Intravascular approach to the treatment of cerebral arteriovenous malformations and dural arteriovenous fistulae

Cerebral arteriovenous malformations (AVMs) may pose as one of the more formidable challenges to a neurosurgeon.' A multi-disciplinary approach including the neurosurgeon, interventional neuroradiologists and radiosurgeon and neurologists, seems to be the ideal modem day treatment of these lesions. Complications due toAVMs include haemorrhage, mass effects, epilepsy and bruit Pieter Fourie MBChB(PreO, MMed(Rad)Pret

:Magnetic resonance imaging can be used as a useful tool in the diagnostic approach to AVMs. The anatomical location, size, venous drainage and condition of the surrounding brain can be demonstrated. (Arrow) The gold standard as a diagnostic tool ishowever angiography. Digital subtraction angiography is of great value especially when one of the newer generation X-ray machines is used with a high pixel rating, magnification and good road mapping abilities. (Figures 2a & b) Intravascu lar approach to the troarrnerit of cercbr<ll AVMs and dural arteriovenous fislulae (rampage 17 History and development The intravascular treatment ofAVMs has its origin with Zuessen-hop et al. 2 They used silastic spheres injected via a direct surgical approach in the internal carotid and vertebral arteries. The spheres were then flow directed to the lesion. It was however non-selective and occluded mostly the proximal feeding vessels. The nidus often recanalised through leptomeningeal, transmedullary and transdural collateral vessels. It was of little value where small arteries supplied the lesion e.g.perforating arteries. Serbinenko' in 1974 described safe selective intracranial catheterisation beyond the circle ofWillis, using detachable balloons to occlude the larger feeding arteries of theA VMs and fistulae. The use ofa calibrated leak balloon on a micro-catheter was reported by Kerber' in 1976. Distal navigation became possible and the use of acrylic agents was introduced for the occlusion of the nidus. These catheters needed to be inflated for the advance into the arterial system butcaused complications likerupture and haemorrhage. 5 Only fluids could be injected through it precluding the use of particles, because of its small lumen diameter. During 1988-89 new micro-catheters were developed that made super selective catheterization deep into the distal arterial tree possible. The new over the wire catheters made it possible to introduce a wide variety of particles into the nidus and supplying pedicles (Figures 3a & b). The flow-guidedcatheters allowedonlyfluidsand very small particles,but could be negotiated into very small tortuous and distal vessels.

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SA JOU RNAL OF RADIOLOGY· September 1996 Each nidus is composed of a series of compartments which could be in contact with one another. The compartments are fed by different arterial pedicles. Because of the high flow (from 150-900 mlIrnin with an average of 490 ml/min)" these pedicles are quite large.According to the Hagen-Poiseville equation the flow in the feeding artery is directly related to the feeding artery's blood pressure and the fourth power of its radius. It isinversely related to the length of the pedicle.

Q=tlPx7tr 4 8xLxll
Tl is the viscosity of the blood.
P is the intraluminal pressure L is the length of the vessel It is generallyaccepted thatlargeAVMs with high flow usually have a low arterial pressure and less chance of haemorrhage than the smaller slow flow but high pressure lesions. The larger lesions present more often with seizures.' Miyasaka et ac oncluded that fewer draining veins increased the risk of haemorrhage.
During embolisation intra-arterial pressure would rise significantly" It is also clear that the intraluminal pressure of the feeding arteries is much less than that of the carotid or vertebral arteries in the neck." Gradients ofup to 7SmmHghave been reported. This gradient however subsides after nidal embolisation.
The high flow state in the feeders,nidus and draining veins causes histological changes that enhance the preponderance oflocal trauma during catheterisation and manipulation.JJ

Grading of AVMs
The surgicalgrading system devised by Spetzler and Maartin J 2 correlates the risk following surgical removal ofAVMs. We find it an excellent way of entrée to the Intravascular approach to the treatment of cerebral AVMs and dural arteriovenous fistulae !rompage 18 treatment of these lesions. Where embolisation is concemed the difficulty in approaching the lesions via the intraluminal paths, the tortuousness and length and number of vessels,asweil as the presence of large fistulae in the nidus play important roles concerning the outcome of the procedure and should be taken into account.

Embolic agents
The ideal material for endovascular embolization ofAVMs has yet to be discovered. Ideally, an embolic agent should be non-biodegradable, non-toxic, and nonmutagenic. It should be easily delivered through a rnicrocatheter, be easily seen on fluoroscopy, and adhere to the walls of the vessels without extravasation or recanalization. Finally, the ideal embolic material should be soft enough to allow retraction of the lesion from surrounding normal tissues during surgical excision.
Many different embolic agents were used like silk, coils, rnicrospheres (metal, polyvinyl alcohol, Spongistan) and liquid adhesive polymers.
Of the liquid adhesive polymers, alkyl cyanoacrylate monomers have been most widely used. Two kinds are used these days viz. isobutyl2-cyanoacrylate (IBCA) and n-Butyl cyanoacrylate (NBCA). Once the monomer is exposed to an ionic fluid (like blood) it polymerizes immediately. A tight bond between tissue and the polymer exists that is used to bond tissues together in surgery13( Figure 5). Vinters et al reported on the long term follow-up of cerebral AVMs treated by embolization with bucrylate." Theyfound bucrylate in the extra-vascular space 41 days after embolization and occasionally earlier.
Although the nidus can be fully embolised with these materials, re-canalization does occur up to 12-20monthslater. ls It is a good embolic agent, but by no means permanent. IBCA is quite brittle and therefore difficult to handle at surgery, without traumatizing the brain. Carcinogenicity is alsoa concem. IBCA has been replaced by n-Butyl cyanoacrylate." Bucrylates have been used for the treatment ofAVMs for the last 15 years without any report in the literature of the proposed mutagenicity having occurred,'? However, NBCA is less brittle than IBCA and has a slightly shorter polymerization time.
Other liquids in the offing are ethylene vinyl alcohol copolymer introduced byTaki et ailS and estrogon alcohol and polyvinyl acetate.'?
Patho-histological changes after embolization with polymers include a foreign body response followed by an inflammatory response" and vessel wall necrosis followed by either aneurysms and! or extra-vascular appearance of the polymer. Haemorrhage may occur due to the secondary formed aneurysms after embohsation.
Haemorrhage associated withAVM embolisationrangesfrom 3-11 %. 21 We administer Nimodipine and steroids intravenously during and after the procedure. Nimodipine isusually administered before the procedure.

Particulate materials
The most commonly used particulate is polyvinyl alcohol. Sizesfrom 7sto 12s0~m are available. The particles are suspended in diluted contrast and injected at small non-laminar flow boluses. Starting from the 19 SA JOURNAL OF RADIOLOGY. September 1996 smaller particles enhances the possible blocking of the smaller intra-nidal vessels followed by the larger ones to occlude larger vessels and fistulae. The main pedicle can be occluded with silk or fibred coils.When fistulae are present pulmonary embolism may occur.
Itis reported that collagen (avitene) may enhance the thrombo-genecity of the mixture 22 Tissue response to PVA is well described by Germano et aP3 in the brain.
They investigated 66 consecutive excised AVMs histologically, that were embolised with PVA before surgery. They found an inflammatory response in the vessels, including angionecrosis of the wall, even as soon as two weeks post-procedurally. Foreign material was found in 63 % of cases. Recanalization occurred in.18% oflesions within four weeks.
Pulmonary embolism during the treatmentis a well known complication. Venous outlet obstruction can pose a high risk if the inflow to theA VM isstill prevalent and extremely high."

Technique
Grading according to Spetzler and Maartin is done on MR or CT, followed by an angiogram for further assessment of velocity, pedicle, nidus size and appearance, draining veins and anterior and! or posterior cerebral supply.
The clinicaljudgement for possible way of treatment resides mostly with the referring neurosurgeon.
In some centres general anaesthesia is administered and in others neurolept analgesia. Purdy et aP s saythat unless the feeding pedicle is fully embolised sodium Amytal testing isnot needed.
. Nowadayswetendtoemboliseourpatients while they are awake and resort to provocative testing.
Our patients are heparinised (5000 units) where the pedicles are not easily to page 20 Intravascular approach to the treatment of cerebral AVMs and dural arteriovenous fistulae 'rompagB 19 negotiable. We prefer not to use heparin when the lesion is easily approachable and where arterial spasm of pedicles is less of a problem. Once the patient is heparinised we prefer not to administer protamine sulphate but allow the activated clotting time (ACT) to come down to 150 seconds before we remove the sheath from the femoral artery.
All our patients are placed in the intensive care unit for a 24-48 hour observation period after treatment. They are discharged as soon as their condition allows it.

Provocative testing
The so-called Wada Test was first done by Wada and Rasmussen." They injected sodium amobarbital (Amytal) within the internal carotid artery (lCA) to evaluate cerebral dominance before epilepsy surgery. When Amy tal is injected into a feeding pedicle of anAVM reversible changes to normal brain can be elicited according to Ranch et al. 27 We now administer ±35mgAmytal before embolisation in two distinct boluses. The first bolus is given slowly to flush the normal distal brain. The second bolus is given as fast as possible to cause, if possible, slight retrograde reflux into the feeding pedicle. Once polymer is injected the flow state of the AVM changes and may cause stasis of blood flow with possible untoward embolisation of the pedicle. Immediately after the administration of the Amytal a neurologist in theatre tests areas of eloquence close to the lesion. When a negative response is elicited embolisation is commenced. Brevital may also be used." Ithas a shorter half life than Amytal and is more readily available in South Africa ( Figure 6).

Clinical materials and methods
BetweenApril1995 and May 199613 patients with AVMs were treated in our unit by means of the endovascular route. The indications for treatment were: Palliation in non-resectableAVMs. Pre-surgicaldevascularization. Diminution of nidus size in combination with radiosurgery: Totalobliteration.
Two patients were treated with PVA as a presurgical adjunct. The rest of the cases were embolised with polymer, of which two were operated on later:Twelvepatients were male and 1female. Their ages varied from 19 to 53 with the average age of3 7.3 years. Seven cases were graded as Hunt & Hess I and four cases as Hunt and Hess II and two asHunt and Hess ill. Thefirsttwo caseswere done under general anaesthesia and last Ilunder local anaesthetics.
Four patients' AVMs were graded as Spetzler andMaartin Grade N and the rest as Grade IIand I. The last Il patients were subjected to sodiumAmytal provocative testing. Staged procedures were done in three patients. We use a mixture ofLipiodol, Tungsten powderandNBCA( Figure 7).Thefasterthe flow,the fasterpolymerization is needed and the lessLipiodol is added and vice visa.The idea is to completely fill the nidus with the polymer without venous occlusion.

Results
All patients has a diminution in size of the AVMs (Figures8a & b).
All the presurgical patients were successfully operated on, one of which was followed up and showed no recurrence. The others are due for follow-up MRI and angiography.
One patient was completely cured on the one year follow-up angiogram.
One epileptic patient has had no seizures since the procedure but remains on anti-epileptic treatment.
One patient with amassivefTontalA VM had a personality change for the better:

Complications
Two patients with lesionsin their dominant hemispheres had temporary speech deficits post procedure. One had a writing deficit that resolved after a few weeks.
One patient developed slow retrograde thrombosis of the callose-marginal artery and subsequently developed hemiplegia.
No deaths occurred and no haemorrhages occurred.
One patient developed severe vascular spasm causing us to terminate the initial procedure. The endovascular therapy for vasospasm due to haemorrhage or catheter manipulation includes papaverine hydrochloride. Up to 300mg can be infused at a time over a period of one hour" Pre-surgical embolisation was achieved step by step using PVA until the proper results had been achieved.
A mixture of polymer and PVA can be helpful with the latter occluding small or evenlargerparts of the residual lesion after initial embolisation with polymer( Figure 10).
Radiosurgery with the gamma knife or other modes of radiation can be important adjuncts to the treatment of these lesions, but is beyond the scope of this article.
Three of these patients had dural arteriovenous fistulas which were treated with polymer. Inthe follow-up angiograrns two of these patients had recurrence of different arteries supplying the fistulae. It is now a known fact that these lesions are acquired usually secondary to venous thromboss" or hypertension". Inmany cases the pathogenesis is unknown. Normal microarteriovenous shunts exist between the arterial and venous systems. Due to abnormal pressures in the venous side caused by ISCA PVA    either thrombosis or trauma to the endothelium angiogenesis factor is released that may enhance the development of these fistula. Djindiian et aP 3 classifiesthese lesions in three grades.The detailed discussion of this very interesting and extensive condition is beyond the scope of this pubkation.

Discussion
The venous drainage pattem must be well demonstrated in all cases" due to the fact that the risk involved with treatment is directly related to it. According to Halbach et aP5 dural fistulas involving the cavernous, inferior petrosal, and marginal sinuses can usually be effectively managed by endovascular techniques exclusively. The fistulae in the ethmoidal region can be treated by surgery alone. The remaining dural fistulae require a combination of endovascular and surgical topage22 Intravascular approach to the treatment of cerebral ;\VMs and dural arteriovenous fistulae from page 21 techniques. Close cooperation between all the clinicians involved is essential.

Conclusion
The endovascular approach to the treatment of arteriovenous malformations of the brain and dural arteriovenous fistulae is an adjunct to surgery and radiation therapy in these very important conditions. Close cooperation between the specialists involved is of utmost importance. The therapeutic vision should be that of total therapy using a multi-disciplinary approach.