20 
Vascular Malformations (Arteriovenous
Malformations and Dural
Arteriovenous Fistulas)
SA MUEL KALB, BRADLEY A. GROSS, PETER NAKAJI
CLINICAL PEARLS
• Cerebral arteriovenous malformations (AVMs) are high-flow,
high-pressure vascular anomalies that cause neurologic
morbidity, resulting in seizures, ischemic or steal symptoms, or
hemorrhage.
• Cerebral AVMs are classified on the basis of treatment risk,
including nidus size, location within eloquent or noneloquent
tissue, and pattern of venous drainage (superficial versus
deep).
• Complete obliteration of AVMs is necessary to reduce the risk
of bleeding and to mitigate the risk of seizures. The medical
literature lacks strong evidence that partial treatment confers
protection from hemorrhage. Treatment modalities for cerebral
or spinal AVMs include surgical resection, radiosurgery,
endovascular occlusion, or a combination of these approaches.
• Cerebral dural arteriovenous fistulas (dAVFs) are a distinct
entity of vascular malformation composed of direct
Introduction
Arteriovenous malformations (AVMs) and dural arteriovenous
fistulas (dAVFs) are the two most common types of arterio-
venous shunts in the central nervous system. AVMs are a
source of neurologic morbidity due to associated ischemic or
steal symptoms, hemorrhage, seizures (if cranial), or venous
hypertension (if spinal). AVMs are composed of pial or dural
arterial vessels that tangle and coalesce into a nidus that shunts
blood flow into leptomeningeal veins in the absence of a capil-
lary network. In contrast, patients with cerebral dAVFs may
present with pulsatile tinnitus, ocular symptoms, or neurologic
deficits secondary to venous hypertension. Cerebral dAVFs are
composed of meningeal arteries that shunt blood flow within
the leaflets of the dura into a venous sinus or into the lepto-
meningeal veins. Patients with spinal dAVFs typically present
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connections between meningeal arteries and dural venous
sinuses or leptomeningeal veins. Neurologic morbidity
associated with dAVFs can result in tinnitus, ocular symptoms,
venous hypertension with neurologic deficits, and intracranial
hemorrhage.
• Cerebral dAVFs are classified by their risk of causing venous
hypertension or hemorrhage due to the presence or absence
of cortical venous drainage, but they can also be influenced by
the presence of venous ectasia and the initial modality of
presentation.
• Spinal dAVFs are the most common type of spinal
arteriovenous shunt. They cause neurologic morbidity due to
venous hypertension. Surgical disconnection is associated with
exceedingly high obliteration rates and low morbidity. Select
spinal dAVFs can be occluded endovascularly.
with signs of spinal venous hypertension; these lesions are
composed of radicular artery feeders that shunt within the
leaflets of the dura into an intradural vein at the junction of
the nerve root dura and the thecal sac.
Since the 1960s, the quest to understand these lesions has
led to the elucidation of many concepts in vascular physiology,
anatomy, and embryology. The management of both AVMs
and dAVFs has also evolved considerably, with advancements
in neuroimaging, surgical techniques, and neuroendovascu-
lar diagnostics and treatment procedures. Nevertheless, the
natural history and unpredictable course of both types of vas-
cular lesions continue to present a challenge for neurosurgeons
and interventionalists, motivating multidisciplinary collab-
orative approaches for a better understanding of the disease
process in the hope of improving overall management and
outcomes.
313
314 PART 3 Vascular Neurosurgery

Classification and Definitions

The formation of a vascular malformation within the central
nervous system is believed to be a dysplastic process. Four types
of dysplastic vascular malformations can be found in the
central nervous system: developmental venous anomalies, cap-
illary telangiectasias, cavernous malformations, and AVMs and
arteriovenous fistulas (AVFs). Developmental venous anoma-
lies are venous structures that drain normal brain tissue through
an abnormally straight venous channel that is usually deep and
fed by a cluster of veins typically referred to as a caput medusa
(Fig. 20.1A). Patients with developmental venous anomalies
are almost never symptomatic and should not be treated. Cap-
illary telangiectasias are small dysplastic capillary vessels that
are believed to be precursor lesions to cavernous malforma-
tions. Cavernous malformations are low-pressure, berry-like
vascular clusters of capillaries (Fig. 20.1B). They have a ten-
dency to bleed and to grow slowly. Over time, they often
provoke seizures or deficits from local tissue effects, which then
necessitates their surgical removal.
The last two categories of vascular malformations, AVMs
and dAVFs, are the main focus of this chapter. The character-
istic that separates AVMs and AVFs from other dysplastic
vascular malformations is the presence of an arteriovenous A
shunt through which oxygenated blood passes directly from
the arteries into the venous system without gas exchange in a
capillary bed. Unlike other vascular malformations, these
shunts are characterized by high blood flow and high-pressure
flow.
The three main types of AVMs found in the nervous system
are plexiform, fistulous, or a combination of the two. The
fistulous type (AVF) is present when an artery connects directly
to a vein without a capillary bed in between. AVFs most com-
monly occur within the dural leaflets in the central nervous
system as an acquired pathology termed a dAVF. Pial AVFs,
often considered congenital lesions, are far less common and
are typically discovered in younger patients. A plexiform mal-
formation (AVM) is an artery that connects to a network of
poorly differentiated, immature vessels (nidus) before reaching
a vein (Fig. 20.2).
There are numerous classification schemes for AVMs and
dAVFs. Although spinal arteriovenous shunt classifications B
have traditionally focused on the anatomy of the lesion itself,
• Figure 20.1  (A) On imaging, a developmental venous anomaly often
cerebral AVM classifications have historically aimed at helping
appears as a straight channel topped by a starburst of feeding veins. (B)
both the patient and the physician understand the risk of Illustration depicts the typical appearance of a cavernous malformation
various treatment modalities. Several classifications have been (arrow) as berry-like in configuration. Cavernous malformations can vary
proposed with the same goal: accuracy of treatment and ease considerably in size and location. (A, Used with permission from Barrow
of applicability.1,2 The Spetzler-Martin grading system3 (Fig. Neurological Institute, Phoenix, Arizona. B, Used with permission from
20.3) is the most widely used and the most commonly cited Thieme.)
classification for predicting the morbidity of surgical resection
of an AVM. It is based on three simple variables: size of the
malformation (1–3 points), the eloquence of the location (1 may be considered for conservative management because of the
point, if in an eloquent location), and the presence of deep high anticipated risk of surgical morbidity. It is important to
venous drainage (1 point, if present). The sum of all three emphasize that this classification scheme refers to surgical risk
variables provides the final grade, which ranges from I to V. and is based on the experience of a highly experienced neuro-
Patients with a grade I or II AVM tolerate resection with surgical team; external validity may thus be limited. In addi-
acceptable morbidity, whereas those with a grade IV or V AVM tion, other factors such as perforator supply and diffuse nidal

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 CHAPTER 20  Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas) 315

angioarchitecture are associated with increased surgical risk,
whereas younger patient age and AVM hemorrhage are associ-
ated with lower surgical morbidity. These factors are not
considered in the original Spetzler-Martin grading scheme;
however, the Lawton supplementary scale incorporates some
of these factors.4
Several grading schemes have been proposed to facilitate
predicting the success of radiosurgical treatment of cerebral
AVMs; they account for AVM size and location. The
radiosurgery-based AVM scale also factors patient age into the
equation: (0.1) × (volume in milliliters) + (0.02) × (age in
years) + 0.3 if the location is in the basal ganglia, thalamus, or
brainstem.5 AVM scores of less than 1 were associated with
obliteration and no radiosurgical morbidity in 89% of cases.
Similar to the Spetzler-Martin grading scale, the Virginia
Radiosurgery AVM Scale assigns points for volume (0 points
if less than 2 mL, 1 point if 2–4 mL, 2 points if more than
4 mL) and eloquence (1 point). An additional point is added
for prior AVM hemorrhage. An AVM grade of 0 or 1 was
associated with a morbidity-free AVM obliteration rate of 83%
and 79%, respectively.6
Cranial dAVF grading schemes help predict natural history
and are based on the original classification scheme by Djind-
jian.7 Type I dAVFs drain into a venous sinus and do not pose
a risk of venous hypertension or intracranial hemorrhage. Type
II dAVFs drain into a venous sinus with reflux into cortical
veins; thus they pose a risk of intracranial hemorrhage. Type
III dAVFs drain directly into cortical veins, and type IV dAVFs
drain into cortical veins with associated ectasia. Borden and
Shucart exclude the type IV dAVF and attempt to extrapolate
Djindjian’s scheme to spinal arteriovenous shunts; although
the Borden and Shucart scheme is not used for spinal lesions,
some use it instead of Djindjian’s today. Cognard and col-
leagues8 elaborated slightly on Djindjian’s scheme (Table 20.1).

• Figure 20.2  Illustration of a cerebral arteriovenous malformation, which
is characterized by feeding arteries (green arrows), a nidus, and draining
veins (blue arrow). (Used with permission from Barrow Neurological Insti-
tute, Phoenix, Arizona.)
Diagnostic Radiology
Noncontrast computed tomography (CT) of the head should
be the first imaging modality in any case of suspected intra-
cranial hemorrhage (Fig. 20.4). Although not useful for ruling
out the presence or absence of an AVM, noncontrast CT can
demonstrate certain AVMs that produce calcium deposits,

TABLE
20.1  Cognard’s Modified Djindjian Scheme

Djindjian Borden-Shucart Cognard

Type I: Drainage into sinus or
meningeal vein
Type II: Initial drainage into sinus with
reflux into other sinuses or cortical
veins
Type III: Initial drainage into cortical
veins
Type IV: Initial drainage into cortical
veins with giant venous pouch
Type 1: Venous drainage directly into dural
venous sinus or meningeal vein
Type 2: Venous drainage into dural venous
sinus with CVR
Type 3: Venous drainage directly into
subarachnoid veins (CVR only)
Type I: Venous drainage into dural venous sinus
with antegrade flow
Type IIa: Venous drainage into dural venous
sinus with retrograde flow
Type IIb: Venous drainage into dural venous
sinus with antegrade flow and CVR
Type IIa+b: Venous drainage into dural venous
sinus with retrograde flow and CVR
Type III: Venous drainage directly into
subarachnoid veins (CVR only)
Type IV: Type III with venous ectasias of the
draining subarachnoid veins
Type V: Direct drainage into spinal perimedullary
veins

CVR, cortical venous reflux.

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316 PART 3 Vascular Neurosurgery

Spetzler-Ponce Grading System Spetzler-Martin Grading System

Grade
I
0 3 6
cm

Size - 1
Eloquence - 0
V. drainage - 0
Class
A

Grade
II
0 3 6 0 3 6 0 3 6
cm cm cm
Size - 1 Size - 1 Size - 2
Eloquence - 1 Eloquence - 0 Eloquence - 0
V. drainage - 0 V. drainage - 1 V. drainage - 0

Class Grade
B III
0 3 6 0 3 6 0 3 6
cm cm cm
Size - 1 Size - 2 Size - 2
Eloquence - 1 Eloquence - 1 Eloquence - 0
V. drainage - 1 V. drainage - 0 V. drainage - 1

Grade
IV
0 3 6 0 3 6 0 3 6
cm cm cm
Size - 2 Size - 3 Size - 3
Eloquence - 1 Eloquence - 1 Eloquence - 0
Class V. drainage - 1 V. drainage - 0 V. drainage - 1
C

Grade
V
0 3 6
cm
Size - 3
Eloquence - 1
V. drainage - 1 © 2017 Barrow

• Figure 20.3  The Spetzler-Martin and Spetzler-Ponce grading systems. The Spetzler-Martin system
divides arteriovenous malformations into five grades (see text). The Spetzler-Ponce system simplifies that
system into just three grades, lettered A to C. (Used with permission from Barrow Neurological Institute,
Phoenix, Arizona.)

which aids the diagnostic process. Contrast-enhanced CT can
demonstrate serpiginous vascular enhancement that is distinc-
tively typical of an AVM. In the case of a dAVF, abnormally
enlarged dural sinuses or draining cerebral veins can be seen
after contrast administration.
CT angiography (CTA) is helpful for recognizing brain
AVMs (Fig. 20.5). CTA allows calculation of the volume of an
AVM nidus, identifies associated vessels, and aids in quantify-
ing any embolic material present within the AVM. In addition,
CTA is useful for characterization and stereotactic localization
of the AVM before surgical resection or radiosurgical treat-
ment. In an AVF, the presence of asymmetrically visible and
enlarged arterial feeding vessels has high sensitivity and speci-
ficity for the diagnosis of dAVFs. CTA can therefore be used

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 CHAPTER 20  Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas)
• Figure 20.4  A plain axial computed tomogram showing hemorrhage.
Subtle evidence of calcification suggests an underlying arteriovenous
malformation. (Used with permission from Barrow Neurological Institute,
Phoenix, Arizona.)
• Figure 20.5  A computed tomography angiogram of a large left-hemi-
sphere ruptured arteriovenous malformation (AVM) shows intraventricular
blood and the prominent tangle of vessels that constitute the AVM. (Used
with permission from Barrow Neurological Institute, Phoenix, Arizona.)
as a screening tool in patients with suspected fistulas. In one
study of 125 cerebral AVMs, the sensitivity of CTA in detect-
ing AVMs was 90%, whereas that for magnetic resonance
angiography was 74%. The sensitivity of CTA increased to
96% for unruptured AVMs and to 100% for AVMs at least
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317
3 cm in size. The study emphasized the significantly greater
sensitivity of CTA in detecting AVM-associated aneurysms
compared to magnetic resonance imaging (MRI).9
MRI is a useful tool in the diagnosis and management of
AVMs (Fig. 20.6A). It can define complex structures such
as the AVM nidus while also localizing adjacent eloquent
structures, which is helpful for treatment planning. On
T2-weighted MRI, hypointense signals are indicative of flow
voids that represent the various feeding arteries, draining veins,
or vessels of the nidus itself. Peripheral to the nidus, hypoin-
tense signals on T2-weighted MRI and gradient echo MRI can
also show hemosiderin deposition, which indicates subclinical
hemorrhage. Magnetic resonance angiography and magnetic
resonance venography may be helpful in delineating the pres-
ence of flow in main vessels to and from the nidus. These
imaging techniques are noninvasive methods for determining
the progress of obliteration after radiosurgical or embolic
therapy. For dAVFs, MRI may show the presence of flow voids
on the surface of the brain or in the soft tissues. If the vascular
lesion is large enough, magnetic resonance angiography may
show an enlarged sinus and possible feeding and draining
vessels. T2-weighted MRI is helpful in visualizing lesions with
associated venous ectasia.
Angiography
Digital subtraction angiography is the gold standard imaging
technique for the diagnosis and angiographic evaluation of
cerebral AVMs and dAVFs (Fig. 20.6B–C). The following
factors should be identified, characterized, and evaluated on
these angiograms: arterial supply (with attention to the pres-
ence of perforator supply); nidus location, size, and architec-
ture (compact or diffuse); feeding artery and intranidal
aneurysms; and drainage pattern (deep or superficial; outflow
stenosis).
The arterial supply is visualized to define the anatomy of
the AVM and to potentially identify pedicles for embolization
if indicated. Early classification schemes focused on the number
of arterial suppliers to the AVM, although modern schemes
have not emphasized this angiographic factor.3,4 Periventricular
AVMs have a particular proclivity to recruit a choroidal arterial
supply, whereas surface AVMs may have a meningeal arterial
supply. A middle meningeal artery supply is a particularly
inviting pedicle for embolization when indicated. A careful
examination for the presence of a perforator supply is critical
for surgical planning. These pedicles can be a surgical nuisance;
coagulation and operative control of these vessels are critical
because the surgeon may have to continue following bleeding
vessels that retract into deep, often eloquent, tissue.10,11 Embo-
lization of these pedicles is a welcome adjunct, although embo-
lization can be challenging and limited by the small size and
tortuosity of the vessel.11
Defining the nidus location is important for predicting both
natural history and treatment risk for the AVM. Deep AVMs
have a worse natural history than superficial lesions.12,13 Fur-
thermore, the treatment of deep AVMs or AVMs in eloquent
regions is associated with a greater risk and an often lower rate
318 PART 3 Vascular Neurosurgery

A B

C
• Figure 20.6  (A) An axial T2-weighted magnetic resonance image (MRI) shows a left occipital arterio-
venous malformation (AVM). The AVM appears dark on T2-weighted MRI because of the presence of
“flow voids.” (B) A magnetic resonance angiogram of the same AVM shows only the vessels of the AVM,
with the brain not visible in the image. (C) An anteroposterior angiogram of the same AVM is shown for
comparison. (Used with permission from Barrow Neurological Institute, Phoenix, Arizona.)

of complete obliteration with any treatment modality.3,4,6,14,15
Although modern studies have not shown a relationship
between nidus size and natural history risk,12,13 larger AVMs
are associated with greater risk and lower rates of complete
obliteration for any treatment modality.3–6,14,16 Similarly, diffuse
(as opposed to compact) nidus angioarchitecture is associated
with greater risk and lower rates of complete obliteration for
any treatment modality.4,10
Feeding artery and intranidal aneurysms are important
angiographic components to identify for both natural history
evaluation and treatment planning. These “high-risk” features
independently increase the prospective risk of intracranial

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 CHAPTER 20  Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas)
hemorrhage. Although they can be addressed during intra-
operative resection, they can also be preoperatively embolized
or treated with embolization alone in the case of inoperative
AVMs.15
The drainage pattern of AVMs is an important factor for
predicting both their natural history and their treatment risk.
Exclusive, deep venous drainage is an independent risk factor
for AVM hemorrhage.12,13 Although less substantiated by
natural history studies, venous outflow stenosis or obstruction
is also a risk factor. Deep venous drainage does not necessarily
impact the risk of radiosurgery or embolization, but it has been
identified as a risk factor for surgical resection.3,4
Epidemiology and Natural History
Across several studies, the prevalence of AVMs has ranged from
5 to 613 cases per 100,000.17,18 Multiple natural history studies
consistently show the overall average patient age at AVM pre-
sentation to be in the third decade, without a significant sex
predilection. Patients with AVMs present most commonly
after hemorrhage. One meta-analysis reported an overall hem-
orrhagic presentation rate of 52%12; patients presented with
seizures in 27% of cases. Other potential presentation variables
include headaches, ischemia, and steal symptoms, which can
also be an incidental finding. A meta-analysis reported an
overall prospective annual hemorrhage rate of 3%; for unrup-
tured AVMs, the hemorrhage rate was 2.2%, and for ruptured
AVMs, the rate was 4.5%, higher within the first year.12 Similar
epidemiologic data were reported in a pooled analysis of 293
patients with spinal AVMs.12 Mean patient age was 29.1 years,
without a sex predilection. Half the patients presented with
hemorrhage, and the reported overall annual hemorrhage rate
was 4%.
A pooled analysis of 395 cerebral dAVFs demonstrated that,
across a cohort of 141 low-risk fistulas (no cortical venous
drainage), mean patient age was 51 years, with a slight female
sex predilection (0.7 : 1, male : female).19 Rarely incidentally
discovered, these fistulas often are found in patients who
present with tinnitus or, if there is involvement of the cavern-
ous sinus, with ocular symptoms. They do not pose a risk of
intracranial hemorrhage and rarely progress to cortical venous
drainage (1.4% of cases). Patients with high-risk dAVFs pre-
sented at a slightly older age (mean, 59 years) with a slight
male sex predilection (1.5 : 1, male : female). In this cohort,
30% of patients presented with hemorrhage and 30% pre-
sented with signs of venous hypertension without hemorrhage.
Other modalities of presentation include incidental, tinnitus,
or ocular symptoms. The overall prospective annual hemor-
rhage rate for this cohort was 6%. The rate increased to 21%
for type IV dAVFs (direct cortical venous drainage with venous
ectasia) and to 46% for lesions in patients who presented with
hemorrhage. The annual hemorrhage rate decreased to 2% for
high-risk fistulas that were found incidentally.
Patients with spinal dAVFs tend to present in their 60s;
there is a known male sex predilection (2–3 males : 1 female).20
Symptoms at presentation are typically myelopathic in patients
with spinal venous hypertension. Hemorrhage is exceedingly
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319
rare and usually occurs only in patients with cervical dAVFs
with intracranial drainage.
Clinical Presentation of Arteriovenous
Malformations
Hemorrhagic presentation of AVMs is linked to many ana-
tomic features. However, it is unknown whether those ana-
tomic features predict the likelihood of AVM rupture. Features
that can increase the risk of hemorrhagic presentation are small
lesion size, infratentorial location, a small number of draining
veins, and a high-pressure feeding artery.13,21–24 Associated
aneurysms and hypertension also increase the risk of hemor-
rhagic presentation.13,25 The sequelae of AVM hemorrhage are
dependent on the location of the lesion. A small, deep AVM
may hemorrhage exclusively in the parenchyma, whereas a
cortical AVM may have a subarachnoid hemorrhage compo-
nent. Intraventricular bleeding can occur from AVMs situated
adjacent to the ventricles. Combinations of bleeding locations
are also seen. Initial management of hemorrhagic presentations
is similar to that of cerebral parenchymal hemorrhage. Patients
with dAVFs may present only with subarachnoid hemorrhage;
thus dAVFs should be considered in the differential diagnosis
of nonaneurysmal bleeding. Patients with a subarachnoid hem-
orrhage in the absence of intracranial aneurysms should
undergo six-vessel cerebral angiography to rule out a dAVF.
Seizures are the second most common presentation of
patients with AVMs, particularly when the AVM is in the
supratentorial location. Approximately 15% to 30% of all
patients with AVMs present with a focal or generalized
seizure.26–28 AVM features associated with epileptogenic pre-
sentation include a cortical location of the nidus or feeding
artery, location of the AVM in the middle cerebral artery
territory, the presence of varices in the venous drainage, and
association of a varix with absence of intranidal aneurysms.27,29
Other factors significantly associated with the onset of sei-
zures include AVMs fed by the external carotid artery and a
temporal or parietal cortical location.29 AVM-related seizures
are thought to result from cortical irritation or remodeling
from ischemia, altered hemodynamics, mass effect, or micro-
hemorrhage. The epileptogenic presentation of AVMs has a
long-term risk profile for hemorrhage similar to that of non-
epileptogenic types of AVM presentations. However, definitive
surgical treatment may not be ideal because of a patient’s age
and comorbid conditions. Seizure control with antiepileptic
drugs is considered the first-line treatment and is used when
surgical treatment is not feasible. A consultation with an epi-
leptologist for multidrug therapy is indicated in patients with
medically refractory seizures. A neurologic consultation can
confirm the location of the epileptic focus using clinical semi-
ology or tools such as electroencephalography, magnetoen-
cephalography, or single-photon emission CT. Because most
AVMs do not harbor functional tissue, the location of this
epileptic focus with respect to the actual AVM nidus may help
determine the best course of treatment, which may include
radiosurgery.30,31
320 PART 3 Vascular Neurosurgery
Other clinical presentations of patients with AVMs are
headaches and focal neurologic deficits. Chronic headaches
occur in 6% to 14% of patients who have no evidence of
rupture, especially in those with occipital AVMs, which may
be a predisposing factor for rupture.26 The headaches can be
similar to migraines, localizing on one side of the brain, but
they may be more permanent in nature. However, this fact
does not necessarily preclude migraines as an independent
pathologic entity, and patients should be informed that the
goal of successful AVM treatment is the obliteration of
the nidus in order to mitigate the risk of a debilitating
hemorrhage.
Neurologic deficits occur in 3% to 10% of patients who
present with AVMs. Deficits may be transient, progressive, or
permanent, and they can vary with the morphologic nature of
the malformation. Deficits typically arise secondary to mass
effect on adjacent structures or hemodynamic disturbances
such as the phenomenon of arterial steal. Arterial steal is the
result of high-volume arteriovenous shunting that disrupts the
vascular supply and regulation of normal brain structures by
redirecting the blood flow toward the shunt at the expense of
the normal vascular beds.31 The theory of arterial steal suggests
that large AVMs should correlate with increased physiologic
evidence of steal. However, arterial steal is thought to be rela-
tively rare because the surrounding brain develops adaptive
responses.31,32
Pathogenesis and Development of
Arteriovenous Malformations
The pathogenesis of intracranial AVMs is not well elucidated.
The traditional thought on AVM development leans toward a
congenital process, meaning that AVMs result from failures in
embryonic development and are present at birth. Embryonic
vascular development is the successive combination of three
processes: vasculogenesis, angiogenesis, and arteriogenesis.33,34
Vasculogenesis refers to the differentiation of vascular progeni-
tor cells into angioblasts (the precursors to endothelium) and
the formation of a haphazard network of immature cells that
eventually fuse to form a primitive capillary plexus. Angiogen-
esis involves selective apoptosis and migration of supporting
vascular smooth muscle cells to form a stable vascular bed. The
complex interactions between vasculogenesis and angiogenesis
in the embryonic stage require multiple steps for cell prolifera-
tion, migration, differentiation, and programmed destruction.
Any misstep during this stage could be the initiating factor in
the formation of a congenital AVM. Arteriogenesis may con-
tribute to observed growth and remodeling of AVMs from the
fetal stage onward. Mediated by vascular wall shear stress,
arteriogenesis is the likely mechanism by which an AVM with
low resistance recruits additional blood supply over time.
The evidence supporting a congenital origin of AVMs is
limited to the histologic resemblance between AVM structures
and the developing embryonic vasculature and genetic links,
such as those found in patients with hereditary hemorrhagic
telangiectasia and Wyburg-Mason syndromes. De novo forma-
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tion, progression, and recurrence after complete surgical resec-
tion have been reported,10,35–37 negating the notion that AVMs
are static. They are indeed dynamic lesions capable of remodel-
ing over time.
Molecular Biology and Genetics
Intracranial AVMs are associated with many factors known to
be present at higher concentrations than in normal tissue,34
some of which are observed in cerebral neoplastic processes.38,39
Further identification of associated angiogenic factors may
allow for future targeted medical therapies. Around 900 genes
have been shown to have altered expression in AVMs.34,40
However, a detailed discussion of the implicated molecular
factors is beyond the scope of this chapter. The factors with
abnormally high levels of expression in AVMs are discussed
here.
Vascular endothelial growth factor (VEGF) is present in
increased amounts not only in AVMs but also in surrounding
tissue. VEGF is normally expressed at high levels during
embryonic development, thus playing a key role in angiogen-
esis, vascular proliferation, and capillary migration. VEGF
expression is typically suppressed in adulthood but can be
rapidly increased by HIF-1 (hypoxia-induced factor) in
response to a low oxygen microenvironment, which stimulates
the growth of AVMs.
Fibroblast growth factors are thought to assist with pro-
genitor cell differentiation to angioblasts during vasculogen-
esis. The differentiation of fibroblasts to smooth muscle cells
is likely regulated by basic fibroblast growth factor, which
is associated with the arterialization of AVM veins. Finally,
angiopoietins regulate the recruitment of smooth muscle
cells and the development of pericytes to endothelial cells,
both of which are thought to promote vascular stabiliza-
tion during angiogenesis. Other angiogenic factors known to
contribute to AVM development are minor trauma, venous
hypertension, exogenous growth factors, inflammation, and
infection.38,39,41,42
These factors suggest that AVMs develop in response to
an environmental insult during development or because of a
genetic predisposition. Genetic alterations may be sporadic or
familial. Several genetic syndromes, such as Wyburn-Mason
syndrome, Sturge-Weber disease, and ataxia-telangiectasia,
are associated with an increased predisposition to develop
AVMs.34
Hereditary hemorrhagic telangiectasia, also known as
Osler-Weber-Rendu disease, is an autosomal dominant disor-
der with variable penetrance. Genetic analysis has isolated two
mutations: HHT1 (chromosome 9q) and HHT2 (chromo-
some 12q). The incidence of AVM with HHT1 mutations is
approximately 10 times that of HHT2, which demonstrates the
connection between genetic mutations and the development
of AVMs.43 In addition to known hereditary disorders, AVMs
often occur within families, suggesting a multifactorial genetic
patterning to their formation. Nonetheless, more than 95% of
AVMs are sporadic, and HHT mutations account for only 3%
of the total.44
 CHAPTER 20  Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas) 321

Physiology therapies include decreasing the blood flow by obstructing the

The hemodynamic properties of AVMs continue to be the
subject of observation and debate. AVM physiology includes
that of the malformation itself and the surrounding brain
structures. The uncertainty surrounding AVM physiology
stems from individual variability in AVM features. For this
chapter, AVM hemodynamics are discussed in terms of flow
rates and pressures through three structures—the feeding
artery, nidus, and draining vein—of an AVM.
In this hypothetical model, any increase in blood flow to
one structure is the same in all structures. Flow increases with
higher feeding arterial pressure, decreasing draining pressure,
or decreasing vascular resistance upon nidus expansion. A
nidus can expand as the diameter of existing vessels increases
or through angiogenesis, thereby reducing vascular resistance.
As a result, feeding artery pressure decreases or its flow rate
increases until the establishment of a new equilibrium. For
pressure to increase in a nidus, flow can be increased by increas-
ing pressure in the feeding artery or flow can be decreased by
increasing pressure (indirectly by increasing distal resistance)
in the draining vein. This model does not consider many of
the complex properties of AVMs such as capacitance (increased
nidus flow with decreased resistance and pressure). It is impor-
tant to note that the hemodynamic consequences of AVMs are
widely dependent on the cross-sectional area of the narrowest
communicating segment between arterial and venous circula-
tion. The primary hemodynamic considerations in AVM
feeding arteries, which is the therapeutic goal, and in contrast,
decreasing the flow by obstructing veins, which increases
the intranidal pressure, and therefore leads to a bleeding risk
(Fig. 20.7).
The congenital nature of the AVM implies that sur-
rounding brain tissue developed in the setting of low perfu-
sion pressure; consequently, the vascular bed receives lower
local arterial pressure. This observation is exacerbated by
the reduction in vascular resistance caused by an enlarging
nidus and the resultant preferential blood flow toward the
AVM. This dynamic can progress until the surrounding brain
is inadequately perfused, which causes neurologic dysfunc-
tion. This phenomenon is known as vascular steal, but it is
difficult to demonstrate definitively.31 Nonetheless, there is
some evidence to support neuropsychological dysfunction
as the result of this phenomenon.45–47 Another consequence
of low perfusion pressure in surrounding brain tissue is the
loss of vascular autoregulation in response to normal pres-
sure changes. This loss becomes important after AVM resec-
tion, when overall systemic vascular resistance is increased.
The dysfunctional vasculature becomes hyperemic, with an
increased risk for postresection hemorrhage. This phenome-
non is known as normal perfusion pressure breakthrough.48 The
theory of normal perfusion pressure breakthrough is neces-
sary to consider in imaging modalities dependent on blood
flow (eg, functional MRI), because it could produce false
results.

A B
• Figure 20.7  (A) A lateral view left internal carotid artery angiogram shows the same occipital arterio-
venous malformation (AVM) as shown in Fig. 20.6. The angiogram shows normal vessels and the large
vessels of the AVM, which fill early compared to the regular circulation. (B) The arterial phase anteropos-
terior angiogram of the AVM shows it filling predominantly off middle cerebral artery branches with some
contribution from the anterior cerebral artery. (Used with permission from Barrow Neurological Institute,
Phoenix, Arizona.)

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322 PART 3 Vascular Neurosurgery
Pediatric Arteriovenous Malformations
Spontaneous intracranial hemorrhage in pediatric patients is
strongly associated with AVMs.49,50 Nonetheless, children fare
better than adults after microsurgical resection of AVMs, likely
because of the neural plasticity commonly observed in pediat-
ric patients.51,52 Like adults with AVMs, children with AVMs
are most likely to present with hemorrhage or seizures.53 Inter-
estingly, a newborn with an AVM may present with congestive
heart failure, which often happens when the malformation is
in the vein of Galen. Congestive heart failure secondary to
left-to-right cardiovascular shunting connotes a relatively poor
prognosis. Advances in pediatric critical care and endovascular
techniques are credited with improving long-term outcomes in
these patients.54
The management of pediatric AVMs is similar to that of
AVMs in adults, with a strong focus on aggressive surgical
resection of low-grade lesions to prevent future hemorrhage
and recurrence. The residual diffuse-type AVM is prone to
recur in pediatric patients.55,56 One possible explanation for
this phenomenon involves microshunting not apparent on
angiography that enlarges over time. This idea is also consistent
with the degree of arteriovenous shunting and the observation
that many pediatric AVMs grow in volume over time. Most
pediatric patients are successfully treated with microsurgical
resection,53,56–58 which is associated with high rates of AVM
obliteration, as confirmed by angiography, and the low rate of
neurologic complications.58 Other therapies include radiosur-
gery and endovascular embolization. Endovascular interven-
tions are typically reserved for preoperative adjunct therapy,
whereas radiosurgery is used for inoperable lesions.56 Stereo-
tactic radiosurgery is safe and effective in inoperable cases and
is most efficacious for small-volume AVMs located in critical
brain regions.59,60 Aggressive multimodality treatment (a
combination of microsurgery, radiosurgery, and endovascular
embolization) for high-grade AVMs (Spetzler-Martin grade
4–5) results in low cure rates and high complication rates.57
Thus prehemorrhagic high-grade lesions are best treated con-
servatively and observed for progression.53 Predictors of poor
outcomes in pediatric patients include poor pretreatment func-
tional status and high-grade and left-sided AVMs.57
Spinal Vascular Malformations
Spinal vascular malformations are rare, making up 3% to 4%
of all space-occupying lesions in the spine.61 The classification
of spinal vascular malformations has been the subject of many
debates and proposed classification systems.61–67 Spinal vascular
malformations are a heterogeneous group consisting of AVMs,
dAVFs, hemangiomas, cavernous angiomas, and aneurysms.
For simplicity, spinal vascular malformations can be divided
into extradural AVFs and intradural AVMs and AVFs. Extra-
dural AVFs are viewed as acquired, slow-flow lesions that
develop over a long time. Extradural AVFs result in perimedul-
lary venous system dilation, stasis, and eventual hypoxia of the
spinal cord. In contrast, intradural AVFs and AVMs are con-
genital lesions. The clinical presentations of spinal vascular
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malformations range from progressive myelopathy (Foix-
Alajouanine syndrome) to acute excruciating back pain sec-
ondary to spinal subarachnoid hemorrhage (coup de poignard
of Michon).
The original classification of spinal vascular malformation
by Anson and Spetzler recognized four different angiographic
types of malformations.62 Type I refers to dAVFs, the result
of a fistula between a radiculomeningeal artery and a radicu-
lar vein. Type I is the most common type of malformation,
making up 70% of all spinal vascular malformations, with a
male predilection.68 The typical presentation depends on the
location of the lesion, which is commonly found in the tho-
racolumbar region,69 and it is the result of venous congestion
and hypoperfusion. Patients with type I lesions rarely have
a hemorrhagic presentation. Type II lesions are intramedul-
lary glomus AVMs with a vascular supply from the anterior
or posterior spinal circulation or both. Patients with these
lesions, which are commonly found in the cervicomedullary
junction, typically present with acute neurolgic symptoms.
Type III lesions are juvenile malformations that can be intra-
medullary or extramedullary in location. Type IV AVMs are
intradural, extramedullary lesions on the surface of the spinal
cord. Type IV lesions are the result of a fistula between a spinal
artery and spinal vein. An alternative method classifies spinal
vascular malformations into intramedullary or extramedullary
locations.70
Treatment
Surgeons use embolization of cerebral AVMs primarily as an
adjunct to surgery, targeting high-risk features such as feeding
artery or intranidal aneurysms (Fig. 20.8). Small, well-selected,
inoperable, ruptured AVMs may be embolized with the
goal of angiographic elimination of perceptible shunting.71,72
N-butylcyanoacrylate (NBCA) and Onyx (ethylene-vinyl
alcohol copolymer) are two typical embolizing agents that are
used and have similar associated morbidity.73 NBCA is a liquid
adhesive that rapidly polymerizes. It is ideal for high-flow
shunts and for when a swift injection is needed.6,74 Onyx is
a copolymer of ethylene-vinyl alcohol dissolved in dimethyl
sulfoxide that precipitates to form a nonadhesive solid.75
Detachable-tip microcatheters are now commonly used; they
may be intentionally glued in and then used for added nidal
penetration with Onyx via the pressure-cooker technique.76
Onyx is used more often than NBCA for AVM embolization
because it allows for longer injections and superior penetra-
tion.75,77 In our institutional experience with 342 AVMs embo-
lized over 446 sessions, most AVMs were embolized adjunctively
before surgery. Procedural neurologic morbidity and mortality
was 9.6% and 0.3%, respectively.77 Similar to the use of embo-
lization in cerebral AVMs, the role of embolization for spinal
AVMs is mainly adjunctive for partial or full targeting of high-
risk features.12
In contrast to the use of embolization as an adjunct treat-
ment in cerebral AVMs, embolization is the initial treatment
of choice for cerebral dAVFs, with the intent of angiographic
obliteration. The introduction of Onyx was a landmark advance
 CHAPTER 20  Vascular Malformations (Arteriovenous Malformations and Dural Arteriovenous Fistulas) 323

A B

C D
• Figure 20.8  (A) A lateral internal carotid artery angiogram shows a temporal arteriovenous malforma-
tion (AVM) with a large nidal aneurysm, which was thought to be the source of the hemorrhage and hence
a good target for embolization. (B) The cast of the aneurysm left behind on the subtracted angiogram
(same view). (C) An angiogram obtained after the subtracted angiogram still shows the AVM, but the
aneurysm has been excluded from the circulation and is notably absent. (D) A plain computed tomogram
shows the hyperdense embolic material. (Used with permission from Barrow Neurological Institute,
Phoenix, Arizona.)

in the endovascular management of these lesions, allowing for
prolonged injections and better penetration of the draining
vein, which is the goal of the procedure. Although indirect
carotid-cavernous fistulas and selected marginal sinus fistu-
las are still often managed via transvenous coil embolization;
most other dAVFs are now typically managed via transarterial
Onyx embolization. In our published institutional experience
with 260 dAVFs, excluding ethmoidal and torcular dAVFs,
the endovascular angiographic obliteration rate was 80% in
the Onyx era. The rate of significant improvement or resolu-
tion of tinnitus or ocular symptoms after initial treatment was
also approximately 80%. The overall complication rate was
8%, with permanent neurologic morbidity occurring in 3% of
cases.78 Although surgery is an excellent and highly successful
modality for surgical disconnection of spinal dAVFs, emboliza-
tion is, at times, an option, with feasible transarterial anatomy

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324 PART 3 Vascular Neurosurgery
for embolization seen in approximately 50% of patients.79 For
both procedures, the goal is disconnection of the AVF at its
fistulous point. For the classic type I spinal dAVF feeding off
a single pedicle, endovascular access and embolization of the
fistulous point at the nerve root sleeve can be curative. From a
surgical standpoint, cure is achieved by exposing and isolating
the lesion via a laminectomy. The surgeon then places a single
clip on the appropriate feeding artery, which is usually suffi-
cient. Angiography and indocyanine green video angiography
are often used to confirm successful disconnection of the fistula.
The treatment of spinal AVMs is somewhat controversial.
Direct resection is considered to carry a very high risk of
Summary
Vascular malformations in the brain have various pathophysiol-
ogies, clinical presentations, prognostic implications, and treat-
ments. Some, such as developmental venous anomalies, should
be recognized for their benign nature. AVFs are acquired lesions
that are pathophysiologically simpler than AVMs and can be
cured by disconnection. AVMs are congenital anomalies that
Acknowledgments
The authors thank the Neuroscience Publications staff of
Barrow Neurological Institute for help with manuscript prepa-
ration and artwork and Soliman Oushy for his contributions
to the chapter.
Selected Key References
Achrol AS, Guzman R, Varga M, et al. Pathogenesis and radiobiology of
brain arteriovenous malformations: implications for risk stratification
in natural history and posttreatment course. Neurosurg Focus.
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Cognard C, Gobin YP, Pierot L, et al. Cerebral dural arteriovenous fis-
tulas: clinical and angiographic correlation with a revised classification
of venous drainage. Radiology. 1995;194(3):671-680.
Gross BA, Albuquerque FC, Moon K, et al. Evolution of treatment and
a detailed analysis of occlusion, recurrence, and clinical outcomes in
an endovascular library of 260 dural arteriovenous fistulas. J Neuro-
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For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
neurologic deficits and is usually reserved for patients with
progressive symptoms or repeated hemorrhaging. Nonethe-
less, some success with surgical resection has been docu-
mented. Compact “glomus” AVMs, in particular, can often
be circumferentially dissected and resected with good out-
comes. Other AVMs are more diffuse and may have func-
tional spinal cord within them. Unlike cerebral AVMs in
which complete removal is an absolute condition of achieving
a surgical cure, some spinal AVMs can be “pruned” at the
surface, leaving channels within the spinal cord parenchyma
that no longer fill with blood and do not carry any risk of
hemorrhage.
vary widely in their anatomy, size, and complexity. The choice
of treatment depends on the presentation, symptoms, and
risks of treatment for the particular lesion. Neurosurgeons may
choose from a variety of treatment modalities including endo-
vascular treatment, radiosurgery, and microsurgery, and obser-
vation alone may be an appropriate option for some patients.
Gross BA, Du R. Natural history of cerebral arteriovenous malforma-
tions: a meta-analysis. J Neurosurg. 2013;118(2):437-443.
Lawton MT, Kim H, McCulloch CE, et al. A supplementary grading
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Stefani MA, Porter PJ, terBrugge KG, et al. Large and deep brain arterio-
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