Brain Arteriovenous Malformations in Adults

Brain Arteriovenous Malformations in Adults

Eric Johnson

OHSU MS3

12/14/07

Eric Johnson

OHSU MS3

12/14/07

The story of AVMs is an interesting one, because . . .

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

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

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)

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 AVMDefinition of an AVM A congenital shunt between the arterial

and venous systems A tangle of abnormal vessels (nidus) Vary in size and location

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 HistoryEpidemiology and Natural History

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)

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.)

(These figures are debated in the literature)

PathogenesisPathogenesis

Poorly understood Genetic variation may play a role

(Hashimoto et al.)

Poorly understood Genetic variation may play a role

(Hashimoto et al.)

PathologyPathology

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

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 PresentationClinical 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

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

DiagnosisDiagnosis 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

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

CT ImagingCT 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

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

Axial

CT

without

contrast

Axial

CT

without

contrast

Al-Shahi et al.

Axial

CT

with

contrast

Axial

CT

with

contrast

Al-Shahi et al.

Axial

CT

with

hemorrhage

secondary

to AVM

Axial

CT

with

hemorrhage

secondary

to AVM

http://www.brain-aneurysm.com/images/avm_pageimages/3.jpg

MRI ImagingMRI Imaging

What to look for: Curvilinear flow-voids

What to look for: Curvilinear flow-voids

Coronal,

unenhanced,

T1- weighted

MRI

Coronal,

unenhanced,

T1- weighted

MRI

Al-Shahi et al.

Saggital,

T1-weighted

MRI

Saggital,

T1-weighted

MRI

http://www.hmc.psu.edu/neurosurgery/services/images/LF1.jpg

AngiographyAngiography

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

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

Cerebral angiogram

ICA: Internal carotid arteryMCA: Middle cerebral arteryDV: Draining veinArrows: AVM nidus

Cerebral angiogram

ICA: Internal carotid arteryMCA: Middle cerebral arteryDV: Draining veinArrows: AVM nidus

http://www.brain-aneurysm.com/images/avm_pageimages/4.jpg

Cerebral

angiogramCerebral

angiogram

http://www.ucl.ac.uk/medical-modelling/myimages/Figure1.jpg

TreatmentTreatment 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:

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:

Spetzler-Martin AVM Grading ScaleSpetzler-Martin AVM Grading Scale

* 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)

Size 0-3 cm 1 3.1-6.0 cm 2 >6 cm 3

Location Noneloquent 0 Eloquent 1

Deep venous drainage Not present 0 Present 1

Size 0-3 cm 1 3.1-6.0 cm 2 >6 cm 3

Location Noneloquent 0 Eloquent 1

Deep venous drainage Not present 0 Present 1

Grading scale adapted from Ogilvy et al.

NeurosurgeryNeurosurgery

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.)

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 RadiosurgeryStereotactic 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

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

Endovascular EmbolizationEndovascular 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%

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%

Some quotes from UpToDate: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.)

“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: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)

“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 . . . But there’s 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.”

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?order=2

SummarySummary 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

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

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!

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!

BibliographyBibliographyAl-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; 230:1812-1818.

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>

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; 230:1812-1818.

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>