Endovascular Treatment of Cerebral AVMs

Successful management of cerebral arteriovenous malformations has become a reality.

By Philippe Gailloud, MD
 

The incidence and prevalence of cerebral arteriovenous malformations (AVMs) cannot be precisely established due to the relative rarity of the disease and the existence of asymptomatic patients.1 The best available estimate of AVM incidence is based on a single population-based study, and shows an overall detection rate of 1.11 per 100,000 person-years, and a rate of .94 per 100,000 person-years for symptomatic lesions.1,2 These values are lower than the commonly quoted prevalence rates derived from autopsy series (.14% to .5%), which probably represent overestimates due to selection bias.1 The prevalence of detected AVMs is unknown, but it is lower than approximately 10 per 100,000 population.1

Despite their congenital nature, cerebral AVMs can become symptomatic in any age category, with a mean presentation age of 31.2.3 More than 50% of AVMs present with intracranial hemorrhage,3,4 which are predominantly intracerebral, but may also be of subarachnoid or intraventricular location. The overall annual risk of rupture ranges between 2% and 4%.5,6 However, the risk of hemorrhage in patients who initially presented with a rupture is as high as 17% during the first year after the event, before decreasing to a baseline level after 3 years.7-9 After a second hemorrhage, this risk further increases to 25% within the first year.7 The overall rate of re-hemorrhage after a first event reaches up to 67%.10

Besides previous rupture, risk factors for intracranial hemorrhage include deep nidus location, impairment of the AVM venous drainage, and the presence of intra- and extranidal aneurysms. Contrary to a commonly held view, the rupture of an AVM is as devastating as that of an aneurysm; if the latter is more lethal, AVM rupture tends to result in more neurologic disability due to the high occurrence of lobar cerebral hematoma.11 Mortality rates of the first AVM-related hemorrhage range between 17.6% and 40.5%, and can be as high as 66.7% for posterior fossa AVMs.4,10 Other types of AVM presentation include general or focal seizures (40%), chronic headache (14%), and persistent or progressive neurologic deficit (12%).3

The basic pathophysiologic element of a cerebral AVM is an abnormal connection (or shunt) between a feeding artery and a draining vein. The capillary bed is congenitally absent in AVMs. Unlike a cortical arteriovenous fistula, which is made of one or a few arteriovenous shunts, an AVM contains a large number of shunts, which are entangled in a central tumor-like component called the AVM nidus. The AVM nidus can have a complex angioarchitecture that combines various types of arteriovenous shunts. Superselective angiographic studies performed prior to embolization frequently document nidus features that are most often not detected by other imaging modalities, such as intranidal aneurysms or high-flow, fistula-like connections hidden among more typical moderate-to-fast arteriovenous shunts.

Diagnostic Imaging

Although digital subtraction angiography (DSA) remains the most accurate technique for diagnosing cerebral vascular disorders, computed tomography (CT) and magnetic resonance (MR) imaging now play a significant part in the diagnosis and management of cerebral AVMs. Fast and widely available, CT is the first-line imaging technique for patients presenting with a suspicion of acute intracranial hemorrhage. Contrast-enhanced CT can confirm the presence of abnormal blood vessels around the hematoma. The role of CT angiography in the characterization of cerebral AVMs remains undefined. Nonruptured AVMs may be apparent on nonenhanced CT, particularly when associated with large draining veins. MR imaging is a sensitive modality for the detection, localization, and sizing of the AVM nidus. It plays an important role in radiosurgery planning, where it is used in conjunction with catheter angiography,12 as well as for the follow-up of treated AVMs. MR angiography provides limited information on the nature of the feeding arteries and draining veins, the dynamic characteristics of the arteriovenous shunts, or the presence of associated vascular lesions such as extra- and intranidal aneurysms and arteriovenous fistulas.13 The diffusion of modern noninvasive cerebral imaging has increased the detection rate and apparent prevalence of intracranial vascular malformations, including AVMs.2 It is important to remember that compression of the nidus by a hematoma may lead to underestimating the actual size of an AVM by any imaging technique, and may even sometimes completely prevent its detection. Such mass effect therefore represents a pitfall for both accurate diagnosis and treatment planning of AVMs.14,15 DSA remains the gold standard imaging technique for the evaluation of cerebral AVMs. Modern DSA carries extremely low risks of complications,16 and offers precise information about the nidus configuration, the number, size, location, and morphology of arterial feeders and draining veins. DSA also documents associated vascular anomalies with significant management and prognostic implications, such as arterial and/or venous stenoses or occlusions, extranidal and intranidal aneurysms, or the presence of surrounding moya-moya-like vasculature that may simulate AVM nidus. Critical hemodynamic characteristics of the AVM are also better analyzed by DSA, including the presence of intranidal arteriovenous fistulas.

THE ROLE OF ENDOVASCULAR THERAPY

The modern management of cerebral AVMs is based on three therapeutic modalities: conventional microneurosurgery, endovascular embolization, and stereotactic radiosurgery.17 Multimodality has been shown to improve overall patient outcomes in adult and pediatric populations,18-21 and has, in particular, opened the door to successful therapy of giant and deeply seated AVMs.22-24 Combined AVM therapy by embolization and surgery has even proved superior to surgery alone in cost-effectiveness analyses.25 When not primarily curative, embolization facilitates subsequent radiosurgery by reducing the volume of the nidus (in particular for AVMs larger than 10 mL),26 prepares the resection of surgically accessible AVMs, and immediately addresses the risks related to associated intra- and extranidal aneurysms and arteriovenous fistulas. Embolization can also supplement radiosurgery for AVMs that have not responded to initial radiotherapy.27 It is essential for the interventional neuroradiologist to understand the role of alternative treatment options and balance the desire to achieve curative embolization in a careful risk and benefit analysis.28,29 Although many AVMs can, from a technical standpoint, be totally embolized, partial embolization followed by surgery or radiosurgery may be ultimately more satisfying in terms of functional outcome. Lesions safely curable by embolization alone are principally small AVMs with one or a few arterial feeders (Figure 1).30

Intracranial aneurysms are frequently associated with AVMs. When they are found in typical aneurysmal locations (ie, the circle of Willis), they should be treated as independent lesions either endovascularly or surgically. In such cases, the presence of AVM feeders and draining veins renders surgical access more challenging. It is usually suggested to treat the aneurysm(s) before the AVM itself,31,32 although the large series of Meisel et al did not document rupture of untreated proximal aneurysms after partial AVM treatment.33 AVM-related hemodynamic stress plays at least a partial role in the growth of aneurysms in typical proximal location, as may be inferred from the progressive shrinkage of these aneurysms sometimes observed after treatment of the AVM.33 Aneurysms located either on the arteries feeding the nidus or within the nidus itself are, on the other hand, directly dependent on the AVM-related increase of flow. Embolization is effective for treating these intranidal aneurysms, which represent a likely site for AVM rupture,34 and should constitute a primary target of endovascular therapy.33

Complications of Endovascular Therapy

Complications potentially associated with endovascular therapy of cerebral AVMs using any type of embolic agent comprise the risks of ischemic and hemorrhagic stroke leading to transient or permanent neurologic deficits, including death. The passage of a significant amount of embolic material on the venous side of the lesion can lead to immediate AVM rupture35 or exceptionally symptomatic pulmonary embolism.36,37 Ischemic stroke may result from endovascular access injury (arterial dissection, clot formation), or inadvertent occlusion of normal cerebral branches by the embolic agent. Hemorrhagic complications comprise vessel perforation during microcatheter/microwire manipulations, or small vessel rupture during contrast and/or embolic agent injection. Other adverse events inherent to angiography classically include local groin complications (hematoma, dissection), contrast allergy, and nephrotoxicity. Infection exceptionally complicates AVM embolization, with a single case of cerebral abscess published so far.38 Although reviews with significant complication rates have recently been used to caution against transarterial embolization,39,40 numerous series reporting low morbidity and mortality rates have now established the safety and efficacy of endovascular therapy, even for AVM in challenging locations such as the rolandic cortex or the basal ganglia.23,41

It has been argued that partially embolized AVMs carry an increased risk of subsequent hemorrhage. Embolization-induced neoangiogenesis, secondary to transient regional hypoxia within the AVM nidus, was advanced as a potential mechanism for subsequent morbidity and mortality.42 This was not confirmed by the study of Meisel et al,43 which showed on the contrary that partially embolized AVMs had a lower risk of hemorrhage than that expected from the natural course of the disease. In a prior series, Gobin et al44 had reported a 3% annual risk of hemorrhage from partially treated AVMs, whereas the rate of hemorrhage during the latency period after radiosurgery, with or without embolization, was also found to be comparable to that expected from the natural history of the disease.45,46 Partial, noncurative embolization can be used as a form of palliative treatment either to improve the patient’s clinical condition or to reduce the risk of hemorrhage.47 Partial embolization can bring symptomatic improvement in patients with a steal phenomenon.30,48

Proximal pressure elevation after nidus embolization has been raised as a potential cause of peri- or postprocedural hemorrhages. However, Henkes et al49 have shown recently that, although proximal pressure does increase after nidus embolization, the changes are minimal and unlikely to result in hemorrhagic complications. The risk of normal perfusion breakthrough phenomenon (ie, the occurrence of postprocedural edema and hemorrhages in cerebral tissue adjacent to the AVM nidus) is more concerning.50 It is believed that the perfusion breakthrough phenomenon corresponds to a disruption of the chronically ischemic capillary bed that surrounds the AVM secondary to the sudden increase in perfusion pressure resulting from nidus resection or embolization.51 This phenomenon can be minimized by staging the surgical or endovascular procedures.52,53 As a rule of thumb, we tend to avoid embolizing more than one third to one half of a large nidus in a single treatment session, keeping a 4- to 6-week interval between successive procedures. Steiger et al54 suggested that residual nidus congestion may occur after embolization and lead to intraoperative bleeding during subsequent surgery. According to these investigators, the nidus outflow requires a few weeks to normalize after embolization, and they advise to delay surgery in cases of suspected congestion of the residual nidus.

It is worth mentioning at this point that the Spetzler-Martin grading system55 is a surgical scale that correlates the AVM location, size, and venous drainage pattern with the risk of AVM resection, but that it does not apply to endovascular treatment or to radiosurgery.56 In fact, Pollock et al have even recently proposed a new scale adapted to outcome prediction for the radiosurgical management of AVMs.56

Endovascular access to cerebral AVMs and embolization technique
Safe superselective catheterization and embolization of cerebral AVMs is based on a comprehensive understanding of endovascular devices and techniques, as well as thorough preprocedural planning.57 As noted by Valavanis and Yasargil, this requires manual skills, knowledge of anatomy, and respect for the vascular wall.47 Safe and efficient AVM embolization depends on a few key therapeutic principles. The importance of having the embolic agent penetrate the AVM nidus rather than simply occlude its feeders was recognized early by Vinuela et al as a key factor in preventing nidus recanalization.58 Also, as already mentioned, procedural staging helps to limit the risk of normal perfusion breakthrough phenomenon.52,53 Adjuvant techniques include intra-arterial sodium amytal administration (superselective Wada test) performed through the microcatheter positioned for embolization, immediately prior to injection of the embolic agent.59 Superselective Wada evaluation can be used to detect hidden cerebral tissue vascularized by the targeted feeder and to test its functional importance. A battery of neurologic and cognitive tests tailored to the AVM location may be used to enhance the sensitivity of the superselective Wada test.60

The following technical account is based on the author’s experience and preferences, and as such only reflects his personal approach to AVM embolization based on the use of flow-guided microcatheters to deliver a liquid embolic agent (N-Butyl 2-cyanoacrylate [NBCA, Trufill, Cordis Neurovascular, Miami Lakes, FL]). After femoral access is secured in a standard fashion, a bolus dose of heparin is administered intravenously (100 units/kg, with a maximal dose of 5,000 units). A 6-F guiding catheter is placed in the arterial trunk that branches off the targeted feeder(s) (ie, the internal carotid, external carotid, or vertebral arteries). Selective biplane angiography is performed; these angiograms will later serve as baseline for evaluating the degree of postembolization devascularization, as well as a control to document the absence of deleterious changes of the cerebral circulation. A flow-guided microcatheter is then advanced into the intracranial portion of the selected arterial trunk (carotid siphon or basilar artery) over a guidewire (usually .008 inch). The guidewire is withdrawn, and the microcatheter is allowed to flow distally until it reaches the AVM nidus. The microcatheter tip is ideally placed within the nidus, although a slightly more proximal position has to be accepted occasionally. All these manipulations are performed under roadmap guidance.

Flow-guided microcatheters are available in different sizes (1.2 F, 1.5 F, 1.8 F), with various tip designs (regular versus olive-shaped). It is possible to shape the microcatheter’s tip with steam, although we do not find it necessary with our microcatheter of primary choice (olive tip 1.2 F). Flow-guided microcatheters are, in our practice, preferred to over-the-wire systems because their extremely soft distal segment virtually eliminates the risk of vessel perforation. As an exception, an over-the-wire technique is chosen when the combined use of NBCA glue and microcoil is anticipated, that is, to treat some AVM-associated high-flow arteriovenous fistulas. Hybrid microcatheters that allegedly combine flow-guided and over-the-wire capabilities have been recently developed, but they have not yet shown navigability characteristics comparable to real flow-guided microcatheters. Biplane superselective angiography is obtained and carefully analyzed for the presence of normal arterial segments and/or a cerebral capillary blush, as well as for intranidal aneurysms.

The hemodynamic characteristics of the nidus determine the mixture of NBCA and ethiodized oil to be used for the selected feeder. The glue is prepared on a separate table to avoid contamination with an ionic fluid such as normal saline or blood that could initiate polymerization. The operators then change their gloves. The glue is loaded in 1-mL slip tip syringes and attached to the microcatheter after its lumen and hub have been liberally flushed with dextrose 5%. Safe NBCA injection requires two operators, a primary operator injecting the glue, and an assistant ready to briskly withdraw the microcatheter at the primary operator’s command. Redundant curves of the microcatheter that may increase friction against the arterial wall during withdrawal are eliminated prior to glue injection. It is important that the primary operator stops injecting the glue before removing the microcatheter. In addition, some operators like to apply negative pressure to the syringe used for the injection before withdrawal.30 When the guiding catheter is placed within the internal carotid or vertebral arteries, it is our practice to withdraw the microcatheter and the guiding catheter together, as a block, in order to avoid detaching glue residue potentially attached to the microcatheter tip. If needed, the procedure is then repeated with a new microcatheter and a new guiding catheter, while the glue mixture itself can be reused if its setting characteristics are adequate for the newly targeted feeder(s).

Particular situations requiring slight modifications to the above protocol include the embolization of very fast arteriovenous shunts or of aneurysms located on the AVM feeder. In the former instance, if one estimates that even a very high NBCA concentration may not prevent passage of glue into the venous side of the lesion, one or several microcoil(s) may be deployed within the feeder prior to glue injection. (A very high NBCA glue concentration is prepared by mixing tantalum powder with a few drops of ethiodized oil in the glass beaker. The total amount of NBCA [between .9 and 1.1 mL depending on the technique used to collect it from the vial] is then added to the mud-like paste thus obtained, resulting in a higher than 90% NBCA concentration.) The microcatheter is placed immediately proximal to the microcoil(s), which will provide an anchor point for the glue. If the feeder morphology does not allow placement of a coil, or if the flow is such that a reasonably oversized microcoil remains unstable, one may have to resort to partial coiling of the venous side of the fistula. As an alternative, flow control may be obtained in certain situations by inflating a balloon proximal to the site of glue injection.61 The contact between NBCA and the isoprene/polypropylene bend of the balloon may, however, cause its sudden deflation.61

Another flow-control technique involves intravenous administration of a bolus of adenosine to induce transient but profound systemic hypotension through a rapidly reversible cardiac pause.62 The embolization of feeder aneurysms is efficiently performed by placing the microcatheter’s tip within the aneurysm itself and injecting a slow glue that will reach the AVM nidus before casting the aneurysmal cavity per se. Another challenging situation occurs when an arterial trunk provides small proximal AVM feeders (the so-called en passant feeders) before terminating into normal cerebral branches. To address such a situation, Groden et al63 have described an endovascular ligature technique, which consists of placing (fibered) coils in the arterial trunk distal to the point of emergence of the feeders to protect its normal terminal branches during subsequent glue injection. It should be noted, however, that the procedure relies on the existence of adequate collateral flow to the tissue previously fed by the blocked branch, and that placement of thrombogenic devices within a flowing artery creates a risk of downstream embolic shower.

CURRENT EMBOLIC AGENTS FOR AVM EMBOLIZATION

This review of the available embolic agents for AVMs is not exhaustive. After briefly describing a few agents that are currently used but regarded here as suboptimal, this article will principally focus on two liquid embolic agents, NBCA and ethylene vinyl alcohol copolymer (EVOH).
Calibrated Particles

Calibrated particles are poor agents for the embolization of cerebral AVMs. Their lack of nidus penetration results in high recanalization rates: 80% of the AVMs that were initially obliterated later recanalized in the series of Sorimachi et al.64 These investigators also reported one death (3%) and five permanent neurologic deficits (14%), while Schumacher and Horton65 quote transient and permanent morbidity rates of 14.3% and 8.6%, respectively.

Silk

Silk is a very efficient embolic agent, but is not optimal for AVM embolization because it has a limited ability to penetrate the nidus. Relatively high complication rates have been reported with the use of silk for AVM embolization, with permanent neurologic deficits in nine of 70 patients (12.8%) in a recent series.66 On the other hand, Schmutz et al67 have shown that the use of silk as an embolization agent does not result in significant inflammatory reactions, as it is sometimes suggested.

Absolute Ethyl Alcohol

Absolute ethyl alcohol can be used as a liquid embolic agent for treating cerebral AVMs. Clinical experience with absolute ethyl alcohol is limited. In the Yakes et al series of 17 patients, the overall complication rate reached 47.2%, with a 17% rate of permanent complication, including two deaths from delayed subarachnoid hemorrhage at 4 and 14 months (11.8%).68 Potential complications of absolute ethyl alcohol include cerebral edema, microcatheter retention, and pulmonary embolism. The rate of AVM recanalization after absolute ethyl alcohol embolization seems to be notably low.68

NBCA

Early reports of cerebral AVM embolization with isobutyl 2-cyanoacrylate (bucrylate) (which had first been injected after surgical exposure of the AVM69) showed relatively high complication and/or recanalization rates.70-75 Part of these early complications (dissections, subarachnoid hemorrhages, microcatheter retention) were related to the use of calibrated leak balloons, the precursors of modern flow-guided microcatheters,76 for the delivery of the embolic agent. These studies nonetheless pioneered the concept of endovascular management of these complex lesions, and opened the way to modern embolization techniques.77 NBCA replaced bucrylate in the late 1980s.78 Interestingly, a large series covering the transition period between bucrylate and NBCA has correlated a sharp decrease in complication rates with the change of embolic agents and the introduction of flow-guided microcatheters.75 These investigators reported a 15% rate of severe complication from 1987 to 1993, but none of these complications occurred after November 1990. In a later analysis of their data, they showed a concurrent improvement in both treatment and clinical outcomes.79 An initial nonrandomized comparison between particulate and acrylic agents documented a decreased number of surgical complications in the acrylic series.80 A similar but randomized comparison considering preoperative embolization of AVMs later led to approval of NBCA by the Food and Drug Administration (FDA) for this specific indication.81 In their series of 103 patients embolized with NBCA, Liu et al reported the occurrence of transient or permanent complications in five patients (4.9%) and two patients (1.9%), respectively, as well as two deaths (1.9%).82

Gobin et al44 reported morbidity and mortality rates of 12.8% and 1.8%, respectively. Although one of the classic complications related to NBCA is retention of the microcatheter within the AVM nidus, the advent of hydrophilic microcatheters has significantly reduced this risk.83 Cyanoacrylate agents induce a chronic inflammatory response in the embolized vessels.84,85 The intensity of the reaction associated with bucrylate has been graded from mild to significant by different investigators. In a long-term evaluation of visceral embolization with bucrylate, Freeny et al86 found a mild histiocytic foreign-body giant-cell reaction, which was confined to the vessel lumen, and did not involve the vessel walls or contiguous parenchymal tissues. Vinters et al, on the other hand, described the occurrence of patchy mural angionecrosis and, after several months, of entirely extravascular bucrylate.87 It is believed that inflammatory alterations of the vascular wall play an important role in the permanency of the occlusion obtained with NBCA. The pattern of inflammatory changes induced by bucrylate and NBCA was shown to be comparable by Brothers et al.78 Gruber et al88 have reported that intranidal recapillarization can occur more than 3 months after embolization if solid casting of the nidus was not accomplished. This is consistent with the need expressed by Vinuela et al of having the embolic agent penetrate the nidus rather than occlude its feeders.58 A series of AVMs treated with NBCA (at a concentration of 20% to 25%) showed no recanalization at follow-up evaluations ranging from 17 to 32 months,89 whereas another long-term study documented the absence of recanalization after a mean follow-up of 5.3 years.90 It appears that occlusion of cerebral AVMs with NBCA is permanent when the AVM is totally occluded by embolization.91 The work of Sadato et al92 indicated that a low glue concentration does not increase the risk of recanalization; in an animal model, no instance of recanalization in vessels embolized with mixtures containing either 20% or 50% of NBCA was found after 3 months of follow-up. From a surgical standpoint, vessels embolized with NBCA are described as compressible and easily cut with microscissors.93 NBCA-filled branches help to establish a boundary zone between the AVM feeders and normal vessels that vascularize the surrounding parenchyma.30 Of note, cyanoacrylate embolic agents with lower adhesiveness than NBCA are currently under investigation.94,95

Our technique for NBCA embolization has, for the most part, been described above. As previously mentioned, the NBCA glue mixture is prepared on a separate table in order to avoid contact with ionic fluids such as normal saline or blood, which could initiate the polymerization process. The glue mixture consists of NBCA and ethiodized oil in various ratios depending on the hemodynamic characteristics of the targeted vessel; a low NBCA concentration (20%-30%) will prolong the apparent NBCA polymerization time and allow penetration of the AVM nidus, while lower NBCA concentrations are associated with a concurrent increase in viscosity that is deleterious to glue propagation. The addition of ethiodized oil does not actually change the intrinsic polymerization characteristics of NBCA; ethiodized oil increases the apparent polymerization time of the glue mixture by protecting NBCA from the contact of surrounding ionic fluids. On the other hand, addition of carefully titrated glacial acetic acid to the glue mixture delays NBCA polymerization time without concurrently increasing viscosity.96,97 In our practice, tantalum powder is added to the mixture in order to guarantee adequate radiopacity when NBCA concentration is equal to or higher than 50%.

EVOH

The use of ethylene vinyl alcohol copolymer EVOH (under the initial abbreviation of EVAL) was reported by Taki et al for AVM embolization in 199098 and for the treatment of giant aneurysms in 1992,99 in parallel with the development of cellulose acetate polymer by the team of Kinugasa and Mandai.100,101 Because both EVOH and cellulose acetate polymer have to be dissolved in dimethyl sulfoxide (DMSO), concerns about the toxicity of this solvent for the intracranial circulation were raised.102 In a first study, Chaloupka et al reported that infusion of DMSO always caused immediate, moderate-to-severe vasospasm, and frequently caused either subarachnoid hemorrhage or stroke.103 However, in a second study using lower total doses and dose rates of DMSO, Chaloupka et al found the solvent to be substantially less angiotoxic than initially perceived.104 EVOH as an embolic agent for preoperative embolization of cerebral AVMs (Onyx, Micro Therapeutics, Irvine, CA) is under review by the FDA as of press time, and few clinical data have been published so far. In an initial study of 23 patients by Jahan et al105 transient and permanent complication rates were of 12% and 4%, respectively. Song et al treated three patients with one permanent deficit (33%). In the series of Hamada et al using EVAL in 57 patients, there were three cases of transient deficits (5.3%), and three cases of permanent deficits (5.3%). Niemann et al recently reported four instances of permanent neurological deficits (7.8%) and no death in their prospective study of 51 patients.106

EVOH is not a glue; it solidifies by precipitation when it is exposed to an aqueous solution and the solvent DMSO diffuses out of the polymer mass. The nonadherent nature of EVOH is often mentioned as a major advantage over NBCA, because it should eliminate the risk of catheter retention within the AVM nidus.30,104,107 Currently available data do not seem to confirm this prediction. For example, in the pivotal study submitted to the FDA by the manufacturer and comparing Onyx to NBCA, there were 10 reports of catheter retention in the Onyx group and none in the NBCA group.108 Additionally, it has been suggested that EVOH has a greater ability to penetrate the AVM nidus than NBCA, a characteristic that may result in a higher cure rate from embolization alone. There is no published evidence confirming this hypothesis. In the pivotal study previously mentioned, there were more reports of poor penetration and visualization in the Onyx group.108 EVOH, on the other hand, seems to offer better handling during subsequent surgery.109 From a histological standpoint, EVAL was found to incite an inflammatory response in the vessel wall and the surrounding tissue, including patchy hemorrhages within and around the nidus.110 Jahan et al found angionecrosis in two of their nine cases with histopathology,105 whereas angionecrosis was also reported by Lagares et al111 in an AVM that was embolized with EVOH and recanalized after 2 months. It is believed that angionecrosis is due to improper injection of DMSO rather than to EVOH itself.30 Some of the vessels embolized with EVOH in the series by Jahan et al were completely filled with the embolic material, whereas others showed the embolic material filling a small portion of the vessel lumen, with the remainder of the lumen filled with thrombus.105 Histological changes found in vessels embolized with EVOH usually spare much of the vessel wall, and allow it to remain viable.30 These findings raise the concern of long-term efficacy of EVOH and the risk of recanalization of embolized vessels, as earlier pointed out by Fukushima et al.110 A long-term follow-up study of AVMs treated with EVOH is not available. In summary, EVOH may be an interesting new agent for the embolization of AVMs, but it has so far not shown superiority over NBCA regarding either safety or immediate and long-term efficacy.

Technically, EVOH embolization is similar to what has been described for NBCA in terms of access and superselective catheterization. EVOH (Onyx) comes in three different concentrations (6%, 6.5%, and 8%) of increasing viscosity and decreasing precipitation rates. There is no need for an ion-free environment preparation. Although Onyx comes in ready-made vials containing EVOH, DMSO, and tantalum powder, it must be shaken for 20 minutes prior to injection, and shaken continuously thereafter if not used immediately to maximize its radiopacity. The dead space of the microcather must be filled with DMSO prior to EVOH injection. EVOH must be injected at a slow rate (maximum of .3 mL/min, .16 mL/min recommended by the manufacturer) to decrease the risk of DMSO angiotoxicity. Because the solvent can damage some microcatheters103,105 DMSO-compatible microcatheters must be used to inject EVOH. The injection of EVOH produces discomfort in many awake patients that may require the induction of general anesthesia, rendering provocative testing difficult.30

Conclusion

Modern treatment of cerebral AVMs is a multimodality endeavor. Transarterial embolization has become a major component of AVM management, either as a stand-alone curative method, or in combination with either surgery or radiation therapy. Continuous progresses in interventional techniques and devices have, in particular, enabled the treatment of lesions that were deemed incurable not long ago. This development must be exclusively driven by patient outcome through a careful risks and benefits analysis, in a case-by-case decision making process, and in a comprehensive multidisciplinary environment. 

Philippe Gailloud, MD, is from the Division of Interventional Neuroradiology, The Johns Hopkins Hospital, Baltimore, Maryland. He is a scientific consultant for Cordis Neurovascular. Dr. Gailloud may be reached at phg@jhmi.edu.

For a complete list of references for this article, please see the July issue at www.evtoday.com.

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