Arteriovenous Malformations

Shikher ShresthaNINAS

Introduction

Distinct entity – fascinated and terrified neurosurgeons for decades

Vascular lesion – risk of debilitating hemorrhage

Do not develop de novo but remains clinically silent for decades

Pathological mass but grow without necessarily displacing functional structures of the brain

Considerable variability in presentation

No two AVMs are alike

Definition

Congenital, high-flow, high-pressure lesions with the primary risk of devastating intracerebral hemorrhage

Important characteristics: nidus size and locationnumber and locations of arterial feederspattern of venous drainage

Only complete removal offers definitive reduction of bleeding risk

Surgical resection, Radiosurgery, endovascular occlusion or combination approaches used for treatment

Classification

Vascular malformations are dysplastic processes

And NOT neoplastic (not to be confused with suffix “oma” used in cavernoma, venous angioma etc.)

Traditionally, 4 different entities recognized:

Developmental venous anomalies

Capillary telangiectasias

Cavernous malformations

AVMs – differs from the rest 3: due to AV shunt whereby oxygenated blood passes directly into the venous system without gas exchange

AVM subtypes:

Plexiform

artery connecting to a network of poorly differentiated, immature vessels before passing into a vein

plexiform network - is termed a nidus (Latin – “nest”)

Fistulous

Diagnostic Radiology

Cross-sectional Imaging

MRI:

Geometric definition of nidus and its relation to adjacent structure

Hypointense signals on T2 represents flow voids of various feeding arteries, draining veins or vessels within the nidus

Hypointensity peripheral to nidus on gradient echo MRI is suggestive of hemosiderin deposits from subclinical

hemorrhage

MRA and MRV for non invasive delineation of flow though temporal sequencing is lacking

CT scan (plain)

acute determination of intracranial hemorrhage

25-30% AVMs have calcium deposition – apparent even in the presence of hemorrhage

iso- to hyperdense serpiginous vessels located at some distance from the hemorrhage

helpful to rule in rather than to rule out AVM

CT angiogram – helpful in an unruptured AVM

Angiography

No cerebral AV shunt can be completely understood without the aid of a selective cerebral angiogram

DSA – subtract out static components of the image (i.e., the skull)

weakness: lack of geometric characterization and

localization of the nidus

feature: early opacification of the nidus or draining veins in the routine arterial phase of the angiogram

Radiological Findings:

Nidus

size of the AVM = size of the nidus

!!! Confounder = adjacent dilated veins

cross sectional imaging for more accurate measurement as for any mass lesion

location – to see for proximity to eloquent areas IMPORTANT

shape characterization for surgical and radiosurgical planning

Arterial supply

Noted for number, size, relative contribution to the nidus, location

Which vascular territory they arise from?

Best to describe its course from the Circle of Willis

For large AVMs, if there is concern for meningeal involvement – angiogram of ECA

Contribution from deep perforating artery noted

AVMs in “vascular border zone” as in temporal and occipital lobe: may have supply from both anterior and posterior circulation

3 types of arterial feeders:

Direct/Terminal feeders – end directly into the nidus

Transit feeders – normal arteries that pass near or even through the nidus while going on to supply normal tissue

can be easily obscured with nidus opacification

eg. Pericallosal artery passing adjacent to mesial frontal lobe nidus before proceeding posteriorly

Indirect feeding or artery en passage – passes near the nidus and contribute to the shunt before continuing on to supply normal brain

Superselective angiography of suspected vessel

shows if it contributes to the nidusdistinguishes a transit artery

Importance!!! –

embolization or surgical ligation of an unrecognized en passage artery -infarcts of normal tissue

Helps identify intranidal or prenidal aneurysms

Supply of AVM from pial collaterals to be noted

Venous Drainage

Note for number, size and locations

Unusual character with tortuous course, ectasias, or stenosis

Note the drainage – surperficial (cortical surface) vs deep (Galen)

Important to recognize the possible existence of normal veins draining functional area adjacent to the lesion like “transit artery”

Such veins opacify later than veins draining the nidus on angiogram; though difficult to distinguish intraoperatively

Special Tests:

Functional MRI (fMRI)

to assess the proximity of language and motor function in relation to AVM

Tractography

aid in assessing the relationship of deep white matter tracts to the AVM

Intraoperative functional mapping – limited value – we cannot do partial treatment as contrast to tumors

Grading Systems

Weaknesses of Spetzler Martin Classification

Lacks the ability to assess risks for interventions other than exclusive microneurosurgery

Studies based on highly experienced vascular team and may not necessarily be applicable to a general neurosurgeon’s ability

Interobserver variability can occur

May oversimplify many AVMs

More recent classification attempts at - Deep perforator supply and nidus diffuseness

Flow characterization ?? / posterior fossa AVMs ??

Weaknesses of Spetzler Martin Classification

Size measurement – linear parameter

Eg. Spherical volume of 5.54 cm diameter AVM – approx. 4 times greater than 3.5 cm AVM; eventhough both assigned 2 points

Treatment with radiosurgery is volume dependent

Volume is a better predictor of microsurgical risk and outcomes

Good point: Simple bedside assessment

Pathological Sequelae

Hemorrhage

>50% of AVMs – discovered after an ICH

small, deep AVM – intraparenchymal hemorrhage; intraventricular bleed if adjacent to ventricles

cortical AVM – subarachnoid hemorrhage

dAVF may only present with SAH; should be considered in the DDx of non aneurysmal bleed – 6 vessels DSA to be performed on suspicion

Seizures

Second most common presenting symptom

Associated with supratentorial AVMs

15-30% patients

Cause: cortical irritation or remodeling from ischemia, altered hemodynamics, mass effect or microhemorrhage

Mostly, well controlled with medical management

Similar long-term risk profile for hemorrhage than with other presentations

Angiographic characteristics of epileptogenic AVMs

cortical location of the nidus or feeding artery (temporal/parietal)

feeding by the MCA or ECAabsence of aneurysms including intranidalpresence of varices in the venous drainage

Subset of patients – medically refractory epilepsy

confirmation of epileptic focus using EEG, MEG, SPECTfollowed by radiosurgery

Headaches..

Presenting symptom in 15% patients without evidence of rupture

Similar to migraine – lateralization to one side but more permanent

Neurological Deficit..

rare presentation

transient, progressive, or permanent

due to mass effect or arterial steal

Development of AVM

Congenital – develop during embryonic stage

For: histological characteristics resembling plexuses of developing vasculature in embryo

predisposition in genetic disorders like Osler-Weber-Rendu

Against: recur though rarely, after post treatment angiographic evidence of obliteration by surgery or radiosurgery

?? Whether they occur de novo or develop into larger structures that can eventually be seen radiographically

Points out – dynamic lesion that can develop or remodel over time

Congenital theory – failure of development of a stable vascular and capillary plexus

Three processes: vasculogenesis, angiogenesis and arteriogenesis play role

Vasculogenesis – creates a haphazard network of immature cells that form angiocysts, which eventually fuse to form a primitive capillary plexus

Angiogenesis – selective apoptosis + migration of supporting vascular smooth muscle cells to form stable vascular bed

Arteriogenesis – plays important role in later growth and remodelling; being mediated by vascular wall shear stress

Molecular Biology and Genetics..

Altered expression of many factors

~900 genes – altered expression in AVMs

Increased amount of VEGF (Vascular Endothelial Growth Factor)

ANG (angiopoetins) – regulates recruitment of smooth muscle cells and pericytes to endothelial cells

FGFs (Fibroblast Growth Factors) – help differentiate progenitor cells to angioblasts during vasculogenesis

Mutation in HHT1 and HHT2 genes found on chromosome 9q and 12q respectively (Hereditary Hemorrhagic Telangiectasia) – as in OWR synd.

Physiology..

Categorized into:

Physiology of the malformation itself

Physiology of the surrounding brain

Physiology within a malformation..

Hemorrhage occurs when the pressure within the vessel wall exceeds the limit for structural integrity

Stress delivered depends on the pressure along with radius and thickness of the vessel

Flow increase – increased arterial pressure, decreased draining pressure, decrease in vascular resistance

Capacitance – ability of the nidus to increase flow without necessarily increasing vascular resistance or therefore pressure

Concept translated to management:

Decreasing flow is best effected by obstructing feeding arteries

Decreasing flow by obstructing veins will increase intranidal pressures, and therefore, bleeding risk

Physiology of surrounding brain..

Normal brain can no longer match the low resistance of AV shunt and becomes underperfused “vascular steal”

Vascular beds of normal brain parenchyma perfused at lower local arterial pressures

Surrounding brain develops relatively low vascular resistance

Increased shunting by a low vascular resistance within an AV shunt

Normal Perfusion Pressure Breakthrough (NPPB)

Becomes hyperemic with increased risk for post resection hemorrhage

Capillary beds not used to higher pressure

Overall systemic resistance increases in response to removal of AVM

Adjacent tissue loses the ability to autoregulate

N.B. .. Clinical utility from the understanding of this concept..

fMRI used for identifying eloquent area for surgical planning utilizes cerebral blood flow changes at the microcirculatory level to determine functional activation of brain

May produce false report due to disrupted autoregulation

Epidemiology and Natural Course

Rarity along with long period of clinical silence makes it difficult to estimate the overall prevalence

Incidence: approx. 1 per 1,00,000 person-years

Risk of Rx to be weighed against no intervention (ARUBA trial)

Though rare – might at times show spontaneous regression

Smaller AVM – increased risk of rupture (probably due to higher feeding pressure)

Risk of annual hemorrhage: 2-4%

Combined morbidity and mortality: 2.7%

Mean time to hemorrhage: 7.7 years

2008 Finnish AVM cohort:

multivarate analysis showed – hemorrhage risk factors to include

previous rupture

infratentorial

deep location

large size

Cumulative probability of an annualized risk for expected years of remaining life…Cumulative probability p = 105-age/100

AVM in the Pediatric population..

More morbid sequelae and devastating consequences

Most likely presenting symptom: Hemorrhage

Others: Seizure, congestive heart failure, neurological deficit

CHF – mostly in newborn due to large amount of left to right shuntEg. Vein of Galen Malformation

Surgically resected – occasionally recur – due to microshunting which grows over time

Rx: microsurgical resection with preoperative embolization unless risk of neurological deficit

AVM and Pregnancy..

Total blood volume increase by 40% and cardiac output by 60%

Arterial pressure can vary: hypertension can occur near delivery

Increased chance of hemorrhage (unclear as if statistically significant)

If pregnant woman presents with a hemorrhage from an AVM, the risk of rebleed during the same pregnancy: ~ 27%

Risk mitigated only with total resection

Rx entails risk to both mother and fetus

AVM and Pregnancy..

Radiosurgery:

risk to fetus and slow rate of occlusionnot a viable option during pregnancy

Endovascular:

risks of exposing the fetus to radiation, IV contrast and embolic solvents

MICROSURGICAL resection: only tool if patient wishes to have treatment before delivery

In general definitive Rx deferred until the pregnancy is over

AVM and Pregnancy..

Followed in high risk pregnancy setting and delivered by c-section

Immediate surgical evacuation for stabilization – if life threatening hemorrhage

Careful discussion with family regarding risks of hemorrhage and disability with intervention

Pregnant with unruptured AVM – definitive Rx after parturition

Seizures – controlled with anticonvulsant with minimal teratogenic risk

AVM and Aneurysms..

Special challenge

Increased flow associated with AVM vessels – predispose to aneurysm formation due to shear stress on vessel wall

4 types:

unrelated to flow vessels (remote)

flow relatedarising at the circle of Willis origin of a vessel supplying the

AVM (proximal)

arising from the midcourse of a feeding pedicle (pedicular)

arising from within the nidus itself (intranidal)

Aneurysm rupture is a possible clinical consequence

Risk of ruptured aneurysm should be considered

4 vessels angiogram (CTA or MRA) to rule out aneurysm

Risk of morbidity and death from aneurysmal SAH is higher than from AVM

Flow related aneurysms may regress spontaneously after AVM resection

Few important questions to ask..

Where is the aneurysm?

Which pathological entity was responsible for the hemorrhage?

Is the AVM sufficiently visualized?

If it is well visualized, can it be safely treated surgically?

AVMs and Aneurysms..

If AVM surgically treatable:

aneurysm secured and both treated in the same setting

If there is doubt as to the resectability of AVM:

treat aneurysm by any means acutely and leave the nidus alone for later, multidisciplinary management

Intranidal aneurysm:can be difficult to visualize in imaging modalitycan be difficult to diagnose it as a cause for bleedingany Rx for AVM, deals with it automatically; hence Rxed

together surgicallyif radiosx being considered; limited endovascular

embolic therapy

Treatment

Treatment

If presents with hemorrhage

Rx based on degree of hemorrhage and neurological status

risk of immediate rebleeding is relatively low; hence, early treatment without advanced understanding of the AVM characteristics can rather be dangerous unless a life threatening hematoma requiring immediate surgical evacuation

Rx delayed to allow time for hemorrhage to resolve and the AVM to stabilize its architecture

prompt intervention if neurological deterioration on observation

EVD if hydrocephalus

Decompression of hematoma while avoiding AVM, if hematoma needs urgent removal

Decompressive craniotomy if brain swelling+

For definitive treatment other options:medical or symptomatic managementembolizationmicrosurgeryradiosurgerymultimodality therapy

The main considerations for choosing the right option:

Size of AVM

Location

Vascular anatomy

Age

Medical condition

Medical Management

Indications:

very extensive, deeply located with blood supply primarily from deep perforating vessels not amenable to endovascular or radiosurgical Rx

very advanced age

comorbidities – advanced heart disease, respiratory insufficiency, cancer with metastasis

Rx – AEDs for seizure control

Embolization

Not considered as exclusive general treatment for most AVMs

rate of permanent morbidity 4-14%

not all vessels of all size and location can be safely embolized and hence, adherence to the goal of complete obliteration of AVM can not be achieved in most instances

reconstitution of shunting by recanalization or de novo vascular development

Technique of Embolization

Transfemoral access

Microcatheter used to access intracerebral vasculature

Selected feeding arteries isolated

Various agents delivered

Avoid premature venous outflow occlusion, which can cause rupture

Often combined with multimodality approach

Knowing the goal is important – volume reduction for safe radiosurgery vs. overall flow reduction to reduce blood loss during later microsurgery or embolization of feeding vessel, which is difficult to be accessed during surgery

Complete embolization NPPB

Staged embolization in multiple sessions can be done with ease

Large amount of embolic material stiff AVM difficult mobilization during surgery

Embolic Agents..

3 categories used:

Occlusive Devicesbraided silk thread/ platinum coils

Particles (45-1180 μm) – appropriate size selection important otherwise lodges in the nidusmixed with contrast before deliveryimportant to note that it does not reflux into the enpassage

artery or normal capillary bedPVA (polyvinyl alcohol)

LiquidsNBCA (N-Butyl cyanoacrylate)/ EVOH (ethylene and vinyl

acohol)

NBCA

Monomer – stabilized in hydrophobic ethiodol solution

Mixed with tantalum for radioopacity

Chemical variant of superglue – used as fast acting skin adhesive

When comes in contact with blood, polymerizes to form a solid cast

Rate of polymerization, manipulated by varying amount of ethiodol

Important for the use in fast flowing fistulous connection vs. large, plexiform nidus

Caution: to prevent polymer from flowing in the venous circulation risking PE

EVOH (Ethylene and vinyl alcohol) - Onyx

Copolymer (mixed with tantalum powder and dissolved in DMSO – dimethyl sulfoxide)

Copolymer precipitates and DMSO diffuses in a lava like manner

Outer portion remains nonadhesive but solidifies

Central core – continues to flow

Remains in patient’s system for several days with a distinctive odor

Timing between Embolization and Surgery

Matter of debate

Should be waited enough for the vascular pedicles to be taken out by embolization

And

Not too long so as there is alteration of hemodynamics of AVM nidus and risk of hemorrhage

Microsurgery..

Positioning

lesion ideally perpendicular to the surgeon’s line of sight

working corridor as short as possible to allow for minimal retraction and a comfortable working length

gravity as an aide to retraction and drainage

special consideration to the locations of the arterial feeders

larger craniotomy to assist in locating the feeders, as well as having a broader perspective of the malformation

General Microsurgery Principles..

Consideration of complex nature of feeding arteries and draining veins

First objective: identification of the nidus location – neuronavigation

Attempt to localize all the major feeding arteries

Then disconnecting them with nidus

Ideally, preoperative angiogram to be studied not only to see the location but to plan, in which order will they be encountered during surgery

General Microsurgery Principles..

Feeding arteries distinguished from draining veinsNOT by sight, but by noting if the distal vessel collapses with

gentle occlusion

Secure the feeder as close to the nidus as possible to ensure there is no en passage artery feeding normal brain

Securing the individual vessels can be done with bipolar coagulation

Coagulation however can be difficult at times due to thin vessel wall and high pressure of blood flow; Sundt vascular microclips may be used

Excessive bipolar usage or premature disconnection can cause vessel to retract within brain parenchyma !!!

Placing cotton patty with gentle pressure may not work due to high flow

Bipolar should be kept at low power and vessels occluded gradually

Dissection of nidus after securing of artery

Nidus separated from surrounding parenchyma; hemorrhage plane may be a good starting point

Maintain a uniform depth with circumferential separation to avoid encountering a poorly visualized vessel.

Careful not to enter the nidus: difficult hemostasis

Dynamic nature of the nidus makes it compressible than the surrounding brain with easy surgical manipulation unlike solid tumor

As more feeders are isolated and secured, the intranidal pressure decreases and allow for more manipulation

Deep arteries generally encountered last

Draining veins should be preserved at all cost to avoid an intranidal pressure increase

Often, however impractical, especially if the veins are superficial to the nidus, thereby tethering it in a way that prevents easy manipulation

Last structure to be secured before removing the nidus are the draining veins

When resecting the nidus, one should exercise caution to note if small feeding arteries are still attached

If intraoperative hemorrhage – need to figure where the hemorrhage is from

If from nidus – cotton ball placed over the location with the least pressure possible to arrest or even slow down the blood loss enough to visualize its source

If hemorrhage deep from the nidus – inadvisable to explore the nidus itself because of risk of creating multiple hemorrhages that are difficult to control

Surgical assistants should exercise caution with excessive suctioning

Small arterial feeders may retract into the parenchyma, preventing easy visualization

Hemorrhage may be due to NPPB from surrounding parenchyma – manifest first by rapid edema

Blood pressure reduction and packing of the surgical cavity may assist in localizing the hemorrhage

Surgical approaches..

For Deeper AVMs.. 3 categories

transcortical-transventricular

interhemispheric

Postoperative Management

Admitted to ICU

Continued arterial blood pressure and neurological checks

Advisable to undergo angiogram to confirm total resection of the AVM prior to discharge

If incomplete resection – reopening craniotomy done during the same admission

Postoperative complications – hemorrhage, seizures, cerebral edema, post-surgical infarcts especially related to venous occlusions

Radiosurgery..

Goal: delivery of sufficient ionizing radiation to the complete nidus

volume to obliterate AV shunting

Adv:ability to treat without need of craniotomyideal for deep seated AVMs and in patients with comorbiditiesless risk of NPPB or immature venous occlusion

Disadv:considerable delay of 2 to 5 years to show effectno reduction in hemorrhage rate during that timeapplying 2.7% annual risk – corresponds to 5.3-12.7% risk,

which is even more if the AVM has recently bledeffects of radiation: postradiation edema, cyst formation &

radionecrosis

Mechanism:

inflammatory response to high dose radiation loss of endothelium and proliferation of smooth muscle cells obliteration

18 Gy to the 70% isodose line means:

periphery of the nidus will receive 18 Gy and the interior will receive up to 18/0.7 = 25.7 Gy

Good predictors of successful AVM obliteration:

Nidus volume less than 3 ml

Nidus smaller than 2 cm in its largest diameter

Sharp delineation of the nidus border on imaging

Younger age

Fewer draining veins

Hemispheric location

Hemorrhage mass effect distortion of AVM 3 D anatomy inaccurate localization for radiosurgical targetting

4-6 wks of waiting before the nidus achieves a stable geometry – then only radiosurgery to be performed

Conservative definition of radiosurgery failure if persistence of AVM on angiography 5 years after the treatment

DURAL ARTERIOVENOUS FISTULAS

Introduction..

Aka Dural AVMs

Acquired lesions and NOT congenital

Most dAVFs occur adjacent to the venous sinuses

dAVF – shunting between the arterial vessels supplying the dura and the sinuses

Mostly idopathic

Inability of spontaneous thrombosis of the high flow fistula due to low pressure of the adjacent venous drainage

Adjacent venous sinus thrombosis rather may be the triggering factor

Thrombosis leads to opening up of microvessels within the sinus and also the release of pro-angiogenesis factors.

Biologically active – can recruit additional arterial supply

Rarer than AVM

Most common region – transverse and sigmoid sinuses

Other locations – cavernous, straight, petrosal and SSS

Carotid Cavernous fistula Type B,C and D are types of dAVFMay be formed due to trauma or rupture of cavernous carotid aneurysm

CCFA – direct communication between ICA and

cavernous sinus

B – meningeal ICA branches and cavernous sinus

C – meningeal ECA branches and cavernous sinus

D – meningeal branches of both ICA /ECA and cavernous sinus

Main morbidity – ICH risk

Do not have well defined nidus

Anatomical presentation influences the risk of rupture

Mechanical strength of dural sinuses withstand arterial pressure more than the intracranial vein minimal risk of rupture than if cortical vein is involved

Basis of Borden and Cognard Classification system

Borden is simpler but Cognard’s advantage over Borden is the use of flow dynamics based on angiography

Other clinical findings:

Bruit/ pulsatile tinnitus/ headache/ papilledema/ seizures/ neurological deficit

CCF – increased IOP visual deficits emergent therapy

Papilledema and features of raised ICP is due to thrombosis of sinus associated in majority of cases

Routine MRI and MRA miss the lesion unless of significant size

It is critical to distinguish sinus drainage vs cortical venous drainage

Selective and superselective angiography including the external carotids and vertebral arteries – required for distinction

Rx – Type I with benign symptoms – observationDebilitating tinnitus – operation

Sinus resection (transverse sigmoid sinus) or even bone may be required

Endovascular or microsurgical techniques to occlude the feeders

Unusual anastomosis between ECA and ICA branches require identification to avoid inadvertent passage of embolic material into the IC circulation, risking neurological deficits

Thank you!!