Endovascular Techniques for Treatment of Carotid-Cavernous Fistula

Abstract

Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous communications in the cavernous sinus. Direct CCFs result from a tear in the intracavernous carotid artery. Indirect CCFs generally occur spontaneously and cause more subtle signs. Direct CCFs, which typically have high flow, usually present with ocular-orbital venous congestive features and cephalic bruit. Indirect CCFs, which typically have low flow, present with similar but more muted clinical features. Direct CCFs are always treated with endovascular methods. The goal is to occlude the fistula but preserve the patency of the internal carotid artery (ICA). Agents include detachable coils or liquid embolic agents delivered transarterially or transvenously. Arterial porous or covered stents are often used adjunctively. In rare cases, the ICA must be occluded. Indirect CCFs are only treated if symptoms are intractable or intolerable or if vision is threatened. The goal is to interrupt the fistulous communications and decrease the pressure in the cavernous sinus. The traditional approach has been transarterial embolization with liquid agents, particularly n-butyl cyanoacrylate (n-BCA). However, the multiplicity of arterial feeders and the low success rate in occluding indirect CCFs by the arterial route has led to a preference for transvenous embolization, most commonly via the inferior petrosal sinus. If that sinus is impassable, alternative routes include the pterygoid venous plexus, superior petrosal sinus, facial vein, or ophthalmic veins. The cavernous sinus is occluded with coils, liquid embolic agents, or both. The use of ethylene vinyl alcohol copolymer (Onyx), an agent that may be superior to n-BCA because it may allow better distal fistula penetration. However, more safety and efficacy data must be accumulated. When experienced interventionalists are involved, the success rate for closing direct fistulas is 85%-99% and for closing indirect fistulas is 70%-78%. Serious complications are relatively infrequent.

CLASSIFICATION

Carotid-cavernous fistulas (CCFs) are abnormal communications between arteries and veins of the cavernous sinus. They may be classified on the basis of etiology (traumatic or spontaneous), rate of flow (high or low), or angiographic architecture (direct or indirect). The most commonly used classification, based on architecture, was established by Barrow et al (¹). It divides CCFs into 4 types depending on the arterial supply:

• Type A (direct): Direct communications between the internal carotid artery (ICA) and the cavernous sinus, usually with resulting high flow rates.
• Type B (indirect): supplied only by the dural branches of the ICA.
• Type C (indirect): supplied only by dural branches of the external carotid artery (ECA).
• Type D (indirect): supplied by dural branches of the ICA and ECA.

Direct CCFs may follow a traumatic tear of the cavernous segment of the ICA or rupture of an aneurysm within this segment of the ICA (^2-4). The exact etiology of indirect CCFs is unknown, but they have been associated with pregnancy, sinusitis, trauma, and cavernous sinus thrombosis (⁵).

CLINICAL PRESENTATION

The classic presentation of direct CCFs is the sudden development of a triad of exophthalmos, cephalic bruit, and conjunctival congestion. Complete disruption of the wall of the ICA allows highly pressurized arterial blood to be directly transmitted to the cavernous sinus and ophthalmic veins, leading to venous hypertension. The principal manifestations of venous hypertension are ophthalmic (including proptosis, chemosis, conjunctival injection, and visual loss) but cranial nerve pareses, bleeding from the mouth, nose, or ears, intracranial hemorrhage, increased intracranial pressure, and steal phenomena are also seen (^6,7).

Compared with direct CCFs, indirect CCFs have a gradual onset, typically with a milder clinical presentation. Indirect CCFs often do not demonstrate the classic triad of symptoms characteristic of direct CCFs. Patients have chronically red eyes because of tortuous arterialization of the conjunctival veins (Fig. 1), but a cephalic bruit is usually absent and exophthalmos is either mild or absent.

FIG. 1: Ophthalmic features of indirect carotid-cavernous fistula. A. Proptosis, ptosis, chemosis, and arterialization of the conjunctival veins of left eye before treatment. B. Resolution of ophthalmic abnormalities 8 weeks after endovascular treatment.

Unlike direct CCFs, most indirect CCFs improve spontaneously, and often all clinical manifestations will resolve without vascular intervention (⁸). However, patients with intractable headache, visual deterioration, elevated intraocular pressure refractory to medication, diplopia, or an intolerable cosmetic deformity are considered for endovascular treatment (⁹).

IMAGING

CT findings in direct and indirect CCFs include proptosis, enlargement of the extraocular muscles, enlargement and tortuosity of the superior ophthalmic vein, and enlargement of the ipsilateral cavernous sinus. MRI findings are similar to those seen on CT, with the addition of orbital edema and abnormal flow voids in the affected cavernous sinus (¹⁰). In the setting of a high-flow fistula and retrograde cortical venous reflux, MRI or CT studies may reveal dilatation of leptomeningeal and cortical veins. In patients with cerebral venous congestion, cerebral edema or hemorrhage may be encountered.

Digital subtraction angiography (DSA) is essential in confirming the diagnosis, classifying the CCF, and delineating the patterns of venous drainage. Such imaging is necessary in planning the optimal treatment approach for these often complex lesions. DSA frame rates of greater than 5 frames per second may aid in evaluating the morphology of high-flow fistulas. If it is not possible to identify the morphology of the fistula on selective high-frame rate ICA angiograms, specific maneuvers to slow flow through the fistula may be tried. The Mehringer-Hieshima maneuver consists of injecting the ipsilateral ICA and manual compression of the ipsilateral common carotid artery while filming at a slower film rate. With this maneuver, the fistula fills at a slower rate and allows for better delineation of the fistula site. The Huber maneuver involves injection of the ipsilateral vertebral artery with manual compression of the affected common carotid artery (¹¹). With this maneuver, the fistula is opacified through a posterior communicating artery, if one exists.

HISTORICAL TREATMENT

Early treatment for direct CCFs consisted of various surgical approaches. In the 1930s, direct CCFs were “trapped” by ligation of the cervical and intracranial ICA. Trapping was followed by embolization using a number of different materials delivered by direct cavernous sinus exposure. In 1974, Parkinson et al (¹²) reported successful treatment of 9 of 11 patients with direct CCFs by surgical exposure and packing of the cavernous sinus with preservation of the ICA. In 1974, Serbinenko et al (¹³) reported the first case of successful embolization of a direct CCF from an endovascular approach using a detachable balloon.

In 1978, Debrun et al (¹⁴) reported the successful treatment of 12 of 17 direct CCFs with detachable balloons. By the 1980s, detachable balloons were widely accepted as the treatment of choice for direct CCFs, even though most balloons used in the United States were imported. The U.S. Food and Drug Administration (FDA) had approved detachable balloons for peripheral vessel occlusion in 1981, but there were problems. The balloons would not detach or they detached inappropriately. They were withdrawn from the U.S. market in 1991. The FDA later approved detachable balloons for intracranial use (DSB; Boston Scientific-Target, Fremont, CA) in 1998, but they were withdrawn from use in the United States in 2003 because of balloon valve leaks.

CURRENT TREATMENT OF DIRECT CCF

A number of different endovascular treatment options for CCFs are currently available. The method chosen in a given patient depends on the anatomy of the fistula and operator or institutional preference.

The goal of treatment in direct CCFs is to occlude the site of communication between the ICA and the cavernous sinus while preserving the patency of the ICA. This can be accomplished with transarterial obliteration of the fistula with a detachable balloon, deployment of a covered stent across the area of the fistula, or obliteration of the ipsilateral cavernous sinus with coils or other embolic material. If the defect is large and cannot be repaired, the ICA may have to be sacrificed or trapped (Fig. 2).

FIG. 2: Schematic rendering of three endovascular methods of treating a direct carotid-cavernous fistula (CCF). A. A tear in the cavernous segment of the internal carotid artery (ICA) allows blood to escape directly into the cavernous sinus (CS). B. Occlusion by placement of a covered stent over the tear in the cavernous segment of the ICA. C. Placement of coils and a porous (noncovered) stent into the CS via a transarterial approach. The stent prevents prolapse of the coils into the parent vessel, the ICA. D. Occlusion of the fistula by placement of multiple coils within the parent vessel (ICA), resulting in its occlusion (long arrowheads). O, ophthalmic artery.

Detachable Balloon

The standard treatment for a direct CCF in the United States had been transarterial obliteration of the fistula with a detachable balloon (^15,16). The balloon could be directed by flow through the fistula into the cavernous sinus. Before detachment, the balloon could be inflated to a volume larger than the orifice of the fistula to prevent its retrograde prolapse into the ICA. This approach was relatively inexpensive, simple, and elegant (Fig. 3).

FIG. 3: Angiographic demonstration of balloon embolization treatment of a direct carotid-cavernous fistula (CCF). A. Lateral angiogram, early arterial phase, shows a tear within the cavernous segment of the internal carotid artery (ICA). B. Lateral angiogram, later arterial phase, shows marked filling of the carotid sinus (CS) and inferior petrosal sinus (IPS) from a high-flow direct CCF. C. Lateral angiogram after detachable balloon placement in the CS. The fistula has been occluded (arrow). D. Nonsubtracted lateral angiogram of C shows the detachable balloon (B) in the cavernous sinus.

However, technical problems were occasionally encountered with detachable balloon embolization, including difficulty fitting the balloon through the rent in the artery, inability to convey the partially inflated balloon from the artery to the vein, and early detachment, deflation, or rupture of the balloon caused by contact with bone fragments (^4,17). Problems with the balloon valve mechanism forced removal of this device from the U.S. market in 2003. It remains available for endovascular use in treating direct CCFs in other parts of the world.

Coils or Other Embolic Material

With the lack of availability of detachable balloons, transarterial or transvenous embolization with coils or other embolic material has become the mainstay of endovascular treatment of direct CCFs. Commonly used embolic agents include detachable platinum coils, n-butyl cyanoacrylate (n-BCA) (Trufill n-BCA; Cordis Neurovascular, Miami, FL), ethylene-vinyl alcohol copolymer (EVOH) (Onyx; ev3 Neurovascular, Irvine, CA), and silk.

Transarterial Embolization

The standard transarterial approach consists of placing a guiding catheter in the cervical carotid artery and advancing a microcatheter into the cavernous segment of the ICA. The microcatheter is selectively advanced across the tear in the carotid artery into the cavernous sinus. Using this microcatheter, embolic material is placed into the cavernous sinus. We prefer detachable platinum coils as they are easy to use and may be adjusted or even removed if the placement is not optimal (¹⁸). Liquid embolic agents such as n-BCA or Onyx may also be used to occlude the fistula (^19,20). During transarterial embolization, a temporary balloon may be placed across the site of the tear to protect the parent vessel and prevent migration of embolic material distally into the cerebral hemisphere.

Transvenous Embolization

The transvenous route usually involves a posterior approach through the internal jugular vein and the inferior petrosal sinus (IPS) up into the cavernous sinus (²¹). If the IPS is occluded or absent, access to the cavernous sinus can be obtained from an anterior approach through the superior ophthalmic vein (SOV) via the facial vein (²²). Other percutaneous transvenous approaches include the contralateral pterygoid plexus, superior petrosal sinus, and cortical veins (^23,24). Less favored alternative approaches include a direct transorbital puncture of the cavernous sinus or access via the inferior ophthalmic vein (IOV) (²⁵). We are aware of only one report of an IOV approach (²⁶). Once cavernous sinus access is obtained, disconnection of the venous outflow from the feeding arteries at the level of the arteriovenous (AV) fistulas can be completed with detachable coils or liquid embolic agents.

Porous (Noncovered) Stent and Coils

CCFs caused by small tears in the ICA can be treated with detachable balloons or coils as described in the preceding sections. However, if there is a large arterial tear, the coils or balloons may migrate through the defect into the parent vessel, potentially causing cerebral vessel occlusion and stroke.

Dedicated self-expanding stents (Neuroform [Boston Scientific/Target Therapeutics Inc., Natick, MA] and Enterprise [Cordis Neurovascular, Miami, FL]) have recently become available for intracranial use. Although these stents are FDA-approved for coil embolization only of wide-necked intracranial aneurysms, they may be used to reconstruct severely injured intracranial arteries in direct CCFs ⁽²⁷⁾. With this technique, a direct CCF with severe injury to the ICA can now be occluded while preserving the ICA.

Covered Stent

Placement of a stent covered with polyfluorotetraethylene (PTFE) or Gore-Tex (covered stent or stent graft) is another treatment option. It may immediately obliterate direct CCFs by placing an impermeable barrier across the site of fistula communication. In addition, it may decrease the risk of ischemic stroke by preserving the ICA (Fig. 4). There have been few reports of the successful application of a covered stent for the treatment of CCFs ^(28-30). Currently, its use is restricted by the FDA to placement in the coronary artery after arterial rupture from balloon angioplasty/stent placement. The disadvantages of this stent are its stiffness and larger caliber, making it difficult to navigate into the distal ICA. Long-term safety data are lacking.

FIG. 4: Angiographic demonstration of treatment of a traumatic direct carotid-cavernous fistula (CCF) by intracavernous placement of coils and a nonporous (covered) stent. A. Axial T2 MRI demonstrates a dilated left superior ophthalmic vein (SOV) and orbital soft tissue edema (arrow). B. Lateral angiogram shows dye escaping from a tear within the cavernous segment of the internal carotid artery (ICA) and filling the cavernous sinus (CS), SOV, and inferior ophthalmic vein (IOV). C. Spot fluoroscopic image shows placement of a covered stent within the cavernous segment of the ICA (arrows). D. Lateral angiogram performed after placement of a covered stent in the cavernous segment of the ICA (arrowheads) still shows some dye escaping into the CS. E. Lateral venogram shows placement of a microcatheter (C) into the CS via the inferior petrosal sinus (IPS) before coil embolization of the CS. SS, sigmoid sinus; IJV, internal jugular vein. F. Lateral angiogram after transvenous placement of a covered stent in the cavernous segment of the ICA (arrows) and coil embolization of the CS shows closure of the fistula. O, ophthalmic artery.

Arterial Sacrifice

Direct CCFs caused by extensive injury to the ICA may not be amenable to endovascular occlusion with preservation of the parent artery. In such circumstances, occlusion of the arterial segment bearing the fistula may be the only viable option. If time permits and the patient is able to cooperate, a temporary balloon test occlusion of the ICA is carried out before permanent occlusion of the artery.

To prevent retrograde backflow of blood from the supraclinoid ICA into the fistula, the occlusion is initiated distal to the site of the suspected tear. Using several coils, the cavernous ICA is progressively occluded up to the arterial segment proximal to the fistula. This technique may be life-saving in a patient with extensive and unstable injuries. Recently, Hydrogel-coated detachable coils that swell on contact with blood have been introduced. Such coils may occlude vessels faster than bare platinum coils and decrease procedure and fluoroscopy times (³¹). The easy-to-deploy and fast acting Amplatzer vascular plug (AGA Medical Corporation, Golden Valley, MN) has been used in arterial sacrifice (³²). However, navigation into the distal ICA is difficult.

CURRENT TREATMENT OF INDIRECT CCF

The goal of treatment for indirect CCFs is to interrupt the fistulous communications and decrease the pressure in the cavernous sinus. These goals can be accomplished by embolically occluding the arterial branches supplying the fistula (arterial approach) or by embolically occluding the cavernous sinus that harbors the fistulous communications (venous approach).

Carotid Self-Compression

Manual external carotid compression is an accepted treatment for indirect CCFs except in patients with retrograde cortical venous drainage and progressive visual decline.

This approach is particularly effective in patients harboring fistulas in the anterior cavernous sinus and in those with acceptably low intraocular pressures and short duration of symptoms (³³). The patient is instructed to sit in a chair or lie in bed and to compress the carotid artery and jugular vein with the contralateral hand for a period of 10 seconds, 4-6 times per hour. This approach is reported to result in clinical cure in 30% of patients (⁸).

Contraindications to manual carotid compression include hypertensive carotid sinus syndrome, atherosclerotic stenosis, ulceration of the cervical carotid artery, and history of cerebral ischemia, as patients with these anomalies cannot tolerate the transient occlusion of the ipsilateral internal carotid artery. This approach is also inappropriate if visual function shows progressive decline, intraocular pressure is intractably high, or there is intolerable periocular pain (³³).

Transarterial Embolization

Transarterial embolization of indirect CCFs requires selective microcatheter placement distally within the arterial feeders to the fistula. An attempt is made to advance the microcatheter tip as close as possible to the point of fistulous communication. Once a satisfactory position of the microcatheter is achieved, an embolic agent is injected under fluoroscopic control. Although coils and particulate agents can be used, these agents cannot cause permanent occlusion of the fistula by themselves. The most commonly used agent for transarterial embolization is n-BCA (³⁴).

n-BCA is a monomeric liquid adhesive whose polymerization time is controlled by the addition of iodized oil (Lipiodol). The advantages of n-BCA are easy delivery through the microcatheter, good penetration, rapid induction of thrombosis, and permanent occlusion after polymerization. A major disadvantage is rapid polymerization time (a few seconds), which causes it to stick to the microcatheter and protective balloons. n-BCA is approved in the U.S. for use in presurgical embolization of brain arteriovenous malformations (AVMs).

Onyx, another liquid embolic agent recently approved by the FDA for the preoperative embolization of brain AVMs, can also be used for transarterial embolization of indirect CCFs. A nonadhesive liquid embolic agent with a lava-like flow pattern, Onyx is supplied in ready-to-use vials in a dimethyl sulfoxide (DMSO) solvent with tantalum. Currently 6% (Onyx 18) and 8% (Onyx 34) concentrations are available in the U.S. When the mixture contacts aqueous media, such as blood, DSMO rapidly diffuses away from the mixture, causing in situ precipitation and solidification of the polymer, with the formation of a spongy embolus. The solidification occurs more slowly than that of cyanoacrylates, and because Onyx is nonadherent to the walls of vessels and microcatheters, its use allows prolonged injection times yet decreased chances of permanent microcatheter retention. Thus, it may allow better distal nidus or fistula penetration compared with cyanoacrylates and offer the possibility of venous sinus packing from a transarterial approach, which may be helpful in patients with previous occlusion of the draining venous structures. Use of Onyx for treating dural arteriovenous fistulas from a transarterial approach was recently described in two single-center cohorts (^35,36).

Although transarterial embolization is a good treatment option, selective distal access into multiple tiny feeder vessels is often difficult or impossible and may require multiple sessions in a staged approach.

Transvenous Embolization

Transvenous embolization has become the preferred method of treatment of indirect CCFs. The advantages of this technique are its simplicity compared with transarterial methods, the ability to cure the fistula often in a single session and a high-long term success rate. The most commonly used pathway for cannulation of the cavernous sinus is the IPS. If the IPS is inaccessible, the pterygoid venous plexus, superior petrosal sinus, facial vein, and SOV can be used (^21-25) (Fig. 5).

FIG. 5: Schematic rendering of the multiple dural sinus pathways that can be used to gain access to the cavernous sinus (CS) in transvenous occlusion of a carotid cavernous fistula: superior ophthalmic vein (SOV), inferior ophthalmic vein (IOV), inferior petrosal sinus (IPS), superior petrosal sinus (SPS), and middle deep temporal vein (MDTV).

Popular choices for embolic materials include coils, n-BCA, and Onyx, either in isolation or in combination. The advantages of coils are their radio-opacity, ease of use, and ability of redeploy or removal if the initial placement is not optimal (Fig. 6). However, a major disadvantage of coils is difficulty in achieving complete occlusion, especially in septated cavernous sinuses. Moreover, the reported rates of cranial nerve paralysis are higher with coils, probably because of their mass effect (³⁷).

FIG. 6: Treatment of an indirect carotid-cavernous fistula (CCF) with intracavernous placement of a porous (noncovered) stent and coils. A. T2 axial MRI shows proptosis of the left eye (arrowhead), engorgement of the intraconal fat (arrow), and enlargement of the extraocular muscles. B. Lateral common carotid angiogram of the same patient demonstrates filling of the cavernous sinus (CS) and inferior ophthalmic vein (IOV) from branches off the internal maxillary artery (IMAX) and internal carotid artery (ICA). There is a small cavernous carotid aneurysm (A). C. Lateral external carotid angiogram with a balloon inflated in the proximal left ICA (arrowhead) shows filling of the CS and IOV from branches of the left IMAX. D. Lateral unsubtracted spot fluoroscopic image shows a porous stent (small arrowheads) within the cavernous segment of the ICA and coils in the cavernous aneurysm (A) in the region of the fistula. A microcatheter is seen in the inferior petrosal sinus (IPS). E. Lateral unsubtracted spot fluoroscopic image shows a microcatheter coursing from the IPS through the CS with its tip in the IOV before coil embolization of the venous outflow of the fistula. A porous stent is seen within the cavernous segment of the ICA (arrowheads) with coils in the cavernous aneurysm (A). F. Lateral angiogram after coil embolization of the venous outflow of the indirect CCF and porous stent-assisted coiling of the cavernous aneurysm shows occlusion of the fistula. Small arrowheads demarcate the stent.

To overcome these disadvantages, liquid embolic agents are being increasingly used, either alone or in combination with coils (^38,39). The liquid embolic agents can permeate different compartments, allowing complete occlusion of the fistula. In a series of 14 patients, Wakhloo et al (³⁸) reported that n-BCA, used alone or in conjunction with coils, was safe and effective in treating complex indirect CCFs.

Onyx is emerging as a potentially useful liquid embolic agent in this setting. However, a dangerous feature of Onyx is its propensity to retrogradely fill other arterial feeders. Therefore, it must be used cautiously in an ECA that could harbor collateral vessels. Multiple angiograms can be obtained during the infusion to monitor the progress of the embolization. Although its use in the treatment of CCFs will probably increase, only a few case reports describe its successful use from a transvenous approach in treatment of indirect CCFs (³⁹). (See also articles by Bhatia et al (⁴⁰) and Gandhi et al (⁴¹) and Editorial (⁴²) in this issue of the Journal.)

TREATMENT SUCCESS RATES

The reported cure rate with balloon embolization of direct CCFs is 88%-99% (^4,43,44). Kobayashi et al (⁴⁵) achieved 80% aneurysmal and 55% post-traumatic CCF closure with a balloon. Higashida et al (⁴⁴) treated more than 200 traumatic CCFs with complete occlusion of the fistula in 99% and preservation of the parent artery in 88%. Gupta et al (⁴⁶) achieved complete occlusion in 86.3%, near total occlusion in 11.0%, and ICA preservation in 98%. Moron et al (²⁷) achieved successful obliteration of 6 direct CCFs by using stent-assisted coil placement. Gomez et al (³⁰) demonstrated occlusion of direct CCFs and preservation of the ICA in 7 patients with PTFE-covered stents. The risks are ICA occlusion and worsening of an ocular motor cranial nerve palsy in 10%-40% of patients (^4,40,47,48).

The reported cure rate for indirect CCFs is 70%-78% with a complication rate of 5% (^9,49,50). Improvement of the patient's symptoms has been reported in 20%-30% of patients without a complete angiographic cure.