General Description

N-butyl-2-cyanoacrylate ([n-BCA]; Trufill, DePuy Synthes) and Onyx (Medtronic) are the only two agents approved by the U.S. Food and Drug Administration for cerebral arteriovenous malformation (AVM) embolization. Theory and practice have demonstrated successful treatment of cerebral AVMs by means of multiple different approaches including transarterial embolization of isolated pedicles to complete obliteration and transvenous approaches. n-BCA is the oldest and most commonly used acrylic embolic agent. This agent polymerizes when it comes in contact with hydroxyl ions in blood. The use of n-BCA has been suggested to allow for easier targeting of lesions that may be distal to the catheter tip as well as allowing experienced neurointerventionists to titrate how far they may be able to inject these flow-directed particles.

Evidence for n-BCA for AVM Embolization

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  Catheter retention was less common with n-BCA than with Onyx (1.6% vs. 9.3%) in a prospective randomized trial that eventually led to the approval of Onyx for use in AVM embolizations.

  
  
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  In 1995, Wikholm et al. ¹ demonstrated that n-BCA offers an effective permanent occlusion after injection for cerebral AVMs.

  
  
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  In 2010, Loh and Duckwiler ² demonstrated the use of Onyx leading to > 50% AVM reduction in 96% of cases versus 85% for n-BCA. However there was no statistically significant difference.

Indications

n-BCA is nearly always permanently occlusive. When mixing n-BCA, experienced neurointerventionists are able to titrate mixtures of ethiodol and glacial acetic acid to adjust the rate of polymerization. This ability to change the rate of polymerization allows n-BCA to be a versatile agent but also can increase the complication rates associated with administration. Polymerized glue is firmer than other agents and can increase difficulty with catheter removal in situations where there is significant reflux. Utilizing flow-directional microcatheters, n-BCA can be guided into large AVM pedicles. These particles travel a significant distance and force the neurointerventionist to be aware of anastomoses and dangerous arterial connections with normal vasculature. What makes n-BCA such a versatile tool includes its ability to be seen clearly on fluoroscopic imaging when mixed with tantalum powder and the ability for the neurointerventionist to use a push technique to enhance the penetration of n-BCA into a target lesion with simultaneous infusion of a 5% dextrose solution, even if the microcatheter is quite proximal from the target.

Neuroendovascular Anatomy

Cerebral AVMs have complex anatomy. To understand the arterial anatomy, anastomotic connections, and the potentially complex venous drainage that can be associated with these lesions, it is critical to complete a full diagnostic cerebral angiogram before planning an embolization procedure. Understanding the arterial bed of the AVM nidus and high-risk features of an AVM, including intranidal aneurysms, plays a role in determining which pedicles require embolization. The Spetzler-Martin grading system highlights important characteristics of AVM anatomy that must always be taken into account, including the eloquence of the region of the brain, deep versus superficial venous drainage, and the size of the AVM nidus. AVMs may arise from any intracranial arterial branches, including the internal carotid artery through all seven segments. Branches or pedicles may arise from middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and posterior circulation perforators. Isolating each circulation or feeding branch is crucial in planning a staged embolization. Understanding deep venous anatomy and ensuring that this is clear on roadmap imaging prior to embolization is equally important to prevent premature occlusion of the draining vein.

Of note, it is very important to have a thorough understanding of contributions from the external carotid artery circulation. There may be arterial pedicles and contributions from the external carotid artery circulation as well as anastomoses that must be considered in the pre-embolization risk assessment.

Periprocedural Medications

Wada testing may be performed in circumstances where there is concern for anastomotic connections or in regions of eloquent cortex. Wada testing with amobarbital (Amytal) and lidocaine is routinely performed at the authors’ institution and can allow for a good functional assessment of a patient prior to embolization.

Systemic heparinization is administered during the procedure because of the risk of intraprocedural thrombus formation. A weight-based intravenous bolus of heparin aimed at an activated clotting time (ACT) of 250–300 s may limit thromboembolic complications. Intraprocedural anticoagulation is frequently held in circumstances of acute rupture or if emergent surgical intervention may be needed. If heparin is administered, protamine should be readily available in case urgent reversal of the effects of the heparin is necessary. During the procedure, a glycoprotein IIb/IIIa inhibitor (e.g., eptifibatide) can be used for acute thrombus formation.

Specific Technique and Key Steps

1. 
   

   A 6 or 8 French (F) sheath is inserted in the femoral artery.

   
   
2. 
   

   After femoral angiography has been performed to confirm the absence of any irregularity or dissection, a guide catheter is advanced over a 0.035-inch curved wire into the aorta. This maneuver is completed under fluoroscopic guidance.

   
   
3. 
   

   A complete cerebral angiogram is performed ( Fig. 32.1, 32.2, Video 32.1, 32.2 ).

   
   
4. 
   

   The guide catheter is advanced into the distal portion of the vessel of interest. The guide catheter can be brought over a Select catheter (Penumbra) and 0.035-inch Glidewire (Terumo).

   
   
5. 
   

   Cerebral angiography is performed to obtain a baseline set of images of the intracranial vasculature ( Video 32.1, 32.2 ).

   
   
6. 
   

   Under roadmap guidance, a microwire loaded into a microcatheter system with a tight J curve at the distal end can be used to navigate into the arterial pedicle of an AVM ( Video 32.1, 32.2 ).

   
   
7. 
   

   Microinjections are performed through the microcatheter to confirm positioning in the pedicle and to demonstrate filling of the AVM nidus.

   
   
8. 
   

   A sterile back table is set up that is physically separate from other sterile areas to avoid sodium chloride (NaCl) ions contacting the n-BCA. Gloves and gown should be changed prior to mixing the n-BCA.

   
   
9. 
   

   Glue preparation involves mixing ethiodol (2.1 mL) in a labeled syringe, n-BCA (0.9 mL) in a glue-compatible syringe, and tantalum powder (0.5 g) ( Video 32.1, 32.2 ).

   
   
10. 
    

    Glacial acetic acid (typically seven drops) is added to change the viscosity and polymerization rate of the solution.

    
    
    
    
    1. 
       

       Rule of thumb: If transit time is < 1 s, at least a 70% glue mixture is used. If transit time is > 2 s, this requires a more dilute concentration closer to 50%.

    
    
11. 
    

    The patient is systemically heparinized with an ACT in the range of 250–300 s in cases without rupture.

    
    
12. 
    

    5% dextrose is injected through the microcatheter to flush the catheter; and after three to four successive injections, the n-BCA mixture is injected slowly ( Video 32.1, 32.2 ).

    
    
13. 
    

    Under a negative roadmap, the n-BCA mixture is injected into the AVM. The injection is quick, steady, and controlled. The glue column should be continuously moving forward.

    
    
14. 
    

    After the embolization is complete (i.e., n-BCA penetration into the nidus) or there is persistent reflux, aspirate on the attached syringe and remove the microcatheter while aspirating from the guide catheter.

    
    
15. 
    

    Final cerebral angiographic runs are performed, and the guide catheter is removed.