Continuing Education Activity

Arteriovenous malformations (AVMs) are abnormal fistulas between arteries and veins without an intervening capillary bed. High arterial flow directly into venous structures can lead to disruption of the venous walls and ultimately cause fatal hemorrhage. Intracranial AVMs are most commonly diagnosed during work-up for an acute intracerebral hemorrhage but are also often found incidentally during evaluation of conditions such chronic headaches and seizures. The most well-known classification system to describe them is the Spetzler-Martin grading scale.This system, initially described in 1986, uses the AVMs size, location in the eloquent or non-eloquent cortex, and description of either superficial or deep venous drainage to estimate surgical risk. This activity describes the evaluation, diagnosis, and management of AVMS and highlights the role of team-based interprofessional care for affected patients.

Objectives:

• Identify the patophysiology of arteriovenous malformations.
• Describe the typical patient presentation of an arteriovenous malformation.
• Outline the management options available for arteriovenous malformations
• Summarize interprofessional team strategies for improving care and outcomes in patients with arteriovenous malformations.

Introduction

Arteriovenous malformations (AVMs) are abnormal fistulas between arteries and veins without an intervening capillary bed. High arterial flow directly into venous structures can lead to disruption of the venous walls and ultimately cause fatal hemorrhage.[1] Intracranial AVMs are most commonly diagnosed during workup for an acute intracerebral hemorrhage but are also often found incidentally during the evaluation of conditions such as chronic headaches and seizures.[2]

Cerebral AVMs are heterogeneous entities that differ significantly in size, location, feeding, and draining vessels. The most well-known classification system to describe them is the Spetzler-Martin grading scale.[3] This system, initially described in 1986, uses the AVMs size, location in the eloquent or non-eloquent cortex, and description of either superficial or deep venous drainage to estimate surgical risk.

Etiology

Animal and human studies of arteriovenous malformations (AVMs)have implicated abnormalities in vessel wall thickness, lack of tight junctions and endothelial continuity, and splitting of the elastic lamina.[4] These findings reflect underlying cellular and molecular changes affecting angiogenesis and inflammation that lead to their development.[5]

Cerebral AVMs are seen both in sporadic cases as well as in genetic syndromes. Concerning genetic associations, studies on syndromic cases have yielded valuable insight. For example, Osler-Weber-Rendu syndrome, the most common syndrome linked with cerebral arteriovenous malformations, has correlated with the insufficiency of transforming growth factor-beta (TGF-beta) signaling genes such as SMAD4 and ENG.[6] Cobb syndrome is another condition in which patients diagnosed with spinal AVMs have abnormal expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP-9), and platelet endothelial cell adhesion molecule 1 (PECAM-1).

Several studies have examined the role of overexpression of genes involving vasculogenesis such as VEGF, angiopoietin-2, Notch4, and MMP-9 in the development and a predisposition to rupture of cerebral AVMs.[7][8][9]

Epidemiology

A systematic literature review by Abecassis and colleagues found the incidence of cerebral arteriovenous malformations (AVMs) ranging from 1.12 to 1.42 cases per 100,000 person-years.[10] Between 36% to 38% of new cases present as a first-time hemorrhage.[10] Annual rupture risk for AVMs overall has been reported in a meta-analysis by Gross and Du as 3.0%, with a rate of 2.2% of cases per year for the unruptured subset at 4.5% per year for the ruptured subset.[11] 

Risk factors associated with a higher risk of AVM rupture include prior hemorrhage, deep AVM location, exclusively deep venous drainage, and associated aneurysms.[11] 

When deep location, deep venous drainage, and prior hemorrhage are all present, a study by Stapf and colleagues reported an annual rupture rate as high as 35.5%.[12] Another meta-analysis by Kim and colleagues found an overall annual hemorrhage rate of 2.3%, with a 1.3% rate for unruptured AVMs and a 4.8% rate for previously ruptured AVMs.[13] Smaller AVMs may have a greater risk of rupture than large AVMs due to higher feeding artery pressure, though this is not the case in all studies.[11][14] A Randomized Trial of Unruptured Brain AVMs (ARUBA) trial found a 2.2% annual risk of hemorrhage for unruptured cerebral AVMs.[15]

Pathophysiology

While arteriovenous malformations (AVMs) were traditionally thought to represent congenital lesions resulting from disordered embryogenesis, other studies have supported the notion that they can also develop postnatally.[16] Altered flow dynamics, structural vascular abnormalities, and underlying molecular mechanisms all play a role in the development of AVMs.[17] Feeding artery pressures may predispose to rupture, possibly due to increased stress on vessel walls.[1] Abnormal venous architecture and venous hypertension also carry implications in the development and rupture of AVMs.[1] One theory purports that AVMs form when a venous occlusion occurs, and blood flow becomes redirected through alternative, preformed connections.[1]

Histopathology

Histopathological examination shows thin- and thick-walled channels connecting arteries and veins without intervening capillary beds. Typically, there is also no intervening normal brain tissue.

History and Physical

The most frequent presentation of brain arteriovenous malformations (AVMs) is a hemorrhage. Other forms of presentation include headache, seizures, bruit, and neurologic deficits (related to local mass effect or ischemia from steal phenomenon).

Following the identification of an AVM, a thorough history and neurologic exam are imperative to determine further workup and treatment for these patients. Age, medical comorbidities, and use of any antiplatelet or anticoagulant medications are essential parts of determining surgical candidacy. In patients presenting with hemorrhage, it is important to also assess for risk factors of related aneurysms (smoking history, family history). History and physical exam may also provide insight as to associated syndromes such as Osler-Weber-Rendu syndrome.

Evaluation

Aside from a thorough history and physical exam, appropriate imaging studies are also essential in the management of cerebral arteriovenous malformations (AVMs). Most patients have a computed tomography (CT) and magnetic resonance imaging (MRI) of the brain to evaluate hemorrhage, ischemia, and anatomy. The most important study for pre-operative evaluation is a catheter angiogram to elucidate anatomy and hemodynamics.

Treatment / Management

The primary treatment modalities for cerebral arteriovenous malformations (AVMs) include surgical resection, endovascular embolization, stereotactic radiosurgery (considered for small lesions < 3 cm), or a combination of the above. 

For unruptured brain AVMs, the ARUBA trial compared medical management alone to medical management along with prophylactic intervention (surgical, endovascular, radiosurgical, or a combination). Out of a total of 223 patients with a mean follow-up of 33.3 months, the primary endpoint of death from any cause or stroke occurred in 11 of 109 (10.1%) patients in the medical group compared with 35 of 114 (30.7%) in the interventional group. These data led to the discontinuation of the study after six years.[15] This study has been heavily criticized, especially regarding the 5-year follow-up period, which was too short to detect potential long-term benefits of interventions while capturing any procedure-related complications.[18] Other criticisms of the study included lack of patient heterogeneity, lack of standardization of the treatment arm, suspected selection bias, lack of subgroup analysis, and inappropriately drawn conclusions.[18] Therefore, the results of this trial should not bear much weight.

In any case, for patients diagnosed with AVMs of the central nervous system (CNS), prompt neurosurgical consultation, and subsequent discussion of treatment options with the patient and family are essential components of the treatment decision-making process.

Differential Diagnosis

Other vascular malformations seen in the CNS include cavernous malformations, capillary telangiectasias, and developmental venous anomalies. 

Radiation Oncology

Stereotactic radiosurgery is an option for select AVMs, particularly those with a nidus < 3 cm in diameter and for deep AVMs. Potential advantages include the ability to be performed as an outpatient, non-invasive approach, and no recovery period. Disadvantages include a 1- to 3-year latency period between radiosurgery and actual ablation of the lesion, during which time the risk of hemorrhage remains.

The Pittsburgh radiosurgery-based arteriovenous malformation-grading scale was developed to predict outcomes after radiosurgery.[19] This system has become widely adopted and correlates well with patient outcomes.

Consultations

Neurosurgical consultation is an essential part of management and treatment of arteriovenous malformations of the CNS. 

Enhancing Healthcare Team Outcomes

Neurosurgical consultation is a crucial part of the work-up and management of arteriovenous malformations (AVMs) of the CNS.

Overall, medical condition, age, vascular anatomy, associated cerebral aneurysms, history of hemorrhage, and other risk factors all merit consideration during clinical decision-making. Risks and benefits of available treatment options (sole medical management, radiosurgery, endovascular embolization, surgical resection, or a combination of interventions) are unique to each patient and AVM and require discussion on a case-by-case basis. Clinicians and nurses need to work together to educate patients and their families regarding the management of potentially life-threatening diseases.