Interventional neurology refers to endovascular, catheter-based techniques using fluoroscopy and angiography to diagnose and treat vascular disease of the central nervous system. Interventional Neurology has evolved (and still evolving ) into a complex field, with a set of techniques and a knowledge base that are distinct from other fields of medicine. Rapid advances in the field of interventional neurology and the development of minimally invasive techniques have resulted in a great expansion of potential therapeutic applications.
Here is a brief view of current endovascular treatments available for various vascular disorders of brain and spine and also future of Interventional neurology.
Also called as Digital subtraction angiography ( DSA). Typical indications include the diagnosis of cerebral aneurysms, arteriovenous malformations, cerebral vasospasm, intracranial stenosis, arteriovenous fistula or small vessel vasculopathy including vasculitis. It is often performed just prior to a planned neurosurgical or neurointerventional procedure, as well as immediately after a neurosurgical case. Despite alternative imaging modalities and safety concerns, the actual indications for catheter angiography have not significantly decreased because of the increasing numbers of suspicious vascular findings seen on the very studies (CTA and MRA) thought to supplant it. Furthermore, since minimally invasive endovascular techniques have gained prominence and sometimes replaced open surgical techniques, catheter angiography remains an indispensable modern imaging modality. Spinal DSA is useful tool in diagnosis and treatment planning of spinal AVM, spinal Dural AV fistula.
3D rotational angiography allows evaluation of the opacified artery and its branches from any angle. The technique facilitates understanding of complex vascular anatomy and is a frequently used application in modern diagnostic as well as therapeutic neurovascular care especially in aneurysm and AVM treatment planning.
Cerebral DSA is gold standard for diagnosis of various vascular disorders like intracranial stenosis, posterior circulation stenosis, Dural AV fistulas etc. DSA is indicated when distinctions affecting treatment are unclear; for example, angiography can assist in cases in which differentiation between carotid and vertebrobasilar TIA or evolving stroke is uncertain on clinical grounds and noninvasive imaging only.
Although the risks associated with cerebral angiography have been gradually decreasing, the risk for any complication is approximately 1% to 5%, of which half are minor groin hematomas. Renal function should be normal as iodinated contrast dye used for DSA is nephrotoxic.
The corner stone of the treatment in acute ischemic stroke (AIS) is revascularization. It was only in 1995 when National Institute of Neurological Disorders and Stroke rtPA Stroke Trial (NINDS Study Group) revolutionalized the management of AIS using recombinant tissue plasminogen activator (rtPA) within 3hrs reducing the stroke morbidity by 30%. Eventually the window period was increased to 4.5 hrs after ECASS III. Inj rtPA ( Actilyse ) and Tenectaplase ( Tenectase) are the IV thrombolytic agents approved for acute Ischemic Stroke and both are available in India. Dose of Inj Actilyse is 0.9 mg/kg (10 % as bolus and remaining as IV infusion over 60 mins ). It can be given upto 4.5 hrs from symptom onset. Inj Tenectaplase is approved by DGCA ,India. It can be given upto 3 hrs from symptom onset and its dose is 0.25 mg/kg ( given as bolus dose). Unfortunately, intravenous thrombolysis (IVT) has higher failure rate in large vessel occlusion (LVO).
Intra-arterial urokinase achieved 66% recanalization in LVO and also prolonged the window period for acute stroke intervention upto 6 hours. In this procedure , drug (urokinase or rtPA) is administered through microcatheter at the site of occlusion. This targeted delivery of drug also minimises systemic side effects of drug. But there is minimal increase of risk of hemorrhagic complications. Though FDA has not approved intraarterial rtPA , it can be used in selected cases within 6 hrs of Stroke onset. American Stroke Association (ASA) has given Class 2 recommendation for this treatment. Thus, while both these therapies improved stroke outcomes, a proportion of patients having large vessel occlusions were not amenable to these measures.
Mechanical thrombectomy (MT) with newer thrombectomy devices have many advantages compared to thrombolysis in LVO stroke. A recent review of literature of five randomized control trials (RCT) proved superiority of MT using stent retrievers over best medical management using IVT. Recently published study of Mechanical Thrombectomy in Acute Ischemic Stroke due to large vessel occlusion by Singh et al showed results comparable with Published RCTs and shows feasibility of this procedure in real world scenario like India. The Merci Retrieval system was the first FDA approved treatment option for embolectomy in cerebral arteries. The Penumbra Stroke System (Penumbra, Alameda) was also approved by FDA in 2008 and is the most widely used thromboaspiration device in the US. Newer generation stent retrievers available give more success rate with fewer complications. Solitaire, Trevo, Eric etc are the stentrivers available in India. With the use of ballon guide catheters ( Merci, Cello, Flowgate) with stentrivers , recanalization rate is over 80%. Recanalization rates with thromboaspiration or stentrivers are comparable and both techniques are equally efficacious. Sometimes both techniques has to be used ( Solumbra technique).
Mechanical Thrombectomy is recommended upto 6 hours of symptom onset. But according to new ASA/AHA 2018 guidelines, in selected cases it can be done in patients with 6-24 hours of symptom onset ! Patients with large vessel occlusion requiring mechanical Thrombectomy should also receive IV thrombolysis and then shifted to Cathlab for mechanical Thrombectomy ( Bridging Thrombolysis ). Procedure of mechanical Thrombectomy :
Procedure is performed through femoral artery access. 8F balloon guide catheter is navigated over Guide wire and placed in the ipsilateral cervical internal carotid artery. The microcatheter is navigated distal to the clot over microwire. Solitaire stentriver is then delivered through the microcatheter and deployed over the thrombus. Solitaire serves dual function, namely, immediate flow restoration by creating temporary bypass through the thrombus and also acts as a clot retriever, trapping thrombus into its cells The balloon of guide catheter is inflated with contrast to provide proximal ICA occlusion and flow arrest during the recovery of the stent retriever. Subsequently, the Solitaire and microcatheter are slowly recovered as a unit under constant aspiration with 50-mL syringe through the balloon guide catheter.
Procedure is performed through femoral artery access. 8F guide catheter or 6 F long sheath is navigated over Guide wire and placed in the common carotid artery. Stenosis is crossed with microwire. Over microwire distal embolization protection device ( Spider ) is placed into ICA. Angioplasty is done using noncompliant Balloon at desired pressure. Inj atropine is given to counteract bradycardia due to carotid body stimulation during angioplasty.Then stent is deployed across the stenosis. This procedure is done generally under local anaesthesia.
Procedure is performed through femoral artery access. 6F guide catheter is navigated over Guide wire and placed in the internal carotid artery / vertebral artery. Stenosis is crossed with microwire. Angioplasty is done using noncompliant ballloon slowly and carefully at desired pressure. Then stent is placed across the stenosis under fluoroscopic guidance.
Most common site of stenosis is at origin of vertebral arteries , also called as osteal stenosis. In some cases traumatic / spontaneous dissection of vertebral artery results in flow-limiting narrowing necessitating stenting. Stenting is generally required in patients with severe stenosis causing symptoms of Vertebro-Basilar insufficiency. Procedure of vertebral artery stenting is generally done under local anaesthesia and stents used are balloon mounted drug eluting stents.
Current surgical interventions to lower the risk of stroke among people with carotid artery stenosis include carotid endarterectomy (CEA) as well as carotid angioplasty and stent placement (CAS).
Carotid angioplasty with stent placement (CAS) was resurrected as an alternative treatment for revascularization of carotid artery stenosis in high-risk surgical candidates. Several Randomized control studies and comparisons with CEA have increased the popularity of CAS. These studies have focused on the safety and effectiveness of CAS. With improving devices and techniques, CAS has become safer than and as effective as surgical treatment.
Patients undergoing CAS have small embolic showers occurring frequently during the procedure. These microemboli are composed of thrombotic and plaque substances. This underlies the importance of using a distal protection device to prevent the microemboli from being released into cerebral circulation during carotid angioplasty and stenting. Distal protection devices include occlusive balloons, filter devices, and flow reversal devices.
Progressive improvements in technology and increasing operator experience and encouraging results from clinical trials have led to a broader acceptance of CAS even in patients not considered high risk for carotid endarterectomy.
Cerebral venous thrombosis (CVT) can occur in the form of cortical venous thrombosis, venous sinus thrombosis, deep venous thrombosis, jugular venous thrombosis, or various combinations of the above. CVT has high mortality rate ranging from 5–30%. The interruption of outflow in the brain circulation leads to augmentation in the pressure of the entire system with venous hypertension, intracranial hypertension, and hemorrhagic events.
The main goal of the treatment of CVT should be the recanalization of venous drainage system with complete reestablishment of normal brain circulation. The treatment of choice is IV anticoagulation followed by local thrombolysis where indicated. Endovascular treatment is indicated for patients unable to receive antico-agulation and for those who deteriorate despite anticoagulation heparin. Endovascular therapy is also indicated in high-risk categories including those with seizures, coma, disturbed consciousness, deep cerebral vein thrombosis, posterior fossa involvement, and/or pro-gressive focal deficits.
The endovascular route used is transvenous through the femoral vein, navigating the catheter into the venous circulation and final placement in the matrix of thrombus. The thrombolytics are given as bolus dose followed by infusion over a period of hours for a better recanalization. The rate of recanalization (partial and total) ranges from 70–95%. Drugs used are urokinase and rtPA.
Intracranial aneurysms (IAs) are localized dilations of the cerebral arteries wall and are prone to rupture, resulting in bleeding. The overall prevalence of unruptured IAs is between 2% and 3.2% in the general population with a male to female ratio of 1:2.1 It is the leading cause of hemorrhagic stroke, responsible for 85% of subarachnoid hemorrhages (SAH).
the outcome for patients with SAH remains poor, with overall mortality rates of 25% and significant morbidity among approximately 50% of survivors.
Long-term follow-up in the International subarachnoid aneurysm (ISAT) trial evaluating exclusively ruptured aneurysm, with a mean follow-up of nine years, has demonstrated the effectiveness of coil embolization in essentially eliminating the risk of future subarachnoid hemorrhage.
Considerable advances have been made in the ability to use coils for endovascular treatment of intracranial aneurysms in situations that might have appeared unsuitable a few years ago. The new designs of coils, including the three-and two-dimensional configurations, have improved results. Focusing on the anatomy of the aneurysm and on the neck and dome ratio, as well as its packing with coils in a step-wise manner, has led to remarkable success in coiling of aneurysms previously considered to be difficult.
Detachable coils were invented by Guglielmi in the 1990s, and transluminal embolization techniques were gradually developed since then.Simple coiling refers to transluminal navigation of a microcatheter into the aneurysmal dome with the help of microguidewires and the delivery and packing of detachable coils within the aneurysmal sac. The goal in coiling is to achieve dense packing and induce rapid blood clot formation within the aneurysmal sac, hence isolating it from active circulation.
BAC was initially described by Moret et al in 1997 in treating IAs with a wide neck. It is described as using 1 or multiple nondetachable temporarily inflated balloons to block the aneurysmal neck during coil placement . For difficult situations or complex cases, multiple balloon technique is used. Besides multiple balloon technique, special balloons are also being developed, such as hypercompliant, roundshaped, and double lumen balloons. The BAC was used frequently in IAs with unfavorable dome-to-neck ratio (1.5, >1.0).
The SAC can overcome the limitations of wide-necked, gigantic, fusiform, and some other complex IAs.56 Similar to BAC, a stent is deployed to block the aneurysmal neck before coil packing. The IAs wit an extremely unfavorable dome-to-neck ratio (1.0) require SACgenerally due to the need of permanent support to prevent coil prolapse and migration.
Y-stenting technique is developed for treating bifurcation IAs, where 1 or more microcatheter are in place with 2 stents blocking the aneurysmal neck (Figure 6B).61 It is by far the best technique for treating bifurcation basilar artery aneurysms.
Flow-Diverting Stent Flow-diverting stents (FDSs) are a new generation of stents designed to treat IAs by isolating the aneurysmal lumen from the circulation via recanalization.
Flow Diverters :
The FDSs are suitable for both wide-necked and fusiform IAs. For large aneurysms it is also advisable to put some coils to prevent imminent rupture due to flow diversion. The main concern with FDSs is the risk of perforator blockage and stent thrombosis.
WEB flow disruption is a new, innovative endovascular technique dedicated to the treatment of ruptured and unruptured wide-neck bifurcation aneurysms.
Referral : To Interventional Neurologist/Neurosurgen/Radiologist
Whom should be referred: All Patients with subarachnoid hemorrhage Cerebral vasospasm.
Despite all therapeutic possibilities, a large number of patients develop angiographic or clinical vasospasm responsible for high morbidity and mortality. Usually the vasospasm is delayed and has a typical temporal course, with onset 3–5 days after the hemorrhage, maximal narrowing at 5–14 days, and gradual resolution over 2–4 weeks. In about half the patients, vasospasm is manifested by the occurrence of a delayed neurological ischemic deficit which can lead to stroke, disability and death.
Endovascular therapy offers an additional treatment for patients who continue to experience delayed ischemic neurological deficits despite optimal medical therapy. Presently, the most commonly employed treatments are PTA and/or intraarterial vasodilation with nicardipine, verapamil, nimodipine, amrinone, or milrinone.
Referral : To Interventional Neurologist/Neurosurgen/Radiologist
Whom should be referred: Patients of subarachnoid hemorrhage with suspected vasospasm. Vasospasm should be suspected if patient of SAH developed worsening of headache, neurodeficit despite Nimodipine and triple H therapy.
Arteriovenous malformations (AVMs) are congenital vascular lesions that may appear throughout the central nervous system. They consist of direct connections between arteries and veins, without an intervening capillary bed. There is a rate of approximately 4% hemorrhagic conversion per year for cerebral AVMs. They carry a combined morbidity and mortality rate of 2.7% per year.
The risk of haemorrhage from an AVM depends strongly on whether there has been a previous haemorrhage. AVMs can cause headaches, seizures, ischemia and developemental learning disorders due to changes in surrounding brain parenchyma by AVM.
The treatment of AVMs is challenging and multifaceted. Surgical excision , radiosurgery and endovascular embolization are the treatment modalities available. They pose a unique problem and often require a combination of therapeutic modalities. Embolization has been used for the following purpose: 1) adjunct to surgery; 2) reduction of size before radiation; 3) palliation; and 4) embolization alone for cure. In cases with large AVMs, generally staged embolization is done.
The ARUBA trial (2014) showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. This is for unruptured AVMs. But if AVMs have weak spots on angiography like intranidal aneurysms it is better to treat them as they have high chance of rupture in near future.
Advancements in catheter design in the 1980s permitted selective catheterization of AVM pedicles. The introduction of the flow-directed Magic catheter was a major breakthrough. With the additional availability of 0.010-in. wires and the addition of hydrophilic coating to the catheters, intranidal catheterization was possible. n-BCA and polyvinyl alcohol ( Glue ) emerged as the most popular embolization materials for AVMs. Ethylene vinyl alcohol copolymer in dimethyl sulfoxide solution (Onyx, Micro Therapeutics, Inc., Irvine, CA) was introduced in 1990.
Other liquid embolizing materials available are SQUID, PHIL. Sometimes after injection of embolizing material into AVM , retrieval of microcatheter can become problematic as it may got stuck into cast. This problem is overcome by detachable tip microcatheters ( Apollo, Sonic).
With advancement in techniques and materials, more and more AVMs can be treated with endovascular embolization with increasing cure rate. Embolization is generally done through arterial route and aim of treatment remains obliteration of nidus with foot of draining vein. In some cases venous route can be used for embolization. Recently developed Pressure Cooker Technique, use of multiple catheters offer promise of complete cure in difficult and complex AVMs.
Intracranial dural AV fistulas (dAVF, dural arteriovenous fistulous malformation) are acquired lesions that usually involve one of the intracranial venous sinuses. They comprise about 10% of all intracranial vascular malformations. Numerous branches of the ECA, ICA, and/or vertebral artery form direct connections to a venous sinus and/or intracranial veins. Any intracranial venous sinus may be involved. Symptoms and physical findings are highly variable and depend on the location and anatomy of the lesion. DAVF can give rise to Pulsatile tinnitus,Haemorrhage,Intracranial venous hypertensionl. Neurological symptoms attributable to elevated intracranial venous pressure include: Progressive dementia, pseudotumor cerebri, Parkinsonism, Cervical myelopathy. Lesions causing arterialization of intradural veins are classically associated with intracranial haemorrhage.
Management options for patients with a dAVFs are Conservative management, endovascular techniques, Surgery , Radiosurgery and combined approach. Conservative management is reasonable in certain situations like asymptomatic or minimally symptomatic lesions.
Generally the most effective treatment of dAVFs is occlusion of the draining vein. In most cases, obliteration of the lesion can only be accomplished by treatment of the venous side of the lesion. Transvenous techniques appear to carry the highest success rates among endovascular techniques.Successful arterial embolization usually occurs only when the microcatheter is positioned well within or adjacent to the nidus, so that embolic material can be pushed through the nidus into the venous side. If only feeding arteries are occluded and not the draining vein, collateral vessels usually develop and the fistula will recur. Conversely, it is equally important to ensure that normal venous drainage is preserved after embolization to avoid exacerbated venous hypertension and risk of haemorrhage.
With availability of good microcatheters ( flow guided microcatheters, detachable tip microcatheters), liquid embolizing agents ( Glue, Onyx, SQUID, PHIL) and advancements in techniques, more and more dAVFs can be safely treated with endovascular route with good results.
Carotico-cavernous fistula (CCF ):
CCF is characterized by a direct shunt between the intracavernous segment of the internal carotid artery (ICA) and the surrounding venous plexus of the cavernous sinus. The pathogenesis is commonly a rupture of the artery and vein, after a penetrating or blunt trauma. Spontaneous fistulas can also occur.
Carotid–cavernous fistulas are characterized by a typical cavernous sinus syndrome with ophthalmoplegia, pulsating exophthalmos, chemosis, and bruit. The symptoms can appear acutely or slowly, progressively days or weeks after the trauma, or have a spontaneous onset. Sometimes presentation is with signs of venous hypertension if there is cortical venous reflux. Treatment is endovascular embolization with detachable balloons, coils, coils + liquid embolizing agents, covered stents. Both arterial and or venous approaches can be used. Parent vessel occlusion is also a valid option.
Transcatheter occlusion of traumatically injured vessels to control life-threatening bleeding represents some of the earliest endovascular procedures.Penetrating injury to the arteries of the head and neck may lead to dissection and pseudoaneurysm formation with the dreaded consequence of high-pressure arterial hemorrhage. Endovascular stenting of dissected intimal flaps aids in tacking down the affected vessel wall and preventing downstream dissection. Aside from endovascular stenting, coil embolization of traumatically induced bleeding fistulas and pseudoaneurysms of the head and neck may also be performed using liquid embolic agents, Bernstein liquid coils, particles (polyvinyl alcohol), Detachable balloons , detachable coils .
Endovascular neurointervention offers a means for preoperative embolization of highly vascular tumors, thus reducing the complexity and complications of blood loss during surgery. In addition to neurovascular tumors that may benefit from embolization, hemangiomas, vascular malformations, and lymphovenous malformations of the head and neck may also benefit from endovascular therapy. Methods of embolization involve a standard angiographic transfemoral approach to the cranial vasculature. Though embolization is usually restricted to the external carotid artery (ECA) system, the internal carotid artery (ICA) is often studied to assess important orbital anastomoses between the ECA and ICA. Superselective catheterization using microcatheters is then undertaken to localize the territory targeted for treatment. Embolization is then performed using 150–250 m polyvinyl alcohol particles, Gelfoam powder or strips, or ethanol. Direct injection of absolute alcohol (dehydrated alcohol, 98% ethylalcohol), or sodium tetradecyl sulfate for the treatment of superficially accessible lesions such as hemangiomas, vascular malformations, and lymphovenous malformations of the head and neck may be performed.
Recent endovascular intervention has involved clinical trials aimed at delivering chemotherapeutic agents directly to the tumor region, with the hypothesis that intra-arterial (IA) delivery would increase the concentration of the medication at the tumor site while minimizing side effects of systemic administration. Many trials are on going with equivocal results.
Spinal arterio-venous vascular lesions are entities with serious consequences if untreated. Spinal vascular lesions include dural arteriovenous fistula (dAVF) , intramedullary arteriovenous malformation (AVM) , Juvenile AVM, intradural perimedullary AVF, Extradural arteriovenous fistulas, Spinal cord aneurysms, Intramedullary cavernous malformations , Vascular spinal tumours Spinal cord ischaemic stroke. dAVFs are the most common spinal vascular lesion, representing approximately 70% of spinal vascular malformations. Catheter angiography is the gold standard for the workup of most of spinal vascular lesions.
Endovascular embolization should be done when the anatomy of the lesion permit obliteration of the nidus and proximal part of the vein. Embolization is feasible in some 75% of cases. Barriers to embolization include advanced atherosclerosis, arterial feeders too small to catheterize and collateralization of the feeding vessel with normal spinal cord vessels. Embolization is most effective when the glue penetrates the proximal portion of the draining vein; if the glue does not reach the draining vein, the fistula may persist or recanalize. Embolization is particularly useful in patients who are poor candidates for surgery, or in some cases as a temporizing measure, to reduce venous congestion until a definitive surgical procedure can be performed. The embolization agent of choice is N-butyl cyanoacrylate ( Glue). Other liquid embolizing agents also can be used.
Endovascular therapy for acute and chronic cerebrovascular diseases and interventional neuroimaging is evolving at a rapid pace. The safety and efficacy of endovascular procedures is expected to improve with new technologies.
Stem cell therapy :
Despite the fact that numerous paths of stem cell transport to the brain in acute ischemic stroke exist, the intra-arterial route of stem cell transport is most attractive and has great potential for clinical translation. Intra arterial delivery of stem cells derived from bone marrow in autologous or transplanted stem cell delivery may help repair damaged regions of the brain. Experimental study on rat model by Watanabi et al suggested optimum timing and Maximum tolerated dose (MTD) of stem cells through Intra arterial route in acute Ischemic stroke. According to their study, administration of stem cells at MTD of 1 x 10 ^5 through the Intra arterial route will not obstruct MCA blood flow and administration during subacute period will more effectively stimulate neuroprotection following cerebral ischemia.