Endovascular Advances for Brain Arteriovenous Malformations

Transcription

1 TOPIC BRAIN ARTERIOVENOUS MALFORMATIONS BRAIN ARTERIOVENOUS MALFORMATIONS Endovascular Advances for Brain Arteriovenous Malformations R. Webster Crowley, MD Andrew F. Ducruet, MD Cameron G. McDougall, MD Felipe C. Albuquerque, MD Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph s Hospital and Medical Center, Phoenix, Arizona Correspondence: Felipe C. Albuquerque, MD, c/o Neuroscience Publications; Barrow Neurological Institute, St. Joseph s Hospital and Medical Center, 350 W Thomas Rd, Phoenix, AZ Neuropub@dignityhealth.org Received, June 10, Accepted, September 12, Copyright 2014 by the Congress of Neurological Surgeons Arteriovenous malformations (AVMs) of the brain represent unique challenges for treating physicians. Although these lesions have traditionally been treated with surgical resection alone, advancements in endovascular and radiosurgical therapies have greatly expanded the treatment options for patients harboring brain AVMs. Perhaps no subspecialty within neurosurgery has seen as many advancements over a relatively short period of time as the endovascular field. A number of these endovascular innovations have been designed primarily for cerebral AVMs, and even those advancements that are not particular to AVMs have resulted in substantial changes to the way cerebral AVMs are treated. These advancements have enabled the embolization of cerebral AVMs to be performed either as a stand-alone treatment, or in conjunction with surgery or radiosurgery. Perhaps nothing has impacted the treatment of brain AVMs as substantially as the development of liquid embolics, most notably Onyx and n-butyl cyanoacrylate. However, of near-equal impact has been the innovations seen in the catheters that help deliver the liquid embolics to the AVMs. These developments include flow-directed catheters, balloon-tipped catheters, detachable-tipped catheters, and distal access catheters. This article aims to review some of the more substantial advancements in the endovascular treatment of brain AVMs and to discuss the literature surrounding the expanding indications for endovascular treatment of these lesions. KEY WORDS: Arteriovenous malformations, Endovascular Neurosurgery 74:S74 S82, 2014 DOI: /NEU Brain arteriovenous malformations (AVMs) are complex vascular lesions that consist of an abnormal connection between cerebral arteries and veins without an associated capillary bed. With a prevalence that is likely less than 10 per , 1 they are relatively rare, but can nevertheless have devastating consequences for patients harboring them. Brain AVMs can present with hemorrhage, seizure, neurological deficit, or headache, and they often remain unrecognized until they become symptomatic. The annual hemorrhage risk is likely 2% to 4% per year for previously diagnosed AVMs. 2-4 Once an AVM ruptures, however, the risk of additional hemorrhage over the first year is increased to 6% to 18%, before returning to 2% to 4%/year. 3,5-7 Ten percent of patients whose AVM ruptures will die as a result, whereas 20% to 30% will be left with ABBREVIATIONS: AVM, arteriovenous malformation; DAC, distal access catheter; EVOH, ethylene-vinyl alcohol; nbca, n-butyl cyanoacrylate a major disability. 6 Largely based on these outcomes, once an AVM is discovered, treatment is often recommended. Options for the treatment of brain AVMs include surgical resection, endovascular embolization, and radiosurgery. Although these 3 options may be used as stand-alone treatment for brain AVMs, they are increasingly being used concomitantly. Because of this increasing interplay between treatment modalities, the endovascular management of brain AVMs may have varying goals. The goal of embolization before surgical resection typically includes decreasing arterial supply or AVM size to facilitate AVM resection. Embolization done before radiosurgery may be done to reduce nidal size or eliminate high-risk features. Other endovascular goals may include curative treatment, palliative embolization in an otherwise incurable AVM, or targeted treatment of high-risk features such as associated aneurysms or fistulas. Much as the treatment of brain AVMs has evolved, so too have the techniques and tools S74 VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT

2 ENDOVASCULAR ADVANCES FOR BRAIN AVMs available to the endovascular physician for the treatment of these lesions. The rapidly changing nature of the endovascular field demands that treating physicians stay apprised of new techniques and devices. Often these innovations are a step forward, and, therefore, by incorporating new techniques and devices into their repertoire, endovascular surgeons are able to provide their patients with optimal care. Of course, occasionally these innovations do not confer any additional benefit to patients; therefore, being familiar with these devices enables the physician to determine when, if ever, there may be a role for their use. With this article we will discuss some of the innovations that have impacted the endovascular treatment of brain AVMs, with particular focus on more recent advances. EMBOLYSATES Perhaps the most substantial advances that have been made for the treatment of brain AVMs have been with the materials used during embolization. The first reported embolization of a cerebral AVM came in 1960, when Luessenhop and Spence 8 described embolization of an AVM with the use of methylmethacrylate embolospheres. Later embolizations were performed by using a variety of particles including Silastic embolospheres, Gelfoam, and muscle Although these early particle embolizations were effective in some cases, the advent of liquid embolics has proved to be a substantial advancement in the endovascular treatment of AVMs. In contrast to particle embolizations in which the lumen of the delivery catheter has to be at least as large as the embolysate, and the materials are already in a solid state, liquid embolics are designed to solidify once in the AVM, and therefore are able to be delivered through much smaller microcatheters. Two of these liquid embolics, n-butyl cyanoacrylate (nbca) (Codman Neurovascular, Raynham, Massachusetts) and Onyx (ev3, Irvine, California), currently represent the lion s share of embolysates used for AVM embolizations. Cyanoacrylates are permanent liquid adhesive compounds that polymerize when they come into contact with blood, or other anionic solutions. A number of cyanoacrylates have been used for the treatment of brain AVMs; however, nbca has widely become the cyanoacrylate of choice at most centers. These are considered a substantial improvement over embolization using particles, because they can be delivered in a more focused fashion through microcatheters, and they may be able to penetrate the AVM nidus. Despite being considered permanent embolic agents, recanalization may rarely occur in vessels occluded with nbca. 11 The other frequently used AVM embolysate is Onyx, an ethylene-vinyl alcohol (EVOH) copolymer that was approved for use in the United States in 2005 for presurgical embolization of AVMs. Unlike nbca, which is adhesive, Onyx is a cohesive liquid agent that polymerizes as the solvent, dimethyl sulfoxide, dissipates. Its cohesive nature lessens the risk of adherence to the microcatheter in comparison with nbca. This confers the ability to start and stop the injection when reflux occurs or if the Onyx is coursing in an undesirable fashion. These properties also allow the physician to pause the injection to perform control angiography before recommencing embolization. Onyx is available in 3 different concentrations based on the percentage of EVOH; however, only 2 of these variations, Onyx 18 (6% EVOH) and Onyx 34 (8% EVOH), are used in AVMs. The higher concentration of EVOH makes Onyx 34 more viscous, and therefore is preferable for forming an Onyx plug at the onset of an embolization. Despite the predominance of these liquid embolics, other options are available that may be useful for the endovascular treatment of brain AVMs. Most notable among these options are detachable coils. These are most useful when used in conjunction with nbca or Onyx for the embolization of particularly high-flow fistulas or arteries. Coils are typically not sufficient to occlude AVM vessels on their own; however, they may slow the flow enough to allow for the use of a liquid embolic without substantial risk of shunting through the nidus into the venous system. In addition to the existing embolysates, this remains an area of potential advancements, as a number of novel or revised materials are in research and development. MICROCATHETERS As liquid embolysates have been implemented for the embolization of brain AVMs, the catheters necessary for embolization have seen substantial changes. In contrast to particle embolizations, which require catheters that have inner diameters at least as big as the particle, liquid embolics allow for the use of much smaller, gentler catheters, which in turn are able to catheterize the fragile vessels closer to the AVM. In addition to the size of the microcatheter, not all catheters are compatible with liquid embolics, although this is more pronounced of an issue with Onyx. Therefore, the development of embolysate-compatible, smaller catheters with the ability to navigate as close as possible to the AVM has been a critical advance in the endovascular treatment of AVMs. The microcatheters in use today are considered either over-thewire or flow-directed. Over-the-wire catheters are standard microcatheters that, other than the necessity for embolysate compatibility (eg, Echelon, Irvine, California), are no different than those used for aneurysm treatments or any other procedure that requires microcatheterization. Certainly the catheters and the wires need to be relatively atraumatic to navigate fragile AVM vessels. Flow-directed catheters are largely based on early work by Serbinenko, 12 in which he took advantage of flow dynamics of the extra- and intracranial vessels to catheterize and occlude vessels with a variety of different sized balloons. When applied to cerebral AVMs, which are generally considered high-flow lesions, this concept can be quite advantageous when navigating a catheter toward an AVM. Today s flow-directed catheters, including the Marathon (ev3, Irvine, California) and Magic (Balt, Montmorency, France), are designed with variable outer diameters and stiffness along the course of the catheter. These characteristics allow the catheters to be driven by flow, again taking advantage of the flow dynamics associated with AVMs. In addition, these catheters can be used with a wire, which NEUROSURGERY VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT S75

3 CROWLEY ET AL allows for the selection of specific pedicles that may arise at a difficult angle, or that may be low-flow compared with adjacent pedicles. Once the catheter is advanced in an over-the-wire fashion, the wire can be retracted back into the catheter, and again advanced in a flow-directed manner. Another recent innovation has been the development of the Scepter balloon (MicroVention, Tustin, California), which is an Onyx-compatible, dual-lumen microcatheter with a balloon at the catheter tip. This catheter allows for the inflation of the balloon through one channel, while embolysate is infused through the second channel. This holds particular promise for high-flow AVMs in which proximal flow arrest of a high-flow pedicle may decrease the risk of embolysate shunting rapidly into the venous component of the AVM, and allow for a more controlled embolization. Lastly, concerns regarding the retention of microcatheters during AVM embolization are currently being addressed with microcatheters that have a breakaway catheter tip. In cases in which the reflux of Onyx or nbca have glued in the microcatheter, applying traction will disconnect a small portion of the catheter tip (1.5-3 cm) from the remainder of the catheter. The Apollo microcatheter (ev3, Irvine, California) is one such catheter. Basically, a revision of the Marathon catheter, it is currently in use in Europe and is being reviewed by the Food and Drug Administration for use in the United States. This promises to be a substantial advance in the endovascular treatment of AVMs, by decreasing the potential for catheter retention, and perhaps by increasing the amount of reflux that is tolerated during an embolization procedure. DISTAL ACCESS CATHETERS The development of liquid embolysates and improved microcatheters has undoubtedly had a substantial impact on the endovascular treatment of brain AVMs. In addition, newer generations of superior guidewires have enabled endovascular physicians to access smaller and more distal vessels than previously seen. With regard to the endovascular treatment of brain AVMs, the combination of these advances has allowed the treating physician to perform superselective embolizations of small, distal pedicles supplying the AVM. This helps avoid en passage vessels and makes nidal penetration of the embolysate more likely. Of course, this means that AVMs, particularly larger lesions, will typically have multiple pedicles that require embolization. Practically, this means that each of these pedicles will require repeat superselective catheterization with a new microcatheter. With the use of traditional methods, the catheterization of each individual pedicle of an AVM requires the physician to navigate from the guide catheter directly to the pedicle of interest. For lesions supplied by the anterior circulation, this requires repeatedly traversing the supraclinoid internal carotid artery and the proximal middle or anterior cerebral arteries, whereas for posterior circulation AVMs it may be necessary to cross the basilar artery into the posterior cerebral arteries multiple times. The need to repeatedly traverse the proximal intracranial vessels has largely been obviated by the development of distal access catheters (DACs). DACs are introduced through the guide catheter, and can often be advanced into the first or even the second segments of the middle cerebral artery, anterior cerebral artery, or posterior cerebral artery (Figure 1). Once the DAC is in place, the microcatheter is then advanced to the desired pedicle over what is inevitably a much shorter distance. This catheter construct confers a number of advantages for the endovascular surgeon. As stated previously, the most obvious advantage is the ability to embolize multiple distal pedicles without having to traverse the proximal arteries numerous times. This may be especially helpful in patients who have tortuous vasculature, particularly when the bifurcations from the internal carotid artery terminus into the middle cerebral artery or anterior cerebral artery, or the basilar artery into the posterior cerebral artery, create acute angles that are difficult to navigate. Other advantages of the DAC include the additional coaxial support it provides that may be useful for more distal lesions, as well as the ability to perform control angiography that produces more selective images during embolization. There are a variety of sizes for DACs, and, when choosing which catheter to use, it is important to consider what is most useful during a particular procedure. In general, we prefer the inch DAC, which is large enough to perform angiography around a microcatheter, yet it is usually small enough to sufficiently access the distal vasculature. Smaller catheters may be able to gain more distal catheter purchase, but do not allow for adequate injections in the presence of a microcatheter, while larger catheters often are not able to track distally enough. ADDITIONAL DEVELOPMENTS Whereas the previously mentioned advancements have been in regards to the devices and embolysates involved in AVM embolization, there are a number of other factors that may also potentially alter the endovascular treatment of cerebral AVMs. One of these factors is the timing of embolization following hemorrhage. Traditionally, an AVM that has ruptured has been observed for a period of time before embolization and resection. Although this is certainly with exceptions, it is generally thought that waiting several days to weeks after the hemorrhage for surgery will allow for improved swelling and visualization during surgery. In addition, it is unclear if partial embolization leaves a patient at greater risk for rerupture, and therefore embolization with a prolonged time period until resection may be accompanied by additional risks. This, however, may not be the case, as recent reports have suggested that early embolization following AVM rupture may be safe, particularly if the goal of embolization is to eliminate high-risk features that may make the AVM more likely to rerupture. 13,14 Another consideration is the use of general anesthesia vs conscious sedation. By and large, performing an embolization under general anesthesia results in clearer images with substantially less motion artifact. Any amount of movement may hinder one s ability to visualize the embolysate as it is injected. This concern is more pronounced when using Onyx, because these embolizations S76 VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT

4 ENDOVASCULAR ADVANCES FOR BRAIN AVMs FIGURE 1. Posteroanterior subtracted (A) and unsubtracted (B) angiographic images of 4-cm right parietal AVM supplied by the MCA. B demonstrates the DAC (white arrow) in the distal M2 of the right MCA and the microcatheter (black arrow) adjacent to the AVM in a distal feeding pedicle. The distal placement of the DAC allowed for easy catheterization of subsequent pedicles following each embolization, without having to repeatedly navigate the supraclinoid ICA and proximal MCA. AVM, arteriovenous malformation; MCA, middle cerebral artery; DAC, distal access catheter; ICA, internal carotid artery. Used with permission from the Barrow Neurological Institute. may be performed over long periods of time. Excessive movement during embolization may result in inadequate visualization of reflux or flow into undesired territories, which can result in unexpected neurological deficits. In addition, these procedures may last several hours, and keeping an awake patient still and comfortable through a long procedure may be challenging. For these reasons, we prefer to perform embolizations under general anesthesia. There are, however, a number of centers that advocate for treatment of some, if not all, AVMs under the use of conscious sedation. This may be particularly useful if done in conjunction with a superselective Wada test Using this combination, it may be possible to identify pedicles that would result in neurological deficit if embolized, and abort or change catheter position based on a positive test. Certainly, in these cases, it is important to consider the possibility of false positives, perhaps from an overly aggressive injection causing reflux into other pedicles, or false negatives that may result from a weak injection or from flow demand to the AVM that shunts the infused drug away from an en passage vessel. These possibilities may make an intraoperative Wada difficult to interpret, and therefore the results of such a test should be weighed along with other features of the angiogram to determine suitability for embolization. Despite these potential pitfalls, awake embolization may provide substantial information for the treating physician. Lastly, as experience and, subsequently, data in the endovascular treatment of cerebral AVMs have accumulated, it has become apparent that some of the factors that increase the surgical risk for an AVM are not necessarily associated with increased risk during embolization. In response to this realization, a number of scales have been proposed for the risk stratification of cerebral AVMs undergoing endovascular treatment. 16,18 Although these scales have been variably adapted, they do help outline factors that may result in a higher-risk profile, including the number of feeding pedicles; the need for multiple embolization sessions; the presence of high-risk features within the AVM such as AV fistulas or aneurysms; the size of the AVM; and the eloquence of the area surrounding the AVM. ENDOVASCULAR TREATMENT GOALS AND RESULTS As experience with endovascular techniques has evolved, so too have the treatment goals associated with these techniques. This is particularly true with regard to the treatment of AVMs. Although early treatments typically resulted in partial embolizations that were either followed by surgical resection or observation, current techniques and technology allow for a variety of endovascular goals. Certainly, preoperative embolization remains the predominant indication in many neurosurgical centers; however, the ability to navigate closer to an AVM, and to penetrate the nidus with embolic material, has now made more thorough embolizations a near certainty, and endovascular cure a possibility in many cases. Other options include embolization before, or after radiosurgery, as well as targeted embolization of high-risk features, or palliative embolization in symptomatic AVMs that have no other good options. NEUROSURGERY VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT S77

5 CROWLEY ET AL PREOPERATIVE EMBOLIZATION Preoperative embolization is the prevailing indication for endovascular treatment of brain AVMs and is currently the only Food and Drug Administration approved on-label indication for the use of Onyx in the United States. Preoperative embolization is done to make surgical resection safer and more feasible. For this reason, the embolization must be done as safely as possible to ensure that the cumulative risks associated with endovascular treatment plus surgery do not exceed the risk of treating the same AVM without embolization. Unlike curative embolization, in which nidal penetration and obliteration is necessary, a successful preoperative embolization can be achieved by decreasing arterial supply to the AVM by occluding its feeding pedicles (Figures 2-5). With this goal in mind, a less aggressive embolization can often be performed, which may result in fewer procedural complications. One possible strategy that may make embolization even safer is targeting only those arterial pedicles that are difficult to access surgically, although many cerebrovascular and endovascular surgeons advocate embolization of all pedicles that are endovascularly accessible. Because nbca has been in use for a longer period of time, there is a larger body of literature surrounding its use in comparison with Onyx. A number of clinical studies have demonstrated that nbca is efficacious in preoperative embolization. Most notably, Jafar et al 19 and DeMerritt et al 20 observed that preoperative embolization improved outcome by effectively reducing the risks of surgical resection of large AVMs to those of small AVMs. Later series confirmed the utility of preoperative embolization, with a relatively low-risk profile. 18 As physicians have gained more experience with Onyx embolization, an increasing number of reports are being published regarding its use in the preoperative setting. Weber et al 21 and Natarajan el al 22 demonstrated its efficacy when they reported that preoperative embolization reduced mean nidus volume 84% and 74%, respectively. Morgan et al 23 recently performed a literature review examining the role of Onyx embolization that included their experience with presurgical embolization with and without Onyx. They concluded that outcomes following surgical resection of cerebral AVMs are not improved with Onyx embolization and may actually be worsened. Possible reasons for this include complications associated with the resection and increased surgical aggressiveness in patients embolized with Onyx. We have subsequently looked at our institutional experience with embolization of cerebral AVMs, the vast majority of which were performed preoperatively, and found no significant difference in complications between patients treated with nbca or Onyx (Crowley et al, unpublished data). PRE- AND POSTRADIOSURGICAL EMBOLIZATION As radiosurgical techniques have evolved, radiosurgery has increasingly been performed in conjunction with the endovascular treatment of cerebral AVMs. Although embolization has more often been performed before radiosurgery, embolization following radiosurgery remains an option that may be useful. The goals of pre- or postradiosurgical embolization can be varied. When performing preradiosurgical embolization, the ultimate goal is typically to eliminate any features of the AVM that make it less likely to respond to radiosurgery. This may include reducing the size of the AVM nidus to less than 3 cm, or treating high-flow FIGURE 2. Posteroanterior (A) and lateral (B) angiogram demonstrate a 5 4 cm right parieto-occipital AVM. Contrast is injected simultaneously into the left vertebral artery and right internal carotid artery. Feeding arteries are seen arising from the right middle cerebral and posterior cerebral arteries. AVM, arteriovenous malformation. Used with permission from the Barrow Neurological Institute. S78 VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT

6 ENDOVASCULAR ADVANCES FOR BRAIN AVMs FIGURE 3. Posteroanterior (A) and lateral (B) angiogram with simultaneous contrast injections through the DACs in the M2 segment of the right MCA (white arrows) and the P2 segment of the right PCA (black arrows). C and D are posteroanterior and lateral unsubtracted angiographic images demonstrating DAC placement in the M2 segment of the right MCA (white arrows) and the P2 segment of the right PCA (black arrows). Microcatheters are seen adjacent to the AVM in the distal MCA (white arrowheads), and the distal PCA (black arrowheads) before Onyx infusion through both catheters simultaneously. DAC, distal access catheter; MCA, middle cerebral artery; PCA, posterior cerebral artery. Used with permission from the Barrow Neurological Institute. fistulas or associated aneurysms. The primary goal of postradiosurgical embolization is obliteration of residual AVM when radiosurgery fails to achieve cure, although the indications for postradiosurgical embolization may expand as future studies are conducted. The literature surrounding preradiosurgical embolization consists of conflicting evidence. In 1996, Gobin et al 24 published their experience with preradiosurgical embolization by using primarily nbca. They decreased AVM nidal size sufficiently for radiosurgery in 76% of lesions, and actually saw that 11.2% of patients had an AVM cure from embolization alone. Of the patients that did go on to have radiosurgery, the rate of complete occlusion was 65%. Henkes et al 25 later saw an obliteration rate of 67% for patients with high-grade AVMs who underwent embolization and radiosurgery. Other smaller series have seen obliteration rates of 60% to 81%. 26,27 In contrast to these reports that largely support preradiosurgical embolization, a few recent studies have shown that preradiosurgical embolization may actually be disadvantageous. In 2007, Andrade-Souza et al 28 reported an AVM obliteration rate of 70% for patients undergoing radiosurgery alone, compared with 47% in patients with preradiosurgical embolization. Recent reviews of the institutional experience at the University of Virginia 29 and the University of Pittsburgh 30 have similarly found decreased NEUROSURGERY VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT S79

7 CROWLEY ET AL Spetzler-Martin grade were higher in the embolized group. Kano et al 30 also concluded that preradiosurgical embolization was associated with a decreased total obliteration rate, although their study predated Onyx. Additionally, they observed significantly improved results when the embolization decreased AVM volume to less than 8 cm. 3 Given the conflicting evidence surrounding the practice of preradiosurgical embolization, its utility remains debatable. CURATIVE EMBOLIZATION FIGURE 4. Posteroanterior unsubtracted angiographic image demonstrates Onyx cast following preoperative embolization using microcatheters in right MCA and PCA. MCA, middle cerebral artery; PCA, posterior cerebral artery. Used with permission from the Barrow Neurological Institute. obliteration rates associated with preradiosurgical embolization. Schwyzer et al 29 reported total obliteration in 33% of patients who were previously embolized vs 61% of patients treated with radiosurgery without embolization, although mean nidus size and Unlike embolization in the preoperative or preradiosurgical setting, curative embolization must include thorough nidal penetration to be successful. Unfortunately, aggressive nidal embolization may be more likely to occlude draining veins earlier than desired, and therefore attempts to cure an AVM endovascularly may be associated with higher complication rates than those seen with other embolizations. AVMs that are the most likely to be cured with endovascular treatment are small AVMs with a limited number of arterial feeders. Depending on the location of these AVMs, these are often also AVMs that are easily treated with surgical resection, and therefore the risks and benefits of each approach need to be carefully weighed. In general, we are more aggressive with such AVMs located in areas that are difficult to access surgically, whereas we are less likely to attempt curative embolization in AVMs that are easily accessible surgically. Historically, AVM cure rates with the use of endovascular methods have been low; however, the introduction of Onyx has altered this substantially. Before the implementation of Onyx, angiographic cure rates largely ranged from 9.7% to 22%, and were thought to be associated with the number of pedicles and AVM volume. Even before Onyx, however, small AVMs had FIGURE 5. Posteroanterior (A) and lateral (B) angiograms demonstrate final postembolization images. The patient was taken for surgical resection of the AVM the following day. AVM, arteriovenous malformation. Used with permission from the Barrow Neurological Institute. S80 VOLUME 74 NUMBER 2 FEBRUARY 2014 SUPPLEMENT

8 ENDOVASCULAR ADVANCES FOR BRAIN AVMs reasonable cure rates, approaching 70% for AVMs with a volume less than 4 ml. 11,24,31-33 Despite the low cure rate in the majority of these published series, Valavanis and Yaşargil 34 saw greater success, with cure rates of 40% in their large series of 387 patients. As Onyx has become increasingly incorporated into the treatment of cerebral AVMs, cure rates from embolization have seen a concomitant increase. In 2011, Saatci et al 35 published their large series of AVMs treated with Onyx. Because Onyx was approved for use in Turkey long before it was available in the United States, they were able to amass long-term follow-up of 350 consecutive patients treated with Onyx, and observed an endovascular cure rate of 51%. Another large series of 101 patients by Katsaridis et al 36 demonstrated a cure rate of 28%, with an additional 18% having near-complete occlusion by using Onyx. Impressive cure rates have also been reported in smaller series by Maimon et al 37 and Abud et al 38 who achieved cure in 55% and 94% of patients, respectively. While the cure rates from embolization are improving, the cure rates, particularly of small AVMs, are substantially higher with surgical resection with concomitantly low risks. Therefore, attempts at an endovascular cure may be most reasonable for smaller AVMs when their location makes it a particularly high risk for surgical resection. TARGETED AND PALLIATIVE EMBOLIZATION Targeted embolization of an AVM consists of obliteration of high-risk features of an AVM in which complete cure is not considered possible. These high-risk features may include high flow fistulas, or intranidal or flow-related aneurysms. Palliative embolization relies on the idea that high-flow AVMs may become symptomatic by stealing blood flow from normal brain. When these AVMs are considered incurable, partial palliative embolization may lessen the flow demand of the AVM, with subsequent amelioration of their symptoms. Both of these approaches are most commonly used for large grade IV or V AVMs, because these are typically the lesions that may be more difficult or risky to achieve a complete cure. There is limited evidence supporting these embolization strategies, however, and that which does exist is largely case reports Ultimately, subtotal embolization may increase the bleeding risk of an AVM 11,45,46 and therefore should likely only be performed when all other options are exhausted. CONCLUSION Largely driven by innovations in devices and techniques, the field of neurointerventional surgery is constantly changing. As these changes have been seen across the entire discipline, the endovascular treatment of cerebral AVMs has seen commensurate advances. Innovations defined by the development of newer and better embolic materials, catheters, and other devices have resulted in safer and more effective embolizations of cerebral AVMs. At this time, endovascular treatment of these AVMs is predominantly done in an adjuvant manner, although these advances have made stand-alone embolization a possibility in many patients. It is therefore important for centers that treat cerebral AVMs to have access to physicians capable of performing open cerebrovascular surgery and radiosurgery in addition to endovascular treatment, with concordant facilities. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Berman MF, Sciacca RR, Pile-Spellman J, et al. The epidemiology of brain arteriovenous malformations. Neurosurgery. 2000;47(2): Crawford PM, West CR, Chadwick DW, Shaw MD. 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