Surgical and Endovascular Management of Unruptured Arteriovenous Malformations

Introduction

Brain arteriovenous malformations (AVMs) are clusters of direct connections of arteries to draining veins without intervening capillary bed . The three main components of an AVM are one or more feeding arteries, the nidus at the site of the arteriovenous shunt, and the draining venous structures. AVMs are high-flow, low-resistant shunts due to a significant pressure difference between the arterial and venous sides. The pressure gradient and resultant high flow trigger remodeling of both arteries and draining veins. Arteries may be dilated and thin walled due to degeneration of the media and elastic lamina or thickened from endothelial proliferation, hypertrophy of the media, and changes in the basal lamina. Remodeling of the venous system is referred to as arterialization and includes thickening of the wall due to cellular proliferation without an organized elastic lamina . The draining veins commonly coalesce and form a major draining vein that eventually drains into a dural venous sinus.

AVMs are equally distributed between both hemispheres and are most commonly seen in the frontal and parietal lobes. Typically, AVMs are pyramid-shaped lesions with the base oriented toward the meninges and the apex pointing to the ventricle or deep into the brain. Three types of feeding arteries have been described and include terminal, pseudo-terminal, and indirect, or en passage, feeders . The surrounding parenchyma may be stained from previous hemorrhage and exhibits edema, necrosis, and gliosis as a result of ischemic injury related to vascular steal and venous hypertension. The overlying meninges tend to have a thickened, fibrotic appearance. While there is usually no functional brain tissue within the AVM, vessels may be separated by normal brain in diffuse lesions . These diffuse lesions with normal brain tissue intermingled between vessels are termed cerebral proliferative angiopathy and may be regarded as separate from classic AVMs . Other distinguishing features include lobar or hemispheric involvement, the absence of dominant feeders or flow-related aneurysms, transdural supply, proximal stenosis of feeding arteries, and the absence of large, early draining veins .

The pathogenesis of the AVM has not been fully elucidated. The predominant theory is that AVMs are congenital in nature and result from incomplete or abnormal resolution of a primitive vascular plexus that occurs during early embryogenesis . One explanation for why they are rarely detected in utero or in infants is that they first appear in utero but then continue to grow after birth. There is also growing evidences for postnatal de novo formation of these lesions . Recent studies have identified some of the factors that may be involved in the formation of AVMs. One of them is endothelin-1, found throughout the normal cerebral vasculature, and a potent vasoconstrictor that plays a role in vascular cell growth. Local repression of endothelin-1 within the AVM has been implicated in the pathophysiology underlying AVMs . Endothelial cell–specific tyrosine kinases that are normally found in developing embryonic blood vessels and vascular endothelial growth factor have been shown to be increased in association with AVMs .

Epidemiology and Natural History

Estimates of the prevalence of AVMs range from 0.005% to 0.6% in the general population and are believed to be about one-tenth as common as intracranial aneurysms . The incidence of first ever AVM hemorrhage is 0.51 per 100.000 person-years. AVMs are slightly more common in males and diagnosed at a mean age of 31.2 years . Up to 9% of patients have multiple AVMs and most of these patients have an associated vascular syndrome, such as hereditary hemorrhagic telangiectasia, Wyburn–Mason syndrome, or Sturge–Weber syndrome. While the majority of AVMs are sporadic, familial intracranial AVMs have also been reported .

Hemorrhage was the most common manifestation prior to noninvasive imaging and is most commonly located in the brain parenchyma often with intraventricular extension. Isolated intraventricular hemorrhage and subarachnoid hemorrhage may also occur . Cortically based AVMs are more likely to cause subarachnoid hemorrhage . The initial hemorrhage or hemorrhage during follow-up appears to carry a lower morbidity than intracranial hemorrhage from other causes . After hemorrhage, seizures are the second most common presenting symptom in about 20–25% of patients . In unruptured AVMs, specific angioarchitectural characteristics, such as location, fistulous component in the nidus, venous outflow stenosis, and the presence of a long pial course of the draining vein, are the strongest predictors of seizures .

Since 2000s the detection rates of unruptured AVMs have doubled due to availability and advances in imaging . Early retrospective data including previously ruptured AVMs estimated the annual rupture rate at about 4% . A more recent prospective study estimated rupture rates as low as 0.9% per year for unruptured AVMs . On the other hand, annual rupture rates may be as high as 34.4% for AVMs that have ruptured previously and are located deep in the brain with deep venous drainage . A meta-analysis estimated the overall annual rupture rate at 3% with a rate of rupture of 2.2% and 4.5% for unruptured and previously ruptured AVMs, respectively . The risk of rerupture is greatest in the first year after the initial hemorrhage at about 7% .

Features that pose increased risk of rupture include previous hemorrhage, particularly within the first year, deep location, deep venous drainage, associated aneurysms along the feeding vessels or within the nidus, location in the posterior fossa or intra- and periventricular, and venous outflow obstruction . The effects of AVM size on hemorrhage risks are controversial . Overall, an annual rupture risk of 2–4% is frequently cited for unruptured AVMs .