Arteriovenous Malformations

Management

AVMs are congenital cerebrovascular anomalies consisting of poorly developed vascular channels forming the nidi and shunting arterial blood directly to the venous system. The high blood flow and malformed vascular wall pose the risk of rupture and intracerebral hemorrhage. Other clinical symptoms patients might experience include seizure, headache, and neurological deficits via the steal phenomenon or from mass effect.

Three management modalities are employed alone or in combination for the management of cerebral AVMs: microsurgery, embolization, and radiosurgery. Several factors should be weighed when choosing the most appropriate choice of treatment. Microsurgery should be used in superficially located nidi because it eliminates the risk of hemorrhage immediately upon a complete total extirpation. Embolization is most commonly used to reduce the size of large AVMs, making them amenable to subsequent microsurgery or radiosurgery. However, new liquid embolization materials (e.g., Onyx) have increased the chance of obliteration solely by embolization.^1,² Radiosurgery is usually reserved for small to moderate-sized AVMs located in deep or critical areas of the brain.

Role of Radiosurgery

History

The first case of AVM treated with radiotherapy was reported by Magnus.³ In a patient he operated on with an AVM at the motor cortex, he did not attempt surgical removal because of the high possibility of neurological deficits. After decompressive craniectomy, he treated the patient with radium therapy and reported that the patient was seizure-free 2 years after radiotherapy. No imaging or histological studies were available. Cushing and Bailey reported the first successful surgery on an AVM.⁴ Cushing explored a vascular tumor and felt that the lesion could not be attacked without fatal hemorrhage. The patient was treated with radiotherapy. He reexplored the lesion 3 years later and described that the tangle of pulsating vessels previously encountered was largely thrombosed and transformed into a multitude of small bloodless shreds which could be easily separated from the adjacent normal cortex.

There was intense interest in the use of radiation for AVMs following Cushing’s discovery, but the initial results were not encouraging. Although some studies ^5,⁶ with small numbers of cases provided evidence of the possible utility of radiation in the treatment of AVMs, most did not provide imaging or histological proof of the efficacy of radiotherapy. This led to an almost unanimous consensus in the assessment of radiation as being worthless in the management of AVMs.

With the introduction of Gamma Knife, the potential value of irradiation in vascular malformations was reassessed. Contributing factors included an increasing body of evidence that the cells constituting the vessel wall were responsive to ionizing radiation. Long-term angiographic follow-up of a small series of AVMs treated with fractionated conventional radiation by Johnson in the 1950s revealed that the AVMs were obliterated in 45% of cases.⁷ In 1970, the first radiosurgical treatment for an AVM was performed by Ladislau Steiner and associates at Karolinska Institute in Stockholm. The patient refused surgery, and given the patient’s renal insufficiency, the risk of surgery was considered too high. Although the intention was to deliver focused radiation to the nidus, because only small collimators were available, the feeding arteries were targeted and 25 Gy was given as the prescription dose to the 50% isodose line. On angiography 19 months after the treatment, the feeding vessels were obliterated, and the malformation no longer filled. Subsequently, larger collimators were available and could cover the AVM nidi, and more patients were treated successfully. Today more than 50,000 AVM patients have been treated with Gamma Knife radiosurgery, which has been proved to be a safe and effective treatment alternative for AVMs.

Modality

The goal of radiosurgery for AVMs is to deliver a high absorbed radiation dose to the AVM nidus, typically in a single session, while largely sparing the surrounding brain significant dose and thereby minimizing undesirable effects from the treatment. As the number of modalities for delivering radiosurgery have increased over time, so have the numbers that have been applied to the treatment of AVMs. Reports in the literature exist for AVM treatment with various radiosurgical modalities including the Gamma Knife, isocentrically mounted linear accelerators,⁸^–¹¹ and robotic linear accelerators (CyberKnife).¹² Regardless of modality, radiosurgical devices achieve the desired characteristics of small fields, fast-dose falloff, and highly accurate targeting through the use of two basic principles: superposition of beams and stereotactic targeting.

Radiosurgery achieves highly conformal dose distributions by spreading the total energy delivered over a targeted volume, either through the superposition of many small beams on the target or through the use of noncoplanar arcs (where each arc can be thought of as a large number of small beams). The energy of any given single beam is too low to cause a significant biological effect. However, the superposition of all the beams at the target delivers a substantial amount of radiation, sufficient to cause biological changes resulting in the occlusion of the AVM nidus.

The details of beam superposition vary by modality. In the case of the Gamma Knife, 192 (or 201, depending on the model of the unit) individual beams are precisely aimed at a focal point, or isocenter, to achieve this effect. The beams are collimated through individual beam channels. In older units, this was achieved with a combination of internal primary and secondary collimation and external “helmet”-based final collimation. In the case of the newer Perfexion model Gamma Knife, the collimator assembly is housed entirely within the main body of the unit.¹³

For early linear accelerators adapted for radiosurgery, finely collimated beams were achieved through the use of circular collimator “cones” that could be attached to the accessory tray of the accelerator.¹⁴ Many currently available accelerators are equipped with micro-multileaf collimators that can achieve irregularly shaped beams that can more precisely conform to the target morphology.¹⁵ Both approaches are often used with a non-coplanar arc technique, which directs the fields at the target while spreading out the overall delivered energy.¹⁶

The ability to create a focal, high-dose distribution does little good in itself if there is no way to precisely and accurately aim at the target. This problem is elegantly solved using the principles of stereotaxy. Traditionally in intracranial radiosurgery a rigid frame is fixed to the skull. This frame defines a coordinate system by which any point within the brain can be localized. Fiducial markers, which are visible in stereotactic imaging studies as part of the procedure, are directly related to this coordinate system; thus, the target can be visualized and localized in “stereotactic space.” Accuracy and precision of treatment are thus guaranteed by the precision and accuracy with which the target can be localized and the assurance that this target will not move during a treatment owing to the rigid head frame. More recent innovations in radiosurgery have included frameless stereotaxy.¹⁷ In these systems image-guidance plays a greater role both before and during the procedure. Less invasive restraint systems such as thermoplastic masks are used in place of the rigid head frame, and periodic imaging is used to track and correct for patient motion.

Histopathology

Several histological studies have described the changes of irradiated vessels with progressive narrowing and obliteration of the lumen.¹⁸ The earliest changes are endothelial damage and endothelial-intimal separation. These are followed by subendothelial and intimal-medial proliferation of smooth muscle cells with elaboration of extracellular matrix components. Cellular degeneration and hyaline transformation of vessel walls follow, and finally the vessels obliterate completely. The above-mentioned histopathological changes are correlated with time after radiosurgery and tend to occur in smaller vessels.

Outcomes

Following radiosurgery, angiography reveals that hemodynamic changes occur before changes in the size and shape of an AVM.²⁰ First, the flow rate decreases progressively. This may be related to the changes in the sizes of the feeding arteries and outflow veins. The outcome of an AVM following radiosurgery may be a total, subtotal, or partial obliteration of the nidus.

Total obliteration of the AVM after radiosurgery was defined as “complete absence of former nidus, normalization of afferent and efferent vessels, and a normal circulation time on high-quality rapid serial subtracted angiography.”²⁰ Any remaining nidus, regardless of its size, is considered partial obliteration. Subtotal obliteration of an AVM means the angiographic persistence of an early filling draining veins without demonstrable nidus.²¹ The early filling venous drainage suggests that some shunting persists. Our studies have shown that these subtotally obliterated AVMs have very low risk of hemorrhage in spite of the fact that per definition the AVM nidus is still patent as indicated by the shunting. It should be noted that more than 70% of them went on to obliterate completely without further treatment.²¹

The reported obliteration rate following radiosurgery ranged between 30% and 92%.^10,²²^–²⁴ One should be cautious in terms of the interpretation of the results owing to the biases injected from different cutoff time and imaging modality used to conclude total obliteration. Studies excluding patients with short follow-up, reporting only patients undergoing angiography, or including MRI as an imaging study to conclude obliteration tend to overestimate the success rate of radiosurgery.^23,^25,²⁶

Since 1989, a total of 1023 patients with AVMs treated with GKS at the University of Virginia with follow-up for at least 2 years were analyzed (82 patients completely lost to follow-up and 139 patients with follow-up less than 2 years were excluded; an additional 106 patients with large AVMs undergoing partial treatment will be discussed later). There were 523 males and 500 females with a mean age of 34.2 years (range 4 to 82 years). The presenting symptoms leading to the diagnosis of AVMs was hemorrhage in 529, seizure in 237, headache in 133, and neurological deficits in 94. In 30 patients, the AVMs were incidental findings. The locations of the AVMs were in the cerebral hemispheres in 630, basal ganglion in 96, thalamus in 82, corpus callosum in 38, brainstem in 84, cerebellum in 68, and insula in 25 patients. The Spetzler-Martin grading of the AVMs were grade I in 174 (17%) patients, grade II in 328 (32.1%) patients, grade III in 440 (438%) patients, grade IV in 78 (7.6%) patients, and grade V in 3 (0.3%) patients. One hundred twenty-two patients (11.9%) had previous partial resection of the nidi, and 244 patients (23.9%) underwent preradiosurgical embolization. The nidus volume ranged from 0.1 to 33 cm³ (mean 3.5 cm³). The mean prescription dose was 21.1 Gy (range 5-36 Gy), and the mean maximum dose was 39.0 Gy (range 10-60 Gy). The mean number of isocenters was 2.7 (range 1-22).

The mean follow-up after GKS was 80 months. GKS yielded a total angiographic obliteration in 552 (54%) and subtotal obliteration in 42 (4.1%) patients (Fig. 47.1). In 290 (28.3%) patients, the AVMs remained patent and in 139 patients (13.6%) no flow voids were observed on the MRI. The angiographic total obliteration was achieved in 65.2% of patients with nidus less than 3 cm³; 43.8% between 3 and 8 cm³, and 27.6% with nidus volume larger than 8 cm³. Small nidus volume, high prescription dose, and low number of isocenters are predictive of obliteration. Preradiosurgical embolization has a negative effect on obliteration.

FIGURE 47.1 A 24-year-old man diagnosed with a left-sided arteriovenous malformation (AVM) at left sensorimotor cortex following a hemorrhage. A and B, Lateral and frontal projections of angiograms. Patient underwent a partial embolization. The nidus obliterated completely 3 years following Gamma Knife surgery (C and D).

Complications

Early Adverse Effects

Patients might experience headache from frame placement and nausea or vomiting from pain or sedative medications. Few patients developed seizure in the immediate post-GKS period; most who did were those with a prior history of seizure.

Radiation-Induced Changes

Radiation-induced change is an increased T2 signal around the AVM seen on MRI (Fig. 47.2). Radiation damage of glial cells, endothelial cell damage followed by breakdown of blood-brain barrier, excessive generation of free radicals, or release of vascular endothelial growth factors have been proposed to explain this imaging finding. The severity of radiation-induced changes on images and associated neurological deficits varies, ranging from asymptomatic, being only a few millimeters of increased T2 signal surrounding the treated nidus to massive brain edema with symptoms and signs of increased intracranial pressure. From our 1500 Gamma Knife procedures performed for AVM patients with follow-up MRI available for analysis, 34.4% of patients developed radiation-induced changes. Among them, 60% had mild (a few millimeters of increased T2 signal surrounding the nidus), 33% had moderate (compression of ventricle and effacement of sulci), and 7% had severe (midline shift) radiation-induced changes. The mean time to the development of radiation-induced changes was 13 months after GKS, and the mean duration of the changes was 22 months. Larger nidus volumes, higher prescription doses, history with preradiosurgical embolization, and nidus without previous hemorrhage were associated with higher risk of radiation-induced changes.