Brain Arteriovenous
Malformations in Adults
Eric Johnson
OHSU MS3
12/14/07
The story of AVMs is an
interesting one, because . . .
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Although rare, they can be fatal
Some AVMs are discovered incidentally in
asymptomatic individuals
Our treatment modalities for AVMs have
evolved faster than our knowledge about
their incidence, prevalence and natural
history
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Widely accepted surgical treatments have
significant risks (neurological deficits,
death)
There are no prospective, randomized
trials comparing surgical treatments to
conservative medical treatments, or even
no treatment (a control population)
However, many (most?) AVMs are treated
surgically (even in asymptomatic
individuals)
More about this later . . .
Definition of an AVM
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A congenital shunt between the arterial
and venous systems
A tangle of abnormal vessels (nidus)
Vary in size and location
http://neuro.wehealny.org/endo/illus/13_01.gif
Epidemiology and Natural History
(These figures are debated in the literature)
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Incidence: about 1 per 100,000 per year
Point prevalence: about 18 per 100,000
AVMs account for:
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1-2% of all strokes
9% of subarachnoid hemorrhages
Annual risk of hemorrhage from unruptured
AVM: about 2% (poor data)
Risk of recurrent hemorrhage: up to %18 in the
first year, uncertain thereafter (poor data)
Annual case fatality: 1-1.5% (poor data)
(Al-Shahi et al.)
Pathogenesis
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Poorly understood
Genetic variation may play a role
(Hashimoto et al.)
Pathology
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AVMs divert blood flow from surrounding
brain parenchyma
This leads to areas of chronic ischemia,
producing gliotic tissue
AVM vessels have abnormal internal
elastic lamina and/or media, making them
prone to rupture
Kumar et al.
Clinical Presentation
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Most commonly present before age 40, some
with more than one symptom:
53% hemorrhage
30% generalized seizure
14% chronic headache
10% focal seizures
7% persistent neurological deficits
5% progressive neurological deficits
Hofmeister et al.
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About one-fifth are discovered incidentally in
asymptomatic individuals
Al-Shahi and Warlow
Diagnosis
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Diagnosis is made or confirmed by
diagnostic imaging
Angiography is considered the “gold
standard” for diagnosis and treatment
planning
However, there is very little data about the
sensitivity and specificity, as well as intraand inter-observer variability of imaging
modalities used to diagnose and classify
AVMs
CT Imaging
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What to look for:
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Vascular tangles that are serpiginous and
possibly hyperdense, due to the pooling of
blood
May contain punctate or curvilinear
calcifications
AVMs will enhance with contrast
An AVM may present as a hemorrhage
Axial
CT
without
contrast
Al-Shahi et al.
Axial
CT
with
contrast
Al-Shahi et al.
Axial
CT
with
hemorrhage
secondary
to AVM
http://www.brain-aneurysm.com/images/avm_pageimages/3.jpg
MRI Imaging
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What to look for:
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Curvilinear flow-voids
Coronal,
unenhanced,
T1- weighted
MRI
Al-Shahi et al.
Saggital,
T1-weighted
MRI
http://www.hmc.psu.edu/neurosurgery/services/images/LF1.jpg
Angiography
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What to look for:
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The three components of an AVM:
Enlarged feeding artery
 Core/nidus
 Enlarged draining vein
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Early venous filling during the arterial phase
of enhancement
Cerebral
angiogram
ICA: Internal
carotid artery
MCA: Middle
cerebral artery
DV: Draining vein
Arrows: AVM nidus
http://www.brain-aneurysm.com/images/avm_pageimages/4.jpg
Cerebral
angiogram
http://www.ucl.ac.uk/medical-modelling/myimages/Figure1.jpg
Treatment
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Surgical options include:
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Neurosurgery (resect the AVM)
Sterotactic radiosurgery (ablate the AVM through
direct radiation, which causes thrombosis over time)
Endovascular embolization (ablate AVM through
direct thrombosis with embolic material)
A combination of these modalities
AVMs are graded in an effort to help guide
treatment decisions. The most common grading
system is the Spetzer-Martin Scale:
Spetzler-Martin AVM Grading Scale
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Size
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1
2
3
Location
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0-3 cm
3.1-6.0 cm
>6 cm
Noneloquent
Eloquent
0
1
Deep venous drainage
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Not present
Present
0
1
* Eloquent brain regions can be defined as “sensorimotor, language, and visual cortex; the
hypothalamus and thalamus; the internal capsule; the brain stem; the cerebellar peduncles;
and the deep cerebellar nuclei.” (Hofmeister et. al)
Grading scale adapted from Ogilvy et al.
Neurosurgery
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Primarily for Spetzler-Martin grade 1 and 2
lesions (Ogilvy et al.)
For complications, one study reported that
8% of patients either had a persistent
neurological deficit or died as a result of
surgery (Mohr et al.)
Stereotactic Radiosurgery
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Primarily for small AVMs, especially in
eloquent brain locations (Ogilvy et al.)
Friedman et al. reported the following
complication rates:
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10% post-treatment hemorrhage
3.7% transient radiation-induced complication
1% permanent radiation-induced complication
Endovascular Embolization
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Primarily a presurgical modality for large
cortical AVMs to reduce nidus size (Ogilvy
et al.)
“Palliative embolization may be used in
large nonsurgical or nonradiosurgical
AVMs” (Ogilvy et al.)
Complication rate (Mohr et al):
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Morbidity: 13%
Mortality: 2%
Some quotes from UpToDate:
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“Surgery is the mainstay of treatment;
radiosurgery is a useful option . . . and
endovascular embolization has become a useful
adjunct to these techniques.”
“There is no evidence from randomized clinical
trials to guide treatment decisions.”
“There are no randomized controlled trials of
radiosurgery for brain AVMs, and none are likely
to be performed as the benefit of radiosurgery
for radiographic obliteration of brain AVMs is
widely accepted.” (Singer et al.)
From the Cochrane Collaboration:
“There is no clear evidence from
randomised trials with clear clinical
outcomes, comparing different
interventional treatments for brain AVMs
against each other or against usual
medical therapy, to guide the
interventional treatment of brain AVMs in
adults.” (Al-Shahi and Warlow)
But there’s hope . . .
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A Randomized Trial of Unruptured Brain AVMs
(the ARUBA trial) is currently recruiting
participants:
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“[Current] treatments are administered on the
assumption that they can be achieved at acceptably
minor complication rates, decrease the risk of
subsequent hemorrhage, and lead to better long-term
outcomes.”
Therefore, the “purpose of this study is to determine if
medical management is better than invasive therapy
for improving the long-term outcome of patients with
unruptured brain arteriovenous malformations.”
http://clinicaltrials.gov/ct/show/NCT00389181?order=2
Summary
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Because AVMs are rare, little is understood
about their epidemiology and natural history
Because they cause significant morbidity and
mortality, they are often treated
Commonly used treatments for AVMs also cause
significant morbidity and mortality
Patients are being treated in the absence of a
sufficient cost-benefit analysis regarding those
treatments
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We need more research on classifying
AVMs based on radiological findings that
are consistent and reproducible among
radiologists
We also need more research comparing
treatments to a control population and to
each other for different classes of AVMs
Stay tuned for the results of the ARUBA
Trial!
Bibliography
Al-Shahi et al. “A systematic review of the frequency and prognosis of arteriovenous
malformation of the brain in adults.” Brain. 2001; 124:1900-1926.
Al-Shahi R, Warlow CP. Interventions for treating brain arteriovenous malformations in
adults. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.:
CD003436. DOI: 10.1002/14651858.CD003436.pub2.
Friedman, et al. “Analysis of factors predictive of successor complications in
arteriovenous malformation radiosurgery.” Neurosurgery. 2003; 52:296-308.
Hashimoto et al. “Gene microaray analysis of human brain arteriovenous malformations.
Neurosurgery. 2004; 54:410.
Hofmeister et al. “Demographic, Morphological, and Clinical Characteristics of 1289
Patients With Brain Arteriovenous Malformation.” Stroke. 2000; 31:1307-1310.
Kumar et al. Pathologic basis of Disease, 7th Edition. Elsevier Saunders: Philadelphia,
PA. 2005.
Mohr et al. “Arteriovenous malformations of the brain in adults.” NEJM. 1999; 230:18121818.
Ogilvy et al. “Recommendations for the Management of Intracranial Arteriovenous
Malformations” Stroke. 2001; 32:1458-1471.
Singer et al. “Brain arteriovenous malformations.” UpToDate Online 2007.
The ARUBA Trial. <http://clinicaltrials.gov/ct/show/NCT00389181?order=2>