A to Z in neurointerventional surgery: A primer for residents
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.158233
Source of Support: None, Conflict of Interest: None
Neurointerventional surgery has evolved rapidly over the last two-and-a-half decades. It is now the treatment of choice for many neurovascular conditions, and its techniques and indications are rapidly expanding. It is the need of the hour that residents in training programs should familiarize themselves with the basic concepts of neurointerventional surgery. There are no set guidelines regarding neuroendovascular training of residents in India. The current article provides an insight into the basic concepts of neurointerventional surgery for residents in training.
Keywords: Balloon; catheter; neuroendovascular; neurointervention; sheath, stent; wire
Endovascular treatment of neurological conditions is a rapidly evolving field that spans across various specialties namely neurosurgery, neuroradiology, neurology, and cardiology and has many names such as endovascular neurosurgery, interventional neuroradiology, and interventional neurology. Neuroendovascular surgery has come a long way and is currently the first line therapy for some of the neurological conditions such as cerebral aneurysms, dural arteriovenous fistulae and acute ischemic stroke due to large vessel occlusion. ,
Endovascular surgery involves accessing the arterial system through a peripheral artery (femoral, radial or brachial) and navigating the catheters to the area of interest. Procedures are performed through the catheters under fluoroscopic guidance.
Knowledge of basic neuroendovascular concepts is a prerequisite for residents training in the current era. The present article attempts to describe the common endovascular equipment, techniques, and concepts.
Arterial access is most commonly obtained via the common femoral artery (CFA). The CFA crosses the inguinal ligament approximately at its midpoint. The target for puncture is the midpoint of CFA between the upward turn of the inferior epigastric artery and the bifurcation of CFA. Arterial puncture is performed using the 19 gauge Seldinger needle or the micropuncture needle. A single wall puncture is preferred to a double wall through-and-through puncture to reduce the risk of inadvertent back wall puncture leak. Commonly, a 5 French (F) sheath is used for diagnostic procedures in adults and a 4F one in children. For interventional procedures, a larger sized sheath is required and therefore, its size may vary from 6F to 9F. Depending on the physician's preference, the length of the sheath may vary from 10 cm to 90 cm.
The radial artery or the brachial artery approach, and the direct common carotid artery puncture are uncommon approaches and only used when either the femoral arterial access is not available or when the great vessels in the neck are tortuous enough to preclude a safe catheterization. The trans-radial approach is gaining popularity as the first line approach for posterior circulation lesions as it avoids the need to navigate through the aortic arch to catheterize the vertebral artery. 
The availability of intracranial compliant balloons has revolutionized the field of neurovascular interventions. The commonly used balloons in endovascular procedures (other than for atherosclerosis) include HyperGlide and HyperForm balloons (ev3/Covidien, Irvine, California, USA), Transform™ balloon (Stryker, Neurovascular, Fremont, CA, USA), the Ascent occlusion balloon catheter (Codman Neurovascular, Raynham, Massachusetts, USA), and the Scepter balloon (Microvention/Terumo, Tustin, California, USA). The HyperGlide, HyperForm, and Transform balloon catheters consist of a single-lumen catheter and a nondetachable, low-pressure balloon. HyperForm and Transform XC (supercompliant) are more compliant than Hyperglide and Transform C (Compliant) balloons. A 0.010-inch or 0.014-inch microguidewire is positioned distal to the balloon catheter to occlude the central lumen and to allow the balloon to inflate through catheter side holes. The HyperGlide is available with 4- and 5-mm-diameter balloons and the HyperForm is available with 4- and 7-mm-diameter balloons. These balloons are used during Balloon Remodelling Technique for embolization of intracranial aneurysms. The Hyperglide and Transform C are generally used for sidewall aneurysms whereas the Hyperform and Transform XC are used for bifurcation aneurysms. These balloons are also used during angioplasty for vasospasm following an aneurysmal subarachnoid hemorrhage.
The Ascent and the Scepter (Microvention/Terumo, Tustin, California, USA) balloon catheters consist of a compliant balloon and a coaxial, dual-lumen shaft that permits passage of a 0.014-inch guidewire through the central lumen and balloon inflation through the outer, independent lumen. Thus, they can be inflated without occluding the lumen with a guidewire. The Ascent balloon is available in two forms, a semicompliant form (4 mm × 10 mm, 4 mm × 15 mm) and a super compliant form (6 mm × 9 mm, 4 mm × 7 mm). The Scepter balloon is available in two forms: The Scepter-C (compliant) and the Scepter-XC (extracompliant). Besides their use in the treatment of intracranial aneurysms, the Ascent and Sceptor balloons are also used in embolization of intracranial vascular malformations as they are compatible with dimethyl sulfoxide (DMSO).
In contrast to endovascular balloons, the balloons used for carotid and intracranial atherosclerosis are noncompliant. The common balloons used in extracranial carotid angioplasty are Maverick (Boston Scientific, Natick, MA, USA) and Sterling (Boston Scientific, Natick, MA, USA); and, that in intracranial angioplasty is Gateway (Stryker, Neurovascular, Fremont, CA, USA). Detachable silicone and latex balloons for the treatment of direct carotid cavernous fistula and Hunterian occlusion of giant intracranial aneurysms is approved for use in Europe, although their use is dwindling. 
Catheters may be classified as diagnostic or guide catheters that are used to access the targeted large vessel (internal/external carotid artery or the vertebral artery), and microcatheters that can be navigated to the vessel of interest in the intracranial circulation. Common catheters used for diagnostic cerebral angiography are 4- or 5-F angled, Simmons 2 or 3 and the head hunter type, whereas a Cobra, Simmons 1 and Contra 2 are used for spinal angiography. The catheters for cerebral angiography are usually 90 cm long whereas those for spinal angiography are 65 cm long, although longer (125 cm) catheters are occasionally used to telescope larger sheaths. The catheters are advanced over hydrophilic wires. The wire should always lead the catheter by at least 8-10 cm. The guide catheters provide a stable support for microcatheters to reach distal small vessels. In general, 6- or 7-F catheters are used in cases requiring the use of two microcatheters. Commonly used guide catheters are the Envoy (Cordis, Johnson and Johnson Company, Warsaw, IN), Cook shuttle (Boston Scientific, Natick, MA, USA), Guider Softip XF (Boston Scientific, Natick, MA, USA), Northstar (Cook, Inc., Bloomington, IN) and Neuron (Penumbra Inc., Alameda, CA, USA). Balloon guide catheters have a balloon at the tip that allows proximal flow arrest and prevents distal embolization. Commonly used balloon guide catheters are the 8-F concentric and the 8- and 9-F Cello (ev3/Covidien, Irvine, California, USA). These are most commonly used in acute stroke interventions.
Nonionic contrast agents should be used in cerebral angiography. They are denominated according to the content of organic iodine per milliliter. Contrast agents with 180-200 mg/mL of iodine provide good vessel opacification on modern machines. In pediatric patients as well as patients with compromised renal function, the use of contrast should be minimized. The general formula for calculating the maximum tolerable volume of contrast is as follows. 
Weight (kg) × 5 (adult) or 4 (child) =Tolerable volume (mL) Serum creatinine (mg/dL) of nonionic contrast 300
In patients with delayed cerebral ischemia due to vasospasm following an aneurysmal subarachnoid hemorrhage, endovascular management may be considered when triple H therapy fails in combating the vasospasm. Intra-arterial vasodilator therapy and transluminal balloon angioplasty are the mainstays of endovascular management of vasospasm. The major advantages of intra-arterial vasodilator therapy over balloon angioplasty are the possibilities of delivering medication to the distal vessels, and of having no risk of vessel rupture. The commonly used pharmacologic agents are as follows:
Mix with heparinized saline to achieve a concentration of 1 g/mL and infuse at the rate of 1 mg/min for 5 min. Reassess after 5 min. Inject a maximum of 15 mg/vessel. 
Mix with heparinized saline to achieve a concentration of 0.1 mg/mL and infuse 1 mg over 5 min. Inject a maximum of 5 mg/vessel.
Mix with heparinized saline to achieve a concentration of 0.1 mg/mL and infuse at the rate of 1 mg over 5 min. Inject a maximum of 5 mg/vessel. 
Mix with heparinized saline to achieve a concentration of 0.1 mg/mL and infuse at the rate of 0.25 mg/min. Inject a maximum of 5 mg/vessel.
There is no evidence for the use of papaverine in vasospasm and the current guidelines do not recommend its use in the management of vasospasm. Hyperform or Hyperglide balloons are used in transluminal balloon angioplasty as mentioned earlier. ,
Therapeutic embolization is an established treatment of many head and neck and intracranial vascular lesions such as arteriovenous malformations (AVMs), fistulas, and hypervascular tumors. The common embolic agents used are:
Polyvinyl alcohol (PVA) particles have traditionally been the gold standard because they are both biocompatible and efficient as a permanent embolic agent. However, PVA particles are hydrophobic, vary in size, and have an irregular surface which may cause clumping and aggregation of particles and catheter or large vessel occlusion. Their use in AVMs has dwindled after the availability of N-Butyl Cyanoacrylate (N-BCA) and Onyx, but they are very popular in the treatment of hypervascular tumor embolization preoperatively, and in the treatment of epistaxis. 
Trisacryl gelatin microspheres (Embospheres)
Embospheres (Biosphere Medical, Rockland, MA) are small spheres composed of a plastic called trisacryl gelatin. They are hydrophilic, biocompatible, nonresorbable, and uniformly spherical. These calibrated microspheres are available in different sizes ranging from 40 μm to 1000 μm and are easy to deliver through a microcatheter. The size of the occluded vessel correlates well with the size of the embospheres. 
N-Butyl Cyanoacrylate and Onyx are discussed elsewhere in the article.
Flow-diverters are "stent-like" endovascular devices that alter the blood flow hemodynamics to promote aneurysmal thrombosis and endoluminal remodeling. In contrast to the intracranial stents used for stent-assisted coiling that have a metal coverage of about 10-15%, the flow diverters have a high metal coverage ranging from 30% to 35%. , As opposed to coil embolization, flow diversion causes aneurysms to occlude over time rather than immediately after the procedure. Currently, the pipeline embolization device (PED) (ev3/Covidien, Irvine, California, USA) is the only Food and Drug Administration approved flow-diverter. The Silk flow-diverter (Balt Extrusion, Montmorency, France) is available for use in Europe. Flow redirectional endoluminal device (Microvention/Terumo, Tustin, California, USA) and Surpass (SURPASS; Stryker Neurovascular, Fremont, CA, USA) are other flow-diverters under investigation. In India, PED, Silk and Surpass are available for use. Flow-diverters are used across the neck of the aneurysm to induce stasis in the aneurysm and thrombosis. Gradually, the stent is endothelized, and a new vessel wall is generated along the stent.
The endoluminal approaches to the aneurysms provided by flow-diverters are gaining rapid popularity for some aneurysms like the large and giant paraclinoid cavernous and posterior circulation aneurysms, as opposed to the endo-saccular approach provided by coils. 
Coils consist of a platinum thread that is looped around a platinum core that is connected to a pusher wire. They differ in size, shape, design, stiffness, presence or absence of bioactive material, and the detachment mechanism. Coil sizes have been traditionally categorized into the 10-system and 18-system, the actual diameter of these two categories of coils being 0.008 inch and 0.016 inch.
Framing coils are three dimensional coils intended to form a frame within the aneurysm to ovalize or sphericize the aneurysm to enable packing of coils within. Example include Micrusphere (Micrus, Mountainview, CA, USA), Target 360 (Stryker Neurovascular, Fremont, CA, USA), and Orbit Galaxy (Codman, Raynham, MA, USA). Filling coils such as Helipaq (Micrus, Mountainview, CA, USA), Target 360 soft (Stryker Neurovascular, Fremont, CA, USA), and Orbit Galaxy (Codman, Raynham, MA, USA) are helical coils and are used to fill the space within the framing coil. Finishing coils such as Deltapaq (Micrus, Mountainview, CA, USA), Deltaplush (Micrus, Mountainview, CA, USA), Target Ultra (Stryker Neurovascular, Fremont, CA, USA), Orbit Galaxy Xtrasoft (Codman, Raynham, MA, USA), and Microplex HyperSoft (Terumo Medical, Somerset, NJ, USA) are the softest coils used to pack the aneurysm. 
It is important to remember that majority of the complications during a neurointerventional procedure are thrombo-embolic, and not hemorrhagic, and hence anticoagulation therapy during the performance of neurointerventional techniques is vital. All patients undergoing interventions are anticoagulated with heparin. The initial bolus dose is about 60-80 U/kg followed by 20-40 U/kg every hour. Activated clotting time is monitored every hour to maintain a level between 250 and 300.  Anticoagulation during diagnostic cerebral angiograms is also usually done, but with a lower dose. The only exception to the use of heparin is in subarachnoid hemorrhage where anticoagulation is deferred until one or two coils are deployed to secure the aneurysm. Unlike in open surgery, the use of antiplatelets or anticoagulants is not stopped prior to the interventions. All the catheters and sheaths should be continuously flushed with heparinized saline (3000-5000 U in 1 L) so as to prevent clot formation and procedural stroke. In patients with heparin-induced thrombocytopenia, bivalirudin (reversible, direct, thrombin inhibitor with a short half-life of 30 min) may be used. The recommended dosage is 0.1 mg/kg/L of normal saline solution. A bolus of 0.75 mg/kg may be administered followed by 0.25-1.75 mg/kg every hour during the procedure. 
Intraoperative neurophysiological monitoring during the neuroendovascular procedures is being used in some centers as the standard of practice. The tests being used during the neuroendovascular procedures are electroencephalography (EEG), somatosensory evoked potentials (SSEPs), brainstem auditory evoked potentials (BAEPs) and transcranial motor evoked potentials. There is no consensus on the usage of intraoperative monitoring. In general, SSEP and EEG are used during the anterior circulation approaches, and BAEPs are added during the posterior circulation approaches. The other monitoring is a variant of the WADA test, which is done during AVM embolization, to find out if the vessel to be embolized is also supplying the normal brain. ,
The "Jailing Technique" is employed during stent-assisted coiling of intracranial aneurysms. The microcatheter used to deploy coils within the aneurysm is navigated, and the tip positioned within the aneurysm. The second microcatheter is navigated past the aneurysm in the parent vessel and the stent deployed. The first microcatheter is thus jailed between the parent vessel wall and the stent. 
Extravascular extravasation of contrast may be noted following aneurysmal rupture during coiling or its perforation while navigating with a microwire. If the extravasation is noted during coiling, continued deployment of coils usually seals the rupture. Endoluminal leakage of contrast is noted in situations where the stent is not completely against the vessel wall either due to inappropriate stent selection or due to vessel tortuosity. Balloon angioplasty may be performed to achieve complete apposition.
Mechanical thrombectomy in acute ischemic stroke is performed in different ways. The two most common techniques are using stentrievers (Solitaire or Trevo) and mechanical aspiration. Solitaire (ev3/Covidien, Irvine, California, USA) and Trevo (Stryker Neurovascular, Fremont, CA, USA) are retrievable stents that are deployed across the clot in a large vessel and then retrieved.  The clot is caught within the stentrievers and retrieved along with them. The latest trials (MR CLEAN, ESCAPE, and EXTEND-1A) have proven the superiority of mechanical thrombectomy over intravenous (IV) t-PA in selected group of patients. ,, Thrombectomy for cerebral venous sinus thrombosis has been reported, although no specific guidelines exist. 
N-Butyl Cyanoacrylate (N-BCA) is a liquid glue. When it is mixed with ethiodol oil, and tantalum powder, it forms a radio-opaque embolic system. It is used under fluoroscopic guidance to occlude or reduce the blood flow to cerebral AVMs via superselective microcatheter delivery. The mixture polymerizes into a solid material on contact with blood or tissue. Higher concentrations of ethiodized oil increase the polymerization time, which allows distal penetration into the nidus of the AVM. High concentrations of N-BCA results in a faster polymerization rate, allowing proximal embolization. Tantalum powder is added to increase radiopacity and lower viscosity. The glue can be delivered through any microcatheter. 
Onyx (ev3/Covidien, Irvine, California, USA) is a liquid embolic agent that is approved for embolization of AVMs. However, it is used off-label for embolization of fistulas and head and neck vascular lesions. It is a copolymer of ethyl vinyl alcohol prepared with dimethyl sulfoxide (DMSO) as the solvent. Tantalum powder is added to make the mixture radio-opaque. Once it comes in contact with blood, it forms a case within the blood vessels. Three varieties are available depending upon the viscosity; Onyx-18, Onyx-34, and Onyx-500. Onyx-18 has the least viscosity, and Onyx-500 is used for the treatment of cerebral aneurysms in some parts of the world. The nonadhesive nature of Onyx allows for longer injection times and the ability to temporarily suspend injection to do an angiogram. DMSO is toxic and should be injected slowly (to flush the catheter before injecting Onyx). Rapid injection of DMSO may lead to vasospasm and necrosis. The microcatheters compatible with DMSO include the Marathon (ev3/Covidien, Irvine, California, USA), Apollo (ev3/Covidien, Irvine, California, USA), Magic Soren and Echelon. ,
Anti-platelet agents are used in neurointerventional surgery to prevent thromboembolism during and after the procedures. , Some of the commonly used drugs are:
Irreversible inhibitor of cyclooxygenase COX-1 and COX-2 that irreversibly inhibits the formation of thromboxane A2. There is no definite loading dose. It is usually administered 300 or 325 mg as the initial dose (peak effect in 30-60 min), and 81 or 100 mg (low dose)/300 or 325 mg (high dose) as maintenance.
An inactive prodrug is metabolized by cytochrome p450 in the liver to an active form that binds to P2Y12 irreversibly. The maintenance dose is 75-150 mg/day. In emergency, a loading dose of 300 mg (peak effect in 3 h) or 600 mg (peak effect in 2 h) orally or rectally may be administered. The effect lasts for 7-10 days and is not reversible.
An irreversible P2Y12 inhibitor. The loading dose is 60 mg orally (peak effect in 2-4 h). The maintenance dose is 5-10 mg/day.
Reversible P2Y12 inhibitor that prevents adenosine diphosphate mediated activation of glucoprotein (gp) IIb/IIIa receptors. The loading dose is 180 mg orally (peak effect in 1-3 h). The maintenance dose is 90 mg twice daily.
Monoclonal antibody that binds to gp IIb/IIIa receptors. Administered IV at 0.25 mg/kg as a bolus and maintenance infusion at a rate of 0.125 μg/kg/min (maximum 10 μg/min) for up to 12-24 h.
Integrilin, Eptifibatide, and Tirofiban are other gp IIb/IIIa inhibitors that are rarely used.
Embolization for epistaxis, head and neck bleeds, carotid blow-out and intra-arterial chemotherapy for retinoblastomas are some of the non-neurological conditions that can be effectively treated with endovascular techniques.
Several stents are used in neuroendovascular procedures depending upon the pathology, site of usage and the intended role of stents. Open-cell stents have connecting and non-connecting struts whereas closed-cell stents have overlapping or fully connecting struts. Common open-cell stents used for extracranial carotid atherosclerotic stenosis are Precise (Cordis, Miami Lakes, FL, USA), Protégé (ev3 Neurovascular, Irvine, CA, USA) and Acculink stent (Abbott Laboratories, Santa Clara, CA, USA), whereas Xact (Abbott Laboratories, Santa Clara, CA, USA) is a closed-cell stent.
The common intracranial stents used for stent-assisted coiling of aneurysms include Neuroform3 (open-cell; Stryker Neurovascular, Fremont, CA, USA), Enterprise (closed-cell; Codman, Raynham, MA, USA) and Low-profile Vascular Intraluminal Support device (LVIS , braided stent; MicroVention, Tustin, CA, USA). The Wingspan (ev3 Neurovascular, Irvine, CA, USA) stent is a self-expanding stent with more radial force than the other intracranial stents and is approved for the treatment of intracranial atherosclerosis.
Thromboembolism frequently occurs during and after neuroendovascular procedures due to many factors such as arterial injury, thrombogenic characteristics of arterial catheters, contrast agents, and implanted devices such as coils and stents. The overall risk of thrombo-embolic complications during a diagnostic cerebral angiography ranges from 1% to 2.6% with permanent neurological deficits in the range of 0.1-0.5%.  The incidence during interventional procedures has been reported between 2.4% and 28%.  Most of these events are clinically silent. A meticulous technique and the judicious use of anticoagulants and antiplatelets are essential to minimize thromboembolic complications.
Transcutaneous ultrasound may be used to guide vascular access in patients with peripheral vascular disease and in children. An endovascular ultrasound is another rapidly developing technology that enables the operator to inspect intraluminal structural features such as the presence of a thrombus. It is currently being used during the extracranial carotid stenting. Its use in intracranial procedures is investigational. 
Manual compression of the CFA against the head of the femur has been the traditional way of achieving hemostasis after an arterial puncture. It represents the natural process of healing. However, it causes discomfort to the patient, causes a delay in achieving hemostasis and may require temporary cessation of anticoagulant therapy. Closure devices aim to achieve hemostasis while reducing patient discomfort and saving time and effort. A number of vascular closure devices are available in the market. The most commonly used closure devices in neurovascular interventions are Angioseal (St. Jude Medical Inc. Minnetonka, MN, USA), MynxGrip (AccessClosure, Inc., Mountain View, CA) and StarClose (Abbott Vascular, Redwood city, CA, USA). The Angioseal is available in 6F and 8F sizes and seals the arteriotomy site by sandwiching the site between an intraluminal anchor and a collagen plug on the external surface. All the components are reabsorbed within 60-90 days. The Mynx seals the arteriotomy site on the extravascular surface by deploying a polyethylene glycol plug along the tract and over the arteriotomy site. It is available in 5F and 6F-7F sizes and is deployed through the vascular sheath. The StarClose device is approved for < 6F arteriotomies and achieves hemostasis using a 4 mm nitinol clip which grasps the arteriotomy edges and pulls the vessel walls together. ,
Guidewires are wires used to select the great vessels arising from the aortic arch. A hydrophilic 0.035 inch angled guide wire is used in most cases to select the great vessels and navigate the catheter over the wire. In the presence of a tortuous anatomy, stiff guide wires (0.038 inch) may be used. Nonhydrophilic guide wires may be used to exchange catheters as they tend to be more stable in the vessel. Microwires have a diameter ranging from 0.007 to 0.021 inch and are used to navigate micro catheters, balloons, stents and other devices intracranially. Most of the devices may be navigated over a 0.014-inch microwire; a larger diameter wire is used in the case of a tortuous anatomy or in order to navigate through occluded vessels. Smaller wires (0.008 or 0.010 inch) are used along with smaller flow-directed micro catheters such as the Marathon.
Neurointerventional techniques are increasingly being used for the treatment of cerebrovascular lesions, and the knowledge of radiation exposure during these techniques is essential to minimize radiation-induced damage. Ka, r, also called the reference point air kerma (cumulative dose or cumulative air kerma) is the dose-to-air exposure at the interventional reference point, which is 15 cm from the isocenter towards the X-ray tube. It is a useful metric for monitoring the dose incurred during a procedure and denotes the cumulative dose to the skin. Ka, r is measured in mGy. The kerma area product (PKA) indicates the total energy entering the patient and is a surrogate measure of the skin dose. Other parameters of radiation exposure are the fluoroscopy time and peak skin dose. The reported radiation exposure during a diagnostic cerebral angiogram ranges from 350 to 4100 mGy. , A number of patient and operator related factors influence radiation exposure. Some of these are the patient's habitus, vascular anatomy, operator's experience, failure to stop fluoroscopy when there is no manipulation of the catheter or the wire, and the use of a single plane in situations where biplanar angiography is not essential. Operators should be actively committed to minimizing radiation during the procedures.
'Y' stenting refers to a technique of stent-assisted coiling of bifurcation aneurysms, most commonly the basilar bifurcation aneurysms. In this technique, a stent is deployed in each of the posterior cerebral arteries extending into the basilar artery. This creates a support for the coils to remain within the aneurysm and not encroach upon the posterior cerebral artery origin. Any combination of stents may be used: Neuroform, Enterprise or the LVIS. The catheter for deploying coils may be jailed prior to deploying the stents. Alternatively, the aneurysm can be catheterized by going through the cells of the stents. In an anterior communicating artery aneurysm, where the origin of both A2s is incorporated in the neck of the aneurysm, a 'Y' stent or an 'X' stent may be performed prior to the coiling. 
Care should be taken to prevent any air from entering the system of catheters, wires, contrast or medications. Injection of air intra-arterially may have devastating consequences.