Endovascular Treatment of Cerebral Aneurysms
Current devices, emerging therapies, and future technology for the management of cerebral aneurysms.
During the past 2 decades, the endovascular treatment of cerebral aneurysms has quickly evolved from a nascent technology to a front-line therapy using sophisticated disease and anatomy-specific devices that allow the minimally invasive treatment of even the most complex cerebrovascular lesions. The available devices have transitioned from implantable balloons to embolization coils, to bioactive embolization coils, to adjunctive intracranial stents for use with embolization coils, and ultimately to "stand-alone" stent-like devices. The fundamental basis for treatment is rapidly shifting from techniques that are targeted at occluding the aneurysm sac (endosaccular occlusion) to those designed to achieve a durable physiological reconstruction of the parent vessel that gives rise to the aneurysm (parent vessel reconstruction). In this article, we review the predicate devices, currently available treatments, and finally the status of new and emerging technologies.
INDICATIONS FOR CEREBRAL ANEURYSM TREATMENT
In general, there are two broad categories of intracranial aneurysms: (1) those that have already ruptured, creating subarachnoid hemorrhage, and (2) those that are unruptured. Typically, unruptured aneurysms are asymptomatic; however, rarely they may become symptomatic—usually due to their size and subsequent mass effect. The management of these two types of lesions differs dramatically.
These lesions are almost always treated provided that the patient is neurologically and physiologically well enough to undergo therapy, either surgical clipping or endovascular coiling. Subarachnoid hemorrhage from aneurysm rupture is a devastating event with a case-fatality rate of 51% and a 50% rate of significant disability among survivors.1,2
Treatment is typically carried out urgently rather than emergently, usually within 24 hours after the arrival of the patient to the hospital. Initially, there was considerable controversy with respect to the treatment modality that was best suited for the right of first refusal for therapy, however, much of this controversy was settled by the International Subarachnoid Aneurysm Trial (ISAT), which demonstrated that for aneurysms amenable to either therapy, patients undergoing coil embolization had better long-term outcomes than those who underwent open surgical clipping.3,4 Although there were some concerns regarding the durability of coil embolization as a treatment modality, an analysis of the ISAT data demonstrated that the superiority of endovascular coiling was preserved for at least 7 years after treatment.3 For this reason, at most institutions, endovascular coiling is granted the right of first refusal for ruptured aneurysms amenable to either treatment modality.
The vast majority of aneurysms discovered incidentally are completely asymptomatic. During the past decade, with the proliferation of noninvasive cerebrovascular imaging studies ordered by referring physicians, we have begun to diagnose small, unruptured aneurysms with increasing frequency. The diagnosis typically is the cause of great anxiety on the part of the patient and referring physician, resulting in immediate referral to a cerebrovascular interventionist for evaluation. At this point, the decision of whether to treat must be based on the best available evidence regarding the risk of rupture of an incidentally diagnosed cerebral aneurysm. Unfortunately, the available evidence and its interpretation are still actively debated, and these decisions are rarely straightforward. Ultimately, three options are typically provided—conservative management (with or without imaging surveillance), open surgical clipping, and endovascular coil embolization—with the patient making a final decision based on a fair and unbiased presentation of the available data regarding all treatment modalities.
The largest study of the natural history of incidentally discovered unruptured intracranial aneurysms (The International Study of Unruptured Intracranial Aneurysms [ISUIA]) is highly controversial and indicated much lower rates of annual rupture than the majority of previous studies on this topic.5-13 It is accepted that the risk of rupture of an incidental aneurysm is most closely related to its size. Kotomar et al,14 in their recent summary of this available literature, estimated a yearly risk of rupture of approximately 1% for lesions between 7 mm and 10 mm, with the risk being much lower in lesions <5 mm and significantly higher in lesions >10 mm. Whereas small aneurysms (<5 mm) are generally left untreated, larger lesions, particularly in patients younger than 60 years, are considered for treatment with the preference toward treatment increasing with aneurysm size. For lesions >10 mm, treatment is generally recommended in most patients who are without significant other comorbidities and are younger than 70 years of age.14
When left untreated, patients are sometimes offered serial imaging for surveillance of the aneurysm, with the idea that any increase in size or change in morphology could represent an indication for treatment. However, as a practical matter, for a small aneurysm (eg, 4 mm), whereas a 1-mm change in the size of the aneurysm might be difficult to detect even with the most advanced noninvasive imaging systems (CTA or MRA), this small change in diameter translates to a doubling of the aneurysm volume. Also, there is no guarantee that an aneurysm will detectably change in size or morphology prior to rupturing. As such, this recommendation of serial imaging follow-up is somewhat controversial, but often provides some piece of mind to the patients (and their physicians), and occasionally might demonstrate significant interval growth of a lesion.
Occasionally, an unruptured aneurysm may become suddenly symptomatic, typically related to either an abrupt increase in size or less frequently acute thrombosis. The most common example is a posterior communicating artery aneurysm that classically produces the acute onset of third nerve palsy. This clinical scenario typically is a harbinger of impending aneurysm rupture and should prompt treatment on an accelerated basis.
A number of strategies for endovascular aneurysm treatment have been employed during the past 3 decades. In 1970, Serbinenko first described the use of implantable latex balloons in the management of cerebral aneurysms.15 Whereas the technique described by Serbinenko usually involved occlusion or deconstruction of the parent vessel and aneurysm, further development of balloon and catheter technology allowed for the placement of detachable silicone or latex balloons directly into cerebral aneurysms, allowing, in some cases, a constructive occlusion of the aneurysm with preservation of the parent vessel.16-18 Given the developmental nature of this technology, the lesions treated were generally limited to those that were believed to be of unacceptably high rates of surgical morbidity (ie, giant aneurysms), particularly involving the posterior circulation and aneurysms in patients too ill to undergo surgery. Predictably, these treatments were associated with very high rates (at least 30%) of serious periprocedural morbidity and mortality.19
Detachable coils. The modern era of neuroendovascular aneurysm treatment was heralded by the development of detachable platinum coils in the early 1990s and their subsequent FDA approval in 1995.20,21 These flexible, soft, detachable coils could be delivered through a microcatheter that could be safely navigated into the targeted aneurysm. Intra-aneurysmal coil placement was also far more atraumatic, controllable, and safer than the manipulation, insufflation, and detachment of the predicate silicone balloons. Once coils were introduced and commercially available, there was a proliferation of reports describing their application in the embolization of intracranial aneurysms. Complex-shaped, three-dimensional coils were developed to facilitate the embolization of wide-necked aneurysms. Coils with faster detachment times were developed to speed the process of embolization and shorten procedure times. As aneurysm embolization with the Guglielmi Detachable Coil (GDC, Boston Scientific Corporation, Natick, MA) became increasingly accepted and more widely performed, competitors emerged, and additional brands of embolization coils became available.
Adjunctive techniques. As coil embolization emerged as a viable alternative to surgical aneurysm clipping, techniques evolved that allowed the treatment of more complex lesions. The primary anatomic impediment to aneurysm embolization is an unfavorably large neck-to-dome ratio (ie, the wide-necked aneurysm). In these lesions, the wide neck of the aneurysm may allow the detached embolization coils to prolapse from the aneurysm fundus, through the wide neck and into the parent vessel, giving rise to possible thromboembolic complications or unintentional parent vessel occlusion. Initially, these wide-necked lesions were labeled as inappropriate for endovascular therapy and were largely referred for open surgical treatment.
In the late 1990s, the technique of balloon remodeling was developed for the treatment of wide-necked aneurysms.22,23 With the balloon remodeling technique, a temporary occlusion balloon is inflated across the neck of the aneurysm while embolization coils are introduced. The balloon functions to prevent the prolapse of coils into the parent vessel. After the introduction of a coil under balloon protection, the occlusion balloon is traditionally deflated, and the coil is observed for prolapse into the parent vessel. If the coil appears stable, it is detached, and the balloon is reinflated for the introduction of the next coil. This technique is repeated until occlusion of the aneurysm is achieved (Figure 1).
Although the temporary occlusion balloons provide support for coils during their introduction, sometimes the introduced coil can prolapse into the parent artery immediately after balloon deflation, necessitating one or more attempts at coil repositioning. It is also possible that the introduction of a new embolization coil could displace a previously detached coil from the aneurysm sac into the parent vessel. Finally, very wide-necked aneurysms or fusiform/circumferential aneurysms oftentimes lack any neck structure at all, making coil placement, even with a balloon remodeling technique, very tenuous or impossible.
These shortcomings of the traditional method of balloon-assisted coil embolization ultimately led to the development of intracranial microstents. The first report of intracranial stent-supported coil embolization was reported by Higashida et al,24 who used a balloon-mounted coronary stent to treat a wide-necked, fusiform, basilar artery aneurysm. The rigidity of the commercially available balloon-mounted coronary stents often precluded their delivery and deployment within the tortuous cerebrovascular circulation.
In the early part of this decade, Dr. Peter Kim Nelson and his team at SMART therapeutics developed Neuroform, the first microcatheter-delivered, self-expanding, intracranial, nitinol microstent designed specifically for application within the intracranial circulation to support the treatment of cerebral aneurysms.25 This device was much easier to deliver and deploy within the cerebrovasculature than the predicate balloon-mounted stents. The commercial release of Neuroform by Boston Scientific Corporation in the US in 2003 led to a marked increase in the number of complex aneurysms that were amenable to therapy. Neuroform was quickly incorporated into practice, and the embolization of wide-necked aneurysms became more routine. In 2007, the Cordis Enterprise Vascular Reconstruction Device and Delivery System (Cordis Neurovascular, Warren, NJ), a second self-expanding intracranial microstent became available (Figure 2).
As experience with the Neuroform grew, operators began to use the device in novel ways to achieve the embolization of increasingly complex lesions (eg, Y-stent reconstructions, stent placement working across the circle of Willis, and the balloon-in-stent technique).26-28
Shortcomings of coil embolization. Although essentially still a nascent technology in the later 1990s, endovascular coiling proved superior to open surgical clipping for the treatment of ruptured aneurysms in the ISAT trial.3,4 During the past decade, coil technology has quickly improved, and technical expertise has grown exponentially as the procedures have became more common and the technology more pervasive. Data from more recent randomized endovascular trials have indicated that the safety of the coiling procedure has improved significantly even in comparison to its track record in ISAT.29
Despite these impressive results, there is still significant room for improvement with respect to the endovascular treatment of aneurysms. The fundamental shortcoming of coiling technology is that it aims to achieve endosaccular occlusion of cerebral aneurysms without addressing the diseased parent vessel that gave rise to the aneurysm. Although this approach is very effective for many of the small, narrow-necked cerebral aneurysms that are commonly encountered in practice, the technology fails with more complex, difficult lesions.
The failures of coil embolization are manifest in two major ways: (1) incomplete treatment (the inability to achieve complete angiographic occlusion of most lesions), and (2) aneurysm recanalization (interval coil compaction with time [usually over months] leading to a deterioration of the results achieved during the original treatment).
Only the minority of aneurysms treated by coil embolization are actually angiographically cured. Raymond et al30 reviewed their results for a series of 383 aneurysms that were treated by coil embolization. The investigators reported only a 38.3% rate of complete angiographic occlusion at 12-month follow-up. In a more recent series of 182 coiled aneurysms, Rivet et al31 reported a <50% rate of complete aneurysm occlusion at follow-up angiography. Although the necessity of achieving complete angiographic cure is debated, the recent Cerebral Aneurysm Rerupture After Treatment (CARAT) study provides evidence that it does.32 In the CARAT study, ruptured aneurysms were followed after either surgical or endovascular treatment to assess the incidence of re-hemorrhage. Although the overall hemorrhage risk was very low after coiling (1.3 re-hemorrhages per 100 person-years), the risk of rebleed increased drastically with decreasing levels of aneurysm occlusion (0.6 re-hemorrhages per 100 person-years for completely occluded aneurysms vs 15 re-hemorrhages per 100 person-years for partially occluded lesions).32
Due to the random distribution of coils within an aneurysm and the tendency of the individual strands to break the aneurysm up into multiple small compartments, the best packing densities that can be routinely achieved with conventional embolization coils (with or without adjunctive devices) range between 30% and 40% in experimental silicone and glass aneurysm models and between 20% and 30% in clinical human aneurysm treatments. The rates are much lower for large and giant aneurysms and for aneurysms with wide necks.33 As such, the majority of the volume (70%–80%) within coiled aneurysms is not filled with metal.
Not only are aneurysms difficult to densely pack with coils, but also contiguously bridging the entire aneurysm neck with coils is extremely difficult, particularly if the aneurysm is wide necked, incorporating a significant percentage of the circumference of the parent vessel. In these situations, even with the most meticulous technique, there are invariably gaps between coils in the region of the aneurysm neck that allow persistent inflow into the aneurysm neck and probably impair the endothelialization and neointimal growth over the aneurysm neck that is ultimately required to achieve complete angiographic occlusion and durable, curative embolization (Figure 3).
The technical limitations with respect to achieving a dense packing of cerebral aneurysms with coils and completely reconstructing the aneurysm neck with coils is also manifest as poor durability of the immediate posttreatment result (Figure 4). Raymond et al30 observed a recanalization rate of 33.6%, which was considerably higher for large (50.6%) and wide-necked (52.3%) aneurysms. Similarly, Murayama et al34 reported recanalization rates of 35.3% and 59.1% for large and giant aneurysms, respectively. In addition, once aneurysms recur and require retreatment, they frequently recur a second (or third) time, with a repeat recurrence rate of 48.6%.30
These shortcomings of coil embolization have resulted in questions about the long-term durability and, for the more complex and larger aneurysms, the long-term efficacy of the technique. As such, after endovascular aneurysm treatment, the patient is consigned to a schedule of serial imaging follow-up. Although much of this follow-up can now be performed noninvasively with MR imaging examinations specifically designed to assess for aneurysm recurrence, follow-up angiography is often required and, in many cases, one or more retreatments may be necessary to preserve adequate aneurysm occlusion.35
Bioactive and coated coils. To address these shortcomings, bioactive coils were developed. Two general categories of modified coils have been introduced: (1) polyglycolic-polylactic acid (PGPLA)-containing coils (eg, Matrix, Boston Scientific; Cerecyte, Micrus Endovascular, San Jose, CA) and (2) hydrogel-coated coils (Hydrocoil, Microvention/Terumo, Alisa Viejo, CA).
The PGPLA-containing coils are designed to stimulate an inflammatory reaction within the aneurysm that induces an accelerated organization of thrombus and ultimately fibrosis and subsequently elicits a faster and more complete neointimal overgrowth of the aneurysm neck. The Matrix coils were the first such PGPLA-containing coils that were commercially available. There is currently a company-sponsored, randomized trial (Matrix and Platinum Science [MAPS]) being conducted to compare these bioactive coils to standard bare platinum coils. The available case series assessing Matrix thus far have been somewhat disappointing, indicating that the angiographic results have been the same (or in some cases worse) than those that have been reported for bare platinum coils. Even fewer data are available for Cerecyte, which is also currently being investigated in a company-sponsored, randomized trial versus bare platinum coils (Cerecyte Coil Trial).
The hydrogel-coated coils are coated with a desiccated hydrogel that absorbs water and swells considerably upon introduction into the blood environment. The -10, -14, and -18 size hydrocoils swell to five, seven, and 11 times the volume of the standard "platinum-10" sized coils. As such, these coils substantially increase the volumetric filling that can be achieved with endosaccular coil embolization, routinely resulting in packing densities between 50% and 100%.36 Hydrocoil was compared with standard bare platinum coils in a randomized trial (HydroCoil Endovascular Aneurysm Occlusion and Packing Study [HELPS trial]) that was completed in April 2006. The initial blinded safety results have been released; however, the unblinded results are still pending.29
Although bioactive and coated coils may enhance the degree and durability of endosaccular occlusion that can be achieved with coils, they still fail to address the diseased parent vessel and, therefore, still represent largely a solution for the more straightforward small and relatively narrow-necked aneurysms.
Parent Vessel Reconstruction: Conceptual Basis
Parent vessel reconstruction represents the most physiological treatment of cerebral aneurysms. With this technique, the diseased parent artery that gives rise to the saccular or fusiform aneurysmal outpouching is primarily reconstructed. This procedure is achieved through the implantation of stents or stent-like devices within the parent artery, which function to achieve several important hemodynamic and biological effects:
- Change in parent vessel configuration: The implantation of a stent within a parent artery may straighten the vessel, altering (possibly in a favorable manner) the flow dynamics within the aneurysm. The magnitude of this effect is affected primarily by the rigidity of the stent.
- Flow redirection: The presence of stent tines over the aneurysm neck functions to disrupt the inflow jet, reducing vorticity and shear stress on the aneurysm wall and reducing the "water-hammer" effect of chronic pulsatile blood flow on an intra-aneurysmal coil mass. The magnitude of this effect is affected primarily by the amount of metal surface area coverage provided by the stent.
- Tissue overgrowth: The presence of a stent across the neck of the aneurysm provides a scaffolding and stimulus for the overgrowth of endothelial and neointimal tissue across the neck of the aneurysm, creating a "biological remodeling" in the region of the aneurysm neck. The magnitude of this effect is affected by the amount of metal surface area coverage, as well as the structure and composition of the stent material.
Parent vessel reconstruction with commercially available self-expanding intracranial microstents. Initially, self-expanding intracranial microstents (eg, Neuroform, Cordis Enterprise Vascular Reconstruction Device) were marketed and applied as adjunctive devices to facilitate the coil embolization of wide-necked aneurysms. When applied in this context, it became evident that these devices were not only facilitating aneurysm treatment, but they were also potentially increasing the durability of the treatment of wide-necked aneurysms and augmenting the rate and extent of progressive aneurysm thrombosis that occurred after treatment (Figure 3).37 In addition, in some cases in which uncoilable and unclippable wide-necked "blister-type" aneurysms or pseudoaneurysms were encountered, successful treatment was achieved with the placement of one or more self-expanding microstents, without embolization coils (eg, stent monotherapy). This observation indicated that parent vessel reconstruction with commercially available stents sometimes represented a viable "stand-alone" technique for the treatment of selected aneurysms that were not amenable to other therapies (Figure 5).38 Typically, this stent monotherapy strategy was only successful with very small blister aneurysms, the saccular component of which was too small to accommodate an embolization coil.
Parent vessel reconstruction with the Pipeline Embolization Device. During the past 2 years, a new generation of self-expanding, microcatheter-delivered, intracranial microstents has been specifically engineered to primarily achieve definitive parent vessel reconstruction of the cerebral arteries giving rise to aneurysms. The only such device that has successfully been applied in human patients is the Pipeline Embolization Device (PED, Chestnut Medical, Menlo Park, CA).
The PED is a self-expanding, microcatheter-delivered, cylindrical mesh device composed of 48 individual braided cobalt chromium and platinum strands. The device has a 30% to 35% metal surface area when fully deployed, which is far greater than the 6.5% to 9% metal surface area coverage provided by the commercially available self-expanding intracranial microstents that are routinely used in practice (Figure 6). Multiple devices can be deployed within each other (telescoped) to create a composite endovascular construct. The degree of metal surface area coverage can be manipulated by varying the technique of device deployment, as well as by choosing the number of overlapping devices placed in a particular vascular segment.
Because the PED reconstructs the entire length of the treated parent vessel, the traditional factors that markedly diminish the efficacy of standard endosaccular aneurysm treatments such as neck width, large or giant size, and the presence of intra-aneurysmal thrombus would not be expected to have an impact on the efficacy of PED. Hypothetically, the parent vessel reconstruction strategy directly addresses those issues that present the greatest impediments to the success of the aneurysm coil embolization. The initial experience with the PED in experimental aneurysm models and human patients has corroborated this hypothesis—the existing data suggest that this technology represents a quantum advance in neuroendovascular aneurysm therapy.
In vivo experimental data. Kallmes et al39 studied the PED in a rabbit elastase animal model and demonstrated that a single construct placed over the orifice of the aneurysms was sufficient to induce aneurysm thrombosis and angiographic occlusion (Figure 7). When these thrombosed aneurysms were harvested and the parent vessel-aneurysm complex was evaluated, the saccular aneurysms were not only thrombosed but often atretic, and the parent vessels were circumferentially reconstructed with the PED structure incorporated into the vessel wall and covered by a lining of well-developed neointima and endothelium. Thus, not only were the aneurysms cured, but the parent vessels from which they arose were essentially reconstructed into a "steel-reinforced" structure. This spectrum of findings would suggest that not only does the PED provide angiographic occlusion of aneurysms, but in these experimental models, effects a durable physiological cure.
In the same series of experimental subjects, Kallmes et al39 placed a single PED within the abdominal aorta, covering the ostia of the lumbar arteries. The rabbit aorta approximates the caliber of human intracranial vessels, and the lumbar artery branches approximate the perforators. Angiography and histology showed that none of the lumbar arteries covered by the PEDs demonstrated either immediate or delayed occlusion. These data indicate that branch vessels—the patency of which are maintained by a pressure gradient—remain patent, even when their ostia are partially occluded by strands of the PED.
Human experience. To date, the PED has been implanted in more than 80 patients for the treatment of intracranial aneurysms; 39 have been in the context of clinical studies (the PED in the Intracranial Treatment of Aneurysms [PITA] trial) or the single-center "Budapest post-PITA study," whereas the remainder have been performed under provisions for compassionate use for aneurysms that were either untreatable or had failed to respond to previous therapy.
The PITA trial was a single-arm, 31-patient, clinical safety study in which patients with wide-necked saccular aneurysms or aneurysms that had failed to respond to previous endovascular coiling underwent treatment with PED. The average aneurysm size was 11.5 mm, with an average neck width of 5.8 mm; thus, the study was predominantly one of large, wide-necked aneurysms. Overall, the device was delivered successfully in 100% of the cases, with a 6% rate of periprocedural complications (two strokes, no deaths). At 6-month follow-up, 28 of 30 lesions (93%) available for evaluation demonstrated complete angiographic occlusion (Figure 8).40 This rate of occlusion surpasses any of the reported occlusion rates for aneurysms after endovascular therapy and far exceeds those reported for large or wide-necked lesions. Results for the post-PITA study are not yet available.
The PED has also been used to treat nonsaccular, fusiform or circumferential aneurysms. Three such cases have been performed in North America under an FDA compassionate use exemption. All three lesions, which were judged to be untreatable with existing endovascular or open surgical technologies, were angiographically cured with PED without technical or neurologic complications (Figure 9). In two cases, eloquent perforator or side branch vessels were covered by the PED construct. None of the covered side branches or angiographically visible perforator vessels went on to occlusion either acutely or at follow-up. Two of these patients now have greater than 1-year clinical and angiographic follow-up and remain cured of their lesions and without neurologic symptoms.41
Limitations. Although the available data for the PED remains extremely encouraging, there remain several theoretical limitations of the device with respect to its application in the treatment of cerebral aneurysms. First, as with any intracranial stent-like device, a course of dual-antiplatelet medications is required for prophylaxis against thrombosis while the construct is becoming endothelialized and incorporated into the parent artery. The optimal duration of dual-antiplatelet therapy remains uncertain, but the current recommendation is for 6 months of aspirin with clopidogrel with aspirin alone thereafter. For this reason, aneurysmal subarachnoid hemorrhage represents a relative contraindication to PED placement, given the potential for complications related to the invasive procedures frequently required during the perioperative period in these patients (eg, ventriculostomy catheters, percutaneous gastrostomy tubes, tracheostomies, etc). Second, the efficacy and safety of the device for the treatment of bifurcation aneurysms remains uncertain, considering that this application would require the "jailing" of one limb of a bifurcation. Although this has not been an issue with the current generation of lower-metal-surface-area coverage, self-expanding intracranial microstents, experience with PED is limited in this setting. Finally, the safety of the PED device in vessels rich with eloquent perforators remains to some extent unknown. The available data, both in experimental animal models and in human patients, suggest that single coverage with a PED is safe; however, until a larger data set is available, the amount of coverage (eg, with telescoped or overlapped devices) that can be applied in these anatomic locations remains uncertain.
Parent vessel reconstructive devices, such as the PED, represent a new treatment paradigm for intracranial aneruysms. The existing data suggest that these devices may provide a definitive cure of those lesions that have proven to be the most challenging to treat with the standard, more conventional, endosaccular occlusion techniques. Many complex aneurysms that were once thought to be "untreatable" or to require a deconstructive treatment with parent vessel occlusion may be definitively and curatively reconstructed with these new devices. Moreover, the major shortcomings of endosaccular aneurysm therapies—incomplete aneurysm occlusion and aneurysm recurrence—are directly addressed through parent vessel reconstruction.
Currently, the PED is not commercially available and has not yet been approved for use by the FDA. Although the existing data have been very encouraging, our experience with the device in humans remains, to some extent, preliminary. We anticipate that the PED will become available in the US within the context of clinical trials sometime during the upcoming year.
David Fiorella, MD, PhD, is is from the Departments of Neuroradiology and Neurosurgery, Barrow Neurological Institute, in Phoenix, Arizona. He has disclosed that he holds no financial interest in Chestnut Medical; receives research grant funding from Boston Scientific; receives speaking honoraria from Cordis and Microvention; receives royalty agreement, consulting and speaking honoraria from Micrus; receives group consulting support from ev3; and receives salary support from the NIH: SAMMPRIS as the National Interventional co-Principal Investigator. Dr. Fiorella may be reached at (602) 406-3000; firstname.lastname@example.org.
Michael E. Kelly, MD, is Assistant Professor, Division of Neurosurgery, Royal University Hospital, University of Saskatchewan in Canada. He has disclosed that he is a paid consultant to Micrus Endovascular. Dr. Kelly may be reached at (306) 966-8023; email@example.com.
Raymond D. Turner IV, MD, is Clinical Instructor, Department of Neurological Surgery and Neuroradiology Neuroscience Institute Medical University of South Carolina in Charleston, South Carolina. He has disclosed that he is a paid consultant to and receives research grants from Microvention and that he is a paid consultant to Micrus. Dr. Turner may be reached at (843) 792-2424; firstname.lastname@example.org.
Pedro Lylyk, MD, is from the Departments of Neurosurgery and Interventional Neuroradiology, Clinica Medica Belgrano, Fundacion para la Lucha contra Las Enfermedades Neurologicas de la Infancia, Buenos Aires, Argentina. He has disclosed that he holds no financial interest in any product or manufacturer mentioned herein. Dr. Lylyk may be reached at email@example.com.