Background Endovascular treatment of wide-necked aneurysms is challenging. Stent-assisted coiling (SAC) is associated with increased complications and requires dual antiplatelet therapy.
Objective To compare treatment of unruptured, wide-necked aneurysms with a dual-microcatheter technique (DMT) versus SAC.
Methods Between 2006 and 2011, 100 patients with unruptured wide-necked intracranial aneurysms were treated with DMT and 160 with SAC. Over time there was a significant decrease in the use of SAC and a corresponding increase in DMT. The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm dome diameter with 120 patients treated with SAC. Outcomes were determined with conditional (matched) multivariate analysis.
Results There were no significant differences in patient or aneurysm characteristics between cohorts, including aneurysm diameter, neck width, or volume. Overall packing density and coil volume achieved was not significantly different between cohorts. There were higher rates of overall complications in those receiving SAC (19.2%) compared with DMT (5.0%; p=0.012), but no significant difference in major complications (8.3% vs 1.7%, respectively; p=0.103). At a mean follow-up of 27.0±18.9 months, rates of retreatment did not differ between DMT (15.1%) and SAC (17.7%). Delayed in-stent stenosis occurred in five patients and in-stent thrombosis in four patients treated with SAC. There was no difference in favorable functional outcome (modified Rankin score 0–2) between those treated with DMT (90.6%) compared with SAC (91.2%).
Conclusions DMT and SAC are effective endovascular approaches for unruptured, wide-necked aneurysms; however, DMT may result in less morbidity. Further long-term studies are necessary to determine the optimal indications for these treatment options.
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Improvements in neurointerventional technology have greatly increased the safety and efficacy of endovascular treatment of intracranial aneurysms. Despite these advances, the treatment of wide-necked aneurysms remains particularly challenging owing to the lack of support of the coil matrix, the increased risk of parent vessel compromise, and the inability to pack the aneurysm densely as compared with classic aneurysms with narrow necks. The presence of a wide neck has been found to be a significant predictor of both procedural complications and aneurysm recurrence.1
Balloons and stents have been used to assist in the coiling of wide-necked aneurysms, but these adjuncts are not without their respective limitations and complications.2–6 Stents require dual antiplatelet therapy, which increases hemorrhagic complications and makes the treatment of patients with subarachnoid hemorrhage more challenging.7 ,8 Additionally, stents are difficult to place in small vessels or in tortuous anatomy and are associated with late complications, including delayed thromboembolic phenomena and in-stent stenosis.5 ,6 Balloon-assisted coiling requires temporary flow arrest and may be associated with an increased risk of vessel rupture and thromboembolic complications.4 Overall morbidity and mortality ranges from 2.2% to 9% in balloon-assisted aneurysm coiling and from 1.4% to 21% with stent-assisted coiling.2–6 ,9–11 One alternative to these technologies is to use a dual microcatheter technique, in which two microcatheters are positioned within the aneurysm so that coils may be deployed either concurrently or sequentially. This method allows the operator to effectively lock the coils in place to form a stable construct and reduce the potential for coil herniation.12
At our institution, we have moved away from stent-assisted coiling (SAC) of wide-necked aneurysms in favor of the dual-microcatheter technique (DMT). In this study, we compare these two techniques in a matched cohort analysis of unruptured, wide-necked aneurysms to assess the rates of aneurysm occlusion, complications, and patient functional outcomes.
The study protocol was approved by the local institutional review board. We queried our prospectively maintained neurointerventional database for all patients with a wide-necked aneurysm who underwent treatment with either DMT or SAC between 2006 and 2012. Clinical and radiographic records were independently reviewed by a member of the research team who did not participate in the treatment of any of the included patients. Patient demographics, treatments details and effects, results of follow-up procedures, and complications were recorded. During this time, 100 patients were treated with DMT and 160 were treated with SAC. Additionally, there was a significant decrease in SAC and corresponding increase in DMT over the same period (p<0.001). The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm size with 120 patients treated with SAC for an unruptured, wide-necked intracranial aneurysm.
A wide-necked aneurysm was defined as a dome to neck ratio of <2 or a neck diameter >4 mm.13–16 Only saccular aneurysms were included in this study. Patients with dissecting, fusiform, and blister aneurysms were excluded.
All patients with wide-necked aneurysms were started on aspirin and Plavix 5-7 days prior to treatment. Aspirin and Plavix was stopped on the day of the procedure in patients that were then successfully treated with DMT. Access to the femoral artery is obtained in a standard fashion, and all patients treated with SAC or a DMT were given an intravenous heparin bolus at the beginning of the procedure to achieve an activated clotting time of 250–300 s. Care must be taken with the selection of a guiding catheter to ensure that it can simultaneously accommodate two microcatheters. The microcatheters can be either preshaped or steam-shaped to improve navigability and stability. The first microcatheter is advanced over a microguidewire into the aneurysm under roadmap guidance in a standard fashion. At this point, attempts may be made to coil the aneurysm using a single microcatheter. Once it is determined that the dual microcatheter technique will be needed, a second microcatheter is introduced and advanced into the aneurysm. To prevent inadvertent manipulation, the microcatheter that is not in use is covered with a towel. The second microcatheter is usually steam shaped with a different curve than the first catheter so that the two microcatheters will occupy different portions of the aneurysm sac. Care must be taken when positioning the second microcatheter since it may cause the first microcatheter to migrate forward. Two distinct general strategies for using DMT are ‘interleaving’ and ‘locking’.
The ‘interleaving’ technique is most often used in particularly wide-necked aneurysms. In these cases it may not be possible to place the framing coil into the aneurysm sac without herniation of coil loops out of the neck. In order to prevent coil herniation, the second microcatheter is placed into the aneurysm and the operator alternates delivery of the coils, first through one catheter and then through the other, thereby ‘interleaving’ the two coils. Typically, the first coil is deployed until a loop begins to herniate. This loop is pulled back into the aneurysm then the second coil is pushed until a loop of the second coil begins to herniate. In this manner the operator alternates pushing the coils through each catheter until both coils have formed a stable matrix within the aneurysm. With experience, patience, and careful manipulation, even very wide-necked aneurysms can be treated in this fashion. Using the longest available framing coils, it is possible to place 60–100 mm of coil before detachment of either coil. Given that such large volumes of coil can be placed, it is usually possible to construct a stable frame with the two initial coils, allowing the remainder of the embolization procedure to proceed successfully. Once the frame is formed, one of the coils is detached. Typically, the smaller coil is detached first (if they are different sizes) or the second coil introduced is detached first (if the coils are the same size). One coil is always left attached to the pusher wire while additional coils are introduced through the second catheter. This maneuver provides further stability to the construct and helps to prevent movement of the frame or herniation of coil loops.
The ‘locking’ technique is as follows: in some aneurysms it is possible to place an entire framing coil without herniation of loops. In many such cases, however, the construct is not entirely stable. Once the coil is detached it may move, and a portion or the entirety of the coil may herniate into the parent artery. In these situations, we often opt to place a second catheter and introduce a second framing coil into the aneurysm. This second coil effectively ‘locks’ the first coil in place. Again, large volumes of coils can be placed in the aneurysm, forming a stable frame before either coil is detached. In this situation, the second coil placed is detached while the first coil is left attached thereby stabilizing the frame while additional coiling proceeds.
Treatment of all elective patients was started with standard oral dual antiplatelet therapy consisting of aspirin 325 mg daily and clopidogrel 75 mg daily for 5–7 days before the procedure. The choice of a Neuroform (Boston Scientific Corporation, Natick, Massachusetts, USA) or Enterprise (Cordis, Miami Lakes, Florida, USA) stent was left to the operator's discretion. When feasible, the aneurysm was accessed through the stent interstices and coiled under roadmap guidance during the same procedure.
All patients were monitored in the neurological intensive care unit after the procedure. Upon discharge, all patients continued with a dual antiplatelet regimen. Starting in October 2007, the VerifyNow system (Accumetrics, San Diego, California, USA) was used to monitor clopidogrel and aspirin platelet inhibition levels. Patients resistant to clopidogrel were prescribed ticlopidine 250 mg twice daily. Clopidogrel was typically prescribed for 3 months while aspirin was continued indefinitely.
Assessment of imaging outcomes was carried out independently by two neuroradiologists who did not participate in the patient's treatment. When there was disagreement about the outcome, a third independent neuroradiologist was asked to evaluate the case. Immediate treatment outcomes were documented in all cases via digital subtraction angiography. At discharge, patients were scheduled for 6- and 12-month angiographic follow-up with the intention of imaging via CT angiography, MR angiography, or catheter diagnostic angiography. Follow-up imaging was evaluated for stability, recurrence, or progressive/delayed occlusion of the aneurysm. In cases of recurrent or residual aneurysms, the remnant was graded according to the Raymond classification.17
Through an exhaustive review of the patients’ medical records, the clinical presentation and outcomes of each patient were recorded. Clinical status was stratified using the modified Rankin Scale, with a score of 0–2 defined as a favorable outcome.18 Complications were classified as major if they resulted in permanent morbidity, transient if they were temporary, and overall as a composite of the two. Overall retreatment included patients undergoing endovascular therapy or microsurgery.
Data are presented as mean and range for continuous variables and as frequency for categorical variables. The Mantel–Haenszel test for linear association was used to assess changes over time. The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm dome diameter. Analysis was carried out using a matched t test and McNemar's test as appropriate. Univariate conditional (matched) analysis was used to test for covariates predictive of the following dependent variables: complications, retreatment, and overall outcome (modified Rankin score 0–2 vs 3–6). Interaction and confounding was assessed through stratification and relevant expansion covariates. Factors predictive in univariate analysis (p<0.20)19 were entered into a multivariate conditional (matched) logistic regression analysis. p Values ≤0.05 were considered statistically significant. Statistical analysis was carried out with Stata V.10.0 (College Station, Texas, USA).
Patient and aneurysm characteristics
There were no significant differences in patient demographics or aneurysm characteristics between the 60 patients treated with DMT and the 120 patients treated with SAC (table 1). The mean age of patients treated with DMT was 57.9±1.5 years vs 56.7±1.0 in those treated with SAC (p=0.486). The mean maximal aneurysm diameter, neck width, and aneurysm volume in patients treated with a DMT compared with SAC were 8.2±4.1 mm vs 8.2±4.4 mm (p=0.936), 4.6±1.3 mm vs 4.8±1.7 mm (p=0.407), and 299.8±490.3 mm3 vs 309.8±564.9 mm3 (p=0.907), respectively.
Aside from the method of treatment (DMT vs SAC), there was no significant difference in aneurysm treatment parameters between the two cohorts (table 1). The volume of Cerecyte, hydrogel, and platinum coil, and the total coil volume were not significantly different between the two cohorts. Additionally, the average packing density was not significantly different in patients treated with DMT (29.1±21.1) versus SAC technique (29.0±57.1; p=0.988).
Initial treatment outcomes
Initial obliteration (>95%) was achieved in 32 patients (53.3%) treated with DMT and 64 patients (53.3%) treated with SAC. Of the aneurysms that were not occluded during the initial treatment, 50% of the DMT cohort and 49% of the SAC cohort demonstrated residual filling within the aneurysm lumen, and 50% of the DMT and 51% of the SAC cohort demonstrated a residual aneurysm neck.
Higher rates of overall complications were found in those undergoing SAC (19.2%) versus DMT (5.0%; p=0.012) but no significant differences in major complications between the SAC (8.3%) and DMT (1.7%) cohorts (p=0.103, table 2). Intraprocedural rupture occurred in one patient treated with DMT (1.7%) and no patients treated with SAC. In the only death in our series, one patient treated with DMT had a significant hemorrhage, hydrocephalus, and died after microcatheter perforation of the aneurysm. In the multivariate analysis, patients treated with SAC were 3.88 times (95% CI 1.08 to 13.85, p=0.037) more likely to have a complication when controlling for other independent predictors: female gender (OR=8.14; 95% CI 1.03 to 64.12, p=0.046) and neurological deficit on presentation (OR=4.64; 95% CI 1.37 to 64.12, p=0.014; table 3).
Follow-up was available at a mean interval of 27.0±18.9 months for 166 patients (113 treated with SAC; 53 treated with DMT). The rates of follow-up obliteration (>95%) were not significantly different in those treated with SAC (63.7%) versus DMT (64.2%). According to the Raymond classification, recurrence was significantly more likely within the aneurysm dome in those treated with SAC and significantly more likely to occur at the aneurysm neck in those treated with DMT (p=0.05). In patients treated with SAC, symptomatic delayed in-stent stenosis occurred in five patients and in-stent thrombosis occurred in four patients.
Analysis of retreatment
Rates of overall retreatment were not significantly different in those receiving DMT (15.1%) versus SAC (17.7%). This includes microsurgical clipping and thrombus resection for progressive, symptomatic mass effect secondary to aneurysm growth that was performed in two patients treated with SAC. Rates of endovascular retreatment were not significantly different between those receiving DMT (15.1%) and SAC (15.9%). In the multivariate analysis, the only independent predictors of overall retreatment were increasing aneurysm maximal diameter (OR=1.16; 95% CI 1.05 to 1.29, p=0.003) and increasing follow-up (OR=1.02; 95% CI 1.01 to 1.04, p=0.025). When controlling for independent predictors, treatment modality was not predictive of retreatment (p=0.701, table 3).
Overall functional outcome
There was no significant difference in overall favorable outcome (modified Rankin score 0–2) at discharge between the SAC (95.0%) and DMT (96.7%) cohorts (p=0.721). There was no significant difference in overall favorable functional outcome (modified Rankin score 0–2) between those treated with DMT (90.6%) compared with SAC (91.2%, p=0.903). In the multivariate analysis, increasing aneurysm volume was predictive of worse functional outcome (OR=1.03; 95% CI 1.01 to 1.05, p=0.042, table 3). When controlling for aneurysm volume, treatment modality was still not predictive of functional outcome (p=0.857).
Wide-necked intracranial aneurysms are one of the greatest challenges to endovascular treatment. The anatomic characteristics of these lesions encourage coil egress from the aneurysm dome, increasing the risk of complications and post-treatment recurrence.1 In this matched cohort study of patients with unruptured, wide-necked intracranial aneurysms undergoing treatment with either DMT or SAC, we have determined that both endovascular treatments are effective for these challenging lesions, with similar rates of aneurysm obliteration, retreatment, and favorable functional outcome. However, when controlling for other independent factors, DMT may provide a benefit in reduced overall complications as compared with SAC.
Baxter et al12 first reported the use of DMT as a rescue technique for the treatment of two wide-necked aneurysms. Since then, there have been case reports and a small case series reporting outcomes with this technique.20–22 DMT makes use of basic endovascular techniques that are familiar to neurointerventionalists.
Despite improvements in tracking and control, adjunctive devices like stents may still be difficult to navigate through tortuous anatomy and can be contraindicated in small vessels.5 As DMT requires only a second microcatheter, these problems are essentially mitigated. Additionally, stents require the use of dual antiplatelet therapy, which increases the risk of hemorrhagic complications in patients with ruptured intracranial aneurysms.7 ,8 This makes DMT a particularly attractive treatment option in cases of subarachnoid hemorrhage, although further studies would be indicated. An ancillary benefit of DMT is that it allows for salvage with stent or balloon assistance in cases where DMT fails.
The DMT technique theoretically may have a higher risk of thrombus formation as a consequence of positioning two microcatheters into the small space of an intracranial vessel, as well as an increased risk of thrombus dislodgement and embolism from repositioning of multiple catheters and coils. However, in our series, overall complications were less frequent in the DMT cohort and major morbidity occurred in 8.3% of patients receiving SAC and 1.7% of those receiving DMT. Death occurred in only one patient (0.6%). Treatment with SAC remained an independent predictor of complications in the multivariate analysis. The overall complications rates in our series are comparable to cumulative morbidity rates reported in the literature; in 2262 SAC procedures the mean morbidity was 7.1% (range 1.4–23.2%).3–6 ,10 ,11 ,23
A potential limitation of DMT is a relatively high incidence of recurrence necessitating retreatment. A wide neck has been found to be a significant predictor of further retreatment which, in previous endovascular aneurysm series, has been reported to occur in 34–50% of lesions.24 In this series, we found that recurrence or retreatment rates were no higher in patients treated with DMT than in those treated with SAC. Our study showed greater than 95% obliteration in 67.1% of all treated aneurysms. Overall retreatment was necessary in 16.9% of cases.
Limitations of this study include the retrospective nature of our analysis and the lack of patient treatment randomization, which might have introduced a selection bias. Additionally, since all patients were treated at a single institution, they were subjected to the treatment biases of its physicians and to the referral biases of the institution. Although SAC has decreased over time as DMT has increased, there may be other inherent patient and aneurysm characteristics that differ between the cohorts that could not be controlled for in multivariate analysis. Further long-term outcomes are indicated in larger cohorts of patients with both unruptured and ruptured cerebral aneurysms to determine the optimal treatment for wide-necked aneurysms.
In summary, both DMT and SAC are safe and effective treatments for unruptured wide-necked aneurysms. Further studies with long-term clinical and radiographic outcomes are indicated to determine the best treatment for these patients, and the optimal indications for these treatment options.
RMS and CRD contributed equally.
Contributors All authors were responsible for concepts, design, definition of intellectual content, literature search, clinical studies, experimental studies, data acquisition, statistical analysis manuscript preparation, manuscript editing, manuscript review and are guarantors.
Competing interests AE is a consultant for Covidien and Stryker. MLJ is a consultant for Covidien. The University of Virginia Interventional Neuroradiology fellowship program is partially funded through a grant from Microvention.
Ethics approval UVA institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.
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