Epidemiology

The frequency of AVMs is 0.5% in autopsy series, with an annual incidence of one seventh to one tenth that of aneurysms and a range of 0.15%–3% [112]. There is a slight male preponderance [113]. Most AVMs become symptomatic by the age of 40 years, with the peak risk of hemorrhage in the 15- to 20-year-old age group [112,113].

AVMs can occur throughout the brain and have three morphologic components:

• the feeding artery or arteries
• the draining veins
• the dysplastic nidus (an abnormal connection between arteries and veins; ie, there is no intervening capillary bed)

AVMs are classified using the Spetzler–Martin classification scheme (see Table 5), which is based on three radiological characteristics: size, location (eloquence of the surrounding brain), and the pattern of venous drainage, either deep or superficial [114]. A total of 15%–20% of AVMs have associated intracranial aneurysms.

Table 5

The Spetzler–Martin scale for evaluating risk of neurological deterioration following surgery for arteriovenous malformation (AVM) resection.

Clinical presentation

Hemorrhage is the initial presenting symptom in 42%–53% of patients. This is followed, in decreasing order of frequency, by seizure (33%–46%), headache (14%–34%), or a progressive neurological deficit (21%–23%) [112]. Patients with AVMs >7 cm³ are more likely to present with a seizure (72%) than with a hemorrhage (28%). In contrast, those with smaller AVMs are more likely to present with a hemorrhage (75%) than a seizure (25%). However, larger AVMs have a higher risk of rebleeding [112,113].

Hemorrhage is the most devastating complication of AVMs, and may be secondary to rupture of the AVM itself, an associated aneurysm, or both. The hemorrhage may be intraparenchymal or subarachnoid in location. The annual risk of hemorrhage is 3%–4% [112,113,115]. Annual mortality is 0.9%–1%, but decreases after 15 years from the last hemorrhage [112]. With each episode of hemorrhage there is a 20% risk of a major neurological deficit and a 10% risk of mortality [112,113,115].

Diagnosis

Cranial CT is the mainstay of AVM diagnosis, whether ruptured or unruptured. CT readily detects hemorrhage and is also very sensitive for calcification, which is frequently associated with AVMs [112]. MRI is more sensitive than CT for detecting unruptured AVMs and allows for the accurate delineation of normal and abnormal brain tissue. This is essential for the adequate determination of eloquence, as defined in the Spetzler–Martin scale [114]. Conventional four-vessel cerebral angiography is the gold standard test for preoperative and pre-embolization assessment. MRA is not an adequate substitute for conventional angiography.

Therapy

There are several treatment options for AVMs, including observation, embolization, stereotactic radiosurgery, microsurgery, or combinations of the above [116,117]. Most patients should be considered for some form of therapeutic intervention because of the poor natural history of AVMs. The goal of AVM therapy is the complete removal or obliteration of the AVM; although partial therapy may offer a palliative effect for headaches, seizures, and progressive neurological deficits, it does not decrease the risk of re-hemorrhage [117,118].

AVMs of Spetzler–Martin grades I–III can be successfully treated with microsurgical excision with a low morbidity (0%–4.2%) [119]. Surgery often results in a cure and should be considered the treatment of choice in this patient group [117,119]. On the other hand, Spetzler–Martin grade IV and V lesions are high surgical risk lesions because of their large size and deep venous drainage, or because they are located in an eloquent location. Endovascular therapy is the treatment of choice for these lesions, either alone or in combination with microsurgery or stereotactic radiosurgery [117,120–122]. The long-term morbidity of microsurgical excision alone is 21.9% and 16.7% in grade IV and V AVMs, respectively [119].

Treatment technique

Biplanar fluoroscopy is particularly useful in AVM embolizations. As with other intracranial procedures, the margin of safety can be greatly increased if the patient is awake for the intervention, facilitating intraoperative neurological assessment. Vascular access should be obtained through a femoral route with insertion of a 6- to 8-Fr guide catheter into the ICA or VA. Superselective catheterization of the feeding arterial pedicles is then performed.

Full radiographic evaluation is required for the planning of embolization (see Figure 6). MRI is essential to detail the proximity of the lesion to eloquent brain, the appropriate operative corridor needed to access the lesion surgically, and the feasibility of preoperative (surgical or radiosurgical) reductive or ablative embolization. High-resolution four-vessel catheter angiography with selective injections of feeding pedicles and high-speed filming rates (≥4 frames/s) is critical in the planning of surgical and endovascular approaches. The studies are performed to define the number and type of arterial pedicles, their relationship to the supply of surrounding normal brain, the size of the nidus, the presence of associated fistulae and aneurysms (both intranidal and remote), and the type of venous drainage (superficial or deep). Higher risks of hemorrhage have been associated with lesions that have deep venous drainage (especially if a venous stenosis is present) or a periventricular location, and intranidal aneurysms [123,124].

Figure 6

A 38-year-old woman with a history of cerebellar hemorrhage presented for preoperative embolization of a cerebellar arteriovenous malformation (AVM). A magnetic resonance imaging scan of the brain (a) showed several large flow voids within the fourth (more...)

The angiographic anatomy of AVMs is quite complex. A variable number of arteries may feed the nidus, with two patterns of supply: the supplying artery either directly terminates in the nidus, or sends feeders (or twigs) to the nidus while the main trunk continues on to supply normal brain distal to the branch point. These latter vessels are known as en passage (or vessel in passage) feeders. The presence of an en passage arterial supply carries a higher risk of posttreatment (surgical or endovascular treatment) ischemic neurological deficits. This is because of the risk of injury or embolization to the parent vessel. Superselective angiography of single pedicles of AVMs with multiple feeders is very helpful. With this technique, it is possible to demonstrate whether a single feeder supplies one portion or compartment of the AVM or if it receives blood supply from multiple feeders. The presence of single-feeding pedicles increases the probability of successful occlusion of that portion of the AVM.

Embolization technique

The entire AVM nidus, including the components nearest the venous side, must be occluded for an endovascular cure or else the nidus will recruit a new arterial supply. Where surgery is indicated, embolization may be performed to reduce both the rate of blood flow and the size of the AVM in order to lessen operative morbidity and to increase the probability of successful treatment with radiosurgery. This is not always straightforward, and to achieve a cure without complications the interventionalist must have a thorough understanding of the polymerization characteristics of the embolic agent, the rate of blood flow through the nidus, the degree of pedicle occlusion by the microcatheter, and the rate of material delivery through any given microcatheter.

Before delivering embolic material to an AVM, the risk of causing focal ischemia and stroke by unintentional embolization of a normal vessel must be assessed by angiography through the microcatheter after it has been placed in its final position. This will show if any normal brain is being irrigated distal to the tip of the microcatheter. When there is doubt as to whether functional brain will be embolized, a provocative challenge can be performed by injecting amobarbital through the microcatheter. This short-acting barbiturate effectively shuts down neuronal activity – therefore, if no clinical deficits develop, embolization of that particular pedicle will be unlikely to cause a significant neurological deficit.

After access is obtained to the appropriate vessel, angiography is performed. The goal of the interventionalist is to determine the following:

• exactly which vessels supply the AVM
• how many feeding pedicles are present
• the relative flow rates in each pedicle
• the number and location of draining veins or nidal aneurysms

The largest pedicles and those feeding aneurysms and large draining veins should be selected as the initial targets for embolization. The location and size of the AVM also plays a role in determining the appropriate treatment strategy. AVMs that are superficially located usually have arterial supply from only one or a few cortical arteries. Large supratentorial AVMs are frequently wedge- or pyramidal-shaped, with their bases at the cortical surface and their apices extending down to the lateral ventricle. These AVMs, and those located entirely in a deep location, often have supply from the choroidal and lenticulostriate systems. Such a deep arterial supply increases the complexity of surgical excision, and the risk of blood loss and surgical complications. Therefore, deep-feeding vessels are ideal targets for embolization.

In deciding on the strategy for embolization, the interventionalist must also consider whether it will be necessary to re-access the feeding pedicles, in which case it will be important to ensure that gluing one pedicle does not prevent access to other pedicles. With a strategy in mind, the flow-directed microcatheter, usually with a tip shaped appropriately for the task at hand, is advanced into the feeding artery and directed into the appropriate pedicle. Selective angiography is then performed through the microcatheter, focusing on forward flow through the pedicle, retrograde flow (if any) into the feeding artery, and the opacification of any normal brain tissue. Once the microcatheter is appropriately positioned and the decision to treat that pedicle is made, the glue mixture is made.

NBCA polymerizes rapidly. For a slower and more controlled polymerization, NBCA is mixed with lipiodol, an oily contrast medium. An advantage of lipiodol is that it also opacifies the glue mixture for fluoroscopic visualization. With experience, the interventionalist can vary the ratios of the components of the cocktail to facilitate penetration of the entire nidus with glue before polymerization. The mixture must also be prepared so that polymerization occurs before the glue reaches the draining vein(s). If the draining veins are occluded, AVM rupture can occur due to increased back-pressure within the nidus. Finally, glue injection must be timed perfectly with withdrawal of the microcatheter to avoid both gluing the microcatheter to the nidus (usually an irrevocable situation) and embolization into normal vessels.

When handling the completed mixture, care must be taken to avoid contact with ionic fluids (eg, normal saline and blood), which could cause premature polymerization. The microcatheter is therefore flushed thoroughly with pure water. The injection of glue is then performed, keeping in mind the shape of the pedicle and the portion of the AVM that it feeds. Once opacification of the nidus and pedicle occurs, the injection is terminated and the microcatheter is quickly withdrawn into the guide catheter in one smooth motion. This is best performed by an experienced assistant at the command of the interventionalist performing the injection. The microcatheter is then removed and the guide aspirated to remove any glue particles before a repeat angiography is performed. This process is repeated as needed (see Figure 6).

Particulate embolic agents are composed of a variety of materials and come in a range of sizes. The smallest are PVA particles, which are manufactured in sizes ranging from 50 to 1,500 μM. For injection, the particles are suspended in radiographic contrast media. The exact size of particle used depends on the rate of flow through the nidus and the presence of intranidal shunts and fistulae. If a large enough quantity of PVA particles pass through the nidus and cross into the venous circulation then transient pneumonitis can develop. To decrease the risk of this complication, intranidal shunts can be partially occluded by mixing the PVA with fibrillary collagen or by using Berenstein liquid coils (Boston Scientific/Target Therapeutics). These coils are composed of fine injectable platinum threads, which promote thrombus formation. When delivered to small feeding pedicles, they will lead to thrombosis and occlusion of the vessel. For very large feeding vessels (3–5 mm diameter), embolization with vortex or "tornado" shaped platinum coils can be performed through the microcatheter. Like the liquid coils, these coils are coated with fibered threads, which promote thrombosis and occlusion.

When a definitive cure is not needed or feasible, AVM embolization can be performed as a palliative treatment – or, more commonly, as a pretreatment prior to radiosurgery or open excision. Preoperative treatment decreases the size of the AVM nidus, which facilitates both radiosurgery and surgical excision. In the case of radiosurgery, embolization decreases the radiation dose required and the size of the treatment field, minimizing the exposure of healthy brain tissue to radiation and increasing the potential for a cure. Despite the complexities inherent in their use and their potential for serious complications, cyanoacrylates are particularly useful in reducing the size of selected AVMs before stereotactic radiosurgery. Their adhesive properties result in permanent occlusion, which is ideal before radiosurgery because the clinical benefit following radiation treatment (in terms of reduction of ICH risk) is delayed for at least 6 months.

Preoperative embolization also facilitates open surgical excision by decreasing the size of the AVM and decreasing intraoperative bleeding, which can be significant. Since open excision is typically performed shortly after embolization, nonpermanent embolic agents (ie, particulates) can be utilized. These agents are somewhat safer and easier to use than the cyanoacrylates and are sufficient because nidus recanalization is often delayed for a few weeks after particulate embolization, which is sufficient time to allow excision.

Results overview

Endovascular therapy results in a cure or complete obliteration in only 5%–20% of AVMs, most of which are small malformations that are also treatable with surgical excision [118,125,126]. However, preoperative embolization is highly effective in decreasing surgical bleeding, which decreases operative time and increases the chance of surgical success in high-grade lesions [117,120,121,127–9]. In one series, endovascular embolization followed by microsurgery was associated with a 5% rate of new major deficits compared with 31% in the surgery-only group [130].

The best results are obtained when surgery is performed within 2–14 days of embolization. Such a short interval decreases the probability of AVM recanalization via new leptomeningeal or deep collaterals [117,118]. Since AVM recanalization occurs with all embolic agents except cyanoacrylate glue, endovascular therapy should be followed by early microsurgery in lesions treated with these nonpermanent agents [117,118]. Large AVMs should be treated with staged embolization to decrease the risk of perfusion pressure breakthrough and ICH [118,119]. The combination of endovascular embolization and radiosurgery has not been adequately studied and is controversial [118,131–4].

Complications of endovascular therapy include embolic stroke, ICH, pulmonary embolism, and microcatheter retention [117,118]. The reported complication rates vary from 3% to 25%, but serious neurological events or death occur in only 3%–8% of cases [117,120]. Staged embolization of large AVMs, meticulous technique, and rapid withdrawal of the microcatheter after injection greatly reduce the risk of complications [117,118].