The n e w e ng l a n d j o u r na l of m e dic i n e

Review Article

AllanH. Ropper, M.D., Editor

Arteriovenous Malformations of the Brain

RobertA. Solomon, M.D., and E.Sander Connolly, Jr., M.D.

A
rteriovenous malformations of the brain are congenital From Columbia University College of
anomalies of the blood vessels that are derived from maldevelopment of the Physicians and Surgeons and the Depart-
ment of Neurological Surgery, New York
capillary network, allowing direct connections between cerebral arteries Presbyterian Hospital, New York. Ad-
and veins.1 The most common presenting symptoms are cerebral hemorrhage and dress reprint requests to Dr. Solomon at
seizures. Focal neurologic deficits and headaches may develop independent of 710 W. 168th St., New York, NY 10032, or
at ras5@columbia.edu.
cerebral bleeding.2 As a result of the widespread use of brain imaging, arteriove-
nous malformations are increasingly being discovered incidentally.3 N Engl J Med 2017;376:1859-66.
DOI: 10.1056/NEJMra1607407
Four therapeutic approaches have evolved to treat arteriovenous malformations: Copyright 2017 Massachusetts Medical Society.
surgery, radiosurgery, embolization, and conservative treatment. There is a lack of
consensus about the choice of treatment, and the specialty of the physician who
first sees a patient with an arteriovenous malformation often determines manage-
ment.4 A major issue that complicates clinical decision making is the variation
among arteriovenous malformations in the brain with respect to size, location,
and detailed vascular anatomy.5
This review addresses arteriovenous malformations involving the brain parenchyma
(pial arteriovenous malformations), which are characterized by a nidus of abnormal
vessels that form a direct transition between arteries and veins without intervening
capillaries. Excluded from this discussion are direct cortical arteriovenous fistulas,
venous malformations, cavernous malformations, and dural arteriovenous fistulas.

R isk of Cer ebr a l Hemor r h age

The annual risk of hemorrhage from a cerebral arteriovenous malformation is ap-
proximately 3%, but depending on the clinical and anatomical features of the mal-
formation, the risk may be as low as 1% or as high as 33%. The risk of cerebral
bleeding is increased if the patient has had previous episodes of bleeding (hazard
ratio, 3.2; 95% confidence interval [CI], 2.1 to 4.3) or if the malformation is located
deep within the brain or brain stem (hazard ratio, 2.4; 95% CI, 1.4 to 3.4) or is
characterized by exclusively deep venous drainage (hazard ratio, 2.4; 95% CI, 1.1 to
3.8).6 On the basis of various models, patients with none of these risk factors are at
very low risk for cerebral hemorrhage (<1% annually), patients with one of these factors
are at low risk (3 to 5% annually), patients with two factors are at medium risk (8 to
15% annually), and patients with all three factors are at high risk (>30% annually).
Other anatomical features that have been associated with bleeding include a
berry aneurysm on an artery feeding the arteriovenous malformation (hazard ratio,
1.8; 95% CI, 1.6 to 2.0) and restriction of venous drainage from the malformation.5
Restriction of venous drainage occurs from narrowing or occlusion of one or more
of the principal draining veins of the arteriovenous malformation. Consequently,
venous outflow restriction is associated with the highest risk when the malforma-
tion has only a single draining vein.7
The clinical consequences of cerebral hemorrhage from an arteriovenous mal-
formation depend on the extent of injury to adjacent brain structures. Damage to
regions of the brain that control motor, sensory, visual, and language functions
(termed eloquent areas of the cortex), damage to deep white-matter pathways

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 The n e w e ng l a n d j o u r na l
and basal ganglia structures, and secondary eleva-
tions of intracranial pressure are associated with
a poor clinical outcome. Of patients who survive
the initial hemorrhage, approximately 25% ulti-
mately have no neurologic deficit, 30% have mild-
to-moderate deficits, and 45% have severe defi-
cits.8 Three months after hemorrhage, almost
20% of initial survivors have died, and one third
of patients remain moderately disabled.8
Specific anatomical features of arteriovenous
malformations form the basis of several com-
monly used grading scales that have been vali-
dated as predictive of the treatment outcome.
The most widely used scale for this purpose, the
SpetzlerMartin grading scale (Table1), was
originally developed to predict the outcome of
microsurgical treatment but can also be used to
predict the radiosurgical outcome.9 The five-grade
scale incorporates points for three features of
the arteriovenous malformation: the diameter
(<3 cm [1 point], 3 to 6 cm [2 points], or >6 cm
[3 points]), presence of deep venous drainage
(1 point), and involvement of an eloquent loca-
tion such as the motor, sensory, language, and
visual cortex or basal ganglia (1 point). Lower
grades (lower total points) indicate lower risk of
treatment. Even more accurate prediction of the
radiosurgical outcome has been achieved with
the Virginia Radiosurgery AVM Scale (VRAS).10,11
The VRAS assigns one of five grades on the ba-
sis of points for volume size (<2 cm3 [0 points],
2 to 4 cm3 [1 point], or >4 cm3 [2 points]), elo-
quent location (1 point), and history of cerebral
hemorrhage (1 point). Grade 1 arteriovenous
malformations have 0 points, and grade 5 mal-
formations have 4 points.
T r e atmen t of Cer ebr a l
A r ter iov enous M a l for m at ion
Stereotactic Radiosurgery
Stereotactic radiosurgery is a well-studied treat-
ment for cerebral arteriovenous malformations.12
Equivalent technologies, such as a gamma knife,
cyber knife, and proton beam, deliver focused,
high-dose radiation to the arteriovenous malfor-
mation, which induces gradual sclerosis of the
blood vessels and thrombosis of the lesion. Suc-
cessful obliteration of the arteriovenous malfor-
mation is predicted on the basis of the size of
the lesion and the dose of radiation delivered
to the margins of the malformation (the mar-
ginal dose).
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of m e dic i n e
Table 1. SpetzlerMartin Grading Scale for Arteriovenous
Malformations of the Brain.*
Lesion Characteristic Points
Size
Small (<3 cm) 1
Medium (36 cm) 2
Large (>6 cm) 3
Location
Noneloquent 0
Eloquent 1
Veins
Superficial 0
Deep 1
* The scale is used to make decisions about treatment
risks while taking into account the anatomical character-
istics of a cerebral arteriovenous malformation. The grade
is the sum of points assigned to the size of the lesion,
the location (in or not in the eloquent cortex), and the
presence or absence of deep venous drainage.
Lesions that respond most favorably to stereo-
tactic radiosurgery are very small, VRAS grade 1
or 2 malformations (<4 cm3), which are treated
with a radiation dose of 18 Gy or more. With
this treatment, the rate of lesion obliteration,
assessed by means of either magnetic resonance
imaging (MRI) or angiography, approaches 80%.
Larger lesions (grades 3, 4, or 5) are treated with
lower marginal radiation doses and are cured less
than half the time (48%), and treatment is associ-
ated with a considerable risk of radiation-induced
necrosis of the adjacent brain (3%) (Fig.1).11
One of the greatest limitations of stereotactic
radiosurgery for an arteriovenous malformation
is the substantial delay in the radiographic oblit-
eration of the lesion, which takes 2 to 4 years on
average. Most data suggest that the risk of bleed-
ing during this period is only slightly lower than
the risk during the period before treatment.13
In a widely cited case series of stereotactic
radiosurgery for arteriovenous malformations,
2236 patients were followed at eight centers for
a mean of 89 months. The annual risk of hemor-
rhage after radiosurgery was 1%. Complete oblit-
eration of the arteriovenous malformation with-
out post-treatment hemorrhage or permanent,
symptomatic, radiation-induced brain injury was
achieved in 60% of the patients.11 SpetzlerMartin
grade 1 or 2 lesions (most of which were <3 cm
in diameter) had the best treatment outcomes,
with 70% of the lesions disappearing without
complications, as compared with 56% for grade
3 lesions (most of which were >3 cm) and 35%
 Arteriovenous Malformations of the Br ain

A B C

Figure 1. Grade 3 Arteriovenous Malformation in a 52-Year-Old Woman.

The patient presented with a small intraventricular hemorrhage into the left temporal horn. A lateral carotid angiogram
(Panel A) shows a 1.8-cm arteriovenous malformation (black arrow) fed by lenticulostriate vessels from the left middle
cerebral artery, with deep venous drainage into the vein of Galen (white arrow). The arteriovenous malformation is
grade 3 on both the SpetzlerMartin scale and the Virginia Radiosurgery AVM Scale because it is located deep with-
in the dominant temporal lobe. An axial T2-weighted MRI (Panel B), obtained 3 years after gamma knife radiosurgery
was performed with 18 Gy to the margins of the malformation, shows no residual flow voids and only mild radiation
changes in the brain at the site of the treated malformation. A lateral angiogram (Panel C) obtained 3 years after treat-
ment shows no flow in the arteriovenous malformation and obliteration of the lesion, with no neurologic deficit.

for grade 4 lesions (all of which were >3 cm,

with some >6 cm) (Table2).
Given the poor response of large, Spetzler
Martin grade 4 or 5 lesions to radiosurgical
treatment, as well as impediments to the use of
the other therapeutic approaches described be-
low, staged, focused radiotherapy has been
proposed as an alternative. With this approach,
the entire arteriovenous malformation is treated
initially with low-dose radiation (12 to 16 Gy) to
limit radiation-induced complications and is re-
treated with a second dose after an interval of
2 to 4 years.17 A similar method is progressive,
staged-volume radiotherapy, which divides the
lesion into sections of approximately equal vol-
ume, with the sections treated successively in
separate sessions at intervals of 2 to 9 months.18-20
A third experimental treatment is hypofraction-
ated stereotactic radiosurgery, in which patients
are treated with 6 to 7 Gy of radiation to the
entire margin of the arteriovenous malforma-
tion in five fractions, for a total dose of 30 to
35 Gy.21 Although clinical series assessing these
variations in staged radiotherapy have been
small and uncontrolled, the combined 5-year
rate of obliteration or near-obliteration of the
lesion without the appearance of a new neuro-
logic deficit has been approximately 50%.22 Fur-
thermore, the rate of cerebral hemorrhage after
these procedures has been as high as 31% at 10
years, and permanent adverse radiation effects
have been seen in 4 to 28% of patients.
Table 2. Overall Favorable Outcomes of Surgical Removal
and Radiosurgery for the Treatment of Cerebral Arterio
venous Malformation, According to the SpetzlerMartin
Grade.*
SpetzlerMartin
Grade Favorable Outcome
Microsurgery Radiosurgery
percent of patients
1 95 70
2 95 70
3 80 56
4 30 35
5 30 35
* Favorable outcome after microsurgery is defined as com-
plete cure of the arteriovenous malformation, according
to angiography, with no neurologic deficit that would pre-
vent the patient from resuming all normal activities and
full-time employment.14-16 Favorable outcome after radio-
surgery is defined as obliteration of the arteriovenous
malformation (confirmed by MRI or angiography), with-
out post-treatment hemorrhage or permanent symptom-
atic radiation-induced brain injury.11
Endovascular Embolization Therapy
Endovascular treatment of arteriovenous malfor-
mations is achieved by microcatheter delivery of
agents such as N-butyl-2-cyanoacrylate or a non-
adhesive ethylene vinyl alcohol copolymer. The
procedure requires superselective catheterization
of arteries feeding the arteriovenous malforma-
tion, with the goal of filling the nidus and oc-
cluding feeding vessels while preserving collat-

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 The n e w e ng l a n d j o u r na l
eral vessels to the normal adjacent brain. Most
often, partial embolization has been used in
preparation for definitive microsurgical resection.
With larger arteriovenous malformations in par-
ticular, preliminary embolization causes a staged
reduction in blood flow and ameliorates the dis-
turbed regional vascular autoregulation, which
can otherwise result in bleeding into the normal
surrounding brain during and after surgical re-
section, a phenomenon termed perfusion pres-
sure breakthrough.23 Preoperative embolization
also reduces surgical morbidity by occluding
deep arterial feeding vessels, minimizing the
need for extensive dissection into deep white-
matter pathways adjacent to the arteriovenous
malformation.24 Nevertheless, preoperative em-
bolization has resulted in persistent neurologic
deficits in 2.5% of patients.24
Embolization before radiosurgery has also been
proposed to reduce large arteriovenous malfor-
mations to a size that permits delivery of a more
therapeutic marginal dose.25 Preradiosurgical em-
bolization may also occlude aneurysms on feed-
ing arteries and aneurysms that occur within the
nidus of the arteriovenous malformation. In pa-
tients presenting with bleeding from such aneu-
rysms, targeted embolization of the aneurysms
before radiosurgery probably reduces the risk of
recurrent bleeding during the interval between
radiosurgery and the disappearance of the arterio-
venous malformation.26 This approach has been
especially effective in dealing with the high-risk
configuration of an aneurysm on a feeding artery
that has ruptured in the posterior fossa.
The drawback of embolization before stereo-
tactic radiosurgery is that embolic material in the
malformation can shield the nidus from ioniz-
ing radiation and may obscure the outlines of the
malformation, making targeting with radiothera-
py difficult.27 In keeping with this limitation,
nearly all studies have shown that preliminary
embolization reduces the efficacy of subsequent
stereotactic radiosurgery.11,27,28
Since the introduction of a second-generation
liquid embolic agent that can be more precisely
infused into the nidus of an arteriovenous mal-
formation, more aggressive embolization proce-
dures have been developed that are designed to
obliterate the entire lesion without adjuvant ra-
diosurgery or microsurgery. In the multicenter
BRAVO (Brain Arteriovenous Malformations Em-
bolization with Onyx) trial, 117 patients were
treated with the newer agent with the goal of
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of m e dic i n e
complete cure.29 The treatment was associated
with a mortality of 4.3% and morbidity of 5.1%;
100% occlusion was achieved in only 23.5% of
the patients, with 82.0% of partially treated sur-
vivors ultimately requiring radiosurgery or micro-
surgery. A single-center study of selected pa-
tients with large arteriovenous malformations
(>3 cm in diameter) showed a higher obliteration
rate with attempted curative embolization (50%)
but at a cost of 11% morbidity and 2% mortal-
ity.30 These results raise the question of whether
this approach can improve on the natural his-
tory of the disorder if left untreated.
Microsurgical Approaches
Craniotomy for surgical resection of an arterio-
venous malformation was first reported in the
1920s, but the surgical procedure has been re-
fined with the use of the operating microscope,
stereotactic guidance, and modern instrumenta-
tion.31 Microsurgical cauterization of feeding ar-
teries and of draining veins allows for complete
removal of the arteriovenous malformation as a
single specimen but necessarily poses some risk
to contiguous brain tissue, since the dissection
plane is outside the boundary of the malforma-
tion. The clinical implications of any damage to
the surrounding tissue depend on the functional
significance of the brain regions contained in
the margins of the proposed surgical resection,
and these implications have to be considered
during the process of treatment selection and
preoperative evaluation.
The SpetzlerMartin grading scale has been
used to determine the risk of postoperative neuro-
logic deficits or death as a result of microsurgical
dissection of an arteriovenous malformation of the
brain.14 In a large, single-center series of patients
with unruptured arteriovenous malformations of
the brain, the risk of a new and permanent deficit
after microsurgery was only 2% for Spetzler
Martin grade 1 or 2 lesions, as compared with a
risk of 17% for grade 3 lesions and 45% for grade
4 or 5 lesions.15 Several studies have provided
similar results and indicate that the 2% morbidity
among patients with grade 1 or 2 lesions (Fig.2) is
associated with a mortality of 0.3%.14,16
The variability in surgical outcomes among
published studies, especially for grade 3 or
higher malformations, may reflect selection bias
and differences in the preoperative status of the
patients.15 Outcomes for unruptured malforma-
tions are generally better than outcomes for le-
 Arteriovenous Malformations of the Br ain

A B C

Figure 2. SpetzlerMartin Grade 1 Arteriovenous Malformation in a 22-Year-Old Man.

An MRI obtained for an unrelated reason (Panel A) shows an incidental 2-cm arteriovenous malformation in the left frontal lobe
(arrow). A lateral carotid angiogram (Panel B) shows that the malformation (arrow) is supplied principally by a dilated branch
of the left middle cerebral artery, with superficial venous drainage into the sylvian fissure. Preliminary embolization through the
middle cerebral artery feeder was followed by craniotomy and microsurgical resection of the malformation. A postoperative an-
giogram (Panel C) shows no residual flow and complete cure of the lesion. The patient recovered without neurologic deficits.

sions that have bled and caused neurologic defi-
cits before surgery. Moreover, published results
reflect experience in specialty centers that oper-
ate on large numbers of patients and may not
reflect risks at centers with lower case volumes.
Observat ion v er sus
In terv en t ion
Choosing among the various types of treat-
ment for cerebral arteriovenous malformation is
complex and should be guided by the specific
characteristics of the vascular lesion (Tables 1
and 2). The SpetzlerMartin scale summarizes
these characteristics, which are related to the
outcomes that have been attained with each
treatment approach (Fig.3).

The risks associated with treatment of cerebral Grade 1 or 2 Malformations

arteriovenous malformations must be balanced
against the risks associated with no treatment.
The Randomized Trial of Unruptured Brain
Arteriovenous Malformations (ARUBA),32 which
randomly assigned 226 patients with unruptured
cerebral arteriovenous malformations to obser-
vation or intervention (radiosurgery, embolization,
or surgery), was stopped early by a National Insti-
tutes of Health safety monitoring board because
of the superiority of observation over interven-
tion. The trial has been criticized because the
data were not analyzed according to the type of
intervention, the patient-specific factors that pre-
dict the risk associated with an intervention, or
the anticipated risk of rupture on the basis of
the characteristics of the lesion.7 The trial con-
firmed a 2.3% annual rupture rate in the group
assigned to observation but did not address the
surgical outcome for patients with grade 1 or 2
arteriovenous malformations, who are the best
candidates for surgery.14,15 Perhaps the strongest
criticism of this trial was that the mean follow-
up was only 33 months, a period that is too brief
to assess the long-term risk of rupture or the
complete therapeutic effects of radiosurgery.
In a meta-analysis of 137 observational studies
with a total of 13,398 patients and 46,314 patient-
years of follow-up, procedure-related complica-
tions leading to permanent neurologic deficits
or death occurred in 7% of patients who under-
went microsurgery or embolization and in 5% of
those who underwent stereotactic radiosurgery.33
Obliteration of the lesion, documented by either
MRI or angiography, was achieved in 96% of
patients after microsurgery, in 38% after radio-
surgery, and in 13% after embolization alone. On
the basis of these findings, surgery is generally
regarded as the best initial option for patients
with arteriovenous malformations associated with
a low risk of a poor treatment outcome, particu-
larly grade 1 or 2 lesions. In centers that treat
large numbers of cerebral arteriovenous malfor-
mations, complete removal or obliteration of the
lesion without complications has been achieved
with surgery in more than 95% of cases and
with radiosurgery in 70% of cases.34
Grade 3 Malformations
The choice of treatment is more complex for grade
3 arteriovenous malformations than for lower-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

grade lesions. For example, some grade 3 lesions Figure 3 (facing page). Examples of SpetzlerMartin
are small, deep arteriovenous malformations in Grades 1 through 4 Arteriovenous Malformations
eloquent parts of the brain. These malformations (AVMs) and Treatment Options.
have deep venous drainage, which is associated Grade 1 lesions are small, superficial malformations
with an increased risk of spontaneous bleeding that do not affect eloquent regions of the brain. Grade 2
if left untreated.10 Radiosurgical cure without com- lesions either affect eloquent brain or are larger than 3 cm
in diameter. Microsurgery, embolization, and stereotactic
plications is most likely for small grade 3 lesions, radiosurgery are all appropriate treatment options for grade
irrespective of factors such as eloquent location or 1 and grade 2 malformations. The grade 3 malformation
deep venous drainage. Therefore, patients with shown is small but deeply located in eloquent brain tissue,
such lesions, especially those who present without with drainage into the deep venous system. Radiosurgery
hemorrhage, have been treated with radiosurgery. is the best treatment option for unruptured lesions in this
category. Grade 4 lesions are all larger than 3 cm in diam-
The treatment of larger grade 3 malformations eter and involve eloquent brain. Such lesions are generally
that involve eloquent cortex is more controversial. treated conservatively, since all treatment options are
For unruptured lesions in this category, there is dangerous and often unsuccessful in achieving a cure.
little evidence that the outcome of any treatment
approach is better than the outcome without treat-
ment. Surgical morbidity has been at least 15%, possible exception of life-threatening cerebral
but published case studies of grade 3 arteriovenous hemorrhage and progressive, disabling symptoms,
malformations treated surgically may not accu- especially in young patients have generally met
rately reflect the risks because of selection bias, with failure and poor outcomes. Surgical series
since these studies have often eliminated patients suggest that overall management-related morbid-
with malformations that were large or that abutted ity is close to 50%, and endovascular and radio-
critical cerebral tissue.34 The radiosurgical outcome surgical approaches have failed to cure these mal-
of complete obliteration without postsurgical formations in the majority of cases.34 When
hemorrhage and without permanent, symptomat- patients present with a grade 4 or 5 arteriove-
ic, radiation-induced brain injury is achieved in less nous malformation and cerebral hemorrhage,
than 50% of patients with grade 3 lesions that are palliative endovascular procedures designed to
larger than 3 cm in diameter. Even with the use of selectively obliterate portions of the malforma-
preliminary endovascular embolization to reduce tion involved with the hemorrhage, or therapeu-
the size of the lesion, followed by radiosurgery, tic occlusion of an aneurysm in a feeding artery,
outcomes have not been better than those in un- may reduce the risk of subsequent hemorrhage.
treated patients. However, the age of the patient,
the psychological effect of fear that the arteriove- Sum m a r y
nous malformation will rupture, and the severity
of the neurologic deficit that might follow treat-
The available data are not adequate to establish
ment are factors that require consideration in mak-
definitive treatment guidelines, but they suggest
ing treatment decisions for individual patients.
that most patients with ruptured arteriovenous
Ruptured grade 3 lesions are particularly prob-
malformations and many selected patients with
lematic because of a high rate of rebleeding if left
unruptured malformations should be treated
untreated.5,6 When there is an associated ruptured
rather than left untreated. The ARUBA findings
aneurysm, the risk of bleeding is even higher, and
provide another perspective on this approach;
urgent endovascular obliteration of the vessel bear-
however, the trials limitations, noted above,
ing the aneurysm is usually undertaken. Ruptured
must be considered. Similar comparative studies
arteriovenous malformations without a clearly that address the known risks associated with
identified point of hemorrhage should also be con-
particular features of arteriovenous malforma-
sidered for multimodal treatment, with preopera-
tions are needed. Patients with SpetzlerMartin
tive embolization followed by either microsurgical
grade 1 or 2 lesions are currently treated with
resection or stereotactic radiosurgery. microsurgery, but radiosurgery and endovascu-
lar approaches are options for some patients.
Grade 4 or 5 and Brain-Stem Malformations SpetzlerMartin grade 4 or 5 lesions tend to do
Attempts at curative treatment of grade 4 and best with conservative management but occa-
grade 5 arteriovenous malformations and most sionally benefit from partial endovascular treat-
intrinsic brain-stem malformations with the ment that addresses features indicating a high risk

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 Arteriovenous Malformations of the Br ain

AVM Grade Treatment Options

Grade 1 Microsurgery

Size 1 point
Eloquence 0 points 0 3 6
Venous drainage 0 points cm

Grade 2

Embolization

Size 2 points
Eloquence 0 points 0 3 6
Venous drainage 0 points cm

Grade 3

Size 1 point
Eloquence 1 point 0 3 6
Venous drainage 1 point cm

Grade 4 Radiosurgery

Size 3 points
Eloquence 1 point 0 3 6
Venous drainage 0 points cm

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Copyright 2017 Massachusetts Medical Society. All rights reserved.
 Arteriovenous Malformations of the Br ain

of cerebral hemorrhage, such as aneurysms on malformations calls for treatment by a collabora-

feeding arteries or in the nidus. Grade 3 lesions
that are deep and small, especially those that have
not ruptured, are usually best treated with radio-
surgery. Several management options are avail-
able for large grade 3 lesions, including observa-
tion. The complexity of cerebral arteriovenous
tive team of physicians who can guide interven-
tion for individual patients by considering the
complete array of available treatment options.
No potential conflict of interest relevant to this article was
reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.

References
1. Friedlander RM. Arteriovenous malfor-
mations of the brain. N Engl J Med 2007;
356:2704-12.
2. Berman MF, Sciacca RR, Pile-Spell-
man J, et al. The epidemiology of brain ar-
teriovenous malformations. Neurosurgery
2000;47:389-97.
3. Stapf C, Mohr JP, Pile-Spellman J, Solo-
mon RA, Sacco RL, Connolly ES Jr. Epide-
miology and natural history of arteriove-
nous malformations. Neurosurg Focus
2001;11(5):e1.
4. Cockroft KM, Jayaraman MV, Amin-
Hanjani S, Derdeyn CP, McDougall CG,
Wilson JA. A perfect storm: how A Ran-
domized Trial of Unruptured Brain Arte-
riovenous Malformations (ARUBAs) trial
design challenges notions of external va-
lidity. Stroke 2012;43:1979-81.
5. Gross BA, Du R. Natural history of ce-
rebral arteriovenous malformations: a meta-
analysis. J Neurosurg 2013;118:437-43.
6. Stapf C, Mast H, Sciacca RR, et al. Pre-
dictors of hemorrhage in patients with un-
treated brain arteriovenous malformation.
Neurology 2006;66:1350-5.
7. Sahlein DH, Mora P, Becske T, et al.
Features predictive of brain arteriovenous
malformation hemorrhage: extrapolation to
a physiologic model. Stroke 2014;45:1964-70.
8. Fukuda K, Majumdar M, Masoud H,
et al. Multicenter assessment of morbidity
associated with cerebral arteriovenous mal-
formation hemorrhages. J Neurointerv Surg
2016 June 22 (Epub ahead of print).
9. Spetzler RF, Martin NA. A proposed
grading system for arteriovenous malfor-
mations. J Neurosurg 1986;65:476-83.
10. Pollock BE, Storlie CB, Link MJ, Staf-
ford SL, Garces YI, Foote RL. Comparative
analysis of arteriovenous malformation
grading scales in predicting outcomes
after stereotactic radiosurgery. J Neurosurg
2017;126:852-8.
11. Starke RM, Kano H, Ding D, et al. Ste-
reotactic radiosurgery for cerebral arterio-
venous malformations: evaluation of long-
term outcomes in a multicenter cohort.
J Neurosurg 2017;126:36-44.
12. Ajiboye N, Chalouhi N, Starke RM,
Zanaty M, Bell R. Cerebral arteriovenous
malformations: evaluation and manage-
ment. ScientificWorldJournal 2014;2014:
649036.
13. Maruyama K, Kawahara N, Shin M,
et al. The risk of hemorrhage after radio-
surgery for cerebral arteriovenous malfor-
mations. N Engl J Med 2005;352:146-53.
14. Spetzler RF, Ponce FA. A 3-tier classifi-
cation of cerebral arteriovenous malforma-
tions: clinical article. J Neurosurg 2011;
114:842-9.
15. Bervini D, Morgan MK, Ritson EA,
Heller G. Surgery for unruptured arteriove-
nous malformations of the brain is better
than conservative management for selected
cases: a prospective cohort study. J Neuro-
surg 2014;121:878-90.
16. Potts MB, Lau D, Abla AA, Kim H,
Young WL, Lawton MT. Current surgical re-
sults with low-grade brain arteriovenous
malformations. J Neurosurg 2015;122:912-
20.
17. Yamamoto M, Akabane A, Matsumaru
Y, Higuchi Y, Kasuya H, Urakawa Y. Long-
term follow-up results of intentional 2-stage
Gamma Knife surgery with an interval of
at least 3 years for arteriovenous malfor-
mations larger than 10 cm3. J Neurosurg
2012;117:Suppl:126-34. sis of adverse radiation effects following
18. Seymour ZA, Sneed PK, Gupta N, et al.
Volume-staged radiosurgery for large arte-
riovenous malformations: an evolving para-
digm. J Neurosurg 2016;124:163-74.
19. Nagy G, Grainger A, Hodgson TJ, et al.
Staged-volume radiosurgery of large arterio-
venous malformations improves outcome
by reducing the rate of adverse radiation
effects. Neurosurgery 2016 February 15
(Epub ahead of print).
20. Hanakita S, Shin M, Koga T, Igaki H,
Saito N. Outcomes of volume-staged radio-
surgery for cerebral arteriovenous malfor-
mations larger than 20 cm3 with more
than 3 years of follow-up. World Neurosurg
2016;87:242-9.
21. Lindvall P, Grayson D, Bergstrm P,
Bergenheim AT. Hypofractionated stereo-
tactic radiotherapy in medium-sized to
large arteriovenous malformations. J Clin
Neurosci 2015;22:955-8.
22. Chen JC, Mariscal L, Girvigian MR, et
al. Hypofractionated stereotactic radiosur-
gery for treatment of cerebral arteriove-
nous malformations: outcome analysis with
use of the modified Arteriovenous Malfor-
mation Scoring System. J Clin Neurosci
2016;29:155-61.
23. Young WL, Kader A, Ornstein E, et al.
Cerebral hyperemia after arteriovenous mal-
formation resection is related to break-
through complications but not to feeding
artery pressure. Neurosurgery 1996;38:
1085-93.
24. Starke RM, Komotar RJ, Otten ML, et al.
Adjuvant embolization with N-butyl cyano-
acrylate in the treatment of cerebral arte-
riovenous malformations: outcomes, com-
plications, and predictors of neurologic
deficits. Stroke 2009;40:2783-90.
25. Lee CC, Chen CJ, Ball B, et al. Stereo-
tactic radiosurgery for arteriovenous mal-
formations after Onyx embolization: a case-
control study. J Neurosurg 2015;123:126-35.
26. Alexander MD, Cooke DL, Hallam DK,
Kim H, Hetts SW, Ghodke BV. Less can be
more: targeted embolization of aneurysms
associated with arteriovenous malforma-
tions unsuitable for surgical resection. In-
terv Neuroradiol 2016;22:445-51.
27. Ding D, Starke RM, Kano H, et al. Ste-
reotactic radiosurgery for Spetzler-Martin
Grade III arteriovenous malformations: an
international multicenter study. J Neuro-
surg 2017;126:859-71.
28. Cohen-Inbar O, Lee CC, Xu Z, Schle
singer D, Sheehan JP. A quantitative analy-
Gamma Knife radiosurgery for arteriove-
nous malformations. J Neurosurg 2015;123:
945-53.
29. Pierot L, Cognard C, Herbreteau D, et
al. Endovascular treatment of brain arte-
riovenous malformations using a liquid em-
bolic agent: results of a prospective, multi-
centre study (BRAVO). Eur Radiol 2013;23:
2838-45.
30. Saatci I, Geyik S, Yavuz K, Cekirge HS.
Endovascular treatment of brain arteriove-
nous malformations with prolonged intra-
nidal Onyx injection technique: long-term
results in 350 consecutive patients with
completed endovascular treatment course.
J Neurosurg 2011;115:78-88.
31. Kretzer RM, Coon AL, Tamargo RJ.
Walter E. Dandys contributions to vascular
neurosurgery. J Neurosurg 2010;112:1182-
91.
32. Mohr JP, Parides MK, Stapf C, et al.
Medical management with or without inter-
ventional therapy for unruptured brain ar-
teriovenous malformations (ARUBA): a mul-
ticentre, non-blinded, randomised trial.
Lancet 2014;383:614-21.
33. van Beijnum J, van der Worp HB, Buis
DR, et al. Treatment of brain arteriovenous
malformations: a systematic review and
meta-analysis. JAMA 2011;306:2011-9.
34. Morgan MK, Stoodley MA, Fuller JW.
Comparison between surgery and Gamma
Knife radiosurgery for brain AVMs. J Neuro-
surg 2017;126:338-41.
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