Contemporary Results of Bare Platinum Coil Embolization for Wide‐Necked Ruptured Aneurysms: A Subset Analysis of the SMART Registry

Abstract

Background

Rupture status and presence of a wide neck are important factors that adversely impact angiographic occlusion after endovascular coiling. A potential strategy to improve occlusion rates in wide‐necked, ruptured aneurysms (WNRA) is modification of coil technology.

Methods

WNRA were chosen from the SMART registry that comprises 905 intracranial aneurysms treated with SMART bare platinum coils (Penumbra Inc., Alameda, USA) in the US and Canada. WNRA were defined as neck ≥4 mm, dome‐to‐neck ratio <2, or both. Clinical and angiographic data at presentation and follow‐up were assessed. Outcomes included adequate occlusion rate (Raymond–Roy occlusion class I or II), occlusion at 1 year, and good functional outcome (modified Rankin score 0–2) at 1 year. Angiographic outcome was compared for neck ≥4 mm versus <4 mm.

Results

A total of 143 patients (mean age 59.3, 74.1% female) with 143 WNRA were included. Median aneurysm size was 5.8 mm. 46.2% had a neck ≥4 mm. Balloon remodeling was used in 35.7% (51/143) and stents in 10.5% (15/143). Intraoperative thromboembolic complication rate was 7.0% (10/143). Overall immediate adequate occlusion rate was 78.3% (112/143); postprocedure occlusion rates were lower (62.1%, 41/66 versus 92.2%, 71/77) for aneurysms with necks ≥4 mm than those with necks <4 mm. At 1 year follow‐up, adequate occlusion was achieved in 82.4% (75/91) patients. Aneurysm occlusion improved in 31.9% (29/91) but worsened in 20.9% (19/91) of all patients at 1 year. Retreatment rate among patients who completed the study was 20.2% (20/99). One instance of intraoperative rupture (0.7%) was noted. Good functional outcome was achieved in 57.7% (41/71).

Conclusion

These results suggest that successful embolization of WNRA with new generation SMART coils can be achieved safely. WNRA continue to require assistive techniques at presentation and also retreatment over time. In addition, neck width may have an adverse impact on angiographic outcome.

Nonstandard Abbreviations and Acronyms

BR

balloon remodeling

D/N

dome/neck ratio

RIA

ruptured intracranial aneurysms

RROC

Raymond–Roy occlusion classification

WNRA

wide necked, ruptured aneurysms

Clinical Perspective

• Incremental improvement in coil technology appears to benefit the difficult subset of wide‐necked, ruptured aneurysms. Immediate adequate occlusion was achieved in 78.3% in the SMART registry series of 143 intracranial aneurysms treated with modified bare platinum coils. However, statistically significant inferior occlusion rates were noted in wide‐necked, ruptured aneurysms with neck ≥4 mm compared to those with neck <4 mm. Favorable safety profile was evident, with intraoperative rupture rate of 0.7%. Similarly, thromboembolic complications were seen in 7%.

• Angiographic follow‐up rate at 1 year was 63.6%. Aneurysm occlusion worsened in 20.9% at 1‐year and retreatment rate was 21.9%. Aneurysm occlusion improved in 31.9% at 1‐year follow‐up. No difference in follow‐up occlusion rates were noted between aneurysms with neck ≥4 mm compared to those with neck <4 mm.

• Among patients available for follow‐up, 1‐year mortality was 15.1%, related to complications from rupture. Good functional outcome (modified Rankin score 0–2) was noted in 57.7%; however, overall clinical follow‐up rate was only 50%.

Coil embolization of ruptured intracranial aneurysms (RIA) is accepted as the contemporary standard of care. ¹ , ² , ³ However, coiling is associated with recurrence rates of up to 40% at the higher end of the spectrum, which leads to increased morbidity from potential for rerupture and need for retreatment. ¹ , ² , ³ , ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ Degree of aneurysm occlusion is one of the main factors predicting recurrence and rehemorrhage after coil embolization. ¹¹ Rupture status and presence of a wide neck are important factors that adversely impact angiographic occlusion. ¹² Efforts to improve angiographic occlusion in wide necked aneurysms have focused on 2 main strategies: (1) adjunctive or novel devices (balloon remodeling [BR], stent assistance, PulseRider [Cerenovus, New Brunswick, NJ]), ¹³ Woven EndoBridge (WEB; Sequent Medical, Aliso Viejo, CA), ¹⁴ and (2) improvement in coil technology, namely better handling ability of bare platinum coils ¹⁵ or use of coated coils. ¹⁶ Currently, adjunctive permanent devices in regular clinical use require dual antiplatelet therapy which is a concern in the ruptured setting.

Modification of coil technology is a logical incremental step in improving endovascular treatment of RIA. The development of SMART coils (SMART; Penumbra Inc., Alameda, USA) was inspired by the need for softer proximal end of a bare platinum coils toward the end of deployment – this ensures stability of the coiling microcatheter such that greater coil volume can be packed in the aneurysm. ^{17 , 18} The SMART registry was established to follow the periprocedural safety, adverse event rate, and clinical and angiographic results of aneurysms treated with SMART coils between June 2016 and August 2018. ^{18 , 19} A total of 905 aneurysm patients were enrolled, making this one of the largest contemporary aneurysm coiling studies; primary endpoints were retreatment at 1‐year (efficacy) and major early (24 hours) device‐related adverse events. ¹⁹ We studied a subset of the SMART registry comprised of wide‐necked aneurysms presenting with rupture and discuss clinical and angiographic results of coil embolization with SMART coil technology.

Methods

The SMART Registry was a prospective, single‐arm, postmarket, multicenter registry designed to evaluate the SMART System (Penumbra, Inc.) in the treatment of intracranial aneurysms and other neurovascular lesions and sponsored by Penumbra, Inc. The SMART Registry was prospectively registered at clinicaltrials.gov (NCT02729740). The study received approval from the Institutional Review Board and Ethics Committee from each participating site with oversight for the duration of the registry. The details of inclusion and exclusion criteria for enrollment in the SMART registry have been described previously. ^{18 , 19} In the study, 905 intracranial aneurysms were treated at 67 North American sites between June 2016 and August 2018. 31.8% (288/905) were ruptured. Wide‐necked, ruptured aneurysms (WNRA) were chosen based on the following definition: aneurysm neck ≥4 mm, dome‐to‐neck ratio (D/N) <2, or both. Demographic data, aneurysm characteristics, use of assisted techniques, intraoperative complications, angiographic occlusion rates postprocedure, and at follow‐up were assessed. Evolution of occlusion was studied based on Raymond–Roy occlusion classification (RROC, class I: complete occlusion, class II: near complete, class III: incomplete). Adequate occlusion was defined as RROC I or II. The aneurysm occlusion outcomes were compared for aneurysms with neck ≥4 versus <4 mm. Written informed consent was provided by patients or their legally authorized representatives.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Statistical Analysis

Descriptive statistics with a 95% 2‐sided Wald asymptotic CI were presented for the primary effectiveness analysis. Continuous variables were summarized with descriptive statistics (n, mean, SD, median, and interquartile range). For categorical data, frequency counts, and percentages of subjects within each category were included. A subgroup analysis was conducted on neck width (≥4 mm against <4 mm), subject to the caveat that the study was not powered for this ad hoc comparison. Two‐sided 95% Wald asymptotic intervals for the difference in binomial proportions and 2‐sided P‐values based on Fisher's exact test for categorical data and the Wilcoxon rank‐sum test using normal approximations for ordinal data were reported for the subgroup comparison. SAS 9.4 (SAS Institute) was used for statistical programming.

Results

Demographics

The SMART registry includes 905 intracranial aneurysms were treated at 67 North American sites between June 2016 and August 2018. Of these, 143 patients with 143 aneurysms had WNRA. Age range was 26–93 years (mean 59.3 years, median 58 years). Female predominance was noted (106/143, 74.1%). A positive family history of intracranial aneurysms was noted in 8.4% (12/143). Nearly half were current or former smokers (47.6%, 68/143). Thirty‐two patients (22.7%) presented with high grade subarachnoid hemorrhage, defined by Hunt and Hess grades 4 and 5.

Aneurysm Characteristics

Of the 143 wide neck ruptured aneurysms, 25.9% (37) were in the posterior circulation. Overall, the most common locations were anterior communicating (29.4%, 42/143) and internal carotid artery‐posterior communicating segment (26.6%, 38/143). Five aneurysms previously treated with coil embolization presented with rupture. Table 1 shows patient and aneurysm characteristics. Median aneurysm size (maximum dimension) was 5.8 mm (interquartile range 3.9, 8.7 mm), ranging from 1.0 to 27.6 mm (mean 7 mm, SD 4.27). A total of 46.2% had a neck ≥4 mm (66/143), defined as the large neck group. Table 2 shows aneurysm characteristics for aneurysms with neck ≥4 mm compared to those with neck <4 mm.

Table 1.

Patient, Aneurysm, and Procedure Characteristics

	Wide‐necked ruptured aneurysms (N=143)
Patient characteristics
Age (y) (mean±SD)	59.3±14.3 (Range, 26–93)
Female sex	74.1% (106/143)
Family history of aneurysm or malformations	14.7% (21/143)
Smoking (current and former)	47.6% (68/143)
Aneurysm characteristics
Lesion location
Anterior communicating artery	29.4% (42/143)
Posterior communicating artery	26.6% (38/143)
Middle cerebral artery	10.5% (15/143)
Other anterior circulation	7.7% (11/143)
Basilar bifurcation	12.6% (18/143)
Other posterior circulation	13.3% (19/143)
Aneurysm size (mm) (median [IQR])	5.8 [3.9–8.7]
Neck width ≥4 mm	46.2% (66/143)
Hunt and Hess Grade IV–V	22.7% (32/141)
Procedure characteristics
Adjunctive techniques
None (unassisted coiling)	55.9% (80/143)
Stent‐assisted coiling	10.5% (15/143)
Balloon‐assisted coiling	35.7% (51/143)

IQR indicates interquartile range.

Table 2.

Aneurysm Characteristics, Stratified by Neck Width

Aneurysm characteristics (ruptured wide‐neck aneurysm subgroup)	Neck size ≥4 mm (N=66)	Neck size <4 mm (N=77)	Neck size ≥4–<4 mm (95% CI)	P value
Aneurysm size (mm)
N	66	77
Mean (SD)	10.2 (4.31)	4.3 (1.33)	5.9 (−7.0, −4.8)	<0.0001
Median [IQR]	9.1 [7.0, 12.2]	4.0 [3.4, 5.2]
Range (Min, Max)	4.6, 27.6	1.0, 7.5
Aneurysm size group
Small	0.0%	50.6% (39/77)	−50.6% (−61.8%, −39.5%)	<0.0001
Medium	59.1% (39/66)	49.4% (38/77)	9.7% (−6.6%, 26.0%)	0.3128
Large	39.4% (26/66)	0.0%	39.4% (27.6%, 51.2%)	<0.0001
Giant	1.5% (1/66)	0.0%	1.5% (−1.4%, 4.5%)	0.4615
Hunt and Hess Grading Scale
Grade I	21.9% (14/64)	15.6% (12/77)	6.3% (−6.7%, 19.3%)	0.3868
Grade II	34.4% (22/64)	35.1% (27/77)	−0.7% (−16.5%, 15.1%)	1.0000
Grade III	20.3% (13/64)	27.3% (21/77)	−7.0% (−21.0%, 7.0%)	0.4296
Grade IV	14.1% (9/64)	15.6% (12/77)	−1.5% (−13.3%, 10.2%)	1.0000
Grade V	9.4% (6/64)	6.5% (5/77)	2.9% (−6.1%, 11.9%)	0.5464
Aneurysm type
Saccular	84.8% (56/66)	93.4% (71/76)	−8.6% (−18.9%, 1.7%)	0.1094
Fusiform	3.0% (2/66)	0.0%	3.0% (−1.1%, 7.2%)	0.2143
Other	12.1% (8/66)	6.6% (5/76)	5.5% (−4.1%, 15.2%)	0.3824

IQR indicates interquartile range.

Aneurysm Treatment

All aneurysms were treated with coil embolization using the SMART coil system. Coil embolization was assisted with BR in 35.7% (51/143). Stent placement was performed in 10.5% (15/143) of cases. Of the 15 stent cases, 12 were planned and 3 were unplanned. Open cell design stents were used for 6 cases, closed cell design were used for 4 cases, braided stents were used for 5 cases, and 1 case utilized a Pulse Rider stent. One case used 2 stents; 1 open and 1 closed cell stent. Loading doses of antiplatelets were administered according to each center's standard of care. Stent placement was performed more often in the neck group ≥4 mm (16.7% versus 5.2%; P=0.031, 95% CI, 11.5% [1.2%, 21.7%]). Hence, over half of the aneurysms in the WNRA series were treated with stand‐alone coiling (Table 1). There was not a significant difference in rates of unassisted coiling or balloon‐assisted coiling between these 2 groups (Table 3).

Table 3.

Adjunctive Procedures, Stratified by Neck Width

Adjunctive treatment – during index procedure	Neck size ≥4 mm (N=66)	Neck size <4 mm (N=77)	Neck size ≥4–<4 mm (95% CI)	P value
Unassisted coiling	50.0% (33/66)	61.0% (47/77)	−11.0% (−27.3%, 5.2%)	0.2370
Stent‐assisted coiling	16.7% (11/66)	5.2% (4/77)	11.5% (1.2%, 21.7%)	0.0305
Balloon‐assisted coiling	34.8% (23/66)	36.4% (28/77)	−1.5% (−17.3%, 14.2%)	0.8630

Subjects may fall into more than one category. CIs are two‐sided 95% Wald asymptotic intervals for the difference in binomial proportions. P‐values are based on Fisher's exact test, subject to the caveat that the study is not powered for subgroup comparisons.

Angiographic Outcome‐Immediate Occlusion

Complete postoperative angiographic occlusion (RROC class I) was achieved in 39.9% (57/143). Near complete occlusion (RROC class II) occlusion was achieved in 38.5% (55/143). Incomplete occlusion (RROC class III) was noted in 21.7% (31/143). Adequate occlusion (RROC class I or II) rate was achieved in 78.3% (112/143) (Table 4 ). Packing density was calculated in 134 aneurysms. Median packing density was 28.4 (interquartile range 21.0, 40) and ranged from 5.0 to 146.5 (mean of 34.6, SD 22.6). Aneurysms with neck ≥4 mm had a lower rate of adequate occlusion (62.1%, 41/66 versus 92.2%, 71/77) than those with necks <4 mm. Overall postprocedure occlusion rates were statistically different between neck width groups (P<0.001) (Table 5).

Table 4.

Raymond–Roy Occlusion Classification

Raymond–Roy occlusion classification	Immediate postoperative
Class I–II (adequate occlusion)	78.3% (112/143)
Class I (complete occlusion)	39.9% (57/143)
Class II (neck remnant)	38.5% (55/143)
Class III (aneurysm remnant)	21.7% (31/143)

Table 5.

Raymond–Roy Occlusion Classification, Stratified by Neck Width

Raymond–Roy occlusion classification	Immediately after procedure			At 1‐year follow‐up
	Neck width ≥4 mm (N=66)	Neck width <4 mm (N=77)	P value*	Neck width ≥4 mm (N=37)	Neck width <4 mm (N=54)	P value*
Class I (complete occlusion)	22.7% (15/66)	54.5% (42/77)	<0.001	40.5% (15/37)	61.1% (33/54)	0.018
Class II (neck remnant)	39.4% (26/66)	37.7% (29/77)		29.7% (11/37)	29.6% (16/54)
Class III (aneurysm remnant)	37.9% (25/66)	7.8% (6/77)		29.7% (11/37)	9.3% (5/54)

Occlusion rates at 1‐year follow‐up do not represent evolution.

^* P values are based on the two‐sided Wilcoxon rank‐sum test using normal approximations, subject to the caveat that the study is not powered for subgroup comparisons.

Angiographic Outcome at Follow‐Up, Evolution of Occlusion, and Retreatment

Of the 143 WNRA patients treated with coils, 19 died, 1 was excluded from the registry by the investigator, 24 were lost to follow‐up, and 8 who returned for clinical follow‐up did not receive follow‐up angiography.

One year follow‐up angiograms were available in 91 patients. RROC class I was noted in 52.7% (48/91) and class II in 29.7% (27/91); adequate occlusion was achieved in 82.4% (75/91). Aneurysm occlusion improved in 31.9% (29/91), remained stable in 47.3% (43/91), and worsened in 20.9% (19/91). There was no statistically significant difference in evolution of occlusion rates based on neck size (≥4 mm against <4 mm). Overall retreatment rate among patients who completed the study was 20.2% (20/99) with similar retreatment rates between aneurysms with neck ≥4 and <4 mm (20.9% versus 19.6%).

Intraoperative Complications

Thromboembolic complications were noted in 10 patients (7.0%). Of these, 4 (2.8%) were asymptomatic and 6 (4.2%) were symptomatic. One patient experienced intraoperative rupture (0.7%) after microcatheter placement; this was managed with balloon control and successful coiling. Access site complications occurred in 2 patients (1.4%).

Clinical Follow‐Up

Among patients available for follow‐up, mortality at 1 year was 15.1% (18/119) and resulted from complications related to rupture at presentation. One additional patient died after 1 year. Functional outcome at 1‐year follow‐up was documented in 71 patients. Modified Rankin score 0–2 was achieved in 57.7% (41/71) of patients.

Discussion

Wide‐necked aneurysms presenting with rupture combine 2 aneurysm characteristics associated with poor outcomes. Multiple large studies have documented both rupture status and presence of wide neck as significant predictors of incomplete coil occlusion and recurrence. ⁴ , ⁵ , ^{6 , 10} , ¹¹ , ¹² Yet, the majority of papers do not address in detail results of coil embolization in the specific subset of WNRA. Viñuela et al described results of coil embolization with Guglielmi detachable coils in 403 RIA in a retrospective study. ¹⁹ A total of 146 (36.2%) had a neck >4 mm. However, a subset of these were assessed under the category “small aneurysms with wide neck” (77/403). When compared to entire cohort, lower rates of total occlusion (31.2% versus 49.8%) and higher rates of aneurysm remnants (10.4% versus 5.7%) and aborted cases (16.9% versus 5.7%) were noted in these 77 WNRA. Pierot et al reported results of a large cohort of 773 RIA treated with Guglielmi detachable coils/or coated coils in the prospective multicenter CLARITY study (Clinical and Anatomical Results in the Treatment of Ruptured Intracranial Aneurysms). A total of 322 were wide necked based on the definition of dome/neck ratio (D/N)≤1.5. On comparing anatomic occlusion rates between D/N≤1.5 and D/N>1.5, there was no significant difference in rates of complete occlusion (47.5% versus 47.2%), presence of neck remnant (39.8% versus 43.5%) or aneurysm remnant (12.7% versus 9.3%). Overall, BR was employed in 20.4% and stent placement in 1.8%; specific numbers in WNRA subset were not reported. ⁴ Mascitelli et al described the results of 177 WNRA (41 treated endovascularly) as part of the prospectively maintained BRAT (Barrow Ruptured Aneurysm Trial) study, focusing mainly on comparison with microsurgical clipping. ²⁰ WNRA were defined as neck ≥4 mm, D/N<2, or both. Balloon/stent assistance was used in 1.7% and 1.1%, respectively. It is interesting that balloon assistance was very sparingly used. Complete occlusion rates noted were 51.2% in immediate postoperative period, 31.8% at 3 years and 35.7% at 6 years. A retreatment rate of 26.8% was encountered at 6 years in the endovascular cohort. In our series, immediate complete occlusion rate (RROC class I) was 39.9%, comparable to the aforementioned series of WNRA. With the inclusion of RROC class II (neck remnants, 38.5%), the rate of “adequate occlusion” was 78.3%, which is again consistent with the published literature.

Neck width per se was found to be an important factor in determining occlusion. On sub‐group analysis of WNRA with neck ≥4 and <4 mm, the difference was significant, with lower adequate occlusion rates in the large neck group. The fallacy of an all‐inclusive definition of wide‐necked aneurysms has been recognized previously. ^{21 , 22} Whether an aneurysm is “overwide” (dome‐to‐neck ratio) or “undertall” (aspect ratio) likely has an influence on the operator's technical ability to achieve complete or adequate occlusion and on the need for balloon or stent assistance. Further analysis of this aspect needs to be explored, ideally in a dedicated investigation of the effect of neck width in different embolization devices in a large sample.

Use of Balloon Assistance

Balloon remodeling is an indispensable tool especially for coiling ruptured aneurysms with a wide neck. Pierot et al described use of BR in 20.4% of 773 RIA in the CLARITY study. ³ They also reported a much higher use of BR in WNRA in a subsequent study from the CLARITY data. Of 114 WNRA, BR was used in 45.6% of cases as compared to 16.5% of the 654 narrow‐necked RIA. Rates of adequate occlusion in the BR group (including both narrow and wide neck) compared to primary coiling group were significantly better. Dinç et al reported use of BR in 51% of 481 RIA treated with coil embolization (majority with bare platinum coils). ⁷ Unfortunately, they did not report separate results for WNRA (49.1% of aneurysms). The present series utilized BR in 35.7% versus 20.3% for the entire SMART cohort. ¹⁸ No significant difference in balloon use was noted between the 2 neck width groups.

Complications

Intraoperative rupture is a vexing phenomenon occurring at a rate of up to 7% in large series of coiling of ruptured aneurysms. ^{3 , 7 , 8 , 15} It is largely consistent across different coil types. Overall intraoperative rupture rate in SMART registry in the ruptured group was 3.4%. ¹⁷ The present series consisted of a single case of intraoperative rupture (0.7%) that occurred from microcatheter placement within the aneurysm. Therefore, SMART coils appear to confer no more increased procedural rupture risk while treating WNRA, which is consistent with its overall premise of better handling.

Evolution of Aneurysm Occlusion

The overall adequate occlusion rate at 1‐year in the ruptured aneurysm group of the SMART registry was 84.3%. The evolution of occlusion at 1 year follow‐up was interesting; improvement in RR class was noted in 31.9%. Published series of coiling for ruptured aneurysms report conflicting improvement rates in occlusion at follow up. For instance, in the mid‐term results of the CLARITY trial, Pierot et al reported improvement in occlusion at 16 months of only 12.9% with Guglielmi detachable coils and 11.3% with the coated coils. ⁴ Gallas et al reported 9.6% improvement in occlusion at mean 36 months follow‐up, among 705 RIA. ⁹ On the other hand, Friedman et al reported 29% improvement at mean 16.8 months follow‐up in a series of 83 RIA treated with Guglielmi detachable coils. ²³ The majority of aneurysms in the present study (47.3%) showed stability in aneurysm occlusion at follow‐up. Worsening in occlusion or recurrence was noted in 20.9% and this is also comparable with previously published series. Large series in literature have documented recurrence rates of 17%–65%. ^{5 , 24 – 26} Despite improvement in coil technology over the years, we are still saddled with a recalcitrant static recurrence rate with endovascular therapy for RIA. Identification of this subset should be the focus of future research. Retreatment rate was 14.0% in the current study, which is comparable to other studies reporting endovascular therapy for WNRA. ^{20 , 27 , 28} Additionally, the higher sensitivity of catheter angiography may have identified more aneurysms in need of retreatment.

Limitations

Angiographic occlusion was operator assessed, as opposed to core‐lab adjudicated independent assessment. While assessing morphological measurements, parameters such as aspect ratio or size ratio were not calculated. This would have been interesting given our observations of the difference in results between aneurysms with neck width ≥4 mm against <4 mm. One limitation of a real‐world study is the potential to lose patients to follow‐up. To minimize loss to follow‐up, sites were required to attempt to contact patients 3 times before sending a certified letter. In addition, one may argue that the follow‐up period of 1 year is not long term enough to adequately assess aneurysm stability.

Conclusions

Introduction of the SMART coil technology is a welcome addition to the armamentarium for coil embolization in WNRA. SMART coils are safe with regard to risk of intraoperative rupture or thromboembolic complications, while providing durable occlusion rates. Yet this challenging aneurysm type continues to require a high percentage of assistive techniques to achieve optimal results. Further, our series suggests a disproportionate effect of neck width on occlusion rates with coil embolization.

Sources of Funding

This study was funded by Penumbra Inc. (Alameda USA). Both the sponsor and authors were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Disclosures

MG Sattur, MS Park, R Bellon: None. BK Woodward: Consulting: Covidien. OO Zaidat: Grant/research support: Genentech, Medtronic Neurovascular, Stryker; Consultant: Codman, Medtronic Neurovascular, National Institutes of Health (NIH) StrokeNet, Penumbra, Stryker. Honoraria: Codman, Medtronic Neurovascular, Penumbra, Stryker. Expert witness. Ownership interest: Galaxy Therapeutics, LLC. AM Spiotta: Consulting: Stryker, Penumbra, Terumo, Siemens, Cerenovus. Research support: Stryker, Penumbra, Medtronic.