Endovascular management of brain aneurysm
Since the publication of the International Subarachnoid Trial (ISAT), endovascular treatment of ruptured intracranial aneurysms has become standard of care.(1) The evolution of endovascular innovation of treatment over that time has led to a great majority of all aneurysms to be safely treated in this manner. In this review we will cover the latest innovations in endovascular treatment of intracranial aneurysms, with focus on devices, techniques, and platforms.
The endovascular treatment of brain aneurysms can now be divided into three major categories; coiling, flow diversion, and flow disruption. Coiling has been studied the most and compared directly with open surgical clipping in randomized controlled trials for the treatment of ruptured brain aneurysms.(1, 2) Flow diversion was the next major treatment innovation, and has largely changed the approach to wide necked unruptured internal carotid artery aneurysms. Flow disruption is the newest innovation and is actively changing the approach to wide necked ruptured bifurcation aneurysms. The goal of all endovascular brain aneurysm treatments is to prevent rupture without causing harm. It is important when considering treatment options that there is a delicate balance between morbidity risk, and a perfect angiographic result.
Endovascular Coiling
Advances in variable stiffness catheters, and microcatheters with the invention of the Guglielmi detachable coil became the nidus for the entire specialty of neurointerventional surgery. The data to support endovascular coiling as a safe and effective treatment of brain aneurysms is robust.(1-3) This treatment modality has become the standard of care for a majority of ruptured brain aneurysms. It’s limitations on safety and effectiveness are mostly tied into the aneurysm’s shape and size. The ISAT trial showed that at 1 year after rupture the relative risk reduction of dependence or death was 22.6% less than surgical clipping and an absolute risk reduction of 6.9%.(1) This effect is a prolonged effect as seen in the 18-year follow up from the initial study in which at 10 years there is still a higher chance of disease-free survival in the endovascular treated patients compared to the surgically clipped patients [OR 1.34, 95% CI 1·07–1·67].(2) This does come at a nearly double but very low risk of rebleed from the target aneurysm with endovascular treatment.(2)
There were of course limitations to the ISAT trial in that 97.3% of the aneurysms were anterior circulation in location, clinical equipoise was determined by the local sites, and therefore this was a carefully selected subgroup of all ruptured aneurysms.(1) Despite these shortcomings, the incidence of endovascular treatment of aneurysms skyrocketed after the publication of this study and has been increasing in popularity ever since.(4) The limitations of coils, which historically have been the risk of recurrence, or re-bleed, and therefore the need for persistent long-term follow up, in addition to worse treatment outcomes in specific size and shape aneurysms has led to an array of advancements in alternate endovascular approaches.
Coils were initially developed to be bare platinum. Bioactive coils were first introduced in 2002 in an attempt to improve treatment durability. Bioactive coils consist of a platinum core enhanced with bioactive components such as polyglycolic acid, polyglycolic acid/lactide, or hydrogel. In a meta-analysis of the randomized controlled trials comparing bioactive coils to bare platinum, there was higher rates of long-term occlusion using bioactive coils compared to bare platinum.(5) There was no significant difference in hemorrhagic or ischemic risk.(5)
The other advancements in coils over the last decade have to do with shapes and sizes. The majority of companies now offer coils as small as 1mm x 1cm. This advancement in coil design has aided in one of coiling’s major limitation which is the treatment of very small aneurysms. The major concerns with the treatment of small brain aneurysms lie in microcatheter access and stability, in addition to the higher potential need for adjunctive therapies such as balloon or stent assistance. There are some reports that the risk of intra-procedural rupture is higher in coiling of very small aneurysms compared to aneurysms of other sizes.(6, 7) Van Rooij et al. found a nearly double risk of intra-procedural rupture in the endovascular treatment of small aneurysms vs medium and large size aneurysms.(7)
Further advancements in coiling have to do with the creation of complex shape coils, which has aided in the ability to treat non-spherical shaped aneurysms, however there has been very little to this date published on how these various complex shapes have impacted clinical outcomes or results. In addition to this variation in degrees of stiffness of the coils have also been developed and from this came techniques of starting aneurysm treatment with a stiffer framing coil and then filling the coil with softer coils. There is some recent evidence to suggest that having an appropriately sized framing coil reduces the risk of aneurysm recurrence. Ishida et al. found that framing coil volume as a percentage of total aneurysm volume <32% was an independent risk factor for aneurysm recurrence.(8)
The second limitation for endovascular treatment with coiling is size greater than 10mm. This has shown to have higher chance of recurrence. Other than size, a wide-neck or low dome to neck ratios both increase the risk of treatment failure with endovascular coiling. In the literature there is discrepancies as to the definition of a wide neck. The most commonly used definition of wide necked aneurysms is neck ³ 4mm or dome to neck ratio < 2mm.(9)
Adjuncts to coiling
Balloon Assisted Coiling
These limitations led to the development of a wide array of adjunctive tools and techniques to increase the efficacy of coil embolization. The balloon remodeling technique was popularized by Moret et al. in 1997.(10) Since this development there are now a wide variety of microcatheter balloons available for use, including ultra-compliant balloons, and coil through microcatheter balloons.(11, 12) Newer generations of microcatheter balloons have improved in their performance, from trackability, to visibility, and risk. (Figure 1) There are some that advocate balloon-remodeling technique as a first line treatment for ruptured aneurysms given the ability to immediately provide flow control in the event of a procedural rupture.(13, 14) The benefits of balloons are they are temporary, and do not require the need for anti-platelet therapy however they still come with an increased risk of procedural related morbidity compared to coiling alone, however these findings may be more related to the aneurysm morphology being treated compared to the technique itself.
Currently balloons microcatheters come in compliant, or super-compliant varieties, and are either single lumen or dual lumen. All of the compliant and super compliant balloons are low-pressure systems, less traumatic to the endothelium and typically inflate at 0.5 atmospheres, 380mmHg. The compliant balloons are usually made with chronoprene, or polyurethane as compared to non-compliant balloons, which are made of nylon or PBx. The super-compliant balloons tend to be optimal for bifurcation aneurysm in which, the compliance of the balloon can be used to shoulder across the neck of the aneurysm. The super-compliant balloon microcatheters range in diameter from 3mm-7mm, and come in a variety of lengths ranging from 7mm-15mm. The compliant balloons tend to be more useful for sidewall aneurysms. The compliant balloons come in a range of diameter from 3mm-5mm. There are benefits, and drawbacks to using a dual lumen catheter.
Stent-assisted Coiling
Stent as an adjunct to coiling offers a more permanent support scaffolding to coils for wide necked aneurysms. (Figure 2) There have been some reports finding higher occlusion rates with stent-assisted coiling (SAC) compared to balloon assisted coiling (BAC) with little difference in peri-procedural morbidity.(15-17) Stent technology has itself improved over time with newer stents such as the Atlas, and LVIS Jr. now deliverable through smaller diameter 0.017-inch microcatheters compared to the older technology stents which used 0.027-inch microcatheter systems. Stent designs have improved as well with products such as the Pulserider, and Barrel stent now available. (Figure 3) There is still concern about using a stent in the setting of an acutely ruptured aneurysm. The need for dual anti-platelet therapy with stent placement likely carries a small but real increased risk for hemorrhagic complications particularly in the ruptured setting when other considerations come into play such as the need for external ventricular drainage (EVD). In a recent case series using the PulseRider stent for ruptured aneurysms 2 out of the 4 patients developed an EVD tract hemorrhage while on dual anti-platelet therapy.(18) The hemorrhagic risk, is equally counter-bound to the thromboembolic risk depending on the exact anti-platelet strategy used for any cohort of patients.(19) Despite these risks, there is likely a subset of patients that stand to benefit using these strategies as compared to traditional open surgical treatments such as for blister-type aneurysms and dissecting aneurysms. Questions like these, hope to be answered in the on-going ISAT-II trial which will compare open surgery to more advanced endovascular techniques for management of wide necked and historically difficult to treat by endovascular approach ruptured aneurysms.(20)
Flow-Diverter Stents
Although these devices were initially approved for wide-necked petrous through superior hypophyseal internal carotid aneurysms (ICA) segments [21], the expansion of the “off-label” applications have made it possible to be the first option in up to one-third of the intracranial aneurysms treated, including ruptured aneurysms. [22] The revolution of flow diverters was due to its capability to treat wide-necked aneurysms through a complex mechanism of action that comprises the interaction between flow diverter, parent artery, and the aneurysm to produce 1) intra-aneurysmal thrombosis and 2) neointimal endothelization at the level of the aneurysm neck. [23] Although, it has been almost a decade since the first flow diverter was approved in the US, the understanding of how important the number, size, design and, material composition to achieve a safe and effective treatment is yet incomplete.
Silk Device
The Silk Device (BALT Extrusion, Montmorency, France) was the first flow diverter stent available for intracranial aneurysms treatment. The SILK pre-clinical studies provided the first evidences regarding the ideal properties for flow diverter design. [24-26] The successful intra-aneurysmal thrombosis following flow diversion is based on 3 properties: porosity, metal coverage, and pore density of the stent. Being porosity the proportion of metal-free area to the total stent area. Metal coverage is the metal-covered area divided by the total stent area. Pore density is the number of pores per area. [24] The property to decrease flow into the aneurysm sac is mostly determined by a low porosity and high pore density properties. Virtual simulations have shown that an ideal porosity of flow diverters should be between 60% and 76%. [26] The porosity for Silk devices ranges from 45% to 60% with a total number of 48 braided nitinol and four platinum microfilaments which provides 35% to 55% of metal coverage, and a pore size of 110-250 mm. [24] This device is not available in the United States of America.
Clinical trials have shown rates of complete occlusion from 49% to 68% at 6 months [27, 28] and up to 87.9% at 1 yr. [28-30] of follow-up. Morbidity has been reported to be 1.4-15%, while mortality 0-4.9%. The introduction of the second Silk Device generation (Silk +) reduced the rates of delayed thromboembolic complications. However, the current evidence strongly suggests higher odds of ischemic complications in vessels rich in perforators due to the low porosity and high metal coverage of the Silk Device [31]. The results from the randomized clinical trial “MARCO POLO” which evaluated the safety and effectiveness of SILK Device compared with endovascular coiling will shed lights on whether the aneurysm occlusion rates overweight the possible risks of neurological complications following SILK Device placement. [32]
Pipeline Embolization Device (PED)
The PED (Medtronic, Irvine, California, USA) is a permanent implant originally approved in 2011 by the FDA for the treatment of giant wide-necked intracranial aneurysms in the ICA. [21] (Figure 4) It is composed of a mesh cylinder woven from 25% Platinum Tungsten and 75% Cobalt chromium nickel alloy wires. It has 48 braids, a porosity of 65% to 70% and 30-35% of metal coverage. [22, 33] The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial showed that occlusion rate at 6 months was 73.6% with a progressively increase over time to 86.8%, 93.4% and 95.2% at 1, 3, and 5 yr., respectively.[21] Regarding safety, the mortality was 3.7% and 96.3% of patients had a modified Rankin Scale scores £ 2.[21] Other multicenter prospective and retrospective studies have assessed PED outcomes as well; whereas, the IntrePED retrospective study [34] provided evidence of periprocedural complications in a “real world scenario”, the prospective PREMIER study formed the basis for the Pipeline Flex Embolization Device FDA approval for the treatment of ICA or vertebral artery unruptured wide-necked aneurysms £ 12mm. The IntrePED study showed a total rate of neurologic complications of 8.4%, a 30-day morbidity rate of 5.5% and 30-day mortality rate of 2.5%; however, the main finding was that risk of neurologic morbimortality with PED were significantly higher when used to treat posterior circulation aneurysms compared to ICA <10mm aneurysms (16.4% vs 4.8%, p=0.01) and thus, made the neurovascular community aware of severe adverse events such as thromboembolic complications, spontaneous aneurysm rupture and intraparenchymal hemorrhage to be substantially more common in large anterior circulation aneurysms and posterior circulation aneurysms. The PREMIER trial at 1 yr. follow-up, 76.8% and 2.1% rates of aneurysm occlusion and morbimortality, respectively were reported. Another important improvement showed in the PREMIER trial was the decrease in the average number of devices implanted compared to the PED (1.1 vs 3 average devices per cases). [35] The pipeline system is now on its second generation named the Pipeline Flex which redesigned its deployment system, enabling the operator to resheath and redeploy the device up to two times. In addition to this advancement, microcatheter technology improvement such as the Phenom-27 microcatheter has helped improve safety and efficacy of stent placement by preventing ovalization of the microcatheter through tortuous cerebrovascular anatomy.
Although, the safety and effectiveness of PED in the clinical setting is well established, the time to reach aneurysm cure remains variable. Based on autopsy studies it has been shown that 7 days post-treatment up to 12 months there is an unorganized intra-aneurysmal thrombus despite the angiographic evidence of complete occlusion. [22, 36, 37] Only few studies have assessed the endothelization process after PED placement, the general conclusion is that the intima formation is completed after 21 days of treatment. [38] Contributions of specific PED properties such as braid number and braid angles in the cellular reconstruction have not been extensively studied. Future bioengineering studies are needed to maximize PED safety and effectiveness while cadaveric studies from patients with implanted PEDs could provide interesting human histopathological evidence.
Flow Redirection Endoluminal Device (FRED)
The FRED (MicroVention Terumo, Tustin, California) is composed of nickel titanium and it is integrated as a dual-layer stent from which the inner mesh has low porosity and the outer mesh, a higher porosity. Therefore, its stent-like outer layer and flow diverter inside design allows an easier navigation through tortuous vessels and a stable apposition of the device against the arterial wall due a lower contact area with the microcatheter during placement and higher radial force of the outer layer. [39] The FRED Jr. is the first FDA approved flow diverter stent which is deliverable through a 0.021-inch microcatheter. (Figure 5)
Its recent approval by the FDA was for the treatment of wide-necked saccular or fusiform intracranial aneurysms (neck width ³ 4 mm or dome-to-neck ratio < 2) from the petrous segment to the terminus of the ICA. [40] The prospective FRED Pivotal study [40] that included 22 centers in the US and 1 from Japan made possible the FDA approval. From the 145 enrolled in this trial, 4.1% had a major stroke within 30 days, 11.9% had a worsening of the baseline mRS at 12 months and 54.8% of the patients with complete imaging follow-up within 12 months were classified as complete aneurysm occlusion. The French experience with the “Safety and Efficacy Analysis of FRED Embolic Device in Aneurysm Treatment” (SAFE) trial [41] showed that out of 103 patients treated, 4.9% developed a thromboembolic complication, with only one event (~1%) associated with morbidity at 6 months, making a total of 2% morbidity and 1% mortality. The FRED Pivotal trial included fusiform (12.4%), and posterior circulation aneurysms (4.1%), and that only 7.1% of patients required 2 or more devices deployment. [40]
Surpass Flow Diverter (Surpass)
The Surpass (Stryker Neurovascular, Fremont, CA) is composed of interwoven platinum tungsten wires within 48 to 96 cobalt chromium braids. It has a porosity of 70% and 15 to 30 pores per mm2. Some of the greatest improvements of the Surpass is the ability to maintain a high radial pressure during placement, in average 5 and 2.5 times higher than the FRED and PED devices, respectively. The Surpass is unique in that it comes pre-loaded into the Streamline Delivery System (Stryker, Fremont, CA). Regarding the push force using the Streamline Delivery System, it is comparable with the force needed with the FRED through the Headway 27 microcatheter, however, the Surpass requires around 40% more push force than the PED-Phenom 27 microcatheter. [42] The major advancement with Surpass, however, is the unique delivery system. The technique involves an Offset catheter (AXS Offset Delivery Assist Catheter, Stryker, Fremont, CA), which enhances the safety of 5F distal access catheters, specifically the CAT-5 (Catalyst 5Fr intermediate Catheter, Stryker, Fremont, Ca). This delivery system was created due to the difficulty to deliver the Surpass through standard intermediate catheters. Recently, Topcuoglu et al., [43] reported a series of cases with 92% of technical success making the CAT-5 bypass the aneurysm in 80% and consequently, placing the CAT-5 intradurally in 88% of cases and at, or distal to, M1 segment in 48% of patients. Colby et al., [44] reported 100% of success with the using the CAT-5 leaving the intermediate catheter proximal to the aneurysm. Although, these advancements are encouraging, a limitation of the Surpass is its stiffness, which can make deployment more difficult in extremely tortuous cases.
The engineering improvements made possible to navigate through tortuous vessels and deploy the stent in distal segments where the PED was not included in their initial studies. Therefore, posterior communicating and anterior choroidal segments, which have significant risk of aneurysm rupture, were treated in the SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms) study. [45] This multicenter prospective trial showed complete aneurysm occlusion rate of 62.8%, acute thrombotic in 3% of cases and 12-month major ipsilateral stroke or neurological death rate of 8.3%. Although, the safety and effectiveness of Surpass were similar to previous PED trials [35, 40, 46], it’s important to highlight that the SCENT study included a significant number of fusiform and difficult-to-treat intradural location aneurysms. Furthermore, the availability of Surpass lengths up to 50 mm made possible to treat most of the cases with one device, conversely to the PUFS trial in which an average of 3 devices were used per case. [46]
More recently the Surpass 2nd generation system, Surpass Evolve, was released in 2020 in the United States, which allows for a more traditional flow diverter delivery technique through a 0.027-inch diameter microcatheter system. The Surpass Evolve is made of 64 platinum tungsten braids which is more robust than the PED.
Comparisons of techniques for US-Approved Flow diverter stents
Pipeline Flex
Each flow diverter stent has its benefits and drawbacks and there are certain situations in which the decision to use one over another is critical to the success of a specific case. The Pipeline Flex is the device longest in the market and therefore many operators have the most experience with it. As there is a learning curve to the use of each device, this should be the primary factor in an operator’s decision in case selection.
There are two popularized techniques for deploying the Pipeline Flex. The first is the “drop and drag” technique. This technique involves deploying the first 10-25% of the stent in a straight segment well distal to the aneurysm. Once part of the stent is starting to open, pulling the system back to the point of the desired distal landing zone, and deploying the remainder of the stent from this position. This technique is helpful when your distal landing zone needs extreme precision or if the landing zone is on a curved segment, which often makes it difficult for the stent to open up as desired from a traditional deployment option. The key for this technique to be successful is to ensure the distal stent has not completely expanded against the arterial wall because if it has then the stent can stretch, and not pull back. Many Pipeline purists would argue that this technique has a higher risk of causing endothelial injury, however no comparative studies have been done.
The traditional technique involves precise position of your distal landing zone on deployment. For this technique you are relying on maintaining your distal landing zone position when the distal stent begins to open. Often when using this technique, the stent will expand and foreshorten. Anticipating this process and adjusting for it during your initial deployment is crucial.
Often when using either technique deploying the proximal 50% of your stent relies on a combination of shifting forward and backward pressure on the system as you deploy to ensure equal vessel wall apposition. This also helps to prevent stent twisting and torsion. This part of deployment has been termed “wagging the tail.” Once the stent is deployed, it is essential to bring the microcatheter back through the stent to maintain distal access. Usually a simple J-microwire through the stent is needed to ensure the stent is fully expanded.
The advantage of pipeline is that it can be deployed reliably in a variety of circumstances as it pertains to vessel tortuosity. As operator experience improves one can compress across the aneurysm neck to selectively increase the metal coverage to increase flow-diverting properties at critical portion of aneurysmal involvement. Due to the variability of porosity of stent based on deployment vectors, stent diameter sizing, and vessel diameter, most studies involving Pipeline stents have a significantly higher number of stents being used per case compared to other flow diverter stents. While all flow diverter stents perform better using a tri-axial system, Pipeline Flex can be deployed in a bi-axial system.
Surpass Streamline
The deployment techniques for Surpass are entirely different than Pipeline. The stent comes pre-loaded in the Streamline Delivery Catheter. Initially the Surpass system failed to be widely adopted because of the stiffness of the stent with the delivery catheter and difficulty to traverse the carotid siphon. After some time, technique advancement made the deployment of this device more user friendly. The technique involves using the Offset microcatheter to traverse the carotid siphon, and to bring an intermediate catheter, usually the CAT-5 intermediate catheter into the M1 MCA segment. Surpass works best when deploying half of the stent inside the intermediate catheter, unsheathing the intermediate catheter and forward loading the system and “pushing” the proximal half of the stent out for deployment. Often with this technique the proximal portion of the stent is not fully expanded and at this point one must relax the system for the proximal stent to open properly.
Since Surpass is stiffer, ensuring vessel wall apposition is more difficult. The Surpass will not expand or foreshorten with a J-microwire technique. There are occasions when balloon angioplasty is needed after stenting to achieve good wall apposition, which will reduce the possibility of an endo-leak.
Given that the most successful deployment technique involves a partial intra-catheter deployment, visualization of the stent can sometimes be difficult. To improve visualization, prepping the stent prior to deployment and bringing the stent to the tip of the Streamline microcatheter is an extremely useful technique. This is known as the “tip to tip” technique. This technique comes with a cost and makes tracking the Streamline around the siphon more challenging. In cases of extreme tortuosity this technique can be more hurtful than helpful.
Since the radial force is greater in Surpass as compared to Pipeline, the Surpass tends to expand with less manipulation, even in areas of severe tortuosity. The Surpass is available in longer lengths than the other stents and can also expand to greater diameters (up to 6.5mm) than Pipeline or FRED, making it preferred stent for larger diameter aneurysms and fusiform aneurysms. There is likely some benefit to leaving a singular stent versus telescoping multiple flow diverter stents as every re-access comes with risk.
Surpass Evolve
The Surpass Evolve deployment is somewhat similar to PED, however given its higher wire and braid design, it behaves stiffer than the PED. Because of this, stiffer intermediate catheter systems, Navien or Sophia EX, aid in delivery of the device compared to more compliant and trackable intermediate catheters, CAT-5 or Sophia. While the stiffness makes it slightly more challenging to open around tortuous curves, it also is more reliable in its distal stent opening compared to PED. This stent also behaves more reliably using a tri-axial system compared to a bi-axial.
FRED 27 & FRED 21.
The FRED system is the most recent flow diverter to the US market and is a nice middle ground between Pipeline and Surpass. It has somewhat better radial expansion than Pipeline yet is not nearly as stiff as Surpass. It is designed for use as a single stent like Surpass, however their main advancement is the ability to use a 21-microcatheter system to deploy the stents up from 2.5mm to 3mm. The deployment behavior of FRED is more similar to the Pipeline than the Surpass, and therefore the learning curve for use is quicker for operators with Pipeline experience. Of all the three flow diverter stents, this deployment is closest to a standard non-flow diverter stent deployment. It is important to note that both the distal and proximal ends of the FRED do not have flow diverter qualities, therefore precise placement is more important when using this device. While tri-axial systems for deployment is preferred, this stent can also be deployed using a bi-axial system.
Endosaccular Flow Disruptors