Curing arteriovenous malformations using …...Neurosurg Focus / Volume 37 / September 2014 Arteriovenous malformation embolization 3 TABLE 1: Arteriovenous malformation embolization

Neurosurg Focus / Volume 37 / September 2014

Neurosurg Focus 37 (3):E19, 2014

1

©AANS, 2014

TreaTmenT modalities for cerebral arteriovenous mal-formations (AVMs) include microsurgical resection, radiosurgical ablation, endovascular embolization,

and combinations thereof. With so many strategies to choose from, the management of AVMs can be as complex as their anatomy. In general, resection is most often used for superficial, noneloquent, or ruptured lesions while ra-diosurgery is ideal for deeper, eloquent lesions with higher surgical risks.15 Endovascular embolization, on the other hand, is typically reserved as an adjuvant treatment, either to devascularize an AVM to make surgical resection safer or to decrease the size of an AVM nidus to facilitate radio-surgery. It is well documented, however, that a subset of AVMs can be angiographically occluded using emboliza-tion. Whether curative embolization should be considered a reliable primary treatment, equivalent to microsurgery and radiosurgery, remains controversial7,24 and is depen-dent upon 3 factors: 1) is there a subset of AVMs that can be predictably cured with embolization; 2) can emboliza-tion be performed with minimal morbidity; and 3) is it a durable treatment?

The recent results of the ARUBA trial (A Random-ized Trial of Unruptured Brain AVMs)36 and the Scottish Intracranial Vascular Malformation Study3 questioned the safety of intervention for unruptured AVMs as com-pared with medical management. These studies, how-ever, combined all AVM interventions in their primary analyses and were not powered to make meaningful com-parisons between specific treatment modalities. Given the complexities of AVM anatomy and the controversy over the role of intervention, it is now imperative that the cerebrovascular community better define the indications and risks of each individual AVM treatment modality to provide the safest and most efficacious management pos-sible. With that in mind, we focus on the role of endo-vascular embolization as a monotherapy for the cure of cerebral AVMs, reviewing the literature with regard to cure rates, predictive factors, techniques, complications, and durability of curative AVM embolization.

Endovascular Embolization in AVM ManagementEndovascular embolization of an AVM was first de-

scribed by Luessenhop and Spence in 1960 when they reported treating a large left-frontal AVM with 4 methyl methacrylate pellets, ranging in size from 2.5 to 4.2 mm,

Curing arteriovenous malformations using embolization

Matthew B. Potts, M.D.,1,2 Daniel w. ZuMofen, M.D.,1,2 eytan RaZ, M.D.,2 PeteR K. nelson, M.D.,1,2 anD howaRD a. Riina, M.D.1,2

Departments of 1Neurological Surgery and 2Radiology, New York University School of Medicine, and Bernard and Irene Schwartz Neurointerventional Radiology Section, NYU Langone Medical Center, New York, New York

Endovascular embolization is typically reserved as an adjuvant therapy in the management of cerebral arterio-venous malformations (AVMs), either for preoperative devascularization or preradiosurgical volume reduction. Cura-tive embolization plays a limited role in AVM treatment but several studies have shown that it is possible, especially with later-generation liquid embolic agents. Given the complexity of AVM anatomy and the recent controversies over the role of any intervention in AVM management, it is critical that the cerebrovascular community better define the indications of each treatment modality to provide quality AVM management. In this review, the authors evaluate the role of curative AVM embolization. Important considerations in the feasibility of curative AVM embolization include whether it can be performed reliably and safely, and whether it is a durable cure. Studies over the past 20 years have begun to define the anatomical factors that are amenable to complete endovascular occlusion, including size, feeding artery anatomy, AVM morphology, and endovascular accessibility. More recent studies have shown that highly selected patients with AVMs can be treated with curative intent, leading to occlusion rates as high as 100% of such prospectively identified lesions with minimal morbidity. Advances in endovascular technology and techniques that support the efficacy and safety of curative embolization are discussed, as is the importance of superselective diagnostic angiography. Finally, the durability of curative embolization is analyzed. Overall, while still unproven, endovascular embolization has the potential to be a safe, effective, and durable curative treatment for select AVMs, broadening the armamentarium with which one can treat this disease.(http://thejns.org/doi/abs/10.3171/2014.6.FOCUS14228)

Key woRDs • arteriovenous malformation • embolization • endovascular • AVM cure

Abbreviations used in this paper: AVM = arteriovenous malfor-mation; EVOH = ethylene vinyl alcohol; IBCA = isobutyl-2-cyano-acrylate; NBCA = N-butyl cyanoacrylate

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M. B. Potts et al.

2 Neurosurg Focus / Volume 37 / September 2014

that were directly placed into the carotid artery.31 These pellets were carried with blood flow through the enlarged middle cerebral artery branch feeding the AVM and re-sulted in significant reduction in flow to the AVM. Since that time, neurointerventionalists have used silk sutures, ethyl alcohol, balloons, metal coils, polyvinyl alcohol particles, and most recently, various liquid embolic agents for embolization of AVMs.50 Today, embolization plays a significant role in AVM management11 with 5 main uses: 1) preoperative flow reduction; 2) preradiosurgical vol-ume reduction; 3) targeting of specific angioarchitectural features; 4) palliative flow reduction; and 5) complete cu-rative occlusion.10,62

The most common, and perhaps most important, role for embolization in AVM management is as a preopera-tive adjunct to either reduce blood flow within the nidus or to embolize deep, surgically inaccessible feeder arter-ies.7 Both N-butyl cyanoacrylate (NBCA)39 and ethylene vinyl alcohol (EVOH) copolymer30 gained FDA approval specifically for this use and several case series have dem-onstrated benefits, especially with larger AVMs.13,22,40 De-spite its widespread use, there are no randomized stud-ies to prove the benefit of preoperative embolization.2 In fact, 1 recent literature review by Morgan et al.37 even suggested that preoperative embolization does not reduce the overall morbidity of surgical treatment, especially in low-grade AVMs. The benefits of preradiosurgical embo-lization to reduce nidal volume are even less clear. While early studies demonstrated reasonable efficacy of preradi-osurgical embolization, more modern series have shown this technique to be of no benefit and even possibly asso-ciated with worsened outcomes compared with radiosur-gery alone.4,21,25,52,55 Again, randomized trials are lacking but the use of preradiosurgical embolization is waning. Occasionally, embolization is also used to treat specific, high-risk angioarchitectural characteristics such as nidal aneurysms to prevent hemorrhage,54 or for palliative flow reduction, as with large, high-flow AVMs causing venous congestion or arterial steal syndromes.62

The final role of AVM embolization, and the main topic of this review, is curative embolization. Many se-ries of endovascular AVM treatments report on subsets of patients in whom complete occlusion was achieved with embolization (Table 1). Immediate angiographic cure rates range from approximately 5% to more than 94% (excluding those studies that only investigated cured AVMs). Such wide variability is likely dependent upon many factors, particularly selection biases (differences in size, location, and others) and goals of embolization (cu-rative vs preoperative devascularization). It is therefore difficult to make direct comparisons between various studies. It is even more difficult to understand how cura-tive intent was implemented or accounted for in various studies. Oftentimes, cure is achieved during the course of planned presurgical or radiosurgical embolization.30 Other studies adopt a general approach of attempting en-dovascular cure with all or most AVMs without stating specific guiding principles and then refer the failures for surgery or radiosurgery.26,60,69 Still other studies report broad guidelines used to select AVMs for curative embo-lization but do not specifically report outcomes for that

subset.38,53 In general, these studies confirm that complete occlusion using embolization is possible and they begin to define the AVM characteristics most predictive of en-dovascular cure. The most important question, however, is whether embolization can reliably cure select AVMs, and this is best demonstrated in series that report unique subgroups of patients chosen specifically for curative em-bolization.1,54,64,72 These latter studies suggest the impor-tance of prospectively identifying specific target subsets of patients with AVMs, the true population of patients for which the success of embolization monotherapy in curing AVMs should be compared with, and further demonstrat-ing that with proper selection, occlusion rates between 60% and 100% can be achieved in targeted lesions.

Factors Associated with AVM Cure

AVM Size

Several studies have identified factors associated with achieving complete AVM obliteration with emboli-zation. The most commonly reported AVM characteristic is small size. Among the 8 patients reported by Cronqvist et al., who attained complete AVM obliteration with em-bolization, 75% had a nidal volume < 6 ml.9 Similarly, Pierot et al. found that AVMs < 3 cm in maximal diam-eter were nearly 5 times as likely to be completely embo-lized compared with AVMs ≥ 3 cm in diameter.49 Series reporting subgroups with curative intent of embolization have used small AVM size as a selection criteria. Sahlein et al. reported a mean AVM size of 21.8 mm (maximum diameter) for their curative intent group54 while Yu et al. only selected AVMs with a maximal diameter of 3 cm or less for curative intent.72 Similarly, studies reporting embolization of micro-AVMs (defined as nidus diameter < 1 cm) have also shown excellent cure rates.5,48 Anatomi-cally, small AVM size may equate to a less complex AVM with fewer feeders. Small size, however, is not universally acknowledged as a positive predictive factor for the suc-cess of AVM embolization. Valavanis and Yaşargil be-lieved that size (as well as number of feeders) chiefly af-fected the complexity of the endovascular embolization and not necessarily the angiographic outcome.63

Feeding ArteriesSeveral features of the pedicles supplying AVMs have

been associated with complete obliteration using emboli-zation. A low number of feeding pedicles has been a pre-requisite for curative embolization in multiple studies of AVMs.14,54,72 Fournier et al. found that the 4 AVMs they cured with embolization all had only 1 or 2 pedicles.14 Yu et al. only included AVMs with ≤ 3 pedicles in their cura-tive intent group,72 while Sahlein et al. found a mean of 2.2 pedicles in their curative intent group (compared with a mean of 5 pedicles in AVMs that they treated for preop-erative or preradiosurgical devascularization).54 Strauss et al. also found that large pedicles (defined as twice the normal diameter) had an odds ratio of 4.6 of complete obliteration compared with small pedicles.60 Feeding ar-tery location is likewise associated with complete oblit-eration, with superficial arteries positively associated



Arteriovenous malformation embolization

3

TABL

E 1:

Arte

riove

nous

mal

form

atio

n em

boliz

atio

n se

ries r

epor

ting

com

plet

e end

ovas

cula

r em

boliz

atio

n*

Auth

ors &

Yea

rNo

. of

Patie

nts†

% S

petzl

er-M

artin

Gra

des

(I/II/

III/IV

/V)

Prim

ary L

iquid

Embo

lic A

gent

Mea

n Emb

oliza

tion

Sess

ions p

er P

atien

tIm

media

te Co

mplet

e Oc

clusio

n (%)

†M

orta

lity/M

orbid

ity

(%)‡

Recu

rrenc

es

in Oc

clude

d AV

Ms (

%)

Leng

th of

Angio

grap

hic

Follo

w-Up

for O

cclud

ed

AVM

s

Lasja

unias

et al

., 198

641

NRIB

CA2

12.2

2.4/4.

9NR

NRFo

urnie

r et a

l., 19

9147

4.3/21

.3/3

4/31

.9/6

.4IB

CA1.9

8.5

2/8

none

NRW

ikholm

et al

., 199

615

03/1

3/47/2

9/9

IBCA

/NBC

A1.9

+13

1.3/6

.6no

neme

an 3.

7 yrs

Gobin

et al

., 199

612

50/1

0/31

/30/

29IB

CA/N

BCA

2.8

11.2

1.6/12

.8NR

NRDe

brun

et al

., 199

754

NRNB

CANR

5.6

3.7/5

.6no

ne3 m

osVi

ñuela

et al

., 199

746

5NR

NBCA

NR9.7

3.8/

7no

neNR

Perri

ni et

al., 2

004

9lim

ited t

o micr

o-AV

Ms

NBCA

1.177

.80/

22.2

none

mean

19.1

mos

Yu et

al., 2

004

cu

rativ

e inte

nt su

bgro

up27

11/41

/15/2

2/11

NBCA

1.622

0/7.4

——

1020

/70/1

0/0/

0NB

CANR

600/

0no

ne17

–32 m

osHe

et al

., 200

522

0/23

/46/2

3/9

Onyx

NR13

.60/

010

03–

9 mos

Pére

z-Hi

guer

as et

al., 2

005

45NR

Onyx

2.5

222/

15.5

206 m

os–5

yrs

Song

et al

., 200

550

NROn

yx1.3

200/1

0no

ne§

6 mos

Valav

anis

et al.

, 200

564

4NR

NBCA

1.840

0.4/1.

5¶3.

9≤3

6 mos

Cron

qvist

et al

., 200

621

19/24

/29/

29/0

NBCA

2.438

0/4.8

NRNR

Haw

et al.

, 200

6

cura

tive i

ntent

subg

roup

306

NRIB

CA/N

BCA

1.710

.62.

6/5.

9NR

NR55

NRIB

CA/N

BCA

NR31

NRNR

NRLe

dezm

a et a

l., 20

0616

88/

31/3

3/26

/2NB

CA1.8

2.3

1.2/3

NRNR

Mou

naye

r et a

l., 20

0794

(53)

5/37

/41/17

/1On

yx2.

227

.7 (4

9)3.

2/8.

5NR

3–6 m

osW

eber

et al

., 200

793

NROn

yxNR

200/1

210

.53 m

osAn

dreo

u et a

l., 20

0825

limite

d to m

icro-

AVM

sNB

CA1

84.6

4/49.5

6 mos

Katsa

ridis

et al.

, 200

810

1 (52

)7/1

8/39

/33/4

Onyx

2.2

27.7

(53.

9)3/

8NR

NRPa

nagio

topou

los et

al., 2

009

8259

(I–I

I)/16

(III)

/7 (I

V–V)

Onyx

1.524

.42.4

/3.8

20me

an 8.

8 mos

Xu et

al., 2

011

863/1

5/52

/22/

7On

yx1.4

18.6

1.2/3

.512

.5me

an 6.

5 mos

Abud

et al

., 201

117

18/2

9/35

/18/0

Onyx

1.494

.10/

5.9

none

6 mos

Reig

et al.

, 201

018

**6/

56/2

2/17

/0NB

CA/O

nyx

2.5

100*

*0/

5.6

11.1

mean

19 m

osLv

et al

., 201

014

4NR

NBCA

/Ony

x1.8

13.9

2.8/4

.9NR

NRSa

atci e

t al.,

2011

350

15/3

0/28

/20/

7On

yx1.7

511.4

/7.1

1.1me

an 47

mos

van R

ooij e

t al.,

2012

††24

NROn

yx1.2

100

0/0

4.33 m

osSa

hlein

et al.

, 201

2

cura

tive i

ntent

subg

roup

131

8/24

/45/2

0/2

NBCA

1.333

0.8/

0.8

NRNR

11NR

NBCA

NR10

00/

0NR

NRPi

erot

et al.

, 201

311

717

/38/

24/21

/1On

yx2

23.5

4.3/5

.1NR

NRSt

raus

s et a

l., 20

1392

(68)

1-2:

30 (I

–II)/

24 (I

II)/46

(IV–

V)On

yxme

dian 2

27 (3

7)2.

2/6.

5NR

‡‡NR

(cont

inued

)


M. B. Potts et al.


with cure60 while feeders arising from lenticulostriate and thalamoperforating arteries were associated with an inability to achieve complete occlusion.69 Importantly, the presence of en passage arteries was found to be negatively associated with complete embolization.60 Arteriovenous malformation size and number of feeders are typically closely related and, as with size, Valavanis and Yaşargil believed that the number of feeders was not a significant factor.63 Instead, they believed that AVM location as it applies to arterial feeders is a more critical concept, with AVMs fed by direct, “dominant” feeders being much eas-ier to catheterize and therefore embolize than those fed by less direct, “supplementary” feeders.63 They describe a topographical classification of AVMs, with sulcal AVMs that occupy the sulci fed by pial arteries while gyral AVMs that are covered by cortex are more often supplied by cortical or medullary arteries that may be deeper. The former are therefore more amenable to safe and effective embolization.

AVM LocationSuperficial AVMs68 and those in noneloquent loca-

tions60 have proven easier to achieve complete emboliza-tion than deeper and eloquent lesions. These associations likely involve technical considerations, as superficial AVMs tend to be fed by larger, more superficial feeding arteries such as the middle and anterior cerebral arteries. Eloquence is significant because ischemic or hemorrhagic complications of eloquent AVMs will be more clinically apparent than in noneloquent lesions. The interventional-ist’s aversion to risk is therefore lower with noneloquent AVMs.

Spetzler-Martin GradeWhile the Spetzler-Martin AVM grading scale was

designed58 and validated17 to predict surgical outcomes, its ubiquitous use in characterizing AVMs has made it an easy factor to associate with embolization results. Both Fournier et al. and Strauss et al. have associated low Spetzler-Martin grades with complete embolization.14,60 This finding is consistent with the fact that both small size5,9,48,49,54,72 and noneloquent location60 have also been associated with complete AVM embolization.

AVM MorphologyValavanis and Yaşargil found that AVM morphol-

ogy was also associated with endovascular occlusion of AVMs. Predominately fistulous type AVMs were, in their hands, easier to embolize than the pure plexiform type.63 These authors postulated that fistulous AVMs were as-sociated with more direct feeding arteries than plexiform AVMs, making it technically easier to embolize fistulous lesions. They also found that single-compartment AVMs were more amenable to complete embolization than mul-ticompartmental AVMs (88% complete occlusion vs 28%, respectively). They observed that there may be intercom-munication between individual AVM compartments that facilitates the embolization of multicompartmental ni-duses.63TA

BLE

1: Ar

terio

veno

us m

alfo

rmat

ion

embo

lizat

ion

serie

s rep

ortin

g co

mpl

ete e

ndov

ascu

lar e

mbo

lizat

ion*

(con

tinue

d)

* In

cludin

g sub

grou

ps in

whic

h emb

oliza

tion w

as un

derta

ken w

ith cu

rativ

e inte

nt. N

R =

not r

epor

ted; O

nyx =

EVO

H co

polym

er.†

Value

s in p

aren

thes

es re

pres

ent p

atien

ts wh

o had

comp

leted

endo

vasc

ular t

reatm

ent.

‡ Re

stricted to pe

rmanent/severe n

eurolog

ical deficits o

r other se

vere co

mplications (such as

hemo

rrhage r

equiring

surgica

l evacuation) rela

ted to en

dovascula

r treatm

ent.

§ On

ly 3 p

atien

ts wi

th co

mplet

ely oc

clude

d AVM

s obt

ained

follo

w-up

angio

grap

hy, a

nd no

ne sh

owed

recu

rrenc

e.¶

For t

he 4

0% of

patie

nts w

ho w

ere t

reate

d with

only

endo

vasc

ular e

mboli

zatio

n.**

Thes

e pati

ents

repr

esen

t a su

bgro

up (1

5%) t

hat a

ttaine

d com

plete

endo

vasc

ular o

bliter

ation

amon

g a la

rger

coho

rt of

122 p

atien

ts wi

th AV

Ms t

reate

d usin

g emb

oliza

tion.

†† T

his en

tire c

ohor

t was

selec

ted fo

r cur

ative

inten

t.‡‡ A

n earlier d

escription

of the fi

rst half of this cohort reporte

d a 12

.5% re

curre

nce r

ate with follow-up of 3–9 months.33




5

Ruptured StatusInterestingly, in a recent prospective study of Onyx

(Covidien) embolization of AVMs, Pierot et al. found that ruptured AVMs were nearly twice as likely to be com-pletely embolized than were unruptured AVMs.49 Multi-variate analysis was not performed, so it is not clear how ruptured AVMs compared with unruptured lesions in terms of other AVM characteristics.

Technical ConsiderationsPerhaps one of the most important aspects of endo-

vascular AVM embolization is accessibility of the lesion to endovascular treatment. This factor encompasses several of the aforementioned variables, including size and loca-tion of feeding pedicles and noneloquent AVM location. Safe and complete occlusion of a nidus cannot be achieved without superselective access to feeding pedicles.72 In addi-tion, Reig et al. found that a complete glue cast of the AVM nidus was essential for a durable cure.51 In their series, 2 of 18 patients with complete occlusion were found to have AVM recanalization on follow-up angiography. These 2 patients were also the only 2 in that subgroup in which a complete casting of the nidus was not achieved.

Superselective Diagnostic AngiographySuperselective catheterization of feeding arteries is re-

quired for successful embolization of AVMs, but this tech-nique should arguably also be used during the diagnostic workup of an AVM to fully appreciate the anatomy44 and better plan management.54,62 For example, superselective microcatheterization has been shown to be more sensitive to the presence of nidal aneurysms than conventional di-agnostic studies.54,61 In addition, superselective catheteriza-tion can accurately define the number and nature of feed-ing arteries, identify multiple compartments within the ni-dus,45 and prove accessibility of an AVM nidus, all factors important in the successful complete embolization of an AVM. The theoretical risks of superselective catheteriza-tion for diagnosis compared with a standard 3- or 4-vessel diagnostic angiogram include vessel injury leading to hem-orrhage or ischemia. In a series of 130 patients for whom superselective diagnostic angiograms were performed at a separate session prior to AVM embolization, only a single patient (0.8%) experienced a permanent neurological defi-cit due to the diagnostic angiogram.54

Embolic AgentsThe success of modern endovascular embolization is

in large part attributable to the development of liquid em-bolic agents. Prior to that, polyvinyl alcohol particles were most commonly used to thrombose AVMs but had a high recanalization rate.20 Cyanoacrylate agents—first isobutyl-2-cyanoacrylate (IBCA) and then NBCA—are adhesive agents that not only occlude supplying pedicles to an AVM, but incite an inflammatory reaction and fibrosis, leading to more permanent occlusion.20 N-butyl cyanoacrylate was approved for preoperative embolization of AVMs in 2000 after a randomized trial comparing NBCA to polyvinyl al-

cohol embolization showed no differences in efficacy or safety39 and it quickly became the mainstay of AVM em-bolization. More recently, the nonadhesive liquid embolic agent EVOH (Onyx, and the newer Squid [Emboflu]) has gained popularity. Unlike NBCA, this agent can be inject-ed slowly for long periods, allowing for a more controlled injection. Flow through a nidus can be somewhat redi-rected by pausing flow to allow injected EVOH to harden, creating new low-resistance pathways.10 While the advan-tages of EVOH have undoubtedly expanded the practice of AVM embolization, successful treatment of AVMs can be accomplished with both NBCA and EVOH (Table 1).24

Advanced Embolization TechniquesIn addition to advances in liquid embolic agents, new

embolization strategies hold promise for increasing the curative potential of AVM embolization.

Transvenous EmbolizationTransvenous embolization of arteriovenous fistulas is

a developing strategy. Such an approach to AVMs, how-ever, has traditionally been avoided for fear of compro-mising venous outflow without a concomitant reduction in arterial inflow, a situation that could lead to AVM rup-ture. This concept was first described in detail in 1999 by Massoud and Hademenos who proposed that sys-temic hypotension or balloon occlusion of arterial feed-ers could prevent hemorrhagic risks.35 The theoretical advantages of a transvenous approach include: 1) easier access through larger, less tortuous veins; 2) prevention of potential ischemic complications caused by arterial embolization; and 3) improved penetration of the AVM nidus. More recently, several groups have demonstrated the safe application of this approach for the endovascu-lar treatment of deep AVMs8,46 or AVMs with en passage feeders.41 Pereira et al. used this method to treat a 2-cm deep temporooccipital AVM fed by branches of the pos-terior cerebral artery with deep venous drainage.46 These investigators performed balloon occlusion of the poste-rior cerebral artery and then injected a liquid embolic agent transvenously and retrogradely into the nidus. This procedure resulted in complete occlusion that was stable on 2-month follow-up. Consoli et al. subsequently dem-onstrated successful complete occlusion of 5 deep AVMs using transvenous or combined transvenous/transarterial methods.8 Nguyen et al. successfully used transvenous embolization to occlude a small Sylvian AVM whose en passage feeding artery precluded safe transarterial embo-lization.41 Massoud has also since studied this technique in large animal experiments.34

Balloon-Assisted EmbolizationThe ability to gain flow control during embolization

with liquid embolic agents is critical for safe and effec-tive delivery, especially with high-flow shunts.10 This flow control is often completed by wedging a microcatheter into a distal arterial feeder or, in the case of EVOH, by building a cast of glue around the microcatheter tip. This latter technique is a necessary but often time-consuming


M. B. Potts et al.


first step when using EVOH for embolization. The recent development of EVOH-compatible balloons (HyperForm and HyperGlide [ev3], and Sceptor C and Sceptor XC [Mi-croVention]) provides improved flow control when using EVOH, allowing for more rapid and aggressive emboliza-tion. Balloon catheters also minimize reflux around the microcatheter, thereby theoretically minimizing the risk of catheter retention. This technology has been mostly re-ported for the treatment of dural arteriovenous fistulas,56 but has also been used successfully for the embolization of cerebral AVMs.23,42

Detachable-Tip MicrocathetersAn inherent risk when using liquid embolic agents

is that the delivery microcatheter can become “glued” in place. The adhesive nature of NBCA and other cyanoacry-lates requires that the delivery catheter be rapidly removed after injection. While the nonadhesive nature of Onyx al-lows for longer injection times and even long waiting pe-riods between injections, an extensive retrograde cast of Onyx around the catheter can also hold tight to the cath-eter, leading to possible vessel injury as the catheter is re-trieved. This risk may limit a neurointerventionalist’s tol-erance for buildup of a cast around the catheter tip, which is sometimes necessary to achieve a successful, deeply permeating embolization of the AVM nidus. The efficacy of detachable-tip microcatheters, such as the SONIC (Balt) and APOLLO (ev3), has been demonstrated with both NBCA44 and EVOH33 and will potentially allow for longer, higher volume injections of liquid embolic agents without the associated risk of retained catheters.

Double Arterial CatheterizationA major challenge in curative AVM embolization is

to fill the entire nidus before occluding the draining vein. While microcatheters can be positioned as close as possi-ble to the nidus, neurointerventionalists have little control over where liquid embolic agents flow within the nidus. With EVOH, slow injections followed by short pauses allow the embolic agent to redirect through the various channels within a nidus; however, casting of the drain-ing vein prior to complete obliteration of the nidus is a real danger that, at its worst, can lead to hemorrhage,6 but otherwise invariably means the embolization procedure must be stopped. In an attempt to improve nidal penetra-tion, Abud et al. have adopted a double arterial catheter-ization method for AVMs with more than 1 feeding ped-icle.1 Through bifemoral access, these authors advance 2 separate microcatheters into 2 separate pedicles and then perform simultaneous EVOH injections. In a series of 17 patients treated using this method, they achieved com-plete AVM occlusion in 16 patients, with 2 procedural complications leading to permanent deficits in 1 patient.1

Complications Associated With Endovascular CureAn exhaustive analysis of the complications associ-

ated with AVM embolization is beyond the scope of this review. In brief, however, the mortality incidence for the series reviewed in Table 1 ranged from 0% to 4.3% while

significant morbidity (permanent neurological deficits or clinically confirmed hemorrhages) ranged from 0% to 22%. Most of these series included only a small subset of patients for whom complete embolization was achieved and included high-grade AVMs with significant surgical or radiosurgical risks. Kim et al. specifically assessed the risk profile of AVM embolization based on the Spetzler-Martin scale and found permanent morbidities of 0% and 5% in Grade I and II AVMs, respectively.27 Ledezma et al. similarly identified Spetzler-Martin Grades I and II to be favorable factors in terms of embolization-associated complications.29 This is important because, as discussed above, low-grade AVMs are associated with complete embolization. In fact, the 2 studies reporting a subgroup of patients who were specifically selected for curative embolization based on AVM characteristics (including small size, few pedicles, and accessibility of the nidus) showed no mortality and no permanent morbidity in these highly selected patients.54,72 Interestingly, Starke et al. performed a multivariate analysis to identify several variables associated with new neurological deficits after AVM embolization and found both small (< 3 cm) and large (> 6 cm) size to be negative prognostic factors.59 Other factors included the need for more than 1 emboli-zation session and, in keeping with the components of the Spetzler-Martin score, eloquent location and deep venous drainage. Starke et al. combined these factors to form a scale to predict new deficits immediately after AVM em-bolization (Table 2).59 The concept of normal perfusion pressure breakthrough is often discussed in association with complete endovascular occlusion of AVMs, and the theoretical risks of hemorrhagic complications after com-plete occlusion have led some neurointerventionalists to stage endovascular treatments. Several experienced neu-rointerventionalists, however, report that they have not observed this phenomenon.28,62

As we further refine the indications for curative AVM embolization, choosing only highly selected patients with a high probability of cure, more studies will be needed to better define the risks involved in such curative emboliza-tion.

Durability of Complete AVM EmbolizationAn important consideration in the curative treatment

of AVMs with endovascular embolization is the durabil-ity of complete AVM occlusion. While angiography at the

TABLE 2: Arteriovenous malformation embolization prognostic score*

Factor Points ScoreRisk of Any Deficit (%)

size <3 cm 1 0 0size >6 cm 2 1 6eloquent location 1 2 15deep venous drainage 1 3 21need for >1 embolization session 1 4 50

* Developed by Starke et al.59




7

conclusion of an embolization case may show complete occlusion, AVM recurrence has been reported (Table 1). Possible reasons for AVM recurrence after complete embolization include: 1) recanalization through incom-pletely embolized channels; 2) revascularization of an unpermeated, transiently thrombosed compartment of the AVM nidus through recruitment of nearby arteries; and 3) incomplete embolization due to a nidal compart-ment not visualized during the initial embolization.62 The last situation is possible in ruptured AVMs in which a hematoma is exerting mass effect on the nidus. Among the series reviewed in Table 1 that included long-term angiographic follow-up,1,5,12,14,19,43,47,48,51,53,62,65,66,68–72 there were a total of 668 patients with immediate angiographic cure with embolization. Of these, only 4.5% had reported recurrence on follow-up angiography. The length of angi-ographic follow-up varied among these studies but some recurrent AVMs were detected as early as 3 months after embolization. Importantly, however, not a single AVM rupture or other major adverse event was reported among these patients due to recurrence of their AVMs, and most were subsequently treated using resection or radiosur-gery. These results suggest that complete angiographic occlusion of an AVM is, in fact, a durable cure but that angiographic follow-up is still warranted.

ConclusionsArteriovenous malformation treatment must be de-

finitive, with the goal of complete obliteration in all but the most complex lesions. Surgery and radiosurgery are currently the mainstays of curative AVM treatment but neither is 100% effective nor 100% risk free, even in se-lected populations. To date, curative embolization has played a very limited role in AVM management but we believe that its true potential has yet to be fully realized, especially as endovascular technologies continue to ad-vance. Still, the AVMs that are most amenable to curative embolization overlap with those most amenable to resec-tion or radiosurgical ablation. With the risks and indica-tions of surgery and radiosurgery fairly well established, we do not propose that curative embolization be used to replace these other modalities. Instead, we believe that neurointerventionalists must work to identify the popu-lation that would benefit most from curative emboliza-tion—perhaps patients with contraindications to surgery, those in whom the hemorrhagic risk of the radiosurgical latency period is too high, or those whose personal pref-erence is for endovascular treatment. Overall, the more options we have to treat AVMs, the better we can tailor our management to these complex lesions. While still un-proven, endovascular embolization has the potential to be a safe, effective, and durable curative treatment for select AVMs, broadening the armamentarium with which we can treat this disease.

Disclosure

The authors report no conflict of interest concerning the mate-rials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation

include the following. Conception and design: Potts. Acquisition of data: Potts. Analysis and interpretation of data: Potts. Drafting the article: Potts. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Study supervision: Riina.

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Manuscript submitted May 15, 2014.Accepted June 23, 2014.Please include this information when citing this paper: DOI:

10.3171/2014.6.FOCUS14228. Address correspondence to: Howard A. Riina, M.D., 530 First

Ave., SKI, Ste. 8R, New York, NY 10016. email: [email protected].


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