Brain Arteriovenous Malformations in Adults

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Brain Arteriovenous Malformations in Adults

• Eric Johnson
• OHSU MS3
• 12/14/07

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The 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

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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 . . .
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Definition 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
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Epidemiology 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.)
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Pathogenesis

• Poorly understood
• Genetic variation may play a role (Hashimoto et
  al.)

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Pathology

• 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.
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Clinical 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
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Diagnosis

• 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

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CT 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

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• Axial
• CT
• without
• contrast

Al-Shahi et al.
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• Axial
• CT
• with
• contrast

Al-Shahi et al.
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• Axial
• CT
• with
• hemorrhage
• secondary
• to AVM

http//www.brain-aneurysm.com/images/avm_pageimage
s/3.jpg
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MRI Imaging

• What to look for
• Curvilinear flow-voids

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• Coronal,
• unenhanced,
• T1- weighted
• MRI

Al-Shahi et al.
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• Saggital,
• T1-weighted
• MRI

http//www.hmc.psu.edu/neurosurgery/services/image
s/LF1.jpg
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Angiography

• 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

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• 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
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• Cerebral
• angiogram

http//www.ucl.ac.uk/medical-modelling/myimages/Fi
gure1.jpg
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Treatment

• 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

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Spetzler-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.
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Neurosurgery

• 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.)

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Stereotactic 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

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Endovascular 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

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Some 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.)

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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)

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But 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
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Summary

• 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!

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Bibliography

• 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