Title: Brain Arteriovenous Malformations in Adults
1Brain Arteriovenous Malformations in Adults
- Eric Johnson
- OHSU MS3
- 12/14/07
2The story of AVMs is an interesting one, because
. . .
- 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
3- 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 . . .
4Definition of an AVM
- 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
5Epidemiology and Natural History
(These figures are debated in the literature)
- Incidence about 1 per 100,000 per year
- Point prevalence about 18 per 100,000
- AVMs account for
- 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.)
6Pathogenesis
- Poorly understood
- Genetic variation may play a role (Hashimoto et
al.)
7Pathology
- 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.
8Clinical Presentation
- 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
- About one-fifth are discovered incidentally in
asymptomatic individuals -
Hofmeister et al.
Al-Shahi and Warlow
9Diagnosis
- 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 intra-
and inter-observer variability of imaging
modalities used to diagnose and classify AVMs
10CT Imaging
- What to look for
- 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
11- Axial
- CT
- without
- contrast
Al-Shahi et al.
12Al-Shahi et al.
13- Axial
- CT
- with
- hemorrhage
- secondary
- to AVM
http//www.brain-aneurysm.com/images/avm_pageimage
s/3.jpg
14MRI Imaging
- What to look for
- Curvilinear flow-voids
15- Coronal,
- unenhanced,
- T1- weighted
- MRI
Al-Shahi et al.
16- Saggital,
- T1-weighted
- MRI
http//www.hmc.psu.edu/neurosurgery/services/image
s/LF1.jpg
17Angiography
- What to look for
- The three components of an AVM
- Enlarged feeding artery
- Core/nidus
- Enlarged draining vein
- Early venous filling during the arterial phase of
enhancement
18- Cerebral
- angiogram
- ICA Internal
- carotid artery
- MCA Middle
- cerebral artery
- DV Draining vein
- Arrows AVM nidus
http//www.brain-aneurysm.com/images/avm_pageimage
s/4.jpg
19http//www.ucl.ac.uk/medical-modelling/myimages/Fi
gure1.jpg
20Treatment
- Surgical options include
- 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
21Spetzler-Martin AVM Grading Scale
- Size
- 0-3 cm 1
- 3.1-6.0 cm 2
- gt6 cm 3
- Location
- Noneloquent 0
- Eloquent 1
- Deep venous drainage
- Not present 0
- Present 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.
22Neurosurgery
- 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.)
23Stereotactic Radiosurgery
- Primarily for small AVMs, especially in eloquent
brain locations (Ogilvy et al.) - Friedman et al. reported the following
complication rates - 10 post-treatment hemorrhage
- 3.7 transient radiation-induced complication
- 1 permanent radiation-induced complication
24Endovascular Embolization
- 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)
- Morbidity 13
- Mortality 2
25Some quotes from UpToDate
- 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.)
26From 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)
27But theres hope . . .
- A Randomized Trial of Unruptured Brain AVMs (the
ARUBA trial) is currently recruiting
participants - 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?orde
r2
28Summary
- 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
29- 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!
30Bibliography
- Al-Shahi et al. A systematic review of the
frequency and prognosis of arteriovenous
malformation of the brain in adults. Brain.
2001 1241900-1926. - 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
52296-308. - Hashimoto et al. Gene microaray analysis of
human brain arteriovenous malformations.
Neurosurgery. 2004 54410. - Hofmeister et al. Demographic, Morphological,
and Clinical Characteristics of 1289 Patients
With Brain Arteriovenous Malformation. Stroke.
2000 311307-1310. - 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 2301812-1818. - Ogilvy et al. Recommendations for the
Management of Intracranial Arteriovenous
Malformations Stroke. 2001 321458-1471. - Singer et al. Brain arteriovenous
malformations. UpToDate Online 2007. - The ARUBA Trial. lthttp//clinicaltrials.gov/ct/sho
w/NCT00389181?order2gt