Stent Placement for Complex Middle Cerebral Artery Aneurysms Yu Zhou, MS,1 Peng-Fei Yang , MD,1 Qiang Li, MD, Rui Zhao, MD, Yi-Bin Fang, MD, Yi Xu, MD, Bo Hong, MD, Wen-Yuan Zhao, MD, Qing-Hai Huang, MD, and Jian-Min Liu, MD

Background: To evaluate the safety and effectiveness of stent placement for ruptured or unruptured middle cerebral artery (MCA) aneurysms in a larger number.

Methods: Between October 2003 and December 2012, data for 70 patients with 72 complex MCA aneurysms treated with stents at our institution were retrospectively collected and analyzed. Results: Eighty-five stents were successfully deployed in this series. However, failure of followed coiling was encountered in 2 (2.8%) tiny aneurysms of them. Of the 63 aneurysms treated with stent-assisted coiling, complete occlusion was achieved in 22 (34.9%), neck remnant in 15 (23.8%), and residual sac in 26 (36.5%). Of the 9 aneurysms treated with stent alone, the results were contrast stasis in 3 aneurysms and no change in 6. Procedure-related complications occurred in 9 (12.5%) procedures, including 7 of 27 (25.9%) with ruptured aneurysms and 2 of 45 (4.4%) with unruptured aneurysms, which resulted in 1 death and 5 disabilities. Univariate and multivariate analyses show that ruptured aneurysm is an independent factor for the outcome of these patients (odds ratio, 7.35; 95% confidence interval, 1.35-40.0). Angiographic follow-up results (mean, 10.5 6 8.8 months) showed that 72.1% (44 of 61) were completely occluded, 4.9% (3 of 61) recurred, and others were stable or had improved. Intrastent stenosis was observed in 1 (1.6%) patient, which was managed conservatively. During a clinical follow-up period ranging from 7 to 113 months (mean, 33.0 6 22.4 months), 1 disabled patient died from severe pneumonia, whereas the clinical status of the others had improved or was stable. Procedure-related morbidity/mortality during the follow-up for the ruptured and unruptured groups were 3.7%/3.7% and 0/0, respectively. Conclusions: Our study shows that stent placement for the treatment of certain wide-neck MCA aneurysms is feasible, safe, and effective. However, stent placement for acutely ruptured MCA aneurysms harbors a much higher complication rate. Key Words: Stent—middle cerebral artery—aneurysms—unruptured—ruptured. Ó 2014 by National Stroke Association

Introduction Because International Subarachnoid Aneurysm Trial investigators published their results, more and more

From the Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China. Received August 27, 2013; revision received November 14, 2013; accepted December 4, 2013. This work was supported by the National Natural Science Foundation of China (81000494), the Dawn Project of Shanghai (11CG043), and the Science and Technology Commission of Shanghai Municipality (10441901902).

intracranial aneurysms are treated via an endovascular approach.1 However, controversies still exist about endovascular treatment for middle cerebral artery (MCA) aneurysms. Although various articles have demonstrated

Address correspondence to Jian-Min Liu, Department of Neurosurgery, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. E-mail: [email protected]. com. 1 The authors contributed equally to this work. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.054

Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-10

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that endovascular treatment for MCA aneurysms is safe, effective, and equivalent to surgical clipping,2-4 the complex anatomies, including wide necks, fusiform morphology, and incorporation of important branches, are still the obstacles for these aneurysms.5 Intracranial stent is one of the most widely used tools in treating these complex lesions and is proved to be safe and effective. But the data are still limited for MCA aneurysms, especially for ruptured aneurysms.6-8 In the previous article, we have published our preliminary experience about stent placement for 16 widenecked MCA aneurysms and demonstrated the feasibility of this technique.9 In this article, we retrospectively analyzed 70 patients with 72 complex MCA aneurysms treated from October 2003 to December 2012. We aimed to evaluate the safety and effectiveness of stent placement for these complex MCA aneurysms in a larger number; possible influence factors of those procedure-related complications were also analyzed.

Patients and Methods Between October 2003 and December 2012, 233 patients with MCA aneurysms were admitted to our institution, treatment decision was based on the following indications: (1) ruptured aneurysm; (2) unruptured aneurysm of 5 mm or more; and (3) unruptured aneurysm of less than 5 mm, but with at least one of the risk factors such as symptomatic presentation, personal history of subarachnoid hemorrhage (SAH) from another intracranial aneurysm, increased size during follow-up, familial history of SAH, recanalization from previous treated aneurysms, and heavy psychological stress. As a result, 187 were treated via an endovascular approach, 22 were clipped because of compressive hematoma requiring immediate surgical evacuation or patient’s preference to clipping, whereas the others were not treated because of the following reasons: (1) the aneurysms were small and asymptomatic and (2) the patients refused treatment because of old age, poor general conditions, or economic problems. Of the 187 patients treated via an endovascular approach, 70 patients with 72 aneurysms, who were treated with stentassisted coiling or stent alone, were included in this series to evaluate the safety and effectiveness of stent placement for complex MCA aneurysms, whereas all others were treated with coiling alone because of simpler morphologies except for 2 patients treated with balloon remodeling. The Institutional Review Board at our institution approved the retrospective review of all the data in this series. As shown in Table 1, there were 35 men and 35 women with a mean age of 55.8 6 9.8 years (range, 31-78 years). Of these 70 patients, 27 were admitted because of SAH or intracranial hemorrhage (ICH) caused by MCA aneurysm rupture, whereas the rest were presented with SAH from other concurrent aneurysm bleeding (n 5 3), headache (n 5 9), recanalization after previous treatment (n 5 6), transient ischemic attack/ischemia (n 5 4), or

Table 1. Clinical and angiographic data of 70 patients with 72 MCA aneurysms treated with stent-assisted coiling or stent alone Patients (aneurysms) Mean age (range) Male:female Hunt and Hess scale 0 I II III IV V Side (left/right) Location M1 segment MCA bifurcation Type Saccular Fusiform Size Tiny (#3 mm) Small (3-10 mm) Large (10-25 mm) Giant (.25 mm) Stenting strategy Stenting before coiling Stenting after coiling Waffle cone Y-configuration Stent alone Type of stent (n 5 85) Enterprise Neuroform Solitaire Leo

70 (72) 55.8 6 9.9 (31-78) 35:35 43 5 12 5 3 2 36/36 21 51 66 6 19 40 9 2 7 51 1 4 9 60 15 6 4

Abbreviation: MCA, middle cerebral artery.

incidental aneurysm finding (n 5 21). Hunt and Hess (HH) grade scales for these 27 patients with ruptured MCA aneurysms when admitted to hospital were grade I in 5 patients, grade II in 12, grade III in 5, grade IV in 3, and grade V in 2 patients. Endovascular treatments were performed by several authors (J.L., Y.X., B.H., Q.H., and W.Z., who had more than 5 years of experience) of this article. All patients with recently ruptured (#1 month) aneurysms were treated emergently after admission. However, because transfer of these patients might have been delayed, the time of treatment varied. Of them, 19 patients were treated within 3 days of the rupture of the aneurysm, 5 patients were treated at an interval of 14-30 days, and 3 patients at an interval of 3-14 days.

Aneurysm Morphology Of these 72 aneurysms, 21 were located at M1 segment (main trunk from MCA origin to where it divides) and 51

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at MCA bifurcation. Six were fusiform aneurysms and the other 63 were wide-necked saccular aneurysms with a large neck ($4 mm)/a dome-to-neck ratio (#2 mm). Of the 66 aneurysms, the size of aneurysms ranged from 1.9-25.7 mm. According to the size of aneurysms, they were classified as tiny (#3 mm) in 18 aneurysms, small (3-10 mm) in 42, large (10-25 mm) in 10, and giant (.25 mm) in 2 aneurysms. Sixteen patients had multiple aneurysms, 4 of which harbored bilateral MCA aneurysms.

Procedures All procedures were performed with the patient under general anesthesia and via the transfemoral approach. After systemic heparinization, a 6F Envoy (Cordis, Miami Lakes, FL) or Chaperon (MicroVention, Columbia, CA) guiding catheter was placed in the distal internal carotid artery. Then the aneurysms were treated with stentassisted coiling or stent alone. Four types of stents were used in this series, including Neuroform stents (Boston Scientific/Target, Fremont, CA), Enterprise stents (Cordis), Leo stents (Balt Extrusion, Montmorency, France), and Solitaire AB stents (ev3, Irvine, CA). All stents were deployed following the standard procedure recommended by the manufacturer. For MCA bifurcation aneurysms mainly involving 1 branch of the MCA, we tried to deploy 1 stent from that branch to M1, which could cover most of the aneurysm neck and would make the uncovered part on the other branch become relatively narrow to avoid coil protrusion. However, for MCA bifurcation aneurysms involving branches equally, Y-configuration stent placement could be considered. For M1 segment aneurysms, the distal segments of the stents were deployed into M1 trunk in all patients except for 3 in which stents were deployed into the early branches because the aneurysms mainly involved these perforators. Totally, 5 different stenting strategies were used in our series: (1) stenting before coiling—the stent was first deployed to bridge the aneurysm neck in 7 aneurysms. Then the microcatheter was positioned into the aneurysm sac through the meshes of the stent, through which the coils were introduced. (2) Stenting after coiling—for 49 aneurysms, the stents were partially (semijailing, n 5 13) or fully deployed (modified jailing, n 5 36) to cover the aneurysmal neck after introducing part of the framing coils. Then additional coils were introduced through the ‘‘jailed’’ microcatheter to embolize the aneurysms. In addition, for the another 2 aneurysms, stents were deployed after complete coiling to preserve the parent artery because of coil protrusion. (3) Y-configuration—for 4 MCA bifurcation aneurysms involving both branches of the MCA bifurcation, we deployed a second stent in a Y-configuration via the interstices of the first stent to reserve the other MCA branch. (4) The waffle cone technique was used in 1 patient. A

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slightly oversized stent with a diameter of 4.5 mm was deployed into the proximal fundus of the aneurysm, which allowed the framing coils to lock into the stent struts and reconstruct the aneurysm neck. (5) Stent alone—we adopted the stent-alone placement technique in 9 unruptured aneurysms. We intentionally applied the stent monotherapy to reconstruct the vessels in 2 dissecting aneurysms, alter the hemodynamics of the aneurysm in 2 recanalized aneurysms with minor neck remnant and 3 tiny aneurysms because the volume of the aneurysm sac was too small to place a coil or accept a clip. For the other 2 aneurysms, coil deployment failed after stent implantation. These patients were kept under close observation. After deploying the first stent, a second stent was deployed in 9 patients because of fusiform morphologies (n 5 6) or coil protrusions (n 5 3). Thus, a total of 85 stents were deployed for 72 aneurysms, including 15 Neuroform stents (Boston Scientific/Target), 60 Enterprise stents (Cordis), 4 Leo stents (Balt Extrusion), and 6 Solitaire AB stents (ev3). After the treatment, we performed computed tomography (CT) scan routinely to detect any aneurysm bleeding.

Anticoagulation and Antiplatelet Management All patients received systemic heparinization after placement of the sheath except for patients presenting with ICH. The activated clotting was maintained at 2-3 times the baseline throughout the procedure. For patients with unruptured aneurysms and remote ruptured aneurysms (.1 month), dual antiplatelet drugs (75 mg/day of clopidogrel and 100 mg/day of aspirin) were given for 3 days before the procedure. For patients with acutely ruptured aneurysms, a loading dose of clopidogrel and aspirin (300 mg each) was administered orally or rectally at 2 hours before stent placement. All patients were continued on aspirin and clopidogrel postoperatively for 6 weeks, followed by aspirin alone, which was maintained indefinitely.

Clinical and Angiographic Follow-up All patients were advised to undergo clinical evaluation at 1, 3, 6, and 12 months after the treatment and yearly thereafter. Postoperative angiographic follow-up was also recommended, including 3-month magnetic resonance angiography (MRA), 6-month digital subtraction angiography (DSA), and MRA/DSA yearly thereafter. Because of possible artifacts caused by the stents, only DSA images, or contrast-enhanced MRA images when DSA examination was refused or unable to be performed, were collected for analysis. The angiographic results were interpreted independently by 2 authors (Y.Z. and P.Y.) and were classified into 4 categories when compared with the immediate embolization degree: (1) occluded, defined as no contrast filling into the aneurysm sac; (2) improved, defined as decreased contrast filling into the aneurysm sac; (3) stable, defined as unchanged contrast filling into

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the aneurysm sac; and (4) recanalized, defined as the increased contrast filling into the aneurysm sac.

Statistical Analysis Univariate analysis using the chi-square test and multivariate analysis using the logistic regression were performed to evaluate whether the age (,65 or $65 years), gender, aneurysm location (M1 or MCA bifurcation), aneurysm size (,7 or $7 mm),7 aneurysm presentation (ruptured or unruptured) affect the occurrence of those ischemic or hemorrhagic complications. Odds ratio was also calculated for independent factors. SPSS software version 16.0 (SPSS, Chicago, IL) was used for statistical calculation. All tests were performed 2-sided, and considered to be significant when a value of P was less than .05.

Results The treatment results and follow-up data of the 70 patients with 72 MCA aneurysms are listed in Table 2.

Immediate Embolization Results During the procedure, 1 delivering difficulty, 1 coil escape, and 2 (2.8%) failed coiling were recorded. In the first case, although finally succeeded, difficulty was encountered when delivering the second Neuroform stent through the interstices of the first one for an MCA bifurcation aneurysm treated with a Y-configuration stentplacement technique. In the second case, a 2mm 3 4cm HyperSoft coil (MicroVention, Aliso Veijo, CA) escaped into the distal part of the parent artery before stent placement, which was later successfully removed with Microsane (Microvena, Boston Scientific, MA) without any clinical complication. In the rest of the 2 patients with tiny aneurysms, coil deployment failed after stent implantation. Other technique adverse events, such as poor stent opening and stent migration, were not recorded. All the 82 stents were successfully deployed. Of the 63 aneurysms treated with stent-assisted coiling, complete occlusion was achieved in 22 (34.9%), neck remnant in 15 (23.8%), and residual sac was present in 26 (36.5%). Of the 9 aneurysms treated with stent alone, contrast stasis in the aneurysm sac was observed in 3 aneurysms and no change was observed in 6 aneurysms.

Procedure-related Complications As shown in Supplementary Table 1, procedure-related complications during hospitalization were reported in 9 (12.5%) procedures, including 7 of 27 (25.9%) with ruptured aneurysms and 2 of 45 (4.4%) with unruptured aneurysms. Four patients with acutely ruptured aneurysms suffered from aneurysm rebleeding. Three of them occurred during introduction of the coils, and we observed obvious extravasation of the contrast media and coil perforation. In the other case (case 9), we did

Table 2. Treatment results and follow-up data of the 70 patients with 72 MCA aneurysms Technique adverse event 2/72 (2.8%) Immediate angiographic results Complete occlusion 22 Neck remnant 15 Partial occlusion 26 Contrast stasis 3 No change 6 Procedure-related complications 9/72 (12.5%) Intrastent thrombus 3 MCA branch obliteration 1 LSA infarction 1 Intraoperative rupture 4 mRS score at discharge (n 5 70)/follow-up (n 5 67) 0-2 61/65 3-5 6/1 Death 3/1 Procedure-related morbidity/mortality when discharged Entire group 5.7%/1.4% Ruptured group 11.1%/3.7% Unruptured group 2.3%/0 Procedure-related morbidity/mortality when follow-up Entire group 1.4%/1.4% Ruptured group 3.7%/3.7% Unruptured group 0/0 Follow-up angiographic results (n 5 61) Complete occlusion 44 (72.1%) Improved 3 (4.9%) Stable 10 (16.4%) Recanalization 3 (4.9%) Stenosis 1/61 (1.6%) Abbreviations: MCA, middle cerebral artery; mRS, modified Rankin Scale; LSA, lenticulostriate artery.

not observe obvious contrast extravasation during the procedure, but Dyna CT immediately after the procedure showed increased hematoma. Subsequent craniotomy was performed for 3 with ICH to remove the hematoma, which respectively led to death in 1, and moderate–severe disability in 2, whereas the other one with slightly increased SAH was managed conservatively, and no obvious neurologic deficit was noted when discharged. Thromboembolic complications, including 3 intrastent thrombosis, 1 inferior branch obliteration, and 1 lenticulostriate artery area infarction, occurred in 5 patients. One patient (case 2 in procedure-related complications as given in Supplementary Table 1) developed hemiparalysis because of intrastent thrombus 10 days after the surgical procedure; thromboelastogram detection showed that she was insensitive to clopidogrel and mildly sensitive to aspirin (50%). Tirofiban was promptly administrated via an intra-artery approach, and a combination of cilostazol (200 mg/day) and aspirin (300 mg/day) was followed. She was fine at 8-month follow-up (Fig 1). One patient (case 4 in procedure-related complications as given in Supplementary Table 1) experienced

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Figure 1. Images of a 56-year-old woman treated with stent-assisted coiling. Preoperative angiogram shows an unruptured middle cerebral artery bifurcation aneurysm on the right side (A). Then the aneurysm was treated with stent-assisted coiling (B). Postoperative angiogram shows sac residue of the aneurysm (C). The patient experienced hemiparalysis 10 days later, angiogram at that time showed complete occlusion of the aneurysm (D), but thrombus formation was observed in the distal part of the stent (white arrow). Tirofiban was administrated immediately via an intra-artery approach and intrastent thrombus disappeared after the procedure (E), 8-month follow-up showed the aneurysm was still completely occluded with patent parent artery (F).

similar symptoms 5 days after the surgical procedure, but because acute infarction had been observed in magnetic resonance imaging, only conservative therapy was adopted. For one complication that occurred during procedure, intra-artery administration of tirofiban was performed immediately, and a second stent was deployed for one of them because coil protrusion was thought to be responsible for the thrombosis. The other 2 patients with side branch occlusions were managed conservatively. These complications were uneventful in 3 patients (cases 1, 3, and 5; the hemiparalysis in case 5 of procedurerelated complications was contributed by initial brain injury, and had been existing before the surgical procedure), and led to hemiparalysis in the other 2. Delayed complication occurred in one 71-year-old male patient. He suffered from gastric bleeding 1 month after the surgical procedure; aspirin was discontinued and clopidogrel was maintained indefinitely, after which he recovered. Thus, these procedure-related complications totally resulted in 1 death and 4 disabilities. Univariate and multivariate analyses including age, gender, aneurysm size, and aneurysm presentation show that ruptured aneurysm was the independent factor for the procedure-related complications (P 5 .021). And the odds ratio for ruptured aneurysms was 7.35 (95% confidence interval, 1.35-40.0).

Clinical Outcome Except for the 9 procedure-related complications, 5 SAH-related complications occurred (Supplementary

Table 1). Totally, 3 of the 70 patients died during hospitalization: 2 from initial severe SAH (HH grade V) and 1 from intraoperative rupture. Four patients experienced clinical deterioration because of intraoperative rupture, intrastent thrombus, or MCA branch obliteration (described in procedure-related complications), 2 experienced transient symptomatic vascular spasms, but the symptoms resolved after intra-artery administration of fasudil, whereas others were stable or had improved. Clinical evaluation was performed in all patients at discharge by using the modified Rankin Scale (mRS) . Sixty-one patients were independent with an mRS score of 0-2 at discharge, whereas the other 9 were dependent (resulting from procedure-related complications, SAH-related complications, or initial brain injury), including 5 with an mRS score of 4, 1 with an mRS score of 5, and 3 with an mRS score of 6. The overall morbidity/mortality values when discharged for the entire group, ruptured group, and unruptured group were 8.6%/4.3%, 18.5%/11.1%, and 2.3%/0, respectively. And the procedure-related morbidity/mortality values when discharged for the entire group, ruptured group, and unruptured group were 5.7%/1.4%, 11.1%/3.7%, and 2.3%/0, respectively. All survived patients were followed up for 7-113 months (mean, 33.0 6 22.4 months). Five of the 6 dependent patients were clinically improved, with an mRS score improved from 4-2 in 3, from 4-1 in 1, and from 5-3 in 1. The other patient (case 5 in SAH-related complications as given in Supplementary Table 1) experienced hydrocephalus after hemorrhage, sequent ventriculoperitoneal shunt was performed, but the symptoms

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Figure 2. Images of a recanalized aneurysm treated with stent-assisted coiling. Angiogram at the first time showed a middle cerebral artery aneurysm on the left side (A). The aneurysm was first treated with coiling alone, which resulted in a neck remnant of the aneurysm (B and C). Six-month follow-up showed the aneurysm recanalized (D), and the coils were impacted (E). The aneurysm was retreated with stent-assisted coiling (F). Although only partial occlusion was achieved on immediate angiogram (G), 31-month follow-up showed the aneurysm was completely occluded with patent parent artery (H).

did not improve, the patient remained severely disabled, and finally died of severe pneumonia. Thus, the overall morbidity/mortality values when followed up for the entire group, ruptured group, and unruptured group were 1.4%/5.7%, 3.7%/14.8%, and 0/0, respectively. And the procedure-related morbidity/mortality values when followed up for the entire group, ruptured group, and unruptured group were 1.4%/1.4%, 3.7%/3.7%, and 0/0, respectively.

Follow-up Angiographic Results As described previously, 4 patients died and, therefore, were not available for follow-up. Fifty-nine of the rest of the 66 patients (61 of 68 aneurysms) underwent at least one follow-up cerebral angiography at intervals ranging from 3-51 months (mean, 10.5 6 8.8 months), whereas the other 7 were not willing to undergo angiographic follow-up for various reasons. The available angiographies included enhanced MRA for 14 aneurysms and DSA for the other 47 aneurysms. Twenty-one initially occluded aneurysms remain completely occluded; 25 aneurysms progressed: 12 aneurysms with a residual sac and 10 aneurysms with a remnant neck improved to complete occlusion (Fig 2), 1 aneurysm with a remnant neck and the other 2 with a residual sac showed decreased intrasaccular contrast filling (Fig 3). One aneurysm with an initial residual sac and 2 aneurysms with a remnant neck were recanalized, one of them was retreated with additional stent-assisted coiling,

9-month follow-up showed a total obliteration. Other aneurysms remained stable without recanalization. Of the aneurysms that were treated with stent alone, 2 were completely occluded, whereas others were stable. Thus, the overall complete occlusion was rate 72.1% (44 of 61) and the recanalization rate was 4.9% (3 of 61). Intrastent stenosis was observed in 1 (1.6%) patient, because the patient was asymptomatic, he was managed conservatively.

Discussion A series of articles have demonstrated that endovascular treatment is a feasible and effective modality for MCA aneurysms in addition to clipping.5 Several articles, including one of ours, further introduced the clinical appliance of self-expanding stent for MCA aneurysms, for which the results were promising.6-9 In this article, we reported clinical and angiographic results of 70 patients with unruptured or ruptured MCA aneurysms. All stents were successfully implanted. However, a quite different outcome was found between ruptured and unruptured groups.

Stent Selection In this series, 4 types of intracranial self-expanding stents were used. The Neuroform stent and Leo stent were the first 2 self-expanding stents imported to China for the treatment of intracranial aneurysms. They are comparatively easier to be navigated and delivered than

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Figure 3. Images of a fusiform aneurysm treated with stent-assisted coiling. Preoperative angiogram (A) and 3-dimensional reconstruction (B) demonstrated a fusiform aneurysm located at the M1 segment of the right middle cerebral artery, a bulge was observed on the top of the aneurysm. To prevent rupture, the aneurysm was treated with semideploying technique (C). Postoperative angiogram shows partial occlusion of the aneurysm, and the bulge has been completely occluded (D). Eight-month follow-up showed the aneurysm had improved (E and F).

previous balloon-expandable stents. In the first few years, they were the only choices and were mostly used. However, they have limitations, such as the impossibility to reposition the stent when it is partially delivered, a low radial force and some deployment difficulties for Neuroform stent,10 and the need for progressively larger profile and stiffer delivery catheters for Leo stent.11 The new generation of Neuroform stent (Neuroform 3) was reported to have undergone several technical modifications to improve deliverability, but there are still reports of failure of stent deployment, and the stent is still unretractable.12 Comparatively, we prefer to use Enterprise stents to treat these complex lesions in recent years. There are 3 reasons: (1) Enterprise stent has a lower profile and higher flexibility, it is easier to be delivered and positioned, which we believe is quite important for MCA aneurysms because the delivery route is always far and the parent vessel may be tortuous,13 and also the close cell design of the Enterprise stent can serve as a better scaffold compared with the Neuroform stent14; (2) because stenting after coiling strategy was preferred in our institution, the microcatheter and stent may need adjustment during the procedure. Choosing Enterprise stents, which were retrievable, was imperative; and (3) in cases who need overlapping stent, the navigation of a second stent is easy, and as we reported previously, even for Y-configuration stenting strategy, we found the Enterprise stent is more favorable than the Neuroform stent because it eases the catheterization, delivery, and deployment.15

Solitaire AB stent (ev3) is a laser-cut, self-expanding, and fully retrievable split-design nitinol device. It has a high degree of flexibility, higher radial force, and is retrievable before detaching, which hence may make the stent more precisely placed and deployed.16 In the 6 cases we treated, we also experienced these advantages as reported previously. But we found that when a second stent is needed because of situations, such as coil protrusion and so forth, the delivery of a second stent would be difficult because of the absence of the delivery wire. Also the large cell size may be a potential drawback, especially for tiny aneurysms. Although we have tried all these 4 stents, we still prefer the usage of Enterprise stent for complex MCA aneurysms.

Safety of Stent Implantation for MCA Aneurysms Until now, all published series concerning stenting for MCA aneurysms mostly focus on unruptured aneurysms (Table 3). Also ischemic events are still major concerns during the treatment. There are many factors that contribute to the occurrence of these events. Besides insufficient antiplatelet therapy because of inadequate drug administration or patient’s insensitiveness to drugs (such as case 2 in Supplementary Table 1), other technique problems such as incomplete stent apposition may also be associated with higher thromboembolic complications. Thromboelastogram examination before the procedure may help detect patients with insufficient antiplatelet therapy. However, it is still difficult to detect incomplete stent apposition during the procedure. Tsuruta et al17

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Abbreviation: NA, not applicable. *In these 2 patients, stents were successfully deployed, but coil deployment failed after stent implantation.

71%/14.6% 67%/6% 90.6%/4.7% 72.1%/4.9% 3.8% (2/52) 20% 4.4%/0 14 6 9 mo 4.3% (1/23) 4/23, 17.45% 0 1.2 y NA 10/91, 11% 1%/1% .6 mo 2.8% (2/72)* 2/45, 4.4% (unruptured group) 0 10.5 6 8.8 mo 7/27, 25.9% (ruptured group) 3.7%/3.7% 52/0 23/0 92/8 45/27 Vendrell et al, 20115 52 (49, 27/22) Fields et al, 20138 23 (23, 7/16) Johnson et al, 20136 100 (91, 18/73) This study 72 (70, 35/35)

Procedure-related complication Technical failure Unruptured/ ruptured Literature No.

1 2 3 4

Complete occlusion rate/recanalization rate Stenosis (%) Interval

Follow-up result

Permanent morbidity/ mortality Number of aneurysms (patients, male/female)

Table 3. Summary of the results of previous reports concerning stenting for complex middle cerebral artery aneurysms

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used the cone-beam CT with a contrast material to check the incomplete stent apposition. This is useful in cases adopting stenting before coiling, but still restricted in cases performing stenting after coiling. However, most of these complications can be managed successfully with prompt administration of abciximab or/and deployment of an additional stent after which most patients recovered. The morbidity/mortality values in the 3 series reported by Vendrell et al, Fields et al, and Johnson et al were 4.4%/0, 0/0, and 1%/1%, respectively. Similar to their results, we also observed good outcome for our patients with unruptured MCA aneurysms. The morbidity/mortality of 0/0 is consistent with previous results6-8 and comparable with that treated with clipping (2.4%-3%)18-20 All these data show that stenting for unruptured aneurysms is feasible and relatively safe. Stenting for ruptured aneurysms has been widely reported and has been in controversy for years. There are always worries about hemorrhagic complications related to the usage of antiplatelet agents within the acute phase of bleeding and thromboembolic events because of insufficient antiplatelet therapy.21,22 Until now, a series of articles about stenting for ruptured aneurysm have been published. However, because the data vary in patients’ demography, patients’ clinical conditions, aneurysmal size/location, and antiplatelet regimen, a review of the literature shows a hemorrhagic rate varying from 0% to 17.5% and an ischemic rate ranging from 0% to 17%.10,21-24 Despite disparate results, some authors believe stent-assisted coiling harbors an acceptable risk/ benefit ratio of acutely ruptured aneurysms.22,25 However, few articles focused on the ruptured MCA aneurysms. In previous research, we have achieved similar results when evaluating the safety of stent placement for aneurysms in other locations.26 Also, in our preliminary report containing 10 acutely ruptured MCA aneurysms, this modality also seems to be safe for ruptured aneurysms. Only 1 procedure-related complication occurred, which did not result in any new neurologic deficit.9 Balloon remodeling and multiple catheter techniques were the other choices for these complex lesions, but we do not take them as first choices because these techniques complicated the procedure, prolonging the operative duration because of the requirement of an additional microcatheter or/and balloon, lack of a long-term duality, also because most of ruptured aneurysms were small in our series, we are worried about the escaping or protrusion of coils after withdrawing the balloon. On the basis of these considerations, we performed stent-assisted coiling for the 27 acutely ruptured aneurysms. Of the 27 acutely ruptured aneurysms in this series, the complication rate is 25.9% (7 of 27) and the overall morbidity/mortality is 14.8%/3.7%. During follow-up, those with symptomatic procedure-related complications were also clinically improved. The overall and procedure-

STENT PLACEMENT FOR COMPLEX MCA ANEURYSMS

related morbidity/mortality were 3.7%/14.8% and 3.7%/ 3.7%. It is difficult to directly compare our result with those treated with surgical clipping because of the difference in patients’ demography and patients’ initial clinical status. However, a rough review shows the result is comparable with the reported result of surgical clipping, in which the mortality and morbidity rates were 4.2%12.9% and 6.5%-10%, respectively.27,28 Also this result is consistent with other series concerning stent-assisted coiling for acutely ruptured aneurysms, in most of which the complication rate ranges from 9.4% to 30%.10,21,23-25 Nevertheless, the complication rate is indeed higher than those of unruptured MCA aneurysms. Multivariate analysis also shows that ruptured aneurysm is an independent factor for the complications in this series. In fact, when analyzing our unpublished data concerning stent-assisted coiling for ruptured aneurysms, we also found that stenting for MCA aneurysms harbors a much higher complication rate and morbidity compared with the aneurysms at other locations. The reasons for a higher thromboembolic event rate compared with unruptured aneurysms may be related to hypercoagulable status after SAH, and it takes time for the antiplatelet drugs to work. Also the patient may be insensitive to antiplatelet drugs. For the 3 cases that rebleeded during introduction of the coils, we observed obvious extravasation of the contrast media and coil perforation. We believe that both the small sizes of the aneurysms and the usage of the stent contributed to the rerupture of the aneurysm. Of these 3 aneurysms, 1 was small and 2 were tiny. When introducing the coils, the microcatheter and introduced coils restricted between the stent and the aneurysm wall may generate a radical force, which may finally result in the rupture of the aneurysm. As reported previously, the complication is higher in treating these small aneurysms than in treating the bigger aneurysms.29 In the other case (case 9), we did not observe obvious contrast extravasation during the procedure, but Dyna CT immediately after the procedure showed increased hematoma. We are not sure of the reason why this rebleeding happened; antiplatelet therapy, subtle coil protrusion, or just incidental rebleeding may be the possible reason. Ever since the result of this study, stent-assisted coiling for acutely ruptured MCA aneurysms are no longer performed actively in our institutions. Staged stenting (subtotal coiling to secure the aneurysmal dome followed by stent-assisted coiling generally 1 month after the acute phase of rupture) or clipping have been approved. However, the safety is in further evaluation.

9 2

containing 12 series, Brinjikji et al ever found the minor recurrence rate was 9.2% and the incidence of major recurrences was 9.6%. However, a series of researches have demonstrated that stent implantation can help divert the blood flow, serve as a scaffold for endothelium healing, and promote the reconstruction of the neck of the aneurysms.10,32,33 For MCA bifurcation aneurysm, the deployment of stent may also potentially change vascular geometry, decrease hemodynamic stress of the bifurcation, and hence improve the outcome of these complex lesions.34 In this series, we also observed excellent results after stent implantation. Despite the complex morphologies, we obtained a good angiographic result: 25 aneurysms progressed and only 3 (4.9%) aneurysms recurred. This result is similar to the result of Johnson et al6 and Fields et al8 (Table 3). These data show that stent-assisted coiling is durable for MCA aneurysms.

Limitations The limitations of this study include its retrospective design, limited cases in one single institution, and the inadequate angiographic follow-up. Moreover, patientselection bias may exist because those ruptured MCA aneurysms with hematomas often need immediate surgical evacuation and were hence transferred to surgery, and we also notice most of our patients harbor a low HH grade in our series. These may all impose biases on the result of our study. However, it is not difficult to conclude from our study that stent placement for acutely ruptured MCA aneurysms harbors a much higher complication rate.

Conclusions Our study shows that stent placement for the treatment of selected complex MCA aneurysms is feasible, safe, and effective. However, stent placement for acutely ruptured MCA aneurysms harbors a much higher complication rate. Acknowledgment: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this article.

Supplementary Data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/ 10.1016/j.jstrokecerebrovasdis.2013.12.054.

References Efficacy of Stent Implantation for MCA Aneurysms One major disadvantage of endovascular treatment is the high recanalization rate, which was reported as high as 26.3% in some large series.30,31 In a systematic review

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