Patients

Self-expanding nitinol stents were used to treat 486 aneurysms in 422 patients between October 2002 and January 2012. The senior author (D.K.L.) performed each procedure, and this period represents his initial decade of experience with SAE. Each patient was provided the options of endovascular repair with possible stent placement, microsurgery, and observation for management of the aneurysm. Each patient signed informed research consent before stent placement as part of the Rush University Medical Center's institutional review board protocol. Patients were enrolled in the study prospectively. Women harbored 362 (74.5%) of the aneurysms. The average patient age was 58.2 years (range 19–86 years; SD 12.8 years).

Aneurysms

Characteristics of the treated aneurysms are provided in Table 1. Aneurysms were classified as small, large, or giant if their maximal diameter was < 10, 10–25, or > 25 mm, respectively. Fusiform aneurysms were defined as those in which the vessel was circumferentially involved. An aneurysm was considered to have a wide neck if the size of the neck was > 4 mm or if the dome-to-neck ratio was < 1. Twelve (2.5%) of the stented aneurysms had acutely ruptured, whereas 11 (2.3%) were coiled after initial rupture and then stented in a delayed, staged fashion.

Stents and Stent Configurations

Open-cell Neuroform stents (Stryker Neurovascular) were used beginning in 2002, and closed-cell Enterprise stents (Cordis Neurovascular) were used beginning in 2007. A Wingspan stent was used in 1 aneurysm with associated intracranial stenosis, and this aneurysm was included in the open-cell Neuroform group for statistical analysis purposes. Stent selection and configuration were determined by the angiographic details of the aneurysm and the known advantages and limitations of each stent design available at the time of treatment.^2,28 Stent-selection and configuration details are listed in Table 2.

Antiplatelet Strategy

Preoperative management for patients with an unruptured aneurysm included dual antiplatelet therapy with aspirin (325 mg) and clopidogrel (75 mg) daily for 5 days before stent placement. Patients unable to complete this regimen were loaded with 600 mg of clopidogrel and 325 mg of aspirin before the procedure. Antiplatelet activity was measured by using point-of-care VerifyNow (Accumetrics) aspirin and P2Y12 platelet function assays. For patients with a ruptured aneurysm and for those in whom antiplatelet therapy was not therapeutic (i.e., > 550 aspirin reaction units or > 230 P2Y12 reaction units), an intraarterial loading dose of 0.25 mg/kg abciximab (0.25 mg/kg) was given at the time of stent placement followed by a 12-hour infusion (0.125 μg/kg/min or 10 μg/min). Abciximab was also given if thrombus developed inside of the stent or if the patient had a new neurological deficit after treatment and head CT revealed no hemorrhage. Patients with a single-stent configuration were continued on dual antiplatelet therapy for 3 months. Patients with multiple stents were kept on dual antiplatelet therapy for 6 months and aspirin for ≥ 1 year.

Procedures

The typical procedure was performed with the patient under general anesthesia with continuous neurological monitoring using somatosensory evoked potentials and electroencephalography. After femoral access was obtained, the patient was given a heparin bolus of 100 U/kg, and the activated clotting time was maintained at > 250 seconds. The preferred SAE technique was stenting followed by coiling through the stent struts.

Radiographic Assessment

Immediate posttreatment digital subtraction angiography (DSA) was performed to assess aneurysm occlusion, and follow-up DSA was performed at 6 months. Long-term imaging follow-up typically was performed with MRI and MR angiography (MRA) beginning 1 year after treatment. Thereafter, MRI and MRA were repeated yearly. CT angiography and/or DynaCT (Siemens) was used in patients unable to undergo MRI and MRA. Aneurysms with either residual filling of > 2–3 mm or with growth of known residual were scheduled for DSA with possible re-treatment. After re-treatment, the follow-up process started again with angiography at 6 months. Re-treatment rates and angiographic results are considered in a separate ongoing study.

Complications

Complications were categorized as transient, minor, major, or death. Transient neurological complications resolved entirely before hospital discharge. Minor complications were nondisabling strokes that resolved within 30 days of hospital discharge. Major complications included permanent disabling neurological events. Death was considered separately but included in the analysis of major complications. For patients with multiple complications, their aneurysm was categorized according to their worst complication.

Every complication was analyzed for association with aneurysm size and morphology, aneurysm location, stent type, and stent configuration. All the complications that could be attributed to the stenting procedure or the treated aneurysm were included and are presented herein.

Statistical Analysis

Both the chi-square test and multivariate logistic regression were used to identify statistically significant risk factors. For aneurysm size and morphology, the subcategories included small aneurysm, small neck (SASN), small aneurysm, wide neck (SAWN), large, giant, and fusiform. Anterior and posterior circulation locations were considered. Stent types included Neuroform and Enterprise. Configurations included single stent, overlapping stents, and Y-configuration stents. The SASN, anterior circulation, and single-Neuroform-stent groups were used as references for odds ratio (OR) calculations of total and major complications for size, location, and stent configuration, respectively.

A separate multivariate logistic regression analysis was performed to compare the ORs of different stent configurations (single vs overlapping vs Y). In this case, the single-stent group, including Neuroform and Enterprise stents, was used as the reference for OR calculations; the overlapping-stents group included Neuroform, Enterprise, and mixed-type stents. All statistical analyses were performed using SPSS version 19 (IBM Corp). Significance was determined by a p value of < 0.05.

Total Complications

Included in the study were 486 original stenting procedures, 52 re-treatment procedures (in 45 patients), and 421 follow-up diagnostic angiograms. During a mean follow-up time of 1.89 years after initial SAE, there were 57 neurological complications (11.7%), including 7 deaths (1.4%), 9 major strokes (1.9%), 18 minor complications (3.7%), and 23 transient complications (4.7%).

Twenty-eight (5.8%) complications, including 7 major strokes (1.4%) and 5 deaths (1.0%), occurred within 24 hours of treatment; 2 of these deaths were secondary to hemorrhage, whereas the other deaths and major strokes were ischemic in nature. Two patients had a giant aneurysm that ruptured within 2 weeks of stent placement, and 1 of these patients died. One patient died after a hemorrhage following repeat treatment with coils only. Timing of the complications that occurred during the follow-up period is shown in Fig. 1. The only major complication beyond 1 year was an ischemic stroke that occurred 371 days after treatment with overlapping stents in a patient with a small posterior communicating artery aneurysm.

Timing of complications that occurred during the follow-up period.

Forty-four nonneurological complications occurred during the study period. There were 31 groin complications, including 5 femoral pseudoaneurysms, 9 retroperitoneal hematomas, and 1 fistula. Surgical intervention was successful in the treatment of 2 ischemic limbs. There were 8 systemic bleeding complications; 4 gastrointestinal, 2 epistaxis, 1 vaginal, and 1 related to a radial arterial line. One of the gastrointestinal bleeds forced the discontinuation of antiplatelet therapy and resulted in a procedure-related death, which was included in the complication analysis. The remaining nonneurological complications included significant occipital hair loss in 1 patient and 4 minor anesthesia-related complications.

Aneurysm Size and Morphology

Among 356 small aneurysms, there were 30 complications (8.4%), of which 6 (1.7%) were major. There were no significant differences in total or major complications in small aneurysms with small necks and those with wide necks. Of the 85 large aneurysms, there were 16 total complications (18.8%), 4 (4.7%) of which were major. Thirteen giant aneurysms had 4 total (30.8%) and 2 major (15.4%) complications; the 32 fusiform aneurysms had 7 total (21.9%) and 4 major (12.5%) complications. The chi-square test revealed higher total complication rates in large (OR 3.43; p = 0.004), giant (OR 6.58; p = 0.006), and fusiform (OR 4.14; p = 0.008) aneurysms, and these results were confirmed in the multivariate analysis. Major complication rate disparities were not statistically significant with respect to aneurysm size or morphology in the multivariate analysis. ORs from the multivariate analyses for all complications and the major ones are summarized in Tables 3 and 4, respectively.

Location

Among 407 anterior circulation aneurysms, there were 47 total (11.5%) and 8 major (2.0%) complications. There was not an increased risk in total complications (10 of 79 [12.7%]) with posterior circulation aneurysms; however, complications in the patients with a posterior circulation aneurysm tended to be worse, with 8 (10.1%) being major complications (significant in the univariate [OR 5.62; p = 0.001] and multivariate analyses [Table 4]).

Stent Type

There were no significant differences in either total or major complication rates between open-cell (Neuroform) and closed-cell (Enterprise) stent use. For each stent type, the complication rate was higher for overlapping-stent treatments than for single-stent treatments. Aneurysms treated with overlapping constructs that included at least 1 open-cell stent fared worse than those treated with overlapping closed-cell stents; however, results of a comparison of major complications in these 2 groups did not reach statistical significance (OR 2.33; p = 0.44).

Stent Configuration

A single-stent configuration was used in the treatment of 386 aneurysms; there were 35 total complications (9.1%) and 5 major complications (1.3%). Overlapping stents were placed across 80 aneurysms; there were 17 total complications (21.3%), 8 (10.0%) of which were major. Y-configuration stenting was used in the treatment of 20 aneurysms; there were 5 total complications (25%), 3 of which (15%) were major. The ORs for all and major complications for different stent configurations (all single-stent constructs were considered together and used as the reference group) were calculated in a separate multivariate analysis, the results of which are summarized in Tables 5 and 6, respectively. Overlapping (OR 2.56; p < 0.01) and Y-configuration (OR 3.17; p = 0.03) stent constructs increased the total complication risk over that of single-stent constructs on chi-square analysis; multivariate analysis revealed that Y-configuration stenting was an independent risk factor for total complications (Table 5). Multivariate analysis revealed that both overlapping and Y-configuration constructs were independent risk factors for major complications (Table 6).

Aneurysm Size and Morphology

Larger aneurysms were associated with more total complications and trended toward having more major complications. Consistent with the literature regarding all treatment modalities, giant and fusiform aneurysms were more dangerous to treat when nitinol stents were used. When the anatomy permits, flow-diverting stents may be the best modality for treating these challenging aneurysms. The Matrix and Platinum Science (MAPS) trial examined aneurysm neck sizes and found a neck diameter of > 4 mm to be an independent risk factor for complications.²⁶ For small aneurysms in our series, there was no significant difference in complications between the small- and wide-necked aneurysm groups; furthermore, there were fewer major complications in the wide-necked aneurysm group.

Location

Aneurysms in the posterior circulation are often more difficult to treat with various modalities, including clipping,⁹ coiling,¹⁹ and stent-assisted coiling.⁴ Posterior circulation aneurysm treatment in our study resulted in an overall complication rate that was comparable to that of anterior circulation aneurysms; however, the complications in the posterior circulation were more severe. This vascular territory is eloquent and generally filled with vulnerable perforating arteries that supply the brainstem; therefore, procedures performed in this area result in a morbidity rate that is higher than that after procedures performed in areas with fewer perforators.

Stent Type

No significant difference was seen in complication risks after placing either of the 2 stent types used in the series (Neuroform and Enterprise). The similarly sized series of Chalouhi et al.⁴ also revealed no difference in risk between Neuroform and Enterprise use. However, the data suggested that closed-cell stents may be safer than open-cell stents when an overlapping-stent construct is used.

Stent Configuration

Multiple-stent constructs have been found to induce greater alteration in flow and intraaneurysmal hemodynamics, which result in more reliable thrombosis.^17,33 The overlapping, telescoping, or “stent-in-stent” technique for aneurysm treatment is widely used, generally for more complex, giant, and/or fusiform aneurysms, but the risk conveyed by additional stents has not yet been defined. Apposition of the second stent to the vessel wall may be limited by the first stent. Furthermore, overlapping stents may increase the risk of perforator occlusion, and the greater number of intraluminal stent struts may increase thromboembolic risk. Results from several smaller series have suggested efficacy and safety with the use of overlapping-stent constructs.^3,8,30 Chalouhi et al.⁴ reported no complications in 28 patients with overlapping stents. Our study may include the largest series of overlapping-stent treatments for aneurysms. With all stent types included in the analysis, an overlapping-stent configuration was a statistically significant independent risk factor for major complications in 80 treated aneurysms.

There has been considerable enthusiasm for Y-configuration stenting since its description a decade ago. Reports from several small series described good results, but few reports from larger series have been published. Y-configuration stenting places the tines of both stents in the lumen of the vessel bifurcation in an unpredictable fashion as 1 stent is opened through a single cell of the other. Furthermore, friction may occur as 1 stent is pulled through the struts of the other, resulting in stress on the cerebral vasculature and predisposing it to vessel perforation.¹ Fargen et al.⁸ combined the single-center experiences of 7 institutions and found that among 45 patients treated with Y-configuration stenting, 3 (7.5%) of 40 had a modified Rankin Scale score of ≥ 3 at follow-up. Spiotta et al.³⁰ reported 4 clinically significant strokes in a series of 19 patients with Y-stented aneurysms, 3 (15.8%) of which seemed to be major complications. Chalouhi et al.⁵ reported 1 significant complication (6.3%) in 16 basilar tip aneurysms treated with Y-configuration stenting. Heller et al.¹² reported 16 cases in which Y-configuration stenting was used without complications or restricted diffusion seen in follow-up MRI. Results from our series suggest that Y-configuration stenting is an independent risk factor when compared with single SAE. Nonoverlapping Y-configuration stenting may be a safer alternative to standard Y-configuration stenting.⁷

Limitations

There were several limitations in this retrospective single-center series. First, there are different indications for each stent type, and stent selection was not randomized. Furthermore, there was no true control group in the study. A limited number of factors were considered in the complication analysis, and some risk factors that other authors have found were not analyzed. For example, fusiform aneurysms are tremendously heterogeneous. Perhaps most important is that analyses of factors that influenced the choice of configuration were not tracked, particularly with respect to technical complications with assisted single-stent embolization, which may have led to overlapping constructs. Thus, some single-stent complications may have been falsely attributed to the overlapping-construct group.

Stent-selection criteria were not uniform because Neuroform stents were introduced into practice before Enterprise stents. The Enterprise-stent group may have had advantageous selection criteria, whereas the Neuroform stent was required for all cases before the availability of the other stents, including those in which overlapping stents were required. The learning curve for stenting may have been steepest for Neuroform stenting because of its early introduction.

Future SAE

Stents have become increasingly tailored to treat different types of intracranial aneurysms. Advances in stent delivery and options for stent size and porosity, including flow diverters, have decreased the need for complex stent configurations. This series provides an example of technological progress in the embolization of many large, giant, and fusiform aneurysms, which was more challenging when first-generation self-expanding nitinol stents were used. As aneurysm-embolization technology continues to evolve, it will provide more precise, safer, and durable treatment for patients with intracranial aneurysms.