Two commonly used particulate materials are Gelfoam (Upjohn Pharmaceuticals, Kalamazoo, MI) and polyvinyl alcohol (PVA) (PVA Foam, Cook, Inc., Bloomington, IN; Trufill, Cordis Endovascular Systems, Miami Lakes, FL; Ivalon, Inc., San Diego, CA; Contour Emboli, Boston Scientific/Target Therapeutics, Inc., Fremont, CA).^2,³ Gelfoam breaks down 72 hours after embolization, and this lack of permanence detracts from its efficacy if surgery is not performed within a few days after the procedure. Gelfoam has been used as a preoperative embolization material for neoplasms that are to be operated on within 48 hours, and for patients with epistaxis in whom the goal is to slow the bleeding sufficiently so that the body’s normal hemostatic mechanisms stop the hemorrhage. Gelfoam powder always should be used with care because its particles (approximately 50 µm) in solution act as a liquid, easily passing through tiny arteries, which may result in skin necrosis or damage to cranial nerves, or through collateral channels communicating with the intracranial circulation.

PVA is more permanent than Gelfoam, but much of the efficacy of the vascular occlusion is a result of a combination of PVA plus intravascular thrombus. The stellate-shaped particles slow the intravascular flow, and thrombus forms.²^–⁴ This thrombus may be metabolized before fibrosis occurs, however, resulting in partial or complete recanalization over weeks to months. PVA is easy to use, being supplied as uniform particles within a narrow range of size (150 to 1250 µm). In most patients with neoplasms, the smallest size (150 µm) is used because the particles can be easily injected through a small microcatheter placed selectively into tiny feeding arteries and penetrate into the tumoral vascular bed.

Because of the stellate shape of PVA particles, they do not form a tightly packed embolic mass, allowing recanalization as the interspersed thrombus undergoes lysis. Various types of beads and spheres have been produced to overcome that limitation, such as Embosphere Clear (Biosphere Medical, Inc., Rockland, MA). Their more uniform size and spherical geometry theoretically produce more complete and more permanent vascular occlusion. Similar spheres might also be filled with a chemotherapeutic or other agent for more prolonged treatment of a nonsurgical neoplasm. Microfibrillary collagen (Avitene; Avicon, Inc., Fort Worth, TX) is a hemostatic agent that may be mixed with contrast material for embolization ⁵ or mixed with other embolic agents such as PVA and ethanol.⁶

There are two broad categories of metallic coils: coils that are pushed from a catheter with a metal coil pusher or guidewire, and coils that are released by breaking a bond between the coil and the pushing wire. The latter is the type used for treating intracranial aneurysms. In head and neck lesions, metallic coils are used for occluding vessels that measure a few millimeters to 1 cm or more in diameter. Their size prohibits their moving more distally into the embolized lesion. They are best used for occluding the feeding artery after particulate embolization; the particles are embolized deeply into the lesion, with the coil producing the final occlusion of the feeding artery. Coils have been used to occlude bleeding vessels, such as in epistaxis or after trauma.

Detachable balloons with a valve mechanism to keep the balloon inflated are currently unavailable in the United States, but should be available again in late 2009. They are used primarily for fistulas with a single artery-to-vein connection. Most experience was with intracranial post-traumatic carotid-cavernous sinus fistulas, but this technique was also used for vertebral artery–vertebral venous fistulas (usually post-traumatic) or for any other type of fistula in the face or neck.⁷^–⁹ They were also used for occlusion of a parent artery leading to an unclippable aneurysm, a dissected carotid or vertebral artery producing embolization into intracranial vessels, or a carotid artery to be sacrificed at tumor surgery. Electrolytically detachable coils are used now instead of the currently unavailable detachable balloons. Many coils are usually necessary, however, to do what one balloon could accomplish, increasing the complexity and expense of the procedure.

There are numerous liquid embolic agents, the most commonly used being absolute alcohol (100% ethanol) and various tissue adhesives, including the cyanoacrylates and Onyx (MicroTherapeutics, Inc., Irvine, CA). Absolute ethanol is extremely toxic to the endothelium,¹⁰ and is highly effective at producing sclerosis of vascular lesions, such as venous and lymphatic malformations.¹¹^–¹³ Although it has also been used to treat arteriovenous malformations and dural arteriovenous fistulas, the problem with these fast-flowing lesions is the need to increase the “dwell time” of the ethanol to interact with the intima, often requiring temporary balloon occlusion more proximally. It has also been used for tumors, via endovascular and percutaneous access, particularly recurrent tumors that are surgically inaccessible.

The injection of ethanol is extremely painful, requiring deep sedation or, more commonly, general anesthesia. It is necessary to see where the embolic agent is going, and so opacification is necessary. Opacification of the ethanol with a liquid contrast agent produces dilution of the ethanol, however, decreasing its effectiveness, which is maximum if used undiluted. Metrizamide powder (Nycomed, Oslo, Norway) was used previously for opacification because a powder does not dilute the ethanol, but provides acceptable opacification. Metrizamide powder is no longer available in the United States, however.

Sodium tetradecyl sulfate (Sotradecol) 3% also is an excellent sclerosing agent, is less painful on injection than ethanol, and may be opacified, although it seems to be less effective than ethanol for venous malformations, and is not considered to be an acceptable alternative. Doxycycline, a tetracycline-like antibiotic, is an effective agent at producing sclerosis of venous, lymphatic, and other slow-flow vascular malformations in which there is an adequate “dwell time.” Tetracycline has been associated with darkening of the tooth enamel in young children, so this drug is usually reserved for patients older than 11 years, after the formation of the permanent teeth. Povidone-iodine (Betadine) can also be injected into lymphatic malformations, with less pain than with alcohol and with good success.

Cyanoacrylates such as isobutyl-2-cyanoacrylate (IBCA) or N-butyl-2-cyanoacrylate (NBCA) produce polymerization of rapidly flowing blood within seconds. They not only produce immediate thrombosis and have tissue adhesive properties, but they also initiate a giant cell inflammatory reaction of the vessel wall.¹⁴ These embolic liquids are excellent for lesions with rapidly flowing blood, such as an arteriovenous malformation or an arteriovenous fistula. Neoplasms have slow flow, so there is no need to use these agents, which are associated with more risk than particulate materials injected intra-arterially or other agents injected percutaneously.

The newest “liquid” agent is Onyx, which is an ethylene vinyl alcohol copolymer containing dimethyl sulfoxide as the agent facilitating absorption through endothelial barriers.¹⁵ This tissue adhesive is a needed new addition to the armamentarium of the neurointerventionalist because it slowly permeates into tiny vessels feeding a vascular lesion, “creeping” into these feeders during fluoroscopic visualization and control, without the rapid setup time of the cyanoacrylates.^15,¹⁶

Any embolization procedure with a liquid agent should be approached with trepidation because occlusion of the end-arteries to the face, tongue, and cranial nerves may lead to necrosis, and intracranial embolization may occur as the liquid passes through tiny collateral channels to vessels feeding normal structures. Liquid embolization should be performed only when superselective catheterization can be done directly into the direct feeders to the lesion, or with percutaneous puncture of the lesion and direct visualization of the flow of the agent,¹⁷ to prevent unwanted extension to the blood supply of vital structures.

Provocative Testing to Ensure the Safety of Embolization

Two important techniques help to ensure the safety of vascular occlusion at the skull base. The first involves the injection of lidocaine (Xylocaine) 1% without preservatives into an arterial feeder that is considered a candidate for embolization, to predict the potential of permanent cranial nerve palsy from the embolization procedure.¹⁸ This provocative test anesthetizes the cranial nerve if there is blood supply leading to it from the vessel catheterized. Critics of this test suggest that a false-positive test may occur because a liquid anesthetic can be injected into the capillary bed, whereas particles used for embolization stop short of terminal arterioles so that devascularization is rare. It is likely that a negative test result is truly negative and reassuring.

The second provocative test is the temporary balloon occlusion test (BOT) of the internal carotid or vertebral artery, with the addition of blood flow measurement for precise quantification of the potential effects on cerebral blood flow during temporary or permanent occlusion of the artery during surgery or endovascular therapy. Carotid or vertebral artery occlusion might be necessary during the surgical removal of a skull base tumor, during the temporary occlusion of a major intracranial artery during surgical clipping of an aneurysm, for the thrombosis of an unclippable aneurysm via occlusion of the parent artery, or if carotid occlusion has to be performed to close a carotid-cavernous sinus fistula or any other type of traumatic vascular lesion.

First, a complete angiographic evaluation of all cerebral vessels is performed to evaluate their contribution to the particular lesion and the adequacy of collateral flow via the anterior and posterior communicating arteries. If communicating arteries are present, the traditional BOT is performed, consisting of occlusion of the internal carotid artery (ICA) with a nondetachable balloon catheter placed at the level of the future permanent occlusion. After systemic heparinization, the balloon is inflated, and the patient is evaluated for 30 minutes. Careful neurologic examinations are performed throughout the occlusion period, with special emphasis on the neurologic functions subserved by the vessel that is being tested. If the patient develops a neurologic deficit, the balloon is immediately deflated. If the patient has no neurologic deficit from the carotid occlusion, it is assumed that blood flow is adequate for permanent occlusion to occur. Such a qualitative test does not provide precise quantification of the blood flow to the hemisphere at risk, however. Blood flow values greater than 20 to 25 mL/100 g of tissue per minute allow normal neuronal function, with values less than that precipitating neuronal dysfunction. It is conceivable that blood flow values slightly greater than 20 to 25 mL/100 g/min would leave the patient without symptoms while on the angiography table, but superimposed intraoperative or postoperative hypotension, decreased cardiac output, or decreased oxygenation might precipitate cerebral infarction.

Different methods have been used during temporary occlusion to evaluate the physiologic effects of the BOT on cerebral blood flow to predict the risk of cerebral infarction after definitive occlusion. These methods include electric studies such as evoked potentials or electroencephalography,¹⁹ measurements of arterial stump pressures distal to the site of temporary occlusion,²⁰ induced hypotensive challenges, and transcranial Doppler studies. Also, several cerebral blood flow imaging methods, including xenon-enhanced CT (Fig. 136-1),²¹ single photon emission computed tomography (SPECT), positron emission tomography, and MRI and CT perfusion studies, have been used to evaluate cerebral blood flow during BOT to determine the potential risk of ischemia after permanent occlusion.^22,²³ We prefer to use SPECT because it adds little to the basic BOT and easily provides the needed information. After the balloon has been inflated for a short time, the radionuclide is injected intravenously, and the patient is scanned a few hours after the completion of the angiographic study (the radiopharmaceutical “sticks” to the brain tissue during its initial circulation in proportion to the blood flow to that tissue).