Stent-Assisted Coiling of Complex Middle Cerebral Artery Aneurysms: Initial and Midterm Results

Complex middle cerebral artery aneurysms are difficult to treat surgically or via endovascular approaches. Here, the authors treated 52 such lesions (41 aneurysms were unruptured and 11 had previously bled) via a combined approach that included stenting and coil embolization. They were able to coil 50 aneurysms after stent deployment and the most common immediate complication was intra-stent clot formation. At 14 months, follow-up showed 7 recurrences and 5 of these were re-treated. No aneurysm bled during this period of time and no intra-stent stenoses developed. The authors concluded that their technique is feasible, safe, and durable. BACKGROUND AND PURPOSE: Clinical outcome and initial and midterm angiographic results of EVT of complex MCA aneurysms by using the stent-assisted coiling technique were retrospectively evaluated in our center where EVT of intracranial aneurysms is the first treatment option. MATERIALS AND METHODS: From November 2003 to October 2009, 49 patients (27 men, 22 women; mean age, 52 ± 12 years) harboring 52 complex unruptured MCA aneurysms (11 ruptured previously and coiled but recanalized and 41 unruptured) were treated by EVT by using self-expandable intracranial stents. Procedural complications, clinical outcome, and initial and midterm angiographic results were evaluated. Initial treatment status and aneurysm sac size were tested as potential risk factors for recurrence. RESULTS: After successful stent deployment, coiling was performed in 50 aneurysms (96.2%) in 47 patients; however, 2 failures (3.8%) occurred in 2 patients. Ten intrastent clot formations (20%) observed on final control angiography induced 2 permanent moderate disabilities (GOS score = 2). Mortality and permanent neurologic morbidity were 0% and 4.3%, respectively. At a mean period of 14 ± 9 months, among 48 aneurysms in 45 patients eligible for follow-up, 34 complete (71%) and 14 partial treatments (29%) were observed, 7 recurrences (14.6%) occurred, and 5 patients (10.4%) needed retreatment. No aneurysm bleeding or symptomatic intrastent stenosis was observed. Aneurysm sac size ≥7 mm and incomplete initial treatment were associated with more recurrences without a statistically significant difference. CONCLUSIONS: For complex unruptured MCA aneurysms, EVT by using a self-expandable intracranial stent was feasible, safe, and durable and could be considered as the first-option treatment.

S ince the International Subarachnoid Aneurysm Trial, EVT of intracranial aneurysms has become a valid therapeutic alternative to neurosurgery and is now performed as the first option in many centers around the world, 1,2 except in the MCA. This aneurysm location presents a favorable superficial anatomy for neurosurgical treatment, while EVT is often unfavorable because of complex vascular anatomy, inducing a high rate of procedure failures, clinical complications, and aneurysm recurrences. 3 Consequently, the optimal therapeutic management of MCA aneurysms is still considered controversial, and surgical clipping remains the standard treatment in many institutions. [4][5][6][7] Although MCA aneurysms were underrepresented in large EVT series, 2,8,9 low morbidity-mortality and aneurysm-recurrence rates have recently been reported in MCA aneurysm series, underlining the potential for EVT. [10][11][12] Furthermore, self-expandable intracranial stents became available in 2003 and have been reported as safe and effective, particularly in the treatment of complex aneurysms, [13][14][15][16][17][18][19] but without consistent data in the MCA location.
The aim of this study was to retrospectively evaluate the clinical outcome and initial and midterm angiographic results of EVT of MCA aneurysms by using the stent-assisted coiling technique.

Patients and Aneurysms
The institutional review board of the University Hospital Center of Montpellier approved this retrospective study, and written informed consent was obtained from each patient. Patients harboring at least 1 unruptured complex MCA aneurysm or 1 ruptured and previously coiled but recanalized aneurysm underwent EVT with a self-expandable intracranial stent. Aneurysm inclusion criteria were the following: 1) aneurysm sac size Ն7 mm, or 2) aneurysm Ͻ7 mm, with 1 of the following conditions: symptomatic patient, personal history of SAH from another intracranial aneurysm, familial history of SAH, or recanalization of a treated aneurysm. From November 2003 to October 2009, EVT by using the stent-assisted coiling technique was attempted on 49 patients harboring 52 complex MCA aneurysms (On-line Table 1). Thirty-six of 52 (69%) were incidental aneurysms that had never been treated, and 16 (31%) were recanalized aneurysms previously coiled by using the remodeling technique (5 unruptured [10%] and 11 ruptured [21%)]). Forty-six of 49 patients had only 1 MCA aneurysm, and the 3 others had 2. Patient characteristics (number, mean age, and sex ratio) and aneurysm characteristics (number, sac, and neck size) were prospectively recorded and analyzed by members of our neurointerventional team.

Aneurysm Treatment
All procedures were performed using a biplane angiographic system (Neurostar T.O.P.; Siemens, Erlangen, Germany), with the patient under general anesthesia and also receiving systemic heparinization for 24 hours. On the day before EVT, patients were premedicated with a loading dose of clopidogrel (300 mg, Plavix; Bristol-Myers Squibb, New York). At the end of the procedure, aspirin (250 mg) was administered to the patient by an intravenous route. Patients were then kept under dual antiplatelet therapy daily for 2 months (clopidogrel, 75 mg, and aspirin, 325 mg) followed by clopidogrel daily alone for 4 months. Since September 2006, platelet aggregation inhibition has been tested just before the beginning of the procedure with the VerifyNow P12Y12 assay (Accumetrics, San Diego, California), and in cases of low efficacy (Ͻ 40% platelet-aggregation inhibition), aspirin (250 mg) was given to the patient during the procedure and a re-loading dose of clopidogrel (300 mg) was promptly administered at the end of EVT. All aneurysms were treated by using only 1 selfexpandable intracranial stent (Neuroform stent, Boston Scientific, Natick, Massachusetts; or Enterprise self-expanding stent, Cordis, Miami Lakes, Florida) placed into the parent vessel, bridging the aneurysm neck.
Stent placement was performed either before coiling (taking advantage of the open cell design of Neuroform stents) or with the jailing technique (with Neuroform or Enterprise stents) when the size of the artery allowed safe navigation of 2 simultaneous microcatheters. In selected cases, the stent was deployed after coiling at the end of the procedure with the aim of securing the parent artery. Coiling was performed by using Matrix coils (Boston Scientific), Guglielmi detachable coils (Boston Scientific), HydroCoils (MicroVention, Aliso Viejo, California), or a combination. In the event of a periprocedural thromboembolic complication, abciximab (ReoPro) was administered intravenously as a single dose (0.25 mg/kg) followed by a 12-hour drip (0.125 g/kg/mn).

Patient Follow-Up
The clinical outcome of patients was evaluated during the following hospitalization period and then was re-evaluated at the first angiographic control, generally performed at 6 months by MRA. Additional controls either by MRA or DSA were then scheduled as follows: 18 months (DSA) and 3 years and 5 years (MRA). In our institution, the MRA sequences (time-of-flight) were analyzed by using mainly source images 10,28 ; maximum-intensity-projection images were irrelevant due to major artifacts caused by the stents. In cases of unreliable MR imaging findings, DSA was promptly performed. One member of our neurointerventional team prospectively recorded angiographic results and GOS scores at discharge and then at each follow-up visit. Thus, morbidity-mortality rates and angiographic results were retrospectively analyzed at initial and midterm follow-ups. Using the Raymond classification scale 29 for comparison of initial and midterm angiographic results, we defined a 3-level assessment profile grading scale, given the evolution of treatment 10 : 1) a favorable result with progression of thrombosis (aneurysms switching from class 3 to class 1 or from class 2 to class 1), 2) a stable result demonstrating no change from the initial result, or 3) an unfavorable result demonstrating any worsening from the initial result. Unfavorable results were further classified as minor or major recurrences as follows: Aneurysms switching from class 1 to class 3 or from class 2 to class 3 were considered major recurrences requiring retreatment, and aneurysms switching from class 1 to class 2 were considered minor recurrences requiring only additional angiographic controls. Two patients were not followed because of death from cervical neoplasia in 1 patient and loss to follow-up in another.

Statistical Analysis
Patient and aneurysm data, as well as angiographic results, were prospectively recorded in a maintained data base and then were retrospectively analyzed. Midterm angiographic results were defined comparing initial and late results and then were classified by using a 3-level assessment-profile grading scale based on the Raymond classification scale. Initial treatment status and aneurysm sac size were tested as potential risk factors for recurrence by using the Fisher exact test. A P value Ͻ .05 was considered a significant difference.

Patient and Aneurysm Characteristics
A total of 49 patients having 52 MCA aneurysms were eligible for EVT by using the stent-assisted coiling technique (On-line Table 1). Fifty (96.2%) were successfully treated, whereas 2 procedure failures (3.8%) due to an inability to catheterize the parent vessel branch occurred and were referred to the neurosurgical team. Twenty-seven aneurysms (52%) with a sac size Ͻ7 mm underwent EVT because of a personal history of SAH from another intracranial aneurysm (n ϭ 10, 19%), familial history of SAH (n ϭ 4, 8%), symptomatic aneurysms (n ϭ 2, 4%), or aneurysm recurrence after coiling alone with or without using the remodeling technique (n ϭ 11, 21%). Only 1 self-expandable intracranial stent was deployed for the treatment of each aneurysm (32 Neuroform and 18 Enterprise stents). Intracranial stent placement was performed before coiling in 47 cases. In 29 of these, the aneurysm was coiled through the struts of the stent (25 Neuroform and 4 Enterprise stents), and in 18, by using the jailing technique (5 Neuroform and 13 Enterprise stents). The stent was deployed after coiling in 3 cases (6%). In these 3 cases, temporary balloon occlusion of the parent vessel was used for coiling and a stent was placed in the parent artery because of instability of the coil packing. According to the definition for complex MCA aneurysm anatomy ("Materials and Methods" section), among the 52 included aneurysms, 37 (71%) were wide-neck aneurysms with parent vessel incorporation and a sac-to-neck ratio of Ͻ2; seven (13%) were wide-neck with parent vessel incorporation; 5 (10%) had a sac-to-neck ratio of Ͻ2; one (2%) arose from an MCA trifurcation; 1 (2%) presented with parent vessel stenosis; and 1 (2%), with a branch vessel arising from the aneurysmal sac.

Angiographic Results at Midterm
Among 47 patients, 45 with 48 treated MCA aneurysms were eligible for follow-up by using either MRA (n ϭ 20, 42%) or DSA (n ϭ 28, 58%) at a mean period of 14 Ϯ 9 months. More than half of the patients (28/45) had an angiographic control at Ͼ12 months. A blurring effect of the stent disturbed MRA interpretation in 3 cases for which DSA was promptly performed. At midterm, 34 complete treatments (71%), 8 residual aneurysms (17%), and 6 residual necks (12%) were observed. Finally, when we compared initial and midterm results, 20 of 48 angiographic results remained stable (as shown in 2 representative cases illustrated in Figs 1 and 2), 21 showed improvement due to a progressive thrombosis, and 7 showed recanalization (14.6%) ( Table 1). Two patients presented with an asymptomatic intrastent stenosis.

Discussion
EVT of MCA aneurysms remains controversial in many centers around the world 4-6 because of favorable surgical results with low morbidity-mortality and recurrence rates at followup. However, low morbidity-mortality (5.4%-12.4%) and aneurysm-recurrence rates (9.5%-10.5%) were observed at mid-and long-term in recent EVT series by using a simple coiling or balloon-remodeling technique. [10][11][12]21,30 In our institution, 1492 aneurysms were treated by EVT, including 234 MCA aneurysms (15.7%) with a high proportion of complex anatomy cases. From our previous experience, we considered that the complex anatomy of MCA aneurysms remains a challenge in EVT, and we hypothesized that the improvement of embolization techniques such as stent-assisted coiling could enhance feasibility, safety, and efficacy of EVT of MCA aneurysms. 10 Thus, this study provided clinical, angiographic, and technical results in patients having complex unruptured MCA aneurysms treated by using a self-expandable intracranial stent. Overall, despite the antiplatelet therapy given to the patient and the test of clopidogrel resistance before the procedure, a high rate of intrastent clot formation was observed, but morbidity-mortality rates remained low as a result of prompt abciximab administration and included only 2 moderate permanent disabilities. Morbidity-mortality rates were in accordance with previous results of an unruptured MCA aneurysm series, using coiling with or without a remodeling technique, which ranged from 2.2% to 9.8%. [10][11][12]31 In addition, the complex MCA aneurysm recurrence rate observed at midterm in our series (14.6%) was lower compared with that in other MCA aneurysm series (20%-27%) 10,11 or with that in series including all aneurysm locations (15%-33%), 8,22,32,33 while rates of major recurrences (10.4%) needing retreatment were similar (5%-17%) to the rates in our series. [10][11][12]23,32,33 Our results clearly indicate that complex unruptured MCA aneurysms can benefit from stent-assisted coiling in terms of feasibility, safety, and midterm anatomic reconstruction. Stentassisted coiling could be applied to a larger range of MCA aneurysms with a simple coiling or remodeling technique. A sac-to-neck ratio of Ͻ2 has been challenged by Brinjikji et al, 34 even if it remains popular among neurointerventional teams. However, their series did not include MCA aneurysms, which often present with a wide neck and parent vessel incorporation. Also, that series did not take into account the mid-and long-term recurrence risk associated with a simple coiling or remodeling technique.
In cases of aneurysmal regrowth, stent placement combined with concomitant double antiplatelet therapy and subsequent coiling may improve mid-and long-term angiographic and clinical results. In our study, rates of procedural adverse events and complications were not enhanced following stent deployment; they were either similar to those reported or even lower, due to standardized antiplatelet therapy. [13][14][15][16][17][18]35,36 As described, stent placement before coiling was predominantly used in our series 17,19,[37][38][39][40] without inducing high complication rates, 15 but technical difficulties in reaching the aneurysm pouch through the struts of the stent accounted for poor initial anatomic results. However, midterm stable or favorable anatomic results stressed that a high rate of complete occlusion was observed regardless of the aneurysm and neck sizes and could be related to the stent arterial-flow diversion   and neointimal growth along scaffolding arterial wall reconstruction. In our series, aneurysm size and initial treatment status were not relevant predictors of recurrence.
In this study, we used mostly Neuroform stents because they were available 2 years before Enterprise stents (2003). In this example, because of the difference in terms of mean follow-up, the comparison between the 2 types of stents was irrelevant. Another limitation of the study was the absence of comparison between our results from the stent-assisted coiling technique and those from neurosurgical clipping, due to a lack of surgical reports concerning the MCA aneurysm topography.

Conclusions
Regardless of the complexity of MCA aneurysms, our results confirm the safety, efficacy, and particularly the feasibility of the stent-assisted coiling technique in most cases. EVT of complex unruptured MCA aneurysms could be considered as the treatment of choice.