RESEARCH HUMAN CLINICAL STUDIES

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1 RESEARCH HUMAN CLINICAL STUDIES RESEARCH HUMAN CLINICAL STUDIES Benjamin Gory, MD, MSc* Joachim Klisch, MD, PhD Alain Bonafé, MD, PhD Charbel Mounayer, MD, PhD Remy Beaujeux, MDk Jacques Moret, MD# Boris Lubicz, MD, PhD** Roberto Riva, MD* Francis Turjman, MD, PhD* *Department of Interventional Neuroradiology, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; Department of Neuroradiology, Helios Klinikum, Erfurt, Germany; Department of Neuroradiology, Montpellier University Hospital, Montpellier, France; Department of Interventional Neuroradiology, Dupuytren University Hospital, Limoges, France; kdepartment of Neuroradiology, Strasbourg University Hospital, Strasbourg, France; #Department of Neuroradiology, Beaujon Hospital, Paris, France; **Department of Neuroradiology, Erasme Hospital, Brussels, Belgium Correspondence: Benjamin Gory, MD, MSc, Department of Interventional Neuroradiology, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, Bron Cedex, France. Received, October 5, Accepted, April 15, Published Online, May 12, Copyright 2014 by the Congress of Neurological Surgeons. SANS LifeLong Learning and NEUROSURGERY offer CME for subscribers that complete questions about featured articles. Questions are located on the SANS website ( Please read the featured article and then log into SANS for this educational offering. Solitaire AB Stent-Assisted Coiling of Wide-Necked Intracranial Aneurysms: Mid-term Results From the SOLARE Study BACKGROUND: Endovascular treatment of intracranial aneurysms can be technically difficult when the neck is wide. The Solitaire AB stent (Covidien, Irvine, California), the only fully retrieved stent, assists in the coiling of wide-neck intracranial aneurysms. OBJECTIVE: To evaluate the mid-term angiographic follow-up of wide-necked aneurysms treated with the Solitaire AB stent. METHODS: SOLARE (SOLitaire Aneurysm Remodeling) is a consecutive, prospective study conducted in 7 European centers. A core laboratory evaluated the postoperative and mid-term (6 month 6 15 days) angiographic results by using the Raymond classification Scale. Recanalization was defined as worsening, and progressive thrombosis was defined as improvement in the Raymond scale score. RESULTS: The mean width of the aneurysm sac was 7.5 mm, and the mean diameter of the aneurysm neck was 4.7 mm. Angiographic mid-term follow-up was obtained in 55 of 65 aneurysms (85.9%). Complete occlusion was achieved in 33 aneurysms (60%); a neck remnant was seen in 16 aneurysms (29.1%) and an aneurysm remnant in 6 aneurysms (10.9%). Of 55 aneurysms, recanalization was observed in 8 aneurysms (14.5%), and progressive thrombosis was observed in 17 aneurysms (30.9%). No bleeding or rebleeding was observed during the follow-up period. CONCLUSION: Stent-assisted coiling of wide-necked intracranial aneurysms was found to be safe and effective with the Solitaire AB stent at 6-month follow-up. Angiographic results improve with time due to progressive thrombosis of the aneurysm. KEY WORDS: Coiling, Intracranial aneurysm, Recurrence, Stenting Neurosurgery 75: , 2014 DOI: /NEU Stent-assisted coiling (SAC) has been used with increasing frequency over the past few years, particularly for addressing endovascular treatment of wide-neck intracranial aneurysms. Chalouhi et al, 1 in the largest series published to our knowledge, reported a 3% combined permanent morbidity and mortality rate after SAC of 552 aneurysms. However, these results concerned the Neuroform stent (Stryker Neurovascular, Fremont, California) and Enterprise stent (Codman, Miami, Florida). Considering the Solitaire AB stent (Covidien, Irvine, California), we recently reported the immediate clinical and anatomic posttreatment results of a consecutive prospective registry ABBREVIATIONS: mrs, modified Rankin Scale; SAC, stent-assisted coiling conducted in 7 European centers. 2 However, the influence of the Solitaire AB stent on the angiographic outcome after endovascular treatment of intracranial aneurysms is unknown because of the lack of prospective data. Our objective was to evaluate the mid-term anatomic results in 64 intracranial aneurysms treated with the Solitaire AB stent and included in a prospective multicenter European registry. METHODS SOLARE (SOLitaire Aneurysm Remodeling) Protocol and Population The SOLARE study including patients with intracranial aneurysms treated with a self-expandable Solitaire AB stent was conducted between June 2009 and July 2010 in 7 European centers. Patients harboring intracranial aneurysms, ruptured or unruptured, arising NEUROSURGERY VOLUME 75 NUMBER 3 SEPTEMBER

2 GORY ET AL from a parent vessel with a diameter of 3.0 mm or greater and 6.0 mm or less with a wide-neck ($4 mm) or dome-to-neck ratio less than 2 were included. Fusiform and dissecting aneurysms, as well as aneurysms associated with an arteriovenous malformation, were excluded. The use of a stent other than the Solitaire AB device was considered as an exclusion criterion. Patients with contraindications to heparin, clopidogrel, or aspirin were also excluded. No antiplatelet medication protocol was specified in the SOLARE study, as antiplatelet drugs were administered at the discretion of each investigating site. The protocol was approved by the ethics committee of each center. Written informed consent was obtained from each patient/legally authorized representative before entry into the study. A total of 64 patients (53 women and 11 men; age range, years; mean age, 53.3 years) harboring 65 aneurysms were included. Clinical presentation was subarachnoid hemorrhage in 5 patients (7.9%). Hunt and Hess scale was grade I in 3 patients (4.7%) and grade II in 2 patients (3.2%). Unruptured aneurysms were present in 59 patients (93.7%). Most aneurysms (81.5%) were located in the anterior circulation, and the carotid-ophthalmic segment was the most frequent location (27.7%). The mean width of the aneurysm sac was 7.5 mm, and the mean diameter of aneurysm neck was 4.7 mm. The mean dome-to-neck ratio of the aneurysm was 1.6. Follow-up Protocol Anatomic results were evaluated on angiogram or magnetic resonance angiogram, including selective contrast injections and 4 projections. For each patient, the postembolization and mid-term (6 month 6 15 days) degree of aneurysmal occlusion was assessed by the core laboratory (Frederic Ricolfi, MD, Radiology Department, University Hospital, Dijon, France) for 63 patients having 64 aneurysms. It was defined by using the simplified 3-point Jean Raymond classification scale: complete occlusion, neck remnant, and aneurysm remnant. 3 Recanalization and progressive occlusion were defined as a change in the Raymond classification, comparing the rate of occlusion postembolization and on midterm follow-up. Recanalization was defined as a worsening of classification: complete occlusion to neck remnant, neck remnant to aneurysm remnant, or complete occlusion to aneurysm remnant. Progressive occlusion was defined as improvement of classification. Clinical Follow-up Bleeding or rebleeding occurrence during the period of follow-up was evaluated. Data Analysis Clinical and procedural data were collected and entered via an electronic Web site by the investigator. Quality of data, exhaustivity, and consecutiveness were checked by clinical research associates at each site. Statistical analysis was independently conducted. All reported adverse events related to the treatment were analyzed blindly by a neuroradiologist (F.T.) and are described in this series. Permanent morbidity and mortality of endovascular treatment were evaluated before and after treatment, at hospital discharge, and at 1- and 6-month follow-up. Morbidity was defined as a modified Rankin Scale (mrs) score of 2 to 5. When preoperative mrs score was greater than 1, morbidity was defined by any increase of mrs. Any modification within 30 days after endovascular treatment was designated as treatment related. Any death within 30 days of endovascular treatment was designated a treatment-related death. RESULTS Clinical Results Of the 64 patients (65 aneurysms) who were initially included in the registry, 1 was excluded (neck length,4 mm), and 1 missed the 6-month follow-up. Finally, 62 patients had a clinical followup. The 6-month clinical results are reported in Table 1. No deaths were reported during the follow-up period. Only 1 patient experienced slight worsening at 6 months, from an mrs score of 0 at baseline to a score of 1 at 6-month follow-up. The permanent 6-month morbidity rate was 0%, and the mortality rate was 0%. Anatomic Results According to the core laboratory evaluation, at 6 months, 4 aneurysms were not assessed (1 with no stent placed, 1 with no coils placed, 1 missed visit, 1 visit by phone only), and 6 were not successfully evaluated due to stent artifacts (magnetic resonance imaging [MRI]). Of the 65 aneurysms that were initially included in the registry, 55 had mid-term anatomic follow-up by angiography after treatment. Progressive occlusion occurred in 17 aneurysms (30.9%), and recurrence in 8 aneurysms (14.5%) (Table 2). Complete occlusion was obtained in 33 (60%) of 55 aneurysms at 6 months compared with 27 (42.1%) of 63 aneurysms in the postprocedure evaluation (Figures 1 and 2). The number of aneurysms with a residual neck remnant decreased from 25 of 64 aneurysms (39.1%) to 16 aneurysms (29.1%). Parent artery patency was seen in all aneurysms. At 6 months, all of the assessable aneurysms had stable stent placement with complete aneurysm neck coverage. DISCUSSION The immediate safety and efficacy of the Solitaire AB stent in the treatment of wide necked intracranial aneurysms were demonstrated and reported previously. 2 In this study, we assessed TABLE 1. Clinical Results of Patients During Pre-procedure and at 1- and 6-Month Follow-up by the Core Laboratory Modified Rankin Scale Score Pre-procedure 1-Month Follow-up 6-Month Follow-up 0 42 (66.7) 47 (74.6) 49 (77.8) 1 12 (19.0) 11 (17.5) 12 (19.0) 2 4 (6.3) 1 (1.6) 0 (0) 3 3 (4.8) 2 (3.2) 1 (1.6) 4 0 (0) 0 (1.6) 0 (0) 5 0 (0) 0 (0) 0 (0) 6 0 (0) 0 (0) 0 (0) Not available 2 (3.2) 2 (3.2) 1 (1.6) 216 VOLUME 75 NUMBER 3 SEPTEMBER

3 SOLITAIRE STENT-ASSISTED COILING TABLE 2. Cross-Table Results of Postprocedural Occlusion and Occlusion at 6 Months by the Core Laboratory a Postprocedure (n = 64) 6 Months (n = 55) Complete occlusion 27 (42.1) 33 (60.0) Neck remnant 25 (39.1) 16 (29.1) Aneurysm remnant 12 (18.8) 6 (10.9) a At the postprocedure assessment, 1 aneurysm occlusion status was not assessed because no stent was placed. At 6 months, 10 aneurysms has no follow-up: 1 with no stent placed, 2 lost to follow-up, 1 visit by phone only, and 6 due to stent artifacts. the mid-term clinical and anatomic results of Solitaire AB SAC of wide-necked intracranial aneurysms. The SOLARE study is the first prospective, consecutive, multicenter study of the Solitaire AB stent. Description of Solitaire AB Stent and Technical Aspects The Solitaire AB stent is used to retain coils within the aneurysm, thus reducing the risk of embolic complications from FIGURE 2. A, digital subtraction angiography demonstrating a wide-necked carotid-ophthalmic aneurysm. B, the Solitaire AB stent was deployed in the parent artery and the microcatheter was placed in the aneurysm sac. C, angiography at the end of procedure showing complete aneurysm occlusion. D, 6-month control angiography showing complete aneurysm occlusion. coil herniation into the parent artery. Compared with Neuroform and Enterprise stents, the Solitaire AB stent is a self-expanding nitinol device that could be completely deployed and fully retrieved at the end of the procedure. Retrievability is a unique feature of the Solitaire AB stent that allows stent repositioning or removal if desired by the treating physician. 4 The goal of the study was to assess whether the characteristics of this device affected the benefits to the patient. Apart from retrievability, this set of characteristics cannot be individually evaluated, and their evaluation is reflected in the global results as safety and efficacy. In the SOLARE study, the stent was used but retrieved at the end of the coiling in 1 patient. FIGURE 1. A, digital subtraction angiography showing a very wide-necked basilar artery aneurysm. B, the Solitaire AB stent was placed and the microcatheter was jailed. C, angiography at the end of procedure showing complete aneurysm occlusion. D, 6-month control angiography showing complete aneurysm occlusion. Safety of the Solitaire AB Stent The results of SAC vary widely across different studies. In a French series of 216 aneurysms treated with stents, the rates of permanent morbidity and mortality were as high as 7.4% and 4.6%, respectively. 5 Elsewhere, morbidity and mortality rates with SAC were found to be lower. 6-9 In this series, mortality was 0%, and permanent morbidity was 0%, which confirms the safety of the Solitaire SAC for wide-necked intracranial aneurysms. In the retrospective series of 104 intracranial aneurysms NEUROSURGERY VOLUME 75 NUMBER 3 SEPTEMBER

4 GORY ET AL treated with the Solitaire AB stent reported by Clajus et al, 9 the morbidity and mortality were evaluated at 3.9% and 2.9, respectively. These results are not different from those reported in the large series of 508 patients treated with Neuroform and Enterprise stents. In these series, the procedure-related morbidity and mortality rates were 3%. 1 Mid-term Anatomic Results of Solitaire AB Stent Despite the fact that this series includes wide-necked aneurysms, the mid-term rates of recanalization were low (14.5%). The recurrence rate in our series is largely in line with previously reported SAC series. Using Neuroform stents, Gentric et al 10 reported a 9.7% rate of recurrence, whereas Maldonado et al 8 reported a 14.5% rate of recurrence rates after Neuroform SAC of 76 aneurysms. A limitation in our series is the fact that at 6 months, 10 aneurysms were not adequately assessed by imaging according to the core laboratory, including 6 due to stent artifacts on MRI. To date, artifacts introduced by stents limit the value of MRI as a follow-up modality after SAC. 12 Contrast administration also improved vessel lumen visualization. 13 Conventional catheter angiography remains the gold standard. There is a need for even later follow-up to assess the rate of long-term recurrence. Intracranial stents offer scaffolding for reconstruction of the intimal layer of the parent artery at the aneurysm neck and may also promote progressive thrombosis. 5,9,10,14-16 In the retrospective series of Clajus et al, 9 dealing with 104 aneurysms treated with the Solitaire AB stent, 39.2% of the aneurysms revealed further occlusion. In the literature survey of Shapiro et al, 13 approximately 45% of 1510 aneurysms were completely occluded at first treatment session, increasing to 61% on the median 6-month follow-up (695 patients provided imaging). Fiorella et al 14 reported, in patients treated with Neuroform stent-assisted coiling, a progressive thrombosis in 52% of the cases. Piotin et al 4 reported, by using Neuroform and Enterprise stents, further thrombosis in 72.6% of aneurysms with significantly fewer recurrences in the stented aneurysm group despite inclusion of larger aneurysms with lower packing densities. The final results of this series are lower than those previously reported, with progressive thrombosis of the aneurysm documented in 30.9% of cases. Although SAC has a lower recurrence rate than conventional coiling, 40% of aneurysms were not completely occluded at 6 months in our series. 17 This rate compares well with the recent review of Shapiro et al. 13 To date, the predictive factors of progressive thrombosis failure are not well known. This could be related to different designs of available intracranial stents: the open-cell design of the Neuroform stent and the closed-cell design of the Enterprise and Solitaire AB stent. Open-cell design stents could, in principle, adjust better to curved and tortuous vasculature, but they may be associated with some adverse mechanistic effects, such as increased cell opening or strut prolapse. 18 However, in the series of Chalouhi et al 1 dealing with 508 patients treated with Neuroform and Enterprise stents, closed-cell stents were associated with significantly lower aneurysm recanalization rates. Thus, the closed-cell design of the Enterprise stent may more efficiently alter intra-aneurysmal hemodynamic parameters and promote saccular thrombosis. We observed no case of in-stent stenosis during the angiographic follow-up period, comparing well with the series of Clajus et al. 9 Forty-nine patients were followed for 13.6 months, and no clinically relevant in-stent stenosis was observed. Neuroform use has been associated with a 5.8% occurrence of delayed moderate or severe in-stent stenosis, 22% of which were symptomatic. 16 To date, the rate of Enterprise in-stent stenosis is not well known because only initial results of Enterprise stent use in SAC was reported. and no follow-up data outside the immediate perioperative were available. 7 CONCLUSION SAC of wide-necked intracranial aneurysms was found to be safe and effective with the Solitaire AB stent at 6-month follow-up. Angiographic results improve with time due to progressive thrombosis of the aneurysm. Disclosure This registry was financially supported by Covidien/ev3. Dr Klisch is consultant for Covidien/ev3. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Chalouhi N, Jabbour P, Singhal S, et al. Stent-assisted coiling of intracranial aneurysms: predictors of complications, recanalization, and outcome in 508 cases. Stroke. 2013;44(5): Gory B, Klisch J, Bonafé A, et al. Solitaire AB stent-assisted coiling of wide-necked intracranial aneurysms: short-term results from a prospective, consecutive, European multicentric study. Neuroradiology. 2013;55(11): Raymond J, Guilbert F, Weill A, et al. Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke. 2003; 34(6): Signorelli F, Gory B, Turjman F. Temporary solitaire stent-assisted coiling: a technique for the treatment of acutely ruptured wide-neck intracranial aneurysms [published online ahead of print]. AJNR Am J Neuroradiol. December 12, Piotin M, Blanc R, Spelle L, et al. Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke. 2010;41 (1): Mocco J, Snyder KV, Albuquerque FC, et al. Treatment of intracranial aneurysms with the enterprise stent: a multicenter registry. J Neurosurg. 2009;110(1): Biondi A, Janardhan V, Katz JM, Salvaggio K, Riina HA, Gobin YP. Neuroform stent-assisted coil embolization of wide-neck intracranial aneurysms: strategies in stent deployment and midterm follow-up. Neurosurgery. 2007;61(3): Chalouhi N, Jabbour P, Gonzalez LF, et al. Safety and efficacy of endovascular treatment of basilar tip aneurysms by coiling with and without stent assistance: a review of 235 cases. Neurosurgery. 2012;71(4): Maldonado IL, Machi P, Costalat V, Mura T, Bonafé A. Neuroform stent-assisted coiling of unruptured intracranial aneurysms: short- and mid- term results from a single-center experience with 68 patients. AJNR Am J Neuroradiol. 2011;32(1): Clajus C, Sychra V, Strasilla C, Klisch J. Stent-assisted coil embolization of intracranial aneurysms using the SolitaireÔ AB neurovascular remodeling device: initial and midterm follow-up results. Neuroradiology. 2013;55(5): VOLUME 75 NUMBER 3 SEPTEMBER

5 SOLITAIRE STENT-ASSISTED COILING 11. Gentric JC, Biondi A, Piotin M, et al. Safety and efficacy of Neuroform for treatment of intracranial aneurysms: a prospective, consecutive, French multicentric study. AJNR Am J Neuroradiol. 2013;34(6): Choi JW, Roh HG, Moon WJ, Chun YI, Kang CH. Optimization of MR parameters of 3D TOF-MRA for various intracranial stents at 3.0T MRI. Neurointervention. 2011;6(2): Lövblad KO, Yilmaz H, Chouiter A, et al. Intracranial aneurysm stenting: followup with MR angiography. J Magn Reson Imaging. 2006;24(2): Shapiro M, Becske T, Sahlein D, Babb J, Nelson PK. Stent-supported aneurysm coiling: a literature survey of treatment and follow-up. AJNR Am J Neuroradiol. 2012;33(1): Lubicz B, Bandeira A, Bruneau M, Dewindt A, Balériaux D, De Witte O. Stenting is improving and stabilizing anatomical results of coiled intracranial aneurysms. Neuroradiology. 2009;51(6): Fiorella D, Albuquerque FC, Woo H, Rasmussen PA, Masaryk TJ, McDougall CG. Neuroform in-stent stenosis: incidence, natural history, and treatment strategies. Neurosurgery. 2006;59(1): Hong Y, Wang YJ, Deng Z, Wu Q, Zhang JM. Stent-assisted coiling versus coiling in treatment of intracranial aneurysm: a systematic review and meta-analysis. PLoS One. 2014;9(1):e Ebrahimi N, Claus B, Lee CY, Biondi A, Benndorf G. Stent conformity in curved vascular models with simulated aneurysm necks using flat-panel CT: an in vitro study. AJNR Am J Neuroradiol. 2007;28(5): COMMENT The authors present their mid-term (6 months) results of the SOLARE (SOLitaire Aneurysm REmodeling) study, which consists of stentassisted coil embolization of wide-necked intracranial aneurysms using the Solitaire AB (aneurysm bridging) stent, currently not available in the United States. This is a follow-up study to the recently published early results of the same study that involved 7 European centers. Using the Raymond classification scale, complete occlusion was achieved in 33 aneurysms (60%) as opposed to the previously reported 42.1%. Further, neck remnants decreased from 39.1% to 29.1%. Progressive occlusion occurred in 30.9%. Aneurysmal recurrence occurred in 14.5%. Only 1 patient experienced worsening (0-1) of their mrs score. The mortality rate was still zero. The authors concluded that using the Solitaire AB to coil embolize wide-necked aneurysms is safe and aneurysmal occlusion improves with time, as seen in other cases of stent-assisted coiling. Endovascular device technology continues to advance with each new one on the market. The Solitaire AB is unique given its ability to be retrieved, repositioned, and deployed at will. This potential advantage may improve the ability and confidence of practitioners to perform stent-assisted coil embolizations, especially given that the use of this device has been shown to have a similar safety profile. What has not been shown are the long-term results with regard to aneurysm occlusion. There are still many questions that remain, especially regarding the use of antiplatelets and their timing and the fact that the cell sizes of the Solitaire AB stent are larger than the both the Neuroform and Enterprise stents. Comparisons with other similar large cell size devices, eg, LVIS, remain to be seen. Ultimately, the goal of all of these devices is to provide a useful tool that is both safe and effective when treating wide-necked aneurysms. This report indicates that the Solitaire AB is at least on that path. CME QUESTIONS Christopher S. Eddleman Abilene, Texas 1. What is an advantage of stent assisted coiling of intracranial aneurysms compared to coiling alone for wide neck aneurysms? A. Progressive thrombosis of aneurysm remnant B. Decreased complication rate C. Decreased cost D. Decreased long-term aneurysm recanalization rate 2. What is the approximate recanalization rate of wide necked aneurysms treated with stent-assisted coiling? A. 5% B. 15% C. 25% D. 35% E. 45% 3. What is the advantage of stent retrievability in stent assisted aneurysm coiling (SAC)? A. Lower incidence of embolic complications B. Avoidance of anticoagulant medications C. Ability to treat wide-necked aneurysms D. Optimization of stent deployment Ability to treat ruptured aneurysm NEUROSURGERY VOLUME 75 NUMBER 3 SEPTEMBER