Symptoms

The size of giant AVMs and the large amount of arteriovenous shunting within these lesions often result in symptoms unique from those with smaller AVMs. Small vascular malformations are typically manifested as headaches,^2,3 seizures,^4–6 or hemorrhage.^5–9 Giant AVMs can have any of these symptoms but can also cause transient and progressive neurological dysfunction through cerebrovascular “steal.” The large blood volume shunting through these malformations can result in relative hypoperfusion in the surrounding neurological tissue with subsequent ischemia.^10–13 This is due to lower blood pressure within the arterial feeders of the AVM than in the surrounding brain, which results in preferential shunting of blood to the AVM away from normal brain tissue.

AVMs have initial hemorrhage rates of 2% to 4% and annual rebleeding rates of approximately 4% to 18%.^7,14–17 Mortality from each hemorrhage approximates 10% to 15%,^5,8 and up to 50% of patients suffer some form of neurological deficit as a result of bleeding from an AVM.⁹ Some authors believe that larger AVMs have bleeding rates slightly lower than their smaller counterparts.^7,18,19 Other studies have shown no consistent relationship between size and risk for hemorrhage,^14,20 and feeding artery pressure (believed to be a risk factor for AVM hemorrhage) did not correlate with AVM size.²¹ However, giant AVMs with components in the basal ganglia, thalamus, and pineal region may be associated with not only a higher hemorrhage rate²² but also increased morbidity if they bleed, with more than 60% of these patients suffering significant morbidity or death from hemorrhage.²³ Angiographic factors that have been shown to correlate with risk for AVM hemorrhage are central venous drainage, periventricular location, and intranidal aneurysms,^24,25 as well as a single draining vein²⁵ and stenotic venous drainage.²⁶ By their size alone, giant AVMs are more likely to have a component of central venous drainage and a portion of the AVM adjacent to or within the ventricle.

Indications for and Contraindications to Surgery

Indications for resection of giant AVMs must consider both the natural history of the AVM and the combined risks associated with multimodality treatment for a particular patient.^27,28 Most angiographically documented giant AVMs are candidates for treatment, particularly if they have hemorrhaged or are causing significant progressive neurological deficits, disabling headaches, or medically intractable seizures. The risk with surgical resection is generally related to AVM size and location and the complexity of arterial feeders and venous drainage,¹ factors that make these giant AVMs a higher risk than smaller AVMs to treat with surgery alone. Larger lesions may require staged surgical resection or multimodality therapy combining microsurgery, embolization, and stereotactic radiosurgery.^27–30 Other factors affecting treatment risk include the patient’s clinical condition and age and surgeon experience.

The location of the giant AVM under consideration significantly affects the risk associated with surgical resection.^27–32 Because of their size, these larger AVMs often involve eloquent cortex, which significantly increases the risk of resection. Resection of giant cortical AVMs may cause motor or sensory deficits (frontal/parietal) or visual field defects (occipital), memory deficits, and changes in cognition and personality (cingulate gyrus and corpus callosum). Treatment of deep portions of giant AVMs within the basal ganglia and thalamus can result in hemiplegia, sensory deficits, dysphasia, and cognitive and memory deficits.^23,33,34 The clinical condition of the patient also has a bearing on surgical resection, with poor-grade patients usually resulting in a poor outcome.²⁹ Younger patients have a better benefit-to-risk ratio for the treatment of giant AVMs for two reasons. First, the brain of a young patient can better tolerate resection of the vascular malformation and has improved recovery after surgery.³⁵ Second, a younger patient translates into longer AVM-free survival on completion of resection.³⁵ Likewise, patients with a significant mass effect from a hemorrhagic clot resulting from AVM rupture should undergo emergency evacuation of the hemorrhage, with resection of the AVM being reserved for a later date. The timing of resection of giant AVMs is similar to that for other AVMs in that resection should be planned under nonemergency conditions to minimize patient morbidity. Resection of the AVM 4 to 6 weeks after hemorrhage, when the blood is liquefied, may improve the ease of resection.^8,23,30,36 In many cases, the hematoma cavity has performed a portion of the dissection around the nidus of the AVM. Furthermore, this short interval allows the patient to achieve stabilization or improvement of any neurological deficits.

Failure of stereotactic radiosurgery and embolization is another indication for surgical resection,^27,30,32 although in the case of giant AVMs, these treatment modalities are generally used as adjuncts in reducing AVM size before planned microsurgical resection. Most studies indicate that partial obliteration after radiosurgery does not confer protection from AVM rehemorrhage,^{23,27,29,33,37,38} and hence an alternative therapy should be sought for residual AVMs seen more than 3 years after radiosurgical treatment. Embolization is a useful treatment of giant cortical AVMs,³⁹ but it is less useful in the treatment of deeper arterial feeders (thalamoperforating, choroidal, and lenticulostriate arteries) within the basal ganglia and thalamus. These vessels primarily arise from the parent vessels at right angles, have small lumens, and are thus difficult to canulate.^23,33,34 Nonetheless, in selected cases, embolization has been extremely helpful in partially obliterating even basal ganglia and thalamic arterial feeders.^29,30,40

Contraindications to the treatment of giant AVMs include poor clinical condition of the patient as a result of AVM hemorrhage, medical conditions precluding surgery, and very elderly AVM patients. Frequently, patients in poor neurological condition may improve over time or with minor procedural interventions, such as placement of a ventriculostomy or ventriculoperitoneal shunt for hydrocephalus, and may then be candidates for treatment. Other patients with significant neurological deficits as a result of hemorrhage can make dramatic improvements with time and would therefore qualify for treatment. Patients who have giant AVMs but are asymptomatic or have minimal symptoms are sometimes best observed clinically rather than treated.

Angiography

Angiography remains the “gold standard” with respect to evaluation of AVMs. Because of the multiplicity of arterial feeders to these giant AVMs, it is important that a four-vessel angiogram be performed to document all of the arterial supply. Giant AVMs may have a portion of their blood supply from extracranial sources, so both external carotid arteries should be evaluated.⁴⁴ As with smaller AVMs, multiple views should be obtained to ensure that the neurosurgeon has a complete understanding of the origin of all the arterial feeders, the size and configuration of the AVM, and the number and direction of veins draining the AVM. A complete initial angiogram also allows better comparison with subsequent angiograms obtained during and after treatment. Angiography can also potentially document patients with a substantial amount of cerebrovascular steal as a result of the giant AVM. In these cases, normal cortical vessels may show more limited flow than other vessels at a distance from the AVM. In addition to standard two-dimensional angiography, the more recent development of three-dimensional angiography has improved the ability to identify the true size of the AVM (Fig. 389-1).⁴⁵

FIGURE 389-1 A 26-year-old woman underwent evaluation for seizures, which revealed a giant left parietal arteriovenous malformation (AVM). Three-dimensional cerebral angiography was performed to further characterize the AVM nidus (A-C). The portion of the AVM nidus filling from the posterior circulation is shown in red, whereas the portion of the AVM nidus filling from the anterior circulation is shown in green.

Post-treatment angiograms should be performed to ensure complete obliteration of the AVM, either soon after microsurgical resection of the final portion of the giant AVM or within several years after stereotactic radiosurgery if this modality is used as the final treatment within a staged approach to a giant AVM. It is critical to confirm complete treatment of an AVM, particularly giant AVMs, because leaving a residual AVM component is more problematic and reports suggest that partial treatment does not protect against future hemorrhage.^{37,38,46–49}

Angiography also plays an important role in the treatment of AVMs with stereotactic radiosurgery. Current radiosurgical systems rely on a fusion of angiography and magnetic resonance imaging (MRI) or computed tomography (CT) as a basis for planning treatment. In older radiosurgical systems, angiography is performed with a stereotactic base ring (or bite block) attached to the patient’s head and a fiducial cage mounted to the base ring. The fusion of angiography and MRI/CT allows improved targeting of the nidus while avoiding extraneous radiation doses to the draining veins or the surrounding cortical tissue. Newer image-guided radiosurgery is performed without a stereotactic ring, and in these cases, three-dimensional angiographic images can be directly fused to stereotactic CT and MRI during the treatment-planning process.⁴⁵

Magnetic Resonance Imaging

Although angiography remain the primary modality for evaluation of giant AVMs, pretreatment MRI provides additional information. MRI shows the relationship of the giant AVM to other intracranial structures, thereby affording the neurosurgeon a better understanding of the anatomy surrounding the AVM. The size and direction of large draining veins can often be noted, as can evidence of previous hemorrhage. MRI is also critical during the planning of stereotactic radiosurgery in conjunction with cerebral angiography. In select cases of giant AVMs with irregular shapes or deep components, intraoperative navigation with MRI-based guidance can be extremely useful. More recent developments in MRI technology have allowed the incorporation of three-dimensional imaging to assess both the AVM nidus itself^50–53 and white matter tracts adjacent to the AVM.^54–56 Functional MRI has also been used to elucidate the relationship between an AVM and eloquent areas of the brain.⁵⁷

Xenon Computed Tomography

Xenon CT is rarely used in the evaluation of smaller AVMs, but for larger AVMs with significant surrounding cortical ischemia as a result of steal, this modality may be useful in determining the degree and distribution of hypoperfusion.⁵⁸ Impaired augmentation indicates failure of autoregulation and may identify patients at high risk for normal perfusion pressure breakthrough bleeding.

Embolization

Because giant AVMs are difficult to treat with microsurgery alone and are too large to be optimal targets for stereotactic radiosurgery, embolization is generally the first course of treatment. Historically, this process consists of using either small polyvinyl alcohol particles³¹ or cyanoacrylate glue^59–62 in an attempt to occlude the feeding arteries. Over the past decade, n-butyl-2-cyanoacrylate (NBCA) has emerged as the main embolic agent of choice because its soft nature after occluding portions of the nidus does not interfere with later surgical resection of the AVM.⁶¹ Recently, ethylene vinyl alcohol copolymer (Onyx, Micro Therapnetics, Irvine, CA) has been studied as an embolic agent, with several clinical series documenting the efficacy of this agent.^63–67 The primary goal of embolization is to reduce volume and flow in the AVM to facilitate safer and more effective subsequent treatment with microsurgery or radiosurgery (or both). Embolization of deep feeders to the AVM or deep AVM components may help in later surgical resection. Occasionally, embolization alone is used for palliation of symptoms from giant AVMs with no intent of obliterating the entire lesion. Embolization is usually performed in several stages, often three or more, for giant AVMs.⁴⁴ Staged embolization allows the AVMs to adjust to changes in flow hemodynamics after each embolic treatment; attempts to embolize large portions of a giant AVM in a single stage are frequently associated with increased risk for hemorrhage. Giant AVMs can have a significant external carotid component, and embolization of these vessels often makes the craniotomy opening easier for the surgeon, as well as reduces blood supply to the AVM. Many giant AVMs have arterial supplies from both the anterior and posterior circulation and frequently from both hemispheres, and therefore multiple vessels need to be cannulated in an attempt to achieve optimal embolization. Care must be taken to avoid passing embolic glue or particles into normal cortical vessels to avoid the development of infarcts.

During embolization, patients with giant AVMs are monitored with electrophysiologic potentials, which provides several benefits.^39,40 First, such monitoring is particularly useful in identifying when normal cortical vessels are inadvertently occluded. Second, electrophysiologic monitoring during embolization can also provide some insight to the neurosurgeon regarding whether the patient’s brain can tolerate periods of relative hypotension (which may be used later during surgery to reduce bleeding). This is particularly relevant when treating an AVM with “steal” or ischemic symptoms. Furthermore, when a particular vessel is in question, amobarbital sodium (Amytal) can be injected into the vessel before embolization to determine whether the vessel is supplying an area of eloquent cortex and hence would cause a neurological deficit if occluded.⁶⁸

Some institutions use intraoperative embolization extensively in treating giant AVMs.³¹ The advantages of this technique are that the risk of reflux into normal vessels is decreased and the surgeon has the opportunity to inject numerous distal vessels inaccessible to the neurointerventionalist in the angiography suite. Intraoperative embolization proceeds once the surgeon has performed the craniotomy and exposed the AVM. Injection of the embolic agent should be performed as close to the AVM nidus as possible to minimize reflux into normal vessels. After temporary occlusion of the proximal portion of the vessel, 27-gauge needles can be introduced and several cubic centimeters of NBCA injected. This process can be repeated for various feeding arteries until flow to the AVM is significantly reduced. After embolization, each feeding artery can be sacrificed with either a small clip or bipolar coagulation.

Stereotactic Radiosurgery

Stereotactic radiosurgery has established itself as successful treatment of certain intracranial AVMs, particularly small or moderate-sized AVMs located in critical brain regions. A number of clinical series using either heavy charged particles (protons and helium ions) or photons (Gamma Knife or linear accelerator) have demonstrated that AVMs less than 3 cm in diameter treated with 20 to 25 Gy equivalents (GyE) have a 3-year obliteration rate of 80% to 95% with a low complication rate (2.5% to 4.5% permanent neurological deficits, 2.5% to 4.5% transient deficits).^{29,37,38,69–77} However, various limitations of stereotactic focused radiosurgery have become apparent after analyzing the results in treating AVMs larger than 3 cm. These AVMs have a much lower obliteration rate, even after 3 years (33% to 58%), and a higher complication rate (20% to 30%) with treatment doses of 15 to 20 Gy.^{29,38,70,73,75–79}

The primary mechanism of AVM obliteration after radiosurgery involves hyperplasia of the vascular intima⁸⁰ with progressive narrowing and ultimately occlusion. Such obliteration typically takes place over a 2- to 3-year period. There are three considerations when weighing surgery versus radiosurgery for the treatment of AVMs. First, AVMs larger than 4 cm in diameter have only a 33% to 50% rate of obliteration at 3 years after radiosurgery but a 20% to 30% complication rate with treatment doses of 15 to 20 Gy.^38,77 The rate of obliteration is increased for larger AVMs when higher doses are used (25 to 45 Gy); however, the risk for radiation-induced complications increases significantly. Second, the risk for intracranial hemorrhage persists during the interval between treatment and complete obliteration.^38,75,77 Third, serial radiographic studies, including cerebral angiography, are necessary to confirm complete obliteration.

Despite these limitations, radiosurgery may be associated with less morbidity than surgical resection in patients with portions of giant AVMs in eloquent brain.^28,30 Radiosurgery can be used as a preoperative adjunct to obliterate portions of giant AVMs and thus decrease the size of the remaining nidus for later surgical resection.²⁹ Some authors have recommended staged stereotactic radiosurgery when treating giant AVMs.⁸¹ In these cases, multiple radiosurgical treatments are delivered to different portions of the AVM at various intervals to avoid delivering treatment to a single large target. This theoretically reduces the risk for radiation necrosis.

Some patients with giant AVMs require more than one course of stereotactic radiosurgery, and this option has been used in selected patients.^29,82 The disadvantages of such an approach are the second latency period of 1 to 3 years before obliteration occurs, the possibility that a second radiosurgical treatment may still not obliterate the AVM, and the risk for radiation-induced injury, which may be higher with a second radiosurgical treatment.

Microsurgery

Generally, microsurgical resection of giant AVMs is planned after staged embolization or radiosurgery (or both) has significantly reduced the size of the AVM and the number of feeding arteries to the nidus. We routinely use corticosteroids and prophylactic antibiotics during resection of all AVMs, and patients are operated on under mild hypothermia (33°C) for neuroprotection. Patients also receive therapeutic levels of anticonvulsants, which are maintained at least during the acute postoperative period or longer if patients had seizures as part of their initial manifestation. Lumbar drainage or the administration of mannitol to achieve brain relaxation is individualized but generally used.

Patients are positioned in a manner to allow optimal exposure of the AVM while maintaining adequate jugular venous drainage. A supine position is preferred because it allows the optimal patient position for maintaining any femoral groin sheaths required for intraoperative angiography, which is difficult in the lateral position and impossible in the prone position. The head is elevated 15 degrees above the heart to improve venous outflow and reduce intraoperative bleeding. The head is placed in three-point head fixation for stabilization, and a radiolucent head frame is used if intraoperative angiography is planned.

The orientation of the incision in the scalp varies with the location and approach to each particular giant AVM, but it should be situated directly over the AVM whenever possible (Video 389-1). The bone flap should be made large enough to allow access to the entire AVM, even if staged resection is planned, because this would permit optimal exposure should any unexpected intraoperative bleeding occur. Hemostasis is achieved, dural tack-up sutures are placed, and the dura is opened in curvilinear fashion. Veins adherent to the dura can be taken down by bipolar coagulation and sharp dissection as long as they are not the primary draining veins. At this point, superficial giant AVMs are usually visualized on the cortical surface. For deeper AVMs that do not appear on the cortical surface, draining veins can be followed back to the malformation. Careful correlation between the pattern of vessels noted intraoperatively and previous angiograms usually allows determination of the major feeding arteries and draining veins.

Once identified, the AVM is resected in systematic fashion under guidance with the microscope, and systemic mean blood pressure is lowered to 60 to 70 mm Hg to minimize bleeding. Feeding arteries are located first and then individually coagulated and cut. The larger feeding vessels are clipped with Sundt micro-AVM or mini-aneurysm clips in addition to coagulation. It is important to proceed with treating one vessel at a time because hemorrhage from multiple sources can rapidly lead to significant bleeding and loss of control by the surgeon. Draining veins are often encountered before the feeding arteries are identified. It is imperative that venous drainage be preserved until all the arterial feeders are transected and the nidus is dissected out. Before transecting a vein, it is useful to first occlude it with a temporary aneurysm clip and observe the nidus. If the nidus begins to swell or bleed, the vein must be preserved until the final stages of resection. Intraoperative quantitative and directional ultrasound (Charbel Micro-flowprobe, Transonic Systems, Inc., Ithaca, NY) can also be used to differentiate arterialized veins from feeding arteries.

Dissection begins on the superficial border of the malformation, and circumferential dissection of feeding arteries is performed around the AVM, with care taken to stay within the gliotic plane immediately outside the AVM when working in noneloquent cortex. Gentle traction on the nidus with a moist cottonoid allows visualization of these feeding arteries. When dissecting adjacent to critical brain parenchyma, it is safer to dissect close to the AVM, even encroaching on the nidus, instead of risking injury to the surrounding brain. Once the superficial borders of the malformation are free, the AVM can be gently retracted so that the deep perforating arteries can be coagulated. Retractors should be adjusted frequently to allow optimal exposure for each particular surgical view. Meticulous hemostasis must be maintained throughout the resection. A self-irrigating or nonstick bipolar coagulation unit is extremely useful during the dissection. Fragile arteries resistant to coagulation can be occluded with Sundt micro-AVM clips. Judicious use of Surgicel (Johnson & Johnson, New Brunswick, NJ), Gelfoam (Pharmacia and Upjohn, Kalamazoo, MI), Avitene (Davol, Inc., Cranton, RI), and small pieces of bulk cotton can also be quite helpful in treating general oozing. Larger feeding arteries can be permanently occluded with Sundt mini-aneurysm clips (Codman and Shurtleff, Inc., Raynham, MA), but care must be taken to preserve any en passage vessels. These vessels are often difficult to identify at first, and care should be taken to follow each of these vessels and only cauterize them once the surgeon is sure that no normal cortex is being supplied by the vessel in question.

Deep ependymal feeding arteries are usually the last, but often the most problematic feeders to deal with. These vessels tend to be fragile, tear easily, and are often difficult to control with bipolar coagulation. Furthermore, they tend to retract into the surrounding brain tissue, which often requires the surgeon to dissect deeper than desirable to find the source of the hemorrhage. Patience on the part of the operating surgeon is required when occluding these vessels with bipolar coagulation or small Sundt microclips to halt bleeding.

The venous drainage of giant AVMs is generally both superficial and deep, but usually toward the midline. During AVM dissection, superficial draining veins can be gently retracted to increase exposure. When possible, draining veins should be sacrificed last, immediately before removal of the nidus; smaller draining veins may have to be sacrificed during resection of the AVM to facilitate removal. When working within the ventricular system, the ventricles should be protected against the accumulation of blood with cotton pads or bulk cotton. This will minimize the likelihood of hydrocephalus developing postoperatively. Once resection of the AVM is completed, the microscope should be used to inspect the resection bed for any signs of residual AVM, which is more likely to occur with giant AVMs that have irregular shapes than with smaller AVMs, and to achieve hemostasis. It is important to check for hemostasis at normotension or even mild hypertension. An intraoperative angiogram can be performed to ensure complete resection of the nidus, but because of the lower quality of these intraoperative images, a conventional angiogram in the radiology suite should also be performed in the postoperative period.

If the surgical procedure is staged because of the size of the AVM, the extent of surgical hemorrhage, or the risk for normal perfusion pressure breakthrough bleeding, the neurosurgeon needs to determine the optimal point at which to complete the initial stage. Giant AVMs frequently have irregular shapes, and resection of one or more lobes of these larger AVMs is often an ideal point to cease surgery. In other cases of AVMs extending down toward the basal ganglia and thalamus, resection of the superficial component of the AVM can be followed by a second stage involving resection of the deeper portion. In the event that the residual portion of the giant AVM after staged surgical resection would place the patient at significant neurological risk, this residual could potentially be treated by stereotactic radiosurgery. When staging surgical resection of AVMs, it is critical that the portion of the AVM exposed but not resected be carefully inspected to ensure hemostasis. If postoperative bleeding is noted, it is generally from the residual AVM.

Because giant AVMs generally involve several different lobes, a compartmental approach to resection may be required, even if the AVM nidus is to be resected in a single operation. For example, a giant AVM within the frontal and temporal lobes may be resected by removing the malformation first from the temporal compartment and, once this is completed, subsequently removing the AVM from the frontal lobe. Major sulci or fissures can assist the surgeon by serving as natural planes of dissection. Compartmentalizing the AVM resection allows the surgeon to operate on several discrete lobes of the AVM rather than on one giant malformation. Frequently, if staged surgeries are planned, surgical resection of one of the compartments/lobes of the AVM may be an ideal stopping point.

Another indication for surgical treatment of giant AVMs would involve resection of radiation necrosis. Radiation injury after stereotactic radiosurgery may result in significant mass effect and edema and require prolonged treatment with high doses of corticosteroids. We have observed several patients with steroid dependence as a result of radiation injury who were successfully tapered off corticosteroids after resecting areas of necrosis, as well as some patients who have shown substantial neurological improvement.⁸³

Before operative closure, meticulous hemostasis is obtained in the resection bed of the AVM, and a final inspection is performed to ensure that the entire malformation has been removed completely. Transient induced mild hypertension (90 to 100 mm Hg) is used to test hemostasis, and the resection bed is then lined with Surgicel. Frequently, a ventricular catheter is placed and connected to an external drainage bag if resection of the AVM has exposed the ventricle. The dura is closed in standard fashion with 4-0 nylon suture and the bone replaced to complete the craniotomy. A subgaleal drain is attached to light suction for 12 to 24 hours. The scalp incision is closed in two layers, the galeal layer is approximated with 3-0 Dexon suture, and the skin is closed with staples. Extubation should be performed in a smooth and deliberate fashion to avoid any elevations in intracranial pressure or venous pressure. During emergence from anesthesia, systemic blood pressure must be carefully monitored to avoid any hypertensive episodes. In cases in which there was significant normal perfusion pressure breakthrough, patients may be left intubated for several days to optimize blood pressure control.

In the intensive care unit, hypotension should be maintained for 24 to 48 hours to prevent rebleeding. Although we previously used prophylactic barbiturates postoperatively after resecting large or giant AVMs, we now use this technique only if uncontrollable bleeding is encountered. Coagulation studies should be performed and coagulation corrected if abnormal. Any changes in neurological findings should be evaluated with emergency CT. A postoperative angiogram is obtained in the first week after surgery unless an intraoperative angiogram was performed with adequate angiographic resolution to confirm complete AVM resection.