Headache is a nonspecific symptom. Some patients with AVMs that have a dural or posterior cerebral artery supply complain of headaches that resolve or improve after embolization.²⁵ Other patients with parietal lobe AVMs complain of worsening headache after embolization of anterior and middle cerebral artery feeders if there is a compensatory increased supply through the posterior cerebral arteries. Headaches by themselves do not represent an indication for treatment of patients with AVMs because the risk for hemorrhage is not changed from that of the general population.

Neurological Deficit

Up to 40% of patients with AVMs have neurological deficits,²⁶ but neurological deficits are uncommon in patients without history of hemorrhage. In our experience and in the reports of others, neurological deficits are present in more than half of patients.²⁵ Although arterial steal and mass effect have been implicated as possible causes,²⁷ venous congestion and ischemia are also probable mechanisms (Fig. 386-4).²⁵ Magnetic resonance imaging (MRI) has demonstrated changes in the venous drainage patterns of adjacent brain tissue with associated edema and partial thrombosis of draining veins of the AVM. If treated by partial embolization, these changes may be reversible in lobar AVMs causing progressive neurological deficits. Partial embolization of deep thalamic and basal ganglia AVMs in patients with progressive neurological deficits has been reported to result in stabilization in 27% and reversal of symptoms in 64% (see Fig. 386-3).²⁸ Further definitive therapy should be carried out to completely obliterate the AVM and remove the risk for future hemorrhage, when possible.

FIGURE 386-4 Palliative embolization of a left frontal and basal ganglia arteriovenous malformation in a patient with hemipareses and uncontrolled seizures. A, On axial T2-weighted magnetic resonance imaging (MRI), notice the malformation and the large draining veins. B, In the early and late phases of the lateral view of the left internal carotid angiogram, notice the malformation nidus (curved arrow) and multiple venous aneurysms (arrows, correlated with the MRI scan) in the deep venous drainage into the basal vein of Rosenthal and in the superficial drainage pathway into the sylvian vein leading through the vein of Trolard to the superior sagittal sinus. C, Axial T2-weighted MRI shows the area after multistage embolization. Notice the marked reduction in the size of the nidus and the venous outflow structures (compare with A). D, In lateral views of the venous phases of repeated carotid angiograms, notice the progressive reduction in size of the venous aneurysm in the basal vein of Rosenthal (arrow), the reduction in size of the venous aneurysm close to the nidus (arrow), and the reduction in size of the vein of Trolard. After palliative treatment, the patient showed clinical improvement with medical control of his seizures.

Architecture of the Arteriovenous Malformation

The vascular architecture of an AVM is an important consideration when planning treatment. Along with a thorough clinical examination, all AVM patients need detailed preoperative radiographic clarification of AVM anatomy, architecture, and associated aneurysms with MRI and high–frame rate digital subtraction angiography. The angiogram must delineate the characteristics of the AVM, including its arterial feeders, venous drainage, internal angioarchitecture, and associated vascular lesions, and it must define the collateral circulation and venous drainage pathways of the normal brain tissue. After a comprehensive evaluation has been performed, decisions can be made regarding the best management approach by comparing the natural history of the lesion with the intervention-related morbidity and mortality.

Determination of the accessibility of an AVM nidus starts with the patient’s past medical history and comorbid conditions. The extracranial or intracranial vasculature in patients with a history of congenital aortic or great-vessel malformations or occlusive disease may impair or preclude access of the microcatheter to the AVM. Further assessment during angiography is imperative because embolization in patients with AVM feeders that cannot be catheterized superselectively carries an increased risk for inadvertent occlusion of nontarget vessels and subsequent stroke. If nidal embolization is not performed, embolization often remains incomplete. In addition to the angioarchitecture of the nidus and feeders, determination of the hemodynamic properties of an individual AVM nidus is crucial for successful endovascular embolization. The number, morphology, and velocity of the arteriovenous shunting determine whether embolic material can be deposited selectively and safely in the nidus.

A decision to treat depends, in part, on the demonstration of areas of weakness in the angioarchitecture indicating potential instability. If there is an associated arterial aneurysm on the feeding pedicle or in the nidus, evidence of venous thrombosis, restriction of outflow, venous hypertension, venous pouches or dilations, venous pseudoaneurysm, or compromised venous outflow, treatment may be indicated and can achieve cure in certain circumstances, or targeted treatment as an adjuvant to definitive treatment may be beneficial (Fig. 386-5; see also Figs. 386-1 to 386-4).

FIGURE 386-5 Angiographic studies were undertaken to define safe embolization in a right parietal arteriovenous malformation. A, The lateral view of a superselective angiogram was obtained with a microcatheter (arrowheads) introduced through the left vertebral artery to the right posterior cerebral artery and into a distal parietal occipital cortical branch. Normal branching arteries supply the cortex with a normal parenchymal blush (arrow). The angiogram shows the distal supply to the malformation (curved arrow). Acrylic embolization will induce ischemia in the surrounding normal cortex. B, The microcatheter was navigated distally, directly to the vessel leading to the malformation (curved arrow) beyond the normal cortex. There is no parenchymal blush. Embolization of the nidus was performed without neurological deficit or diffusion abnormality, as assessed by follow-up magnetic resonance imaging. Precise anatomic studies may eliminate the need for functional testing before the deposition of acrylic. C and D, On lateral vertebral angiograms before (C) and after (D) embolization, notice the obliteration of the whole posterior compartment of the malformation, preservation of normal cortical branches (as in A), and immediate regression of collateral circulation to the nidus (arrow).

A number of radiologic variables have been associated with an increased risk for hemorrhage, including small AVM size, elevated feeding artery pressure, periventricular or intraventricular location, basal ganglia location, deep venous drainage, impaired venous drainage, single draining vein, intranidal aneurysm, multiple aneurysms, and vertebrobasilar blood supply.^15,²⁹^–³⁶

Data from the New York Islands AVM Hemorrhage Study, an ongoing, prospective, population-based survey to determine the incidence of AVM-related hemorrhage and the associated rates of morbidity and mortality in a zip code–defined population of 10 million people, showed that increasing age (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.03 to 1.08), initial hemorrhagic AVM manifestation (HR, 5.38; 95% CI, 2.64 to 10.96), deep brain location (HR, 3.25. 95% CI, 1.30 to 8.16), and exclusive deep venous drainage (HR, 3.25; 95% CI, 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% in patients without a hemorrhagic AVM manifestation, deep AVM location, or deep venous drainage to as high as 34.4% in those harboring all three risk factors.^6,^12,²⁰ The authors also studied predictors of residual dysplastic vessels on cerebral angiography after AVM treatment. The number of patients showing angiographic evidence of dysplastic vessels was significantly associated with increasing size of the AVM, and symptomatic postoperative intracerebral hemorrhage was associated with dysplastic vessels on the postoperative angiogram.³⁷

Location, Size, and Deep Venous Drainage

Although the location, size, and deep venous drainage of a malformation are important factors in determining the risks associated with microsurgical or radiosurgical therapy,³⁸ these factors are of lesser concern in the endovascular treatment of AVMs. In performing embolization of AVMs, meticulous technique is important to prevent embolization of nontarget tissue and stroke (see Fig. 386-5).

Associated Lesions

Aneurysms are associated with AVMs in 10% to 40% of patients.³⁹^–⁴² Such aneurysms may be flow related (i.e., proximal or distal on a feeder vessel), intranidal, or remote and apparently unrelated (Figs. 386-6 and 386-7; see also Fig. 386-2).³⁹^–⁴² This weakness represents a marker for future hemorrhage and increases the risk for hemorrhage from 3% to 7%.¹³ Patients with subarachnoid hemorrhage, intracerebral hemorrhage, or both and an angiographically demonstrated AVM with an associated aneurysm should have therapy directed first toward the lesion that is suspected to be the source of hemorrhage. In the presence of acute subarachnoid hemorrhage, the source of hemorrhage is often a feeding artery aneurysm. When an intracerebral hematoma exists, the more likely source of hemorrhage is the AVM, including nidal and perinidal locations (see Fig. 386-3). Enlarging pseudoaneurysms represent an unstable situation and deserve special attention to prevent early hemorrhage. Ventricular hemorrhage or parenchymal hemorrhage may be venous in origin.

FIGURE 386-6 Preoperative embolization of a right frontal arteriovenous malformation (AVM) with a proximal left superior hypophysial aneurysm. A, Anteroposterior angiographic views of the right and left internal carotid arteries (ICAs) demonstrate the malformation. A large, proximal venous aneurysm (arrow) and pial supply by the left anterior cerebral artery (ACA) and left middle cerebral artery (MCA) (curved arrows) cortical branches are seen. B, On the lateral angiographic view of the left common carotid, notice the left superior hypophysial aneurysm (arrow) and the left MCA pial supply (curved arrow). C, A road map lateral view was obtained during endovascular occlusion of the aneurysm with Guglielmi detachable coils (GDCs) (arrow). D, A live fluoroscopic, subtracted anteroposterior oblique view demonstrates the acrylic cast (arrowhead) achieved by embolizing the malformation through a left ACA feeding cortical branch. E, The final radiopaque acrylic cast (arrowhead) is seen on a radiograph of the skull. Notice the GDCs in the aneurysm (arrow). F, The lateral angiographic view of the left ICA after embolization but before surgery shows a small, residual malformation (open arrow) supplied by MCA frontal branches. The left hypophysial aneurysm is completely obliterated by the coils. G, The patient underwent uneventful microsurgical resection of the residual AVM. A follow-up lateral angiogram of the left ICA confirms complete removal and stable occlusion of the aneurysm.

FIGURE 386-7 Left, posterior-frontal arteriovenous malformation (AVM) and a large, proximal aneurysm. Combined endovascular occlusion of the aneurysm and AVM nidus was achieved before radiosurgery. A, On coronal T1-weighted magnetic resonance imaging (MRI), notice the high-flow cortical-gyral AVM. B, On global and magnified views of the anteroposterior angiogram of the left internal carotid artery (ICA), notice the proximal middle cerebral artery (MCA) aneurysm (arrow) and the cortical wedge shape of the malformation supplied by the left MCA and anterior cerebral artery distal branches. C, On the anteroposterior skull radiograph obtained after the last endovascular procedure, notice the radiopaque acrylic cast in the nidus (curved arrow) and coils in the proximal aneurysm (arrow). D, On the anteroposterior angiogram of the left ICA after the last endovascular procedure, notice the small, residual nidus deep within the white matter that drains to the deep venous system (small arrow). Complete occlusion of the MCA aneurysm (large arrow) was achieved, and the patient was treated by radiosurgery for the residual malformation. E, Postembolization coronal T1-weighted MRI shows the acrylic casting of the nidus as a bright signal secondary to Lipiodol in the acrylic mixture. F, In the follow-up study after radiosurgery, the anteroposterior arterial and venous phases of a left ICA angiogram show complete obliteration.

High blood flow to an AVM may induce aneurysms to form on feeding arteries. Such “flow-related” aneurysms may regress after complete or partial obliteration of the AVM by endovascular embolization, and regression is more likely to occur the closer the aneurysm is to the nidus of the AVM.⁴¹ If the aneurysm is located close to the AVM, it should be obliterated at the time of embolization. If the aneurysm is within the planned resection field, it may be clipped at the time of microsurgery. If on follow-up angiography 6 to 12 months after AVM embolization there is no regression of the associated aneurysm, active treatment of the aneurysm should be considered. We recommend treating large, irregular, proximal aneurysms early as part of a global treatment plan (see Figs. 386-4 and 386-5). However, the treatment-associated morbidity must be low to justify the procedure in light of the unknown natural history of the aneurysm in the absence of the AVM.

Treatment Goals

Endovascular embolization is most commonly used as an adjunct to surgical resection or stereotactic radiosurgery. Embolization can be performed as the sole treatment (curative or palliative) in carefully selected patients, or it may result in excessive complications.⁴³

Curative Embolization

Curative embolization is discussed in greater detail elsewhere in this textbook. The prerequisite for curing an AVM with endovascular embolization techniques alone is angioarchitecture that permits solid casting of the AVM nidus with permanent embolization material. Curative embolization is complete anatomic obliteration of the malformation by endovascular embolization, occlusion of the nidus, and early venous shunting, and it therefore requires the use of a permanent, nonbiodegradable embolic agent to form a cast within the pathologic angioarchitecture (Fig. 386-8). Particles or resorbable agents should not be used for curative embolization.

FIGURE 386-8 Right temporal micro–arteriovenous malformation (micro-AVM) in a patient with a large parenchymal hematoma. A, On the early arterial and capillary phases of a lateral angiogram of the right internal carotid artery (ICA), notice the posterior temporal micro-AVM (small arrow) with early cortical venous drainage (large arrows). B, On the early and late phases of a lateral superselective angiogram performed through a microcatheter (arrowheads) in a minimally enlarged superior temporal branch, notice the normal proximal cortical branches with a parenchymal blush and the distal cortical supply to the malformation (arrow). C, The early and late arterial phases of a lateral postembolization angiogram of the right ICA show that complete obliteration was achieved without residual nidus or early venous shunting.

In addition to the immediate postembolization angiogram, 6-month and, preferably, 12- to 24-month postprocedural angiograms are useful to confirm the durability of treatment. Long-term angiographic follow-up is needed to detect small remnants that may not have been appreciated on the immediate postembolization angiogram and to exclude recanalization caused by the radiopaque embolic material mixing with nonopaque autologous blood at the time of embolization.⁴⁴^–⁴⁶ Another important reason for long-term angiographic follow-up is to rule out the potential recruitment of arterial collaterals. These collaterals probably develop by a mechanism of nonsprouting angiogenesis because of insufficient penetration of the embolic agent and lack of obliteration of the nidal-venous junction, with occlusion of only the proximal feeding vessel. Although delayed thrombosis may occur, it must be confirmed on long-term angiographic follow-up.⁴⁴ After thrombosis of the venous outlets has occurred, no new veins can be recruited and a cure has been achieved. In general, when long-term follow-up angiography demonstrates complete obliteration of the malformation without residual opacification of the lesion, no arteriovenous shunting, and no stasis in the nidus, future recanalization is not expected.

Complete obliteration of an AVM is possible if it is a small lesion with a single pedicle and a terminal feeder (see Fig. 386-8). Our experience in total obliteration of small malformations is limited. We emphasize the need for late angiographic follow-up to confirm the lack of residual small shunts. With the future development of permanent embolic agents that are nonpolymerizing in nature, a higher cure rate may be achieved. Currently, studies using Onyx (ethylene vinyl copolymer, eV3, Plymouth, MN) have not demonstrated increased cure rates with primary embolization. In general, complication rates appear to be higher and patients are exposed to greater radiation,⁴⁷^–⁵¹ but further studies may demonstrate improved outcomes.

Palliative Targeted Embolization

Palliative embolization generally has limited application because it does not completely remove the risk for hemorrhage. The rationale for partial embolization might include a patient with an inoperable AVM. After partial embolization, clinical assessment and follow-up imaging are used to verify the results. If the intended goal of the embolization was obliteration of the angioarchitectural weakness deemed responsible for a recent hemorrhage, follow-up angiography should be performed within days of the procedure to verify that the therapeutic goal was achieved, thereby confirming the reduction in future risk for hemorrhage.

If embolization was performed to reverse a progressive neurological deficit, clinical and MRI follow-up is recommended to determine whether the goal has been achieved and whether additional treatment stages are necessary (see Fig. 386-4). We believe that reduction of venous pressure and venous hypertension is the goal of this mode of treatment and can be documented by angiography and MRI. This management strategy should be discussed with the patient before treatment because it can facilitate patient compliance during the treatment and follow-up stages.

Combination Treatments

Anatomic cure can be accomplished by a combination of two or more modalities, one of which is usually endovascular embolization. A multimodality treatment plan can minimize risk and improve outcome.

Preoperative Embolization

During the past 2 decades, the role of presurgical embolization of AVMs has become well accepted and firmly established.^26,⁵²^–⁵⁶ The goal of preoperative embolization is to facilitate surgical removal of the AVM (see Fig. 386-6). Studies have demonstrated that preoperative embolization leads to decreased operative time, blood loss, and morbidity and mortality in cerebral AVM surgery.^46,^55,⁵⁷ To provide the best outcome with the lowest overall morbidity, communication between the neurointerventionalist and the vascular neurosurgeon regarding the specific goals of embolization is imperative.

The goals of adjuvant embolization are staged reduction of blood flow in an AVM by stepwise occlusion of the AVM nidus over a period of several weeks; elimination of deep-feeding arteries such as the lenticulostriate arteries, which could require extension of the resection plane beyond the margin of the nidus; and occlusion of any other feeding arteries not readily accessible during surgery, such as skull base dural collaterals (see Fig. 386-6).

We believe that whenever possible, surgical resection, mostly for large lesions, should be delayed for 1 to 3 weeks after embolization to allow progressive thrombosis, which may occur after presurgical embolization, and stabilization of local and regional hemodynamic changes.

Embolization And Radiosurgery

The two major goals of embolization before stereotactic radiosurgery are a reduction in overall AVM size and targeted embolization of specific angioarchitectural abnormalities (see Fig. 386-7). The use of embolization before radiosurgery is controversial.²³ Mixed results have been reported regarding the effect of endovascular procedures on radiosurgical morbidity. One study found a lack of prior embolization to be predictive of neurological deficit and edema,⁵⁸ whereas others have found that a history of prior embolization was associated with decreased obliteration rates, increased morbidity, or both.⁵⁹^–⁶¹ The latency period of obliteration after radiosurgery may be 1 to 5 years,^62,⁶³ and embolization before radiosurgery may increase the risk for hemorrhage during this period.

Embolization of an AVM before radiosurgery may be performed to decrease the size of the lesion to a volume suitable for radiosurgery. The volume of the AVM is one of the most important indicators predicting the success of stereotactic radiosurgery in achieving complete obliteration.^23,^60,⁶⁴ However, global size reduction by endovascular embolization of large-volume AVMs is not always possible. This is most difficult to achieve in lesions with feeders from multiple territories and in lesions located in areas with marked potential for collateral supply (i.e., the occipital and temporal lobes). In such cases, to avoid induction of collateral supply, intranidal deposition of embolic material is mandatory (see Fig. 386-7). Although limited data are available concerning the success rate of embolization for size reduction as the primary goal of treatment,⁶⁵ it remains the only method available to reduce AVM size to within the range amenable to radiosurgery.

Targeted AVM embolization before radiosurgery may be performed in patients with angioarchitectural abnormalities believed to increase the risk for hemorrhage. Distal flow-related aneurysms, intranidal pseudoaneurysms, venous aneurysms, and restriction of venous outflow should be targeted with a liquid adhesive. Large, irregular, multilobulated, proximal aneurysms should be occluded with microcoils such as the Guglielmi detachable coils to eliminate the risk for future rupture and subarachnoid hemorrhage (see Figs. 386-6 and 386-7). In deep AVM structures in which there is both a surgically accessible arterial supply (choroidal or circumferential) and a surgically inaccessible perforator supply, one can wait for the results of embolization to conclude the final treatment plan.

We believe that a permanent embolic agent such as N-butyl-2-cyanoacrylate (NBCA) should be used for preradiosurgical embolization, regardless of the indication (i.e., size reduction or targeted embolization). There is no role for embolization with temporary embolic material such as polyvinyl alcohol (PVA) particles or proximal occlusion agents such as platinum coils because no permanent obliteration of the nidus can be achieved. Conversely, permanent occlusive agents such as NBCA should not be used for occlusion of only proximal feeders because it leads to induction of a collateral supply and destabilization of the lesion.^46,⁶⁶

Techniques Of Embolization

Endovascular accessibility to the brain greatly reflects the angioarchitecture of its feeding arteries. Significant improvements in the field of microcatheter technology now permit superselective catheterization of most pial AVM feeders. An understanding of the different catheters, embolic agents, and endovascular techniques is critical to increase the opportunity for obliteration while decreasing complication rates.

Selective cerebral angiography should include bilateral carotid and vertebral artery angiography, as well as mapping of the pial and dural territories. Correlation of the axial imaging (MRI) and angiographic studies is important when planning global treatment, including endovascular goals and possible microsurgery or radiosurgery by a multidisciplinary group. The diagnostic angiographic studies are performed most commonly as elective outpatient studies or before the first therapeutic procedure. The use of small-caliber diagnostic catheters (4 or 5 French), road mapping, and high-quality angiographic equipment (preferably biplane) helps reduce risk and complications. Three-dimensional rotational angiography may occasionally help one appreciate the architecture of the nidus, flow dynamics, and compartmental structure.

For embolization procedures in cooperative adult patients, we recommend light sedation, local anesthesia, neurophysiologic monitoring, and provocative anesthetic testing with amobarbital and lidocaine. Other groups advocate general anesthesia without neurophysiologic monitoring.

Catheter Selection

Early attempts at catheterization and occlusion of blood vessels involved aneurysm patients and were done via an open surgical approach, which has many of the same risks and morbidity as open neurosurgical procedures.²¹ These techniques were transitioned for use in AVM patients. The first microcatheters that allowed access to AVM feeders were flow directed. Mounted calibrated leak balloons helped control flow and allowed the release of contrast material and cyanoacrylate embolic material, but these balloons were easy to overinflate and had a high rate of vessel perforation.⁶⁷

Subsequently, a torqueable guidewire system that allowed passage of a catheter was developed (Advanced Cardiovascular System, Santa Clara, CA). Modifications were also made in the microcatheters, including softer distal segments with improved versatility.^68,⁶⁹ A thick-walled proximal catheter segment controls torque and transmits longitudinal movements, the intermediate catheter segment is flexible but still transmits torque, and the distal segment is soft and thin walled. There are now many vendors of microcatheters designed for intracranial navigation. However, because the cerebral arteries are more tortuous and fragile than the extracranial systemic arteries, specialized training is required for safe navigation.

Control of Flow

When a microcatheter has been positioned in the feeding artery or nidus of an AVM, an individual compartment can be cast if the surrounding blood flow can be controlled. As discussed, high-velocity arteriovenous shunting, unsuitable nidal architecture (i.e., fistulous single-hole compartments), or both can increase the risk of off-target embolization. If the angiogram shows congestion of the nidus (i.e., slow or stationary dye) after the injection of embolic material, downstream (i.e., venous outflow) occlusion may have occurred. High-grade stenosis of draining veins is a risk factor for AVM rupture.⁷⁰ Small amounts of glue passing through the shunt can occlude the stenotic portion of the draining vein. In multicompartmental AVMs with multiple feeders and one draining vein, casting of one compartment, including the venous outlet, can obstruct the drainage system for the other compartments. Because there is no significant stromal support for the pial arteries, particularly in or around the AVM nidus, hemorrhage is likely to occur. For this reason, venous occlusion must be avoided.

To overcome these difficulties, several techniques were historically proposed. First, some microcatheter designs permitted control of flow in the feeder during embolization (calibrated leak balloon catheter). Second, soft platinum wires (available as straight and coiled wires) were designed to be injected through the microcatheter into high-flow fistulas before glue embolization to slow the torrential blood flow.^71,⁷² These liquid coils (Boston Scientific/Target Therapeutics, Fremont, CA) remain in the fistula site and prevent a large amount of glue from migrating through the fistula. Finally, embolization can be performed with the patient under induced systemic arterial hypotension. Although the liquid coils are no longer manufactured and systemic hypotension is rarely if ever used, these techniques have historical interest.

Embolic Agents

Cyanoacrylates

Cyanoacrylate polymers are the most widely used of the liquid agents. Zanetti and Sherman first introduced polymerizing cyanoacrylates as liquid embolic agents for endovascular embolization.⁷³ Because of their low viscosity, cyanoacrylates can be delivered through small, flexible, flow-directed catheters that can easily be manipulated to allow penetration deep into the AVM nidus. They are delivered and polymerize quickly, generally in seconds. Cyanoacrylates have high resistance to in vivo biodegradation.^74,⁷⁵ An intense inflammatory response helps maintain vessel occlusion and stimulate fibrosis. Although recanalization can occur, it is rare after complete embolization. The risk for recanalization is increased if there is proximal occlusion with minimal or no penetration of the nidus.⁷⁶ In such cases, when the nidus remains active, collateral changes commonly develop to revascularize the nidus and may be unfavorable for future endovascular occlusion and present additional challenges during surgical resection of the AVM.

The first cyanoacrylate used was isobutyl-2-cyanoacrylate, which was discontinued after studies demonstrated that it exhibited some carcinogenic potential in animals.⁷⁷ Histoacryl blue (NBCA) is now the embolization material of choice. NBCA is mixed with low-viscosity oily contrast medium (e.g., Ethiodol Ultra-Fluid), with or without additional tantalum or tungsten powder for radiologic visualization. NBCA polymerizes immediately on contact with free hydrogen ion in blood. The delivery catheter is rinsed with dextrose to prevent premature initiation of the polymerization. The main disadvantage of NBCA is related to its adhesive properties and the risk of adherence of the catheter to the adjacent blood vessel wall, which can cause injury to the vessel or inhibit removal. Modifications in cyanoacrylate’s chemical structure endeavor to reduce its adhesiveness and increase its cohesiveness for AVM embolization.

Ethyl Alcohol Copolymer in Dimethyl Sulfoxide Solvent

In the late 1980s, ethyl alcohol–dimethyl sulfoxide (DMSO) was first used for the embolization of AVMs.⁷⁸ This liquid precipitate is also approved for the embolization of AVMs and is currently available in the United States as Onyx. This agent is viscous and precipitates in the biologic environment as the DMSO organic solvent diffuses into the lipid-rich environment. Onyx can be used to fill AVM vessels, and it does not specifically adhere to the delivery catheter. This permits more time for operator control over volume and rate of delivery, but prolonged fluoroscopic observation and periodic control angiography to assess the status of obliteration of the AVM are necessary.

Preliminary studies found that DMSO induced vasospasm and angionecrosis.^38,⁷⁹ Further studies found that decreasing the volume of DMSO and the rate of introduction could reduce these effects.⁸⁰ In a study of 23 AVM patients, Jahan and coauthors reported one complication related to distal vasospasm that developed during injection, as well as histopathologic evidence of angionecrosis in two AVM specimens resected 24 hours after embolization.⁶⁶ A recent study reported angionecrosis in 42.9%, but subsequent studies have not commented on this effect.^47,⁴⁹^–⁵¹ ^,81 Although long-term data are lacking, Murayama and associates demonstrated no recanalization in swine after 6 months of follow-up,⁸⁰ and Jahan and colleagues reported no recanalization in a limited number of patients imaged up to 20 months after embolization.⁶⁶ In a series of 47 patients, Weber and coworkers reported 84% initial nidal reduction with recanalization in 11% noted on angiography at 3 months.⁵¹ A study of patients undergoing microsurgical resection after Onyx embolization reported recanalization of embolized vessels in 14.3% on inspection by pathology,⁸² but recanalization rates as determined by angiography or pathology have not been reported in other recent studies.^47,^49,^50,⁸¹

Use of Onyx is not without complications. Authors have reported cerebral artery perforations because relatively stiff-walled microcatheters that can resist the high pressures needed to inject Onyx must be used.⁵¹ Catheters tend to become lodged in the Onyx cast as the polymer precipitates around the shaft, even though the precipitate is nonadhesive.⁵¹ Onyx AVM embolization requires longer fluoroscopic and procedure times than needed for NBCA, and further investigation is necessary to justify the increased radiation exposure and procedure time associated with Onyx.⁸³ Because Onyx remains relatively new at the time of this writing, its role in the treatment of cerebral AVMs remains to be defined.

Polyvinyl Alcohol

PVA is the most commonly used particulate agent historically for the embolization of AVMs. PVA particles (50 to 1000 µm) can be used in various size ranges at the discretion of the operator. A microcatheter with a diameter large enough to accommodate the particle size selected is necessary to prevent occlusion of the microcatheter. Larger catheters have decreased flexibility in the tortuous cerebral vasculature and thus make superselective angiography of small or distal vessels more difficult.²

Recanalization is also more likely with particulate embolization ⁸⁴^–⁸⁶ than with cyanoacrylate embolization, and particulates are therefore indicated only for preoperative embolization when surgical resection will follow closely. In a randomized clinical trial comparing embolization with NBCA versus PVA, the trial investigators found no difference in the degree of nidal reduction, number of vessels embolized, surgical resection times, need for transfusions and fluid replacement, and outpatient outcomes. There was a significant increase in the incidence of postsurgical hematomas in the PCA group.² This study lead to Food and Drug Administration approval of NBCA with an indication for preoperative occlusion of brain AVMs.

Alternative Embolysates

A number of other agents have been used for the embolization of AVMs, including Silastic pellets, blood clots, dura, silk sutures, and Gelfoam.⁸⁷^–⁹⁰ Undiluted absolute ethyl alcohol (98% dehydrated alcohol injection, U.S. Pharmacopeia) has also been used for the embolization of AVMs. Of the 17 patients treated with embolization, 7 were cured by embolization alone, 3 patients after microsurgery, and 1 additional patient after radiosurgery. Despite these promising results, 2 patients with partially treated lesions died, and 8 patients experienced complications related to therapy. Absolute ethanol also results in significant brain edema and can precipitate vasospasm. These significant side effects have not led to widespread use of ethanol for the embolization of brain AVMs.

Balloons and microcoils usually occlude vessels proximally rather than distally, but their role can be beneficial in the overall obliteration of AVMs. Silicone balloons are no longer available in the U.S. market. Latex balloons remain available in Europe.

Postoperative Monitoring And Follow-Up

Careful postoperative monitoring in the intensive care unit is a cornerstone of postoperative management. Monitoring of vital signs and neurological status is essential in preventing and detecting hemodynamic or neurological changes. We advocate axial imaging, even without any detectable neurological deficit, to visualize the residual malformation and surrounding change in parenchymal signal, to observe the venous drainage pathways, and to detect silent unexpected hemorrhage (see Figs. 386-4 and 386-7).

When curative embolization is the goal of therapy, long-term follow-up may be necessary. Complete angiographic embolization of an AVM does not guarantee that future hemorrhage will not occur because the nidus of the AVM remains active and there is a possibility of delayed recanalization through collateral channels.⁹¹ Permanent, complete endovascular cure is considered possible with the use of cyanoacrylate; however, the degree of permanent obliteration is probably high but remains unknown.⁹¹

Outcomes And Complications

Treatment of AVMs is a multidisciplinary team effort that combines several stages and modalities. In accordance with the experience reported in the literature, only complete obliteration of a malformation can be considered a cure that abolishes future risk. In most published series, the number of completely and permanently embolized AVMs is small. In overall cohorts of patients treated by embolization, the success rate for curative embolization is chiefly in the range of 5% to 20% but varies greatly from 0% to 70%.^28,^54,^56,^65,^70,^76,⁹²^–¹⁰⁰ Curative embolization rates have been similar in patients treated with Onyx and NBCA and range between approximately 15% and 50%.⁴⁷^–⁵¹ Curative rates are higher in patients chiefly selected for curative embolization, but rates are still less than 70% and risks may be higher. For these reasons, curative embolization is reserved for only a select number of patients. In contrast, embolization as an adjunctive treatment is a cornerstone of AVM treatment.

After a comprehensive evaluation has been performed, decisions can be made regarding the best management approach by comparing the natural history of the lesion with the intervention-related morbidity and mortality. A critical question is how the natural history for a particular patient of a given age with specific AVM architecture compares with the risk associated with treatment.

In the literature there has been a wide range of reported rates of morbidity (0% to 50%) and mortality (1% to 4%) after embolization of AVMs.* Rates are dependent on many factors: patient selection, embolic agents, means of delivering the occlusive agent, preexisting neurological morbidity, the goals of embolization (i.e., primary curative or adjuvant therapy), and the time at which outcome is assessed.^† Typically, neurological deficits occur in 10% to 14% of patients, disabling deficits in 2% to 5%, and death in approximately 1%.^2,^43,^{52–54,56,57,85,100,116–121} Recent studies using Onyx have reported similar results.^47,⁴⁹^–⁵¹ ^,66 ^,82 When embolization is used as a primary treatment, adjuvant therapy, or palliative therapy, the following factors are predictive of postembolization deficits: number of embolization procedures, number of arterial feeders embolized, eloquent location, location in the basal ganglia, deep venous drainage, size smaller than 3 cm, size larger than 6 cm, Spetzler-Martin grade III to V, venous penetration of the glue cast, and AVMs with a pure fistula or a nidus with a fistulous component.^43,^54,^116,^118,¹²¹ Additionally, a patient’s age and general medical condition can alter the expected procedural risks. Although previous studies have not found these factors to be significantly predictive of postembolization deficits, this is most likely due to patient selection. Atherosclerotic vessels increase the risk for embolic complications from dislodged atherosclerotic plaque. Additionally, risks from inappropriate endovascular technique and insufficient neurointerventional equipment are evident and not discussed.

We have reviewed our treatment of 275 AVM patients between 1997 and 2006 to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral AVMs.²⁶ Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), 19 of which were moderate or significant and 10 were mild or transient.

The most common and serious complication of embolization is intraprocedural or delayed hemorrhage (Fig. 386-9). Hemorrhagic complications associated with embolization occur in 1% to 2% of procedures (3% to 15% of patients).^55,^120,^122,¹²³ Hemorrhage during or after embolization may be due to vessel perforation during catheterization, AVM rupture, intranidal aneurysm rupture, or hemodynamic changes as a result of alterations in feeder pressure, normal perfusion breakthrough, or obstruction to venous outflow.^120,¹²⁴^–¹²⁷ We have found that hemorrhage during or after embolization is more likely with AVMs smaller than 3 cm in diameter or larger than 6 cm in diameter.²⁶ Small AVMs may be technically more difficult to embolize than medium-sized AVMs. The increased propensity of small, untreated AVMs to bleed has been demonstrated in many studies and may be due to increased pressure within small AVMs.^30,^31,³⁶ Deficits and hemorrhage are more likely to occur after the embolization of larger AVMs because it is more difficult to achieve complete embolization. Although accessibility and a reduced number of feeding vessels are associated with decreased complications, we have found small (<3 cm) versus medium (3 to 6 cm) size to be predictive of neurological deficits, intraprocedural hemorrhage, and infarction after embolization used as adjuvant therapy to microsurgery or radiosurgery.

FIGURE 386-9 Late complications after endovascular embolization of a symptomatic left temporal arteriovenous malformation. A, The lateral view of the left vertebral angiogram demonstrates posterior temporal branches off the left posterior cerebral artery that supply the posterior compartment of the malformation with cortical venous drainage. B, The arterial and late venous phases of the lateral view of the left internal carotid artery (ICA) angiogram show that the left middle cerebral artery temporal branches (curved arrow) supply the anterior compartment. Notice the multiple ectasia in the nidus, with cortical venous drainage via the vein of Labbé (arrow) and secondary venous reflux to the parietal and temporal cortical veins. C, As shown on a lateral view, a radiopaque acrylic cast was achieved by embolization through the temporal branches. D, The arterial and late venous phases of the lateral view of the left ICA angiogram show embolization of the anterior compartment, reduction of the size of the malformation, and shunting and maintenance of patent venous outflow (arrow). E, After embolization, the lateral angiographic view of the left vertebral artery demonstrates, as in the baseline study, the posterior compartment with patent venous outflow. F, A computed tomographic scan 8 hours after the procedure demonstrates an acute, large, left temporal hematoma, intraventricular hemorrhage, a mass effect, and a midline shift. The patient, who was neurologically intact immediately after embolization, experienced delayed, acute deterioration. He underwent emergency surgery for evacuation of the clot and decompression.

In our series, postembolization deficits resolved in a significant number of patients (P < .0001) over a mean follow-up of 43.4 ± 34.6 months.²⁶ Five patients suffered persistent neurological deficits on long-term follow-up (1% of procedures; 2% of patients). In multivariate analysis, the following variables significantly predicted the development of new neurological deficit after embolization: complex AVM with a treatment plan specifying more than one embolization procedure (odds ratio [OR], 2.7; 95% CI, 1.4 to 8.6), diameter smaller than 3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter larger than 6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), and eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7).

Variables predictive of embolization-related deficits in multivariate analysis were weighted and used to compute an AVM Embolization Prognostic Risk Score for each patient. Patients receive 1 point if their treatment plan requires more than one embolization procedure, 1 point for a small-diameter (<3 cm) AVM, 1 point for an eloquent location, 1 point for deep venous drainage, and 2 points for large size (>6 cm). Summation of each patient’s points yields a score of 0 to 5. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6% (100% moderate/significant), a score of 2 predicted a new deficit rate of 15% (40% moderate/significant), a score of 3 predicted a new deficit rate of 21% (71% moderate/significant), and a score of 4 predicted a new deficit rate of 50% (100% moderate/significant) (P < .0001). Nevertheless, because a significant number of patients with treatment-related neurological deficits improved over time, the AVM Embolization Prognostic Risk Score was not predictive of long-term outcome. The low incidence of permanent neurological deficits underscores the utility of adjuvant embolization in carefully selected patients.

Conclusion

Continuous technical developments and advancements in microcatheters and micro-guidewires with miniaturization, increased flexibility, and hydrophilic coating have enhanced the safety of endovascular approaches to malformations. Distal cortical and deep perforator territories are accessible while reducing the complications of vascular injury and retained glued catheters. We emphasize the use of a permanent liquid embolic agent (i.e., NBCA) for obliteration of the malformation core and shunts within the nidus-venous junction. The future development of nonadhesive permanent agents may improve the success rate for total nidus obliteration and achieve angiographically confirmed anatomic cure. Effective embolization of AVMs is instrumental in facilitating microsurgical resection or stereotactic radiosurgery, reducing complications and procedural risks, and improving treatment success rates. Our experience in treating AVMs over the past 25 years has shown a progressive decrease in operative complications and significantly decreased operative time and blood loss as endovascular techniques have improved; the result has been more complete, staged preoperative AVM occlusion.

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