blood loss when used for embolization of meningiomas, presumably because of more distal penetration (Bendszus et al. 2000). In general, smaller particles are used for embolizing tumors (45–150 μm), because they will better penetrate small tumor capillaries. Because small PVA particles may migrate into the pulmonary circulation when embolizing AV shunts, larger particles up to 1000 μm have to be used for TAE of DCSFs.

Injection of PVA is performed under fluoroscopy after the particles are suspended in iodine contrast material (Berenstein and Graeb 1982; Szwarc et al. 1986), the concentration of which should be adjusted to the inner lumen of the microcatheter and to the flow in the targeted territory.

The use of particles and embospheres is different from injecting acrylic glue into an AVM nidus. In order to allow for particles and embospheres to reach the desired vascular target, sufficient flow must be maintained within the feeding pedicle. The concentration of PVA in the contrast suspension is chosen depending on the size of the vessels supplying the DCSF, but should be very dilute at first to avoid obstruction of the microcatheter. According to changes in the local hemodynamics that progressively occur during injection due to increasing blockage of the vascular bed, the concentration of particles and their size may be adjusted throughout the procedure. To start with smaller and continue with gradually increased particle sizes is usually most effective. For optimal visual monitoring of the embolic flux and early detection of reflux a magnified “blank road mapping” is strongly recommended. The more distal a catheter is placed, the smaller the particles that should be chosen. On the other hand, the injection of particles smaller than 150–300 μm into the MMA, IMA or AMA may lead to cranial nerve palsy. A more global injection into the IMA using larger particles (possible through a 4-F diagnostic catheter) may show an immediate angiographic change, but is usually ineffective to achieve a long-term occlusion of an AV shunt. As an adjunct for transvenous coil occlusion, or when the aim is mainly to induce flow reduction and to promote thrombosis, such a strategy may be appropriate. The angiographic endpoint should be slow antegrade or stagnant flow.

8.2.2

Stainless Steel Coils

Coils made of stainless steel, also named Gianturco coils after its inventor Cesare Gianturco

(Anderson et al. 1977, 1979; Braun et al. 1985; Chuang et al. 1980), have a diameter between 0.035 and 0.038 inches and have been used for a long time for embolizations in peripheral vascular territories. Interwoven Dacron fibers increase the thrombogenicity of the coils, which require a larger diagnostic catheter, limiting their application in the neurovascular territory. They are the forerunners of the various detachable and non-detachable platinum coils available today.

8.2.2.1

Platinum (Non-detachable) Pushable Microcoils (Fig. 8.6)

These coils have also been called “free” or pushable coils and are available in different lengths, diameters and shapes (straight, helical, flower or spiral) (Graves et al. 1990; Morse et al. 1990; Yang et al. 1988), provided by several companies. Some manufacturers have added Dacron fibers to increase the thrombogenicity while friction is minimized for the use in small microcatheters. Constant flushing of the microcatheter with heparinized saline is required to avoid friction within the microcatheter that may cause blockage and damage of the catheter lumen, necessitating exchange. Such catheter change often leads to loss of a distal position, lengthening of the procedure or even necessitates rescheduling for a subsequent session. Thus, for pushing coils, specifically fibered coils, it is recommended to have little or no friction at all, minimal wall tension and preferably no kinks in the catheter. Especially larger coils may produce friction when advanced through a sharp vessel turn and sometimes have to be deployed by forceful injection of a saline bolus using a 2- or 5-cc syringe. This will propel the coil through the catheter lumen, a technique that may save time and costs. Coil positioning can be slightly less accurate and some coils may be malpositioned by flow reversal. Thus, this technique should be applied only with some experience in endovascular techniques. In general, the use of pushable coils may in some cases be associated with coil migration or recoil of the microcatheter, leading to coil placement in unwanted and sometimes catastrophic positions (Halbach et al. 1998). Pushable fibered coils have only been used by the author in addition to detachable coils, to increase the thrombogenicity of the bare platinum coil mesh. They are also available in complex configurations, such as VortX-coils (Boston Scientific). VortX-coils and other fibered coil

configurations have become available with a detachment system as GDCs (Halbach et al. 1998). Other manufacturers have developed similar devices such as the nylon fibered coils (NXT, EV3), in sizes ranging from 2×20 mm to 3×100 mm, combining the advantages of being highly thrombogenic and controllable by a similar detachment system (Henkes et al. 2004; Hung et al. 2005; Takazawa et al. 2005; Zink et al. 2004). One main advantage of platinum as a material for coils is its high opacity compared to stainless steel and its MR compatibility.

Some operators have used this type of coil for transarterial embolization of ECA feeders (Gioulekas et al. 1997). However, while their placement leads to a proximal occlusion, resulting in a shunt reduction, it seldom produces a permanent obliteration. The major downside of transarterial coil embolization in AV shunting lesions is that future arterial approaches through the same pedicle are compromised and new treatment sessions may become jeopardized, unless TVO is used (Fig. 8.7). Thus, proximal arterial occlusion with coils should be avoided whenever possible. It has never been considered useful by the author, except when targeting a selective vessel blockage to avoid untoward migration of embolic agents via ECA-ICA anastomoses (e.g. MMA-OA anastomoses in preoperative embolization of meningiomas).

On the other hand, for transvenous occlusions of DAVFs in general, and for DCSFs in particular, even non-detachable fibered coils are quite useful and effective in accelerating the occlusion process due to their high thrombogenicity. However, if these coils are not properly positioned or densely enough packed, the chances of leaving a residual AV shunt in a compartmentalized CS is high.

8.2.2.2

Detachable Platinum Coils (Fig. 8.5)

The first detachable coil, the GDC system (Guglielmi detachable coil system), is a non-fibered, soft bare platinum coil mounted on a stainless steel wire that can be detached by electrolysis after placement in the desired location. This coil system was primarily developed for safer embolization of intracranial aneurysms, after it became evident in the 1980s that using pushable coils and detachable balloons was associated with too many serious complications due to their inherent limitations.

Mullan (1974) was already able to induce an occlusion of a CSF using an electric current applied

through copper wires surgically introduced into the CS. Guglielmi became interested in animal experiments on electrothrombosis in arteries and in 1979, accidentally observed, during attempts to induce electrothrombosis in an experimental aneurysm, a detachment of the electrode from the steel wire (Strother 2001). This incident was in principle the discovery of the electrolytic detachment of platinum coils that was implemented in the GDC system in 1991 and subsequent systems. GDC has meanwhile proved highly effective in the treatment of intracranial aneurysms and was FDA approved in 1995.

The use of a precise detachment mechanism is important not only for aneurysm treatment, but also for transarterial or transvenous occlusions of AV shunting lesions. Proper positioning of the coils in a distant location, while always having the possibility to retrieve the coil, is of key importance for safely and effectively performing TVOs. In fact, one of the first successful treatments using GDCs was a direct CCF, occluded by F. Vinuela in 1990 using only two coils (Guglielmi et al. 1992).

GDCs are made of a soft platinum alloy and are usually available in the configurations shown in Table 8.1.

GDC Soft coils are made of a thinner wire than standard coils and thus more pliable (e.g. GDC-10 Soft coils are 38% softer than GDC-10 standard coils). In order to minimize the mechanical stress applied to cranial nerves coursing through the CS, the use of softer coils for the CS packing is beneficial. At the same time a denser coil mesh can be achieved that is similar to aneurysm treatments – a major factor for achieving complete occlusion of the fistula.

The use of coils with a complex or spherical configuration at the beginning of the coil packing, when a basket in a certain compartment of the CS needs to be accurately built, is also advantageous. This is the case at the connection between the CS and the SOV or a cortical vein. Buckling and kick-back of

Table 8.1. Available lengths and diameters of GDCs

a microcatheter has occasionally been a problem, especially with the relatively stiff first 3D-GDC generation from BSC. This has been overcome with newer coils from other manufacturers (Fig. 8.5d–f). SR Coils (stretch resistant coils) have interwoven double strands of polypropylene or other material that prevent stretching and unraveling, which is advantageous when a long-used microcatheter develops friction or even kinks and cannot be replaced. Although coil unraveling or failure to detach during TVO are technical complications, their consequences are less dramatic than during aneurysm treatment. As a bail out, the coil may be “mechanically detached” (Lee and Yim et al. 2008) by 15–20 clockwise rotations until it breaks, which does not cause harm, even when the rest of the basket in the CS gets entangled (personal unpublished experience; see also Fig. 8.4).

So-called UltraSoft coils (BSC) provide a further stiffness reduction of about 50%, allowing for a packing density of up to 55% in experimental aneurysms (Piotin et al. 2004). These coils may be deployed in extremely small vascular pockets (Benndorf et al. 2002). Recently, a new HyperSoft coil (MicroVention

*

Fig. 8.7. Ineffective transarterial embolization of IMA branches with coils. Right ECA injection. AP view shows an AV shunt at the righ CS (asterisk) draining to the left side and causing cortical venous drainage. This patient was tranferred from another institution after undergoing TAE with coils (arrows). Proximal occlusion of ECA supply of an AVF with any type of coil (or glue) usually has little or no effect. It seriously compromises future attempts of catheterization instead and should be avoided. This patient was successfully managed by TVO and fully recovered (Benndorf et al., 2000a)

Inc., Aliso Viejo, CA) with a remarkable compliance and a shorter, softer detachment zone has been introduced (Fig. 8.5g). This coil allows high packing density while minimizing microcatheter movement and proves very useful for treating DCSF (Case Illustrations V).

Platinum detachable coils have been used to a large degree in the group of patients studied by the author and only in some cases have been combined with fibered coils. Detachable coil systems from various other manufacturers are available today providing equal, if not better, mechanical properties compared to GDCs. Beside electrolysis, other detachment techniques have been developed using a mechanical mechanism such MDS (Balt Extrusion) or DCS (William Cook Europe), heat (Micrus Endovascular Corporation, San Jose, CA) or hydraulic pressure (MicroVention, Cordis Neurovascular) that allow deplopment of a platinum coil in a quick, safe and reliable manner.

The additional coating of coils with bioactive materials such as polyglycolic-polyactic biopolymer (PGLA) to promote fibrocellular proliferation and increased endothelialization is of little relevance for occlusion of DCSFs. A fundamentally different approach to the problem of coil compaction and long-term occlusion of aneurysms has been the introduction of coils covered with a hydrogel (HydroCoils).

a

8.2.2.3

HydroCoils (Figs. 8.8–8.10)

Among the new coil generations with a “bioactive” surface coating, hydrogel, mounted on a detachable platinum coil (HydroCoil, HES,) has attracted attention for the treatment of DAVFs. The HydroCoil™ is a platinum-based coil with a Hhydrogel coating, a material that expands while in contact with water or blood. The water absorption leads to swelling of the material which results in an increase of the coil diameter after being deployed in the blood circulation. This rather unique property of the HES proved advantageous in treating cerebral aneurysms (Kirsch et al. 2006; Goto and Goto 1997; Nemoto et al. 1997; Hanaoka et al. 2006;

Schuknecht et al. 1998; Mironov 1994; Halbach et al. 1992; Satomi et al. 2005; Taptas 1982). It is currently believed that while the HES increase their diameter, they actually do not “over-swell”, so that additional mechanical pressure will not occur. A HydroCoil 18 expands from 0.018s to 0.034s, a HydroCoil 14 expands from 0.014s to 0.027s and the HydroCoil 10 expands from 0.013s to 0.022s. The maximum reposition time of these coils is 5 min. in a 0.021s, 0.019s or 0.015s inner lumen microcatheter, respectively. A new detachment system (V-Trak) utilizes thermo-mechanical technology by sending a current to a heating coil at the end

b

of the pusher. The coil is attached with a polymer tether under tension. The heat severs a polymer tether, detaching the coil in about 0.75 s.

The use of HES for AV shunting lesions is described only in a limited number of reports to date (Marden et al. 2005; Morsi et al. 2004). First, the swelling of the hydrogel is ideal for progressive mechanical occlusion of a venous AVF compartment, as it will adjust to the irregular surrounding anatomy better than bare metal coils. Such a progressive swelling and occlusion process can help to reduce the total number of coils needed for transvenous occlusion, as seen in cerebral aneurysms (Deshaies et al. 2005). Second, the softness of the gel will allow a dense packing of the coils, while reducing mechanical pressure on intracavernous structures and the risk of CN deficits. It has been shown that the hydrogel expansion does not contribute to any change in the intraaneurysmal pressure (Canton et al. 2005). Intervals of 5–10 min between control angiograms after each coil deployment (allowing for a full expansion of the gel) may already reveal a significant reduction of the AV shunting flow, indicating progressive occlusion and thrombosis. The swelling may increase the diameter of the coils up to five to 11 times of a standard platinum coil, which allows for achieving higher volumetric packing than possible with bare platinum coils while reducing the total amount of metal. The fact that the gel will swell after the coil has been deployed makes this coil very suitable for progressive occlusion of larger venous compartments such as dural sinuses.

Thus, the usefulness of HydroCoils for occluding DAVFs and DCSFs is rather obvious. In Case Illustration IV, effective transvenous occlusion using HydroCoils is demonstrated.

8.2.3

Liquid Embolic Agents: Cyanoacrylates (N-butyl-cyanoacrylate, Acrylic Glue, Histoacryl, TrufillTM n-BCA, GlubranTM)

In the 1980s, NBCA (N-butyl-2-cyanoacrylate), initially known as Avacryl in the US and as Histoacryl in Europe (Braun-Melsungen, Germany) replaced IBCA (Isobutyl-2-cyanoacrylate), being the first acrylic glue for medical application (Brothers et al. 1989). Histoacryl is a tissue adhesive that polymerizes when in contact with ion solutions such as contrast, saline or blood, and was initially developed for use in dermatology. Cyanoacrylate was for a long

time considered the only agent capable of causing a permanent occlusion when injected intravascularly. Because of this property, it has been widely used in the treatment of brain AVMs and AVFs. The experience in using glue is extensively published (Brothers et al. 1989; Duffner et al. 2002; Liu et al. 2000a,b; Henkes et al. 1998; Cromwell and Kerber 1979; Kerber et al. 1979; Gounis et al. 2002; Li et al. 2002; Sadato et al. 2000; Raffi et al. 2007;

Troffkin and Given 2007; Wakhloo et al. 2005). Its liquid form allows penetration into very small vessels and is particularly suitable for completely occluding an AVM nidus (Brothers et al. 1989).

The polymerization of NBCA starts after a few seconds of contact with blood and can be controlled only to some degree, depending on various factors such as blood flow velocity, speed of the injection, pH of the blood and temperature of the glue. In order to increase radiopacity for fluoroscopic control, Histoacryl is mixed by most investigators with Lipiodol (ethiodized oil), a cottonseed-oil-based contrast agent made by Laboratorie Guerbet (France). In addition, this mixture decelerates the polymerization depending on the concentration of lipiodol from 1–30 s (Cromwell and Kerber 1979). Introducing the mixture with lipiodol significantly improved the handling of glue (Stoesslein et al. 1982). While concentrations of approximately 50% (60/40) were used in early years, glue has been increasingly diluted recently. For AVMs, dilutions of 20%–25% or less are meanwhile preferred. A concentration below 15%, although still usable, significantly impairs the polymerization; its adhesive properties are reduced, and the glue may easily migrate into the venous side of the AV shunt. Because of the potential hazardous complications, the handling of acrylics has to be studied and practiced extensively before it may be safely and effectively used. Prior to the embolization with glue, the microcatheter must be flushed with 5% glucose (dextrose in water) to avoid premature polymerization within the catheter. Each injection of glue must be carefully observed under fluoroscopic control in order to recognize early even the smallest reflux into the proximal feeder and to avoid gluing the catheter to the vessel wall. Additional use of tantalum powder in the mixture further enhances radiographic visibility. A small reflux (up to 5 mm) may be tolerated with modern hydrophilic catheters, depending on the concentration of the glue and the location of the microcatheter, prior to removal. When glue is injected directly into a sinus or a venous compartment such as the CS, gluing of

the microcatheter is less of a problem. It has been found that polymerization of glue may be further prolonged by adding tantalum powder. A concentration as low as 10%–15% has been used by adding tungsten and lipiodol for TAE of five complex DCSFs (Liu et al. 2000b). Gounis et al. (2002) showed that predictability of the embolization process with NBCA can be improved by adding glacial acetic acid to the embolic mixture. Due to regulatory issues in North America in the 1990s, the use of acrylic glue was limited in the US compared to Europe. In 2000, a slightly modified version of Histoacryl, TrufillTM n-BCA (Cordis Neurovascular, Miami lakes, FL) received FDA approval for treatment of brain AVMs, and showed a good combination of penetration and permanence (Jordan et al. 2005). It is also mixed with Ethiodol (TrufillTM-NBCA Cordis Neurovascular) in various concentrations from 2:1, 3:1, etc. The intravenous injection of glue for occlusion of DCSFs has been reported only to a limited degree (Wakhloo et al. 2005) and was used in a few cases in the studied group of patients (Benndorf et al. 2004 , see also Fig. 8.35). A modified cyanoacrylate, GlubranTM (and Glubran 2TM), was recently introduced in Europe (Raffi et al. 2007).

8.2.4

Onyx™ (Ethylene-Vinyl Alcohol Copolymer) (Fig. 8.11)

Ethylene-vinyl alcohol copolymer (EVOH, Onyx, EV3, irvine CA) is a newer liquid embolic agent whose main characteristic is its non-adhesiveness. In contrast to adhesive acrylates, Onyx™ is a precipitating embolic agent that mainly causes a mechanical vessel occlusion. It prevents microcatheters from gluing to the vessel wall, and thus allows significantly prolonged injection times (up to 40 min or more). It is mixed with a solvent, dimethyl sulphoxide (DMSO) and tantalum powder (Jahan et al. 2001) and comes in ready-to-use vials for AVMs and AVFs in three concentrations: 6% (Onyx 18), 6.5% (Onyx 20) and 8% (Onyx 34), dissolved in DMSO (Suzuki et al. 2006).

Onyx is a pre-mixed, radiopaque, injectable embolic fluid that solidifies upon contact with aqueous solutions or physiologic fluids. In contrast to NBCA, this property allows for temporarily pausing the injection to prevent untoward leakage into a non-targeted territory (Jordan et al. 2005). It forms a spongy polymeric cast and a “skin” – solidifying

from the outside while continuing to flow, “much like lava”, in the liquid center. Thus, Onyx™can be delivered in a relatively cohesive manner.

The initial description of its use for embolization of AV shunting lesions came from Taki et al. (1990) and Terada et al. (1991). The authors reported the successful embolization of cerebral AVMs with EVAL (ethylene vinyl alcohol copolymer) dissolved in DMSO. Safety concerns emerged after animal studies conducted by Chaloupka et al. (1994), who discovered significant angiotoxicity of the DSMO. A reexamination, however, showed no acute hemodynamic effects, and no infarction or SAH at slower injections rates of 30, 60 and 90 s (Chaloupka et al. 1999).

Subsequent studies revealed that the main factors influencing vascular toxicity are the contact time with the arterial wall and the total volume of DMSO. It was demonstrated that DMSO enters the bloodstream, is absorbed into tissue and metabolized to dimethyl sulfone (DMSO2) and dimethyl sulfide (DMS) (Chaloupka et al. 1999). These metabolites are eliminated via the kidneys (within 1 week; 80%), and via the skin or lungs, causing a garlic odor to the breath until complete elimination: 13–18 days.

Onyx received FDA approval for the treatment of cerebral AVMs in 2005 and has been increasingly used since (Nogueira et al. 2008; Mounayer et al. 2007; Toulgoat et al. 2006; Cognard et al. 2008; Arat et al. 2004).

The use of Onyx has a number of technical advantages over cyanoacrylate, the most important of which is the possibility of prolonged injections in a slow and controlled fashion. If properly performed, it allows achieving deeper nidus penetrations in AV shunting lesions. Whether or not long-term occlusion rates are comparable or superior to the ones obtainable with NBCA remains to be answered by ongoing and future studies.

Among the disadvantages of Onyx is its limitation to DMSO compatible microcatheters such as the Rebar, a braided, relatively stiff microcatheter, the Ultraflow and the Marathon (Ev3, Irvine CA) both flow-guided microcatheters. The Echelon is a nitinol braided, over-the-wire catheter and is available as Echelon 10 (1.7F) and Echelon 14 (1.9F). It has a preshaped tip of 45 or 90 degrees and is particularly useful for transvenous occlusions, as it also allows placement of coils (see Figs. 8.31 and 8.34). Other compatible catheters are the flow-guided 1.2-F–1.8- F Baltacci and the braided Corail+ balloon catheter (Balt Extrusion, Montmorency, France). A novel