg. vol. 85. 1996. pp. 838-45. (This study is a retrospective immunocytochemical analysis of 19 pediatric and adult AVMs. The authors demonstrate that VEGF an angiogenic factor, is associated with AVMs, and focal cellular staining of VEGF is associated with recurrent pediatric AVMs.)

Akimoto, H, Komatsu, K, Kubota, Y. “Symptomatic de novo arteriovenous malformation appearing 17 years after the resection of two other arteriovenous malformations in childhood: case report”. Neurosurgery. vol. 52. 2003. pp. 228-32. (This is a case report of a de novo AVM formation, which calls into question the natural history of AVMs.)