AVMs are compact collections of abnormal, thin-walled vessels that connect dilated arteries to veins without an intervening capillary network. These persistent primitive connections between arteries and veins are formed during the late somite stages of the fourth embryonic week; they develop from the sinusoidal vascular network that perfuses the early developing telencephalon. The absence of capillaries produces a low-resistance shunt, which results in rapid arteriovenous shunting within the malformation.

Patients with cerebral AVMs most commonly present as a result of spontaneous intracerebral hemorrhage (up to 61% of cases) during late childhood (37) or as a young adult (38), but affected patients can present at any age or, rarely, with seizures (39). Intraparenchymal hemorrhage can cause significant injury at any age, with 30% to 50% neurological morbidity and 10% mortality (40). Consequently, a premium has been placed upon identification and treatment of AVMs at major neurosurgical centers throughout the world.

The prevalence (total number of cases in a population at a given time) of AVMs has been estimated in autopsy series between 0.06% and 0.11% (38,41,42,43). Symptomatic AVMs were detected in 1 per 100,000 person-years, and prevalence was inferred from the incidence data to be less than 10 per 100,000 in a US population study (44,45) and 5 per 100,000 in Australia (46). Thus, although the precise numbers are not known, it seems that a significant percentage of AVMs become symptomatic during the average human lifetime, usually due to hemorrhage (38,46,47).

The vascular channels of AVMs that develop instead of normal capillaries are characterized by fibrointimal thickening and elastic tissue disorganization (48). These features probably take time to develop and, thus, classic brain AVMs (those with the classic tangle of vessels that compose the nidus) are not typically seen before birth or in early infancy. No classic AVMs have been described prenatally, although three fetal cases with pial fistulas (direct connections between artery and vein without the tangle of abnormal vessels) have been identified (40). In neonates, AVMs are generally seen as direct arteriovenous communication without intervening nidus. Thus, AVMs seem to evolve, not becoming fully developed until later in life (49). No definite genetic linkage has been identified with the exception of Rendu-Osler-Weber (50) and Wyburn Mason syndromes (51). Birth-related or other trauma has been suggested as an inciting event (52), but this is not supported by experimental data. Dysautoregulation of vascular growth factors has been implicated in the subsequent development and maturation of the vascular malformation (53). De novo development of AVMs has rarely been documented in children or adults (54,55).

AVMs can increase in size with age, as a result of increase in size of the nidus and progressive dilation of the feeding arteries and draining veins. Astrogliosis and atrophy is often seen in surrounding brain tissues. This was at one time thought to be a consequence of low-resistance shunting of blood through the nidus, causing parenchymal hypoperfusion (vascular steal). However, current thought suggests that edema and subsequent parenchymal injury results from venous stenosis/venous
hypertension, caused by high pressure and shear stresses from turbulent blood flow and consequent stenosis in draining veins (56,57). Thus, contrary to earlier descriptions, AVMs can have mass effect unassociated with hemorrhage. Rapid flow in the feeding arteries may result in the development of arterial aneurysms, both in the same distribution as classic berry aneurysms (circle of Willis) and in feeding arteries (pedicle and nidal aneurysms) close to the malformation (Fig. 12-1). In addition, varices (venous aneurysms) can develop upstream to the stenosis and cause hemorrhage if they rupture. As a result of all these factors, AVMs are the vascular malformations that most commonly cause neurological defects other than seizures, despite the fact that they are not the most common form of vascular malformations.

Patients with AVMs usually present with seizures, recurrent headaches, progressive neurological deficits, hydrocephalus, or hemorrhage. Approximately 20% become symptomatic before the age of 20 years (37). The mortality associated with the initial rupture of an AVM is 10%, with morbidity between 30% and 50% (36,58). Morbidity and mortality increase with each subsequent hemorrhage.

AVMs are the cause of up to 40% of spontaneous intracranial hemorrhages (2,59,60), most of which occur in the cerebral parenchyma. However, superficial malformations can rupture into the subarachnoid space and deep malformations may cause intraventricular hemorrhage. Symptomatic vasospasm and rebleeding are relatively rare unless the source of hemorrhage is an associated aneurysm. The risk of rehemorrhage from an AVM has been estimated to be higher in children than adults (58). In children less than 15 years of age, AVMs are the most common cause of spontaneous intracranial hemorrhage and account for 20% of all strokes (2).

Seizures occur in approximately 70% of patients with AVMs, with one half of the seizures being generalized (61); most patients are well controlled with anticonvulsants. Seizures are most common in AVMs that are located in the cerebral cortex and have associated varices. Their
cause is probably cortical injury and gliosis from previous hemorrhage (62) or venous ischemia (63,64).

Chronic recurrent headaches may be the presenting symptoms in some patients with AVMs, and are likely caused by engorged dural vessels. Headaches are most common in cortical/subcortical AVMs and in those that develop stenosis or occlusion of feeding cerebral vessels. AVMs located in the occipital region are associated with an increased frequency of migraines, often with visual symptoms during the migrainous episodes.

Progressive neurological deficits occur in a small percentage of children with AVMs, particularly if the malformation is large and located close to the motor cortex. The probable cause of neurologic deficit is venous hypertension, as increased venous pressure is transmitted through the AVM, impairing the venous drainage of normal brain sharing the same venous drainage pathway (65). This mechanism has long been understood as a cause for neurologic deficit in the spinal cord, but has only recently been recognized in the brain. Venous hypertension may be so marked that it impairs the resorption of cerebrospinal fluid, producing hydrocephalus (see Chapter 8).

Finally, with the advent of CT and MRI, asymptomatic AVMs are more commonly discovered.

The diagnostic workup of vascular malformations usually includes x-ray CT, MRI, and MRA. CT evaluation (using a low dose, see Chapter 1) remains the standard of care as an effective screening technique to study patients with suspected intracranial hemorrhage in the acute phase (<2 weeks). A noncontrast CT scan may reveal abnormal high density of the associated acute hematoma or calcifications within the interstices of the AVM. In addition, CT may show acute subarachnoid hemorrhage, which sometimes accompanies rupture of a superficial AVM or an associated aneurysm. During the ensuing 1 to 2 weeks after hemorrhage, the subacute hematoma becomes progressively isointense with brain and may show a rim of peripheral enhancement following intravenous contrast administration; this appearance is nonspecific and may be mistaken for infection, cavernoma, or neoplasm. While MRI has largely supplanted CT in the evaluation of AVMs, vascular malformations may be detected on contrast-enhanced CT as a region of enhancement adjacent to a high-density, acute hematoma. CTA shows detailed resolution of the cerebral vasculature, but can be associated with significant radiation exposure. Its role in the architectural evaluation of AVMs remains undefined.

MRI is an excellent initial screening modality for the evaluation of intracranial AVMs (66,67). Fast-flowing intraluminal blood in AVMs appears as regions of decreased signal or “flow void” on spin-echo sequences. A tangle of serpiginous flow-void represents the nidus of the malformation (Fig. 12-1). Rapid flow within draining veins can be difficult to distinguish from feeding arteries in or around the nidus. The multiplanar capability of MRI helps to delineate the location of the malformation in relation to critical anatomic structures. Parenchymal hematomas evolve through a recognizable and often specific pattern of signal characteristics (see Chapter 4 [68,69]). The residua of previous hemorrhages adjacent to malformations remain detectable many years after hemorrhage as areas of very low intensity on T2 or T2^*-weighted images. In the subacute and chronic phases of intraparenchymal hemorrhage, MRI is more sensitive and specific than CT for the detection of blood products. In patients with AVMs, rapid sequence catheter angiography must still be performed to delineate the angioarchitecture, distinguish feeding arteries from draining veins, and to identify any associated arterial aneurysms or venous restriction that would be associated with a poorer natural history.

The decision to undertake treatment for symptomatic AVMs should consider the natural history of the disease and the projected risks and benefits of the therapy. A complete discussion of the natural history and current therapeutic options is beyond the scope of this book, and the reader should consult a more complete text for the discussion of management (70,71,72). Briefly, the therapeutic options fall into three categories: surgical excision, radiosurgery, and endovascular embolization or occlusion. Often, combinations of these techniques are utilized for the treatment of complex malformations.

With the improvement in microneurosurgical techniques, even large and complex malformations can be excised with relatively low morbidity and mortality (70,73). The nidus or core of the malformation infrequently contains cerebral parenchyma and, if the surgical excision is performed along the margins of the malformation with attention to preserving the surrounding brain, an excellent outcome can often be achieved. Total excision of the malformation is the goal of surgery, as prior studies have shown that subtotal resection or ligation of feeding vessels is inadequate to prevent subsequent hemorrhage (74,75).

Radiation therapy produces hyperplasia of the blood vessel walls; the AVM is completely obliterated in selected cases. To minimize the risk of radiation-induced damage to adjacent normal parenchyma, only focused techniques are utilized today, such as the Bragg-peak proton beam therapy or intersecting beam techniques using gamma knife or LINAC (linear accelerator) therapy units. Occlusion rates range from 35% to 92% depending on a number of variables including AVM size, location, and radiation dose. The results of radiotherapy have been quite encouraging with small (<3 cm) malformations (76,77,78,79,80). The major disadvantages of radiosurgical techniques include the difficulty in treating larger lesions, the 1 to 2 year latency before development of significant vascular intimal hyperplasia and fibrosis (during which interval the patient remains at risk for hemorrhage), and the risk of delayed radiation necrosis in the surrounding brain tissue.

Endovascular techniques have emerged as a third modality for the treatment of symptomatic intracranial malformations (81). Complete angiographic obliteration following embolization of large malformations is unusual; however, complete obliteration can be obtained with smaller AVMs (82). Endovascular embolization can palliate patients whose symptoms do not warrant more aggressive therapy or where the size or location of the malformation precludes more traditional forms of therapy. These procedures can now be performed with a low risk of complications and appear to make craniotomy for surgical resection safer (70,83). Patients who present with intractable unilateral headache frequently have recruitment of dural vascular supply to the malformation (82,84). These dural vessels can be selectively catheterized and embolized, often resulting in alleviation or resolution of headache. Patients with progressive neurological decline from arterial steal or venous hypertension can demonstrate clinical improvement following partial embolization of their malformation.

The vast majority of AVM embolization procedures performed at our institution are performed as a preoperative adjunct (70). The most commonly used embolization agent is the liquid acrylic, n-butyl cyanoacrylate. A relatively new embolic agent preferred by some neurointerventionalists called Onyx (eV3, Maple Grove, MN) is a precipitate of ethylene vinyl alcohol suspended in an organic solvent (DMSO). While high rates of nidal occlusion are possible with this agent, complication rates appear comparatively higher based on currently published series (85). By occluding the deep or inaccessible feeders to the malformation, surgical excision is facilitated (86). Preoperative embolization can reduce the size and pressure within the nidus, making subsequent surgical excision easier and reducing intraoperative blood loss (86).
In larger malformations, the adjacent brain parenchyma can lose its ability to autoregulate; thus, staged palliative embolization is used to gradually re-establish regulatory control in the microcirculation and prevent the development of normal perfusion pressure breakthrough (86). In reducing the size and rate of flow through a malformation, improved obliteration of AVMs may be achieved by radiosurgery, although posttreatment evaluation is warranted.

We and others (87,88) have identified a group of patients with solitary arteriovenous connections who present in childhood with hemorrhage or neurologic deficit (Figs. 12-2 and 12-3). All 15 patients were treated by transvascular embolization techniques with placement of either platinum coils or balloons at the fistula site. Fourteen of the fifteen patients were completely cured and the fifteenth patient underwent surgical excision without incident.

Malformations involving the vein of Galen are rare congenital connections occurring between intracranial arteries (usually thalamoperforator, choroidal, and anterior cerebral arteries) and the vein of Galen or other primitive midline vein (37,69). These connections can be large direct fistulas, numerous small connections, or a combination thereof. The cause of these connections is unknown. Some investigators have noted a strong association with venous anomalies (absent straight sinus, persistent falcine and occipital sinuses) and suggested that intrauterine straight sinus thrombosis with recanalization is responsible (69). Raybaud et al. demonstrated that the dilated primitive venous structure represents persistence of the embryonic median prosencephalic vein of Markowski (89). They suggested that early obstruction of the straight sinus might result in persistence of the primitive veins based upon the need for venous drainage pathways. Moreover, in our experience, vein of Galen malformations are associated with certain cardiovascular anomalies, most commonly aortic coarctation and secundum atrial septal defects (90).

Over 90% of the vein of Galen varices falls into the group called “choroidal” malformations (91). Choroidal malformations are arteriovenous connections from a plethora of vessels, usually numerous choroidal, pericallosal, and thalamoperforator vessels, to the anterior wall of the prosencephalic vein, resulting in a great deal of arteriovenous shunting (92,93); the consequence of the shunting is presentation as neonates with CHF. Choroidal malformations have the poorest prognosis, and are usually fatal without treatment. The second, less common, category of vein of Galen malformation is the so-called “mural” malformation (91). Mural malformations are characterized by fewer (usually one to four) but larger caliber connections with the prosencephalic vein; the posterior choroidal or collicular arteries are most commonly involved. Patients with mural malformations usually present in infancy with developmental delay, hydrocephalus, and seizures but mild or no signs of CHF. The treatment approach to these malformations varies although endovascular therapy has become the method of choice for both and offers a high rate of cure with low morbidity (94,95,96).

The clinical presentation of vein of Galen malformations can be categorized into three groups: (i) the neonate presenting with intractable CHF and loud intracranial bruit, (ii) the infant presenting with hydrocephalus and/or seizures, and (iii) the older child or young adult presenting with hemorrhage (97). As mentioned in the preceding section, patients in group 1 typically have choroidal malformations, whereas patients in groups 2 and 3 have mural malformations.

With improvements in quality and availability of prenatal imaging, many vein of Galen malformations are now diagnosed antenatally (98,99). Prenatal sonograms show a large hypoechogenic to mildly echogenic midline mass that is seen to have rapid flow on Doppler studies. MRI identifies the varix best (Fig. 12-4) and feeding vessels, and can be used to identify any associated structural abnormalities such as malformation or ischemic injury. If such a patient is identified, the interventional neuroradiology service must be alerted and available to provide assistance at the time of delivery and in the perinatal period. If the patient is found to have neonatal heart failure that is refractory to medical therapy, the neurointerventionalist may need to treat these patients (100).

If the vein of Galen malformation is not diagnosed prenatally, postnatal neuroimaging becomes critical to making the proper diagnosis. On imaging studies, the dominant feature of the vein of Galen malformation is the varix, which appears as a large mass in the incisural region, sometimes extending rostrally and anteriorly displacing the third ventricle (Fig. 12-4). On sonography, the varix will appear mildly echogenic on two-dimensional (2D) imaging and show turbulent flow on Doppler (Fig. 12-5); it is important to demonstrate continuity with the straight sinus or a persistent falcine sinus. Doppler studies may be useful to quantify the rate of flow within the varix for future reference. On CT, the varix will be iso- to hyperdense to brain prior to contrast administration (Fig. 12-5). Mixed attenuation may be seen if the varix is partially thrombosed. Areas of low attenuation (encephalomalacia, usually secondary to ischemia) and high attenuation (hemorrhage or dystrophic calcification) are often present in the brain parenchyma. The extent of brain injury should be carefully analyzed, and the parents informed of likely neurological and developmental sequelae, before therapy is begun. On MRI, the varix will be hypointense (Fig. 12-4) resulting from a loss of phase coherence of the mobile protons; mismapped signal will often be seen across the image in the plane of the phase-encoding gradient (Figs. 12-4 and 12-6). Feeding vessels will be identified on axial images as round areas of signal void in the ambient cisterns and on MRA as thin, curvilinear structures demonstrating flow-related enhancement and connecting to the varix. Areas of acute thrombosis will usually be isointense to brain on T1-weighted sequences and hypointense on T2-weighted sequences, whereas subacute thrombus will have a high intensity on both T1- and T2-weighted sequences. Thrombus of varying age usually lines the wall of the varix. Areas of damaged brain will typically appear hyperintense on T1-weighted images and hypointense on T2-weighted images in the neonate (Fig. 12-6); they may be difficult to see on FLAIR. Diffusionweighted images will show acute injury as regions of reduced diffusivity (Fig. 12-6). As the brain begins to myelinate, injured brain is better seen on T2-weighted images and then on FLAIR images (see explanations in Chapter 4). If left untreated, the fistula will continue to grow, recruiting additional blood supply and engendering new fistulas (Fig. 12-7).

Aggressive medical management of the cardiac failure associated with Galenic malformations is an essential adjunct to surgery or endovascular procedures, but medical management alone can rarely control the failure. Johnston’s review of neonates presenting with CHF revealed a mortality of 95%, and none were stabilized without surgical intervention (101). Surgical ligation of the anomalous connections has been described, but the results have been disappointing. In a review of 60 neonates treated by surgery, there were only six survivors; half of the survivors suffered from neurological deficits (101). Several series have reported the efficacy of endovascular procedures as a palliative or definitive treatment (102,103,104). In the early 1980s, these procedures consisted of free particle embolization. While the majority of these emboli would lodge in the fistulous connections, the risk of an errant embolus occluding a normal cerebral blood vessel was inversely proportional to the flow in the fistula, and the majority of these procedures were palliative. With the development of newer microcatheter delivery systems and embolic agents such as platinum coils (105), silk sutures, and liquid adhesives (91), superselective embolization of the fistula connections alone can be achieved (Figs. 12-5 and 12-8). Mickle et al. developed a technique where the torcular is surgically exposed, a small catheter is placed transvenously through the straight or falcine sinus into the involved vein of Galen, so metal coils can be deposited to diminish the arteriovenous shunting (104). Although useful in the presence of bilateral transversesigmoid or occipital sinus hypoplasia or occlusion, the transtorcular approach is not often necessary, as embolic agents can be placed via transfemoral venous access.

Over the past 10 years, 34 children with Vein of Galen malformations have been treated at our institution; 26 harbored the choroidal variety and presented with CHF (94,103,106,107). The first five patients were treated by craniotomy and attempted clipping of the feeding
vessels. All five patients died during or shortly after the surgery. The subsequent eight patients underwent transvascular embolization techniques. Six of the eight survived while two died despite treatment (103). Of the survivors, one suffered a severe middle cerebral infarct resulting from an errant embolus. Another had a partial visual field deficit, presumably a result of ischemic damage secondary to the underlying disease. The remaining patients are neurologically and developmentally normal with marked reduction of the fistula flow following treatment. At long-term independent follow-up, 61% of patients who survived their initial presentation were neurologically normal or demonstrated only minor developmental delay (96).

Improvements in technique and embolic materials allow vein of Galen malformations to be treated by transarterial or transvenous approaches. These new materials and approaches have resulted in a high rate of successful therapy; indeed, greater than 50% angiographic cure and 75% symptomatic improvement have been achieved in our recent patients, even in those with the high-flow choroidal malformations (106,107). Our cure rate is 100% for the less common mural type of vein of Galen malformation that most commonly presents later in infancy with hydrocephalus, seizures, and failure to thrive (94).

The following are the current recommendations for treatment of vein of Galen malformations presenting with severe congestive failure.
If the diagnosis is established prenatally, the delivery should be performed at an institution offering endovascular techniques to palliate the patient should intractable CHF develop. Severe heart failure in utero can result in polyhydramnios and hydrops fetalis, which can be an indication for induced delivery. Close coordination among the obstetricians, neurointerventionalists, neonatologists, and neurosurgeons is essential to optimize planning. Baseline ultrasonography with color flow Doppler should be performed to serve as a baseline for blood flow in evaluating the results of the endovascular techniques. If possible, umbilical arterial and venous catheters should be placed at the time of delivery to allow repeated vascular access for both diagnostic and therapeutic procedures. These indwelling catheters obviate the necessity for repeated femoral punctures in the fragile neonatal femoral artery. A CT or MRI should be performed to assess any parenchymal damage already produced by the congenital fistula, disclose hydrocephalus, which may require ventriculoperitoneal shunting, and serve as a baseline.

If intractable congestive failure persists despite aggressive medical management, angiography is performed to delineate the vascular anatomy. Palliative arterial embolization can be performed at this time, preferably with superselective catheterization of each feeding pedicle to reduce the risk of ischemic damage to normal surrounding brain. The embolization procedure may be repeated if congestive failure persists. If the congestive failure continues and further arterial embolization is considered risky or technically impossible, transvenous embolization may become necessary. An arteriogram is performed to localize the draining venous sinuses. If the draining venous sinuses are patent, the transfemoral or transumbilical routes can be used to access the varix. On rare occasions, when the lateral sinuses are absent or severely hypoplastic, surgical access to the intracranial venous system is necessary. A small burr hole is made over the draining falcine or straight sinus. A needle puncture is made into the sinus, a catheter advanced into the varix, and platinum coils deposited. These techniques can be curative or palliative. When palliative, they alleviate the congestive failure and allow the child to develop normally until a definitive treatment can be performed with further surgical or radiological techniques. MRI scanning is useful in our experience to assess brain development, the degree of thrombosis in the fistula site, and delayed development of hydrocephalus.

Cavernous malformations, also called cavernomas, are spherical collections of sinusoidal (cavernous) vascular spaces (36). Multiple cavernous hemangiomas are common and are associated with a familial predisposition. Three causative genes have been identified: KRIT1 (CCM1) at chromosome 7q11.2-q21 (108); CCM2/malcavernin at chromosome 7p13 (51,109); and PDCD10 (CCM3) at chromosome 3q26.1 (51,109). The proportions of families linked to these loci have been estimated to be close to 40% (CCM1), 20% (CCM2), and 40% (CCM3) (109). The proportion of patients with onset of symptoms before the age of 15 years is highest in the CCM3 group (109), but the number of affected individuals per family is lowest in this group. A 50% incidence of multiplicity is found in familial cases, whereas only a 13% incidence of multiplicity is found in sporadic cases (110,111,112,113). A significantly lower number of lesions are seen in CCM2 patients than in CCM1 patients (109).

Cavernomas are dilated, hypertrophied capillary beds containing dilated pockets of clotted and unclotted blood in various stages of oxidation. They have very slow circulation and arteriovenous shunting is not present; as a result, the caliber of feeding arteries and draining veins is normal. Venous malformations and capillary telangiectasias are often found in association with cavernomas (114,115), giving rise to speculation that venous hypertension from obstructed outflow of venous malformations initiates a cascade of events resulting in formation of cavernomas (114).

Symptoms from cavernomas depend upon their location and whether they cause hemorrhage. When located in the brainstem, they may cause acute neurological deficits such as hemiparesis, cranial neuropathy, or obtundation; these slowly resolve as the hemorrhage is resorbed. Those located in the cerebrum can cause seizures and, rarely, clinically manifested hemorrhage, but many are discovered incidentally. The importance of cavernomas lies in the high frequency with which they are detected on routine neuroimaging studies; they should not be mistaken for neoplasm and should always be considered a potential cause when small hemorrhages (<3 cm) are identified in young adults and children. In the absence of acute hemorrhage, cavernomas appear on noncontrast CT as slightly hyperdense masses with little mass effect. Mild enhancement is seen after contrast administration. Although this appearance is rather characteristic, it is not definitive, as slow growing tumors can exhibit the same CT appearance. On MRI, the characteristic appearance of nonhemorrhagic cavernoma is a sharply marginated, lobulated mass without surrounding edema. The lobules typically have different signal characteristics, with some areas having high signal intensity on T1- and T2-weighted images, others high signal intensity on T1 and low signal intensity on T2, and still others intermediate signal on T1 and variable signal on T2-weighted images (Fig. 12-9) (116). Although hemorrhagic tumors can rarely mimic this appearance in adults, the appearance seems rather specific in children. The specificity of MRI, without the necessity for administering intravenous contrast, makes MRI the imaging modality of choice in children with suspected cavernous malformations. If contrast is administered, a developmental venous anomaly may be identified in close proximity to the cavernoma, particularly in the brainstem (Fig. 12-9C-E) (114,117). The identification and location of the venous malformation may prove useful in surgical planning.

Some authors have proposed a system for grading cavernous malformations, based upon the signal intensity within the lobules of the mass (118). They postulated that some grades of cavernomas have a higher propensity for hemorrhage than other cavernomas. However, other authors have found no relationship between the grade of cavernoma and the incidence of hemorrhage (119). Kim et al. (120) classified lesions into four types (Table 12-2) based on MRI characteristics recently used to stratify patients into treatment groups. Surgery was performed for the following reasons: histological confirmation when in
question, decompression for mass effect causing neurological deficits, and intractable or chronic seizures (121).