Pipeline embolization of distal posterior inferior cerebellar artery aneurysms

Abstract

Background and purpose

Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED.

Materials and methods

Clinical and angiographic data of eligible patients was retrospectively obtained and assessed for key demographic characteristics and clinical and angiographic outcomes. Principal outcomes included rates of aneurysm occlusion, ischemic or hemorrhagic complication, technical complication, and in-stent stenosis.

Results

Three female and 2 male patients underwent placement of PED in the PICA for treatment of 5 distal PICA aneurysms. Clinical and angiographic follow-up was obtained for all patients. Complete aneurysm occlusion was observed in 100% (5/5) of treated aneurysms at 6 month and longest angiographic follow-up. While there were no ischemic or device-related complications, delayed hemorrhagic complications occurred in 20% (1/5) of patients.

Conclusion

Pipeline embolization of distal PICA aneurysms can be performed in select patients. Further study is necessary in larger cohorts to better define clinical scenarios in which flow diversion in the distal PICA should be considered.

Introduction

Aneurysms of the posterior inferior cerebellar artery (PICA) are challenging to treat due to close proximity of the brain stem, complexity of surgical access, high morphological variability, and overall low incidence.^1–3 As such, a variety of open and endovascular treatments can be considered when treating these aneurysms.^3–6

Flow diverting stents are a promising endovascular treatment for intracranial aneurysms. The most widely used flow diverter, the Pipeline Embolization Device (PED), has demonstrated high levels of safety and efficacy when used for aneurysm treatment in approved regions of the internal carotid artery.^7–10 Use of PED to treat distal PICA aneurysms is sometimes considered due to the potential challenges of more conventional treatments, but this use is considered off-label and is not well studied. Some series studying outcomes of flow diversion in the posterior circulation have included a small number of PICA aneurysms treated with PED, ¹¹ while other reports on PICA aneurysms primarily include PEDs placed in the vertebral artery to treat aneurysms at the PICA origin. ¹² , ¹³ There is therefore a need to assess the safety and efficacy of PED for treatment of distal PICA aneurysms in order to guide therapeutic decision-making. In this work, we report clinical and angiographic outcomes of flow diversion with PED in the distal PICA to share our treatment strategy and outcomes of flow diversion in this region.

Methods

Patient selection

Institutional review board approval was obtained to conduct this study. All patients that underwent PED treatment of aneurysms in the distal PICA at our center between October 2011 to March 2020 were reviewed. Placement of the PED entirely within the PICA was a requirement for inclusion. Aneurysms of the PICA origin are not included in this analysis, and all aneurysms included in this study were located within the 5 distal segments of the PICA.

Embolization procedure

Informed consent for each procedure was obtained for all patients per clinical routine prior to treatment. Dual antiplatelet therapy comprising aspirin plus clopidogrel or ticagrelor was initiated prior to treatment, and dose was titrated based on the VerifyNow assay. ¹⁴ Heparin was administered during the procedure and titrated to a target activated clotting time of approximately 2.5 times above baseline. All reviewed patients underwent embolization via a transfemoral or transradial route in the supine position in a biplane neurointerventional suite. Vascular access was established using 6, 7, and 8 French Shuttle sheaths (Cook Medical, Bloomington, IN) depending on patient factors and access site selection. Guide catheters used were the 058 Navien (Medtronic Neurovascular, Irvine, CA), 6 French Sofia (Microvention, Aliso Viejo, CA), and Phenom Plus (Medtronic Neurovascular). All PEDs were deployed using either a Marksman (Medtronic Neurovascular) or Phenom 27 (Medtronic Neurovascular) microcatheter. Post-procedural care, including the use of closure devices and access site monitoring, was performed per clinical routine. Initial angiographic follow-up was generally performed approximately 6 months post-treatment. In most cases, dual antiplatelet therapy was continued for 6-12 months, followed by indefinite aspirin monotherapy.

Data acquisition and classification

Patient characteristics (age, sex, major comorbidities, indication for treatment), aneurysm characteristics (location, size, shape), peri-procedural details (antiplatelet dosage and activity corresponding to the available PRU closest in time to the treatment angiogram, patient level of function), treatment details (retreatment status, access site, PED delivery system, device size, challenges in deployment, immediate procedural complications), angiographic follow-up (aneurysm occlusion, in-stent stenosis), and clinical follow-up (patient level of function, ischemic or hemorrhagic complications) were collected. Assessed comorbidities were hypertension, diabetes mellitus, hyperlipidemia, and recent smoking history. Patients who quit smoking more than 6 months before PED placement did not have smoking counted as a comorbidity. Total duration of follow-up was determined as the time from PED placement to the most recent angiography. Angiography performed 6 ± 2 months after PED placement is considered 6-month follow-up angiography. Patients who declined follow-up were still included in this study to acquire relevant periprocedural data.

Aneurysm location is reported based on the PICA segment (anterior medullary, lateral medullary, tonsillomedullary, telovelotonsillar, or cortical) in which the aneurysm was located. Aneurysm size is reported based on the largest dimension recorded before treatment. Aneurysm volume reduction and occlusion was determined using the O’Kelly-Marotta grading scale measuring degree of angiographic contrast filling, where total filling is defined by >95% filling of the aneurysm, subtotal filling is defined by 5-95% filling of the aneurysm, entry remnant is defined by <5% filling of the aneurysm, and occlusion is defined by 0% filling of the aneurysm. ¹⁵ In-stent stenosis is reported as a percentage decrease in luminal caliber relative to normal distal artery. Aneurysm occlusion status was reported for both 6-month follow-up angiography and most recent follow-up angiography in patients that presented for later imaging. Rates of aneurysm occlusion and ischemic or hemorrhagic complication were calculated on a per-aneurysm and per-patient basis, respectively. In-stent stenosis rate and technical complication rate were calculated on a per-treatment basis. Baseline and post-procedural level of function was measured with the modified Rankin Scale (mRS). ¹⁶

Results

Patients and aneurysms

Five patients with 5 distal PICA aneurysms were treated with PED at our center. Details of these patients and aneurysms are outlined in Table 1. Three aneurysms had fusiform morphology and 2 were saccular. Mean aneurysm size was 5.0 mm (range 3.2–6.0 mm). One aneurysm was recently ruptured and one aneurysm was unruptured but symptomatic due to progressive mass effect on the brain stem. Deployed PEDs had diameters ranging from 2.5–4.25 mm and lengths ranging from 10–25 mm. Four of 5 treatments involved a single PED.

Table 1.

Patient and aneurysm details.

Patient number	Age	Sex	Clinical indication	Previous treatment	Comorbidities	Aneurysm location	Aneurysm size (mm)	Aneurysm morphology
1	71	F	Incidental	None	Hyperlipidemia, smoker	Left PICA, tonsillomedullary segment	5.4	Fusiform
2	72	M	Recurrence (previous rupture)	Coiling	Hypertension, hyperlipidemia, cardiovascular disease, intracranial hemorrhage, stroke	Left PICA, lateral medullary segment	5.0	Fusiform
3	81	M	Symptomatic (mass effect)	None	Hypertension, hyperlipidemia, cardiovascular disease	Right PICA, lateral medullary and tonsillomedullary segments	6.0	Fusiform
4	59	F	Rupture	None	Hypertension, intracranial hemorrhage	Right PICA, lateral medullary segment	3.2	Saccular
5	49	F	Incidental	None	Diabetes	Left PICA, telovelotonsillar segment	5.4	Saccular

Clinical outcomes and complications

Technical complications caused by catheter navigation or device deployment were observed in 0% of procedures (0/5). Procedural details are provided in Table 2. Two procedures required use of the “buddy wire” technique in which two microwires were inserted through the microcatheter in parallel to facilitate trackability, one procedure required three-dimensional roadmapping, and one procedure required microcatheter tip steam shaping. Clinical follow-up was available in all patients treated with PED. Mean clinical follow-up time was 25 months (range 5–89 months). The overall rate of ischemic or hemorrhagic complications was 20% (1/5). Follow-up details of our cohort are outlined in Table 3.

Table 2.

Procedural technique.

Patient number	PED size (mm)	Parent vessel size (mm)	Access site	Delivery system	Special techniques
1	2.5 × 16	2.2	Femoral	7 French Cook Shuttle, 058 Navien, Marksman	“Buddy wire” technique, steam-shaped microcatheter tip
2	2.5 × 14	1.7	Femoral	8 French Cook Shuttle, 058 Navien, Marksman	None
3	3.0 × 20, 3.5 × 25, 3.75 × 25, 3.5 × 16a	2.6	Radial, femoral	6 French Cook Shuttle, Phenom Plus, Phenom 27	None
4	2.5 × 16	1.8	Radial	6 French Cook Shuttle, 058 Navien, Phenom 27	None
5	2.5 × 10	2.3	Femoral	6 French Cook Shuttle, 6 French Sofia, Phenom 27	Three-dimensional roadmapping, “buddy wire” technique

^aAll PEDs placed in a telescopic construct in a single treatment session.

Table 3.

Clinical and angiographic follow-up.

Patient number	mRS (baseline, follow-up)	Clinical follow-up (months)	Complications	Angiographic follow-up (months)	6-month in-stent stenosis	6-month aneurysm patency	Final in-stent stenosis	Final aneurysm patency
1	0, 0	14	None	14	None	Occluded	None	Occluded
2	1, 3	89	None	19	None	Occluded	None	Occluded
3	3, 6	5	Intracranial hemorrhage	4	None	Occluded	None	Occluded
4	0, 0	10	None	6	None	Occluded	None	Occluded
5	0, 0	8	None	8	None	Occluded	None	Occluded

Patient 3 underwent flow diversion without any immediate perioperative clinical or technical complications. The patient was discharged to home after treatment at neurological baseline. Five months later, the patient was admitted to another hospital with severe hypertension and found to have a hypertensive intracranial hemorrhage in the basal ganglia. The patient expired shortly thereafter. Flow diversion was unlikely to be the cause of intracranial hemorrhage, but PED-related dual antiplatelet therapy could have contributed to the severity of hemorrhage. There were no ischemic complications in our cohort.

Angiographic outcomes

Angiographic follow-up was available in all patients treated with PED, with a mean angiographic follow-up time of 10.2 months (range 4–19 months). 100% (5/5) of aneurysms showed complete occlusion at 6-month and final follow-up for patients undergoing subsequent angiography. No instances of in-stent stenosis were observed. Pre, intra, and post-operative imaging for representative patients are shown in Figures 1 and 2.

Figure 1.

Angiographic images in Patient 3. (a) Axial T1-weighted post-contrast MRI shows a partially thrombosed fusiform aneurysm of the right PICA with mass effect on the brain stem. (b) Pre-treatment angiography showing irregular 6.0 mm lumen of the partially thrombosed aneurysm. (c) Spot image showing complete PED construct containing 4 devices (arrows). (d) 4-month post-treatment angiography demonstrates complete occlusion of the aneurysm.

Figure 2.

Angiographic images in Patient 5. (a) Pre-treatment 3 D angiography showing a 5.4 mm saccular aneurysm of the distal left PICA. (b) Pre-treatment 2 D angiography image showing aneurysm. (c) Spot image showing single 2.5x10 mm PED deployed across the aneurysm (arrows). (d) 8-month post-treatment angiography demonstrates complete occlusion of the aneurysm.

Discussion

In this work, we report outcomes of flow diversion for distal PICA aneurysms using PED. Among 5 treated aneurysms, there was complete occlusion in 100% of aneurysms and ischemic or hemorrhagic complications in 20% of patients.

The use of flow diversion as a primary method of treatment for intracranial aneurysms has increased dramatically in the past decade, particularly after the publication of clinical trials demonstrating favorable safety and efficacy of PED in approved regions of the internal carotid arteries. ⁹ , ¹⁰ As experience in clinical practice has increased, neurointerventionalists have often utilized PED in off-label applications, particularly for cerebrovascular regions other than the internal carotid arteries.

Real-world experience has suggested higher complication rates of flow diversion in the posterior circulation. Notably, the IntrePED study reported neurologic morbidity or mortality in 16.5% of posterior circulation aneurysms treated with PED, and a meta-analysis of non-saccular posterior circulation aneurysms by Kiyofuji et al. observed periprocedural stroke in 23% of aneurysms treated with flow diversion. ¹⁷ , ¹⁸ Many of these complications may be attributable to the high density of perforating arteries arising from the distal vertebral, basilar, and proximal posterior cerebral arteries that supply critical and highly eloquent brain structures.^19–22 As a result, even small infarcts resulting from coverage of these perforating arteries by PED can be disabling.

In this respect, the distal PICA may be functionally different from other arteries in the posterior circulation. The majority of perforating arteries that arise from the PICA to supply crucial structures such as the lateral medulla originate from the very proximal segment of the PICA. Beyond this point, the PICA supplies only the cerebellum and may have redundant supply from other cerebellar arteries. Indeed, a recent study on the hemodynamics of PICA aneurysms treated with PED revealed that while aneurysmal inflow was slowed, flow into perforators and branches was not compromised. ²³

Our focus on distal PICA aneurysms, in which the PED is deployed entirely within the PICA, is also of relevance to our outcomes. Wallace et al. have suggested that PICA origin aneurysms have a lower rate of occlusion following PED placement due to persistent flow into the PICA. ¹³ Thus, distal PICA aneurysms specifically may represent an attractive target for flow diversion. The appeal of PED is especially high for distal PICA aneurysms that would otherwise require surgical trapping and bypass.^24–27 In these circumstances, flow diversion offers distal flow preservation that obviates the need for surgical bypass. Further, unintentional occlusion of the PED would likely have similar consequences as unintentional occlusion of a bypass graft. Despite these features of Pipeline embolization, surgery remains an effective treatment modality for many of these aneurysms. ²² , ²⁸ A meta-analysis by Petr et al. reported high rates of safety and efficacy in PICA aneurysms treated surgically, with lower rates of procedure-related morbidity associated with distal PICA aneurysms compared to proximal PICA aneurysms. ²⁹ Given the heterogeneity in morphology and presentation, the selection of appropriate treatment of distal PICA aneurysms likely requires multimodal expertise. ³⁰

While flow diversion with PED in the PICA may be effective, this treatment presents technical challenges that mostly relate to navigating a 0.027 inch microcatheter into a small, distal, tortuous artery. ³¹ This challenge required the use of a “buddy wire” technique to increase microcatheter trackability in two cases, three-dimensional roadmapping in one case, and microcatheter steam shaping to facilitate vessel selection in one case. Additionally, access site was changed from radial to femoral in one case to improve the approach angle and avoid system prolapse. Given these challenges, we caution that considerable operator experience is needed to safely navigate robust, PED-compatible microcatheters into the small and tortuous PICA, though other reports have demonstrated that PED can be delivered safely in small vessels. ³¹ , ³² Moreover, the more recent introduction of flow diverters such as Silk Vista Baby (Balt Extrusion, Montmorency, France) and FRED Jr (Microvention), which are deliverable through 0.017 inch and 0.021 inch microcatheters, respectively, may also facilitate flow diverter placement in the distal PICA. ²²

The principal limitation of this study is that aneurysms in our cohort are not representative of all distal PICA aneurysms. Each of these patients was considered for alternative open and endovascular therapies by a multidisciplinary team of experts, and the use of PED in these highly selected patients reflects the difficulty of other treatments, general perioperative risk, or failure of prior treatment. The small number of aneurysms in this series prevents major conclusions regarding the PEDs safety and efficacy from being drawn. Additional limitations of our study include its retrospective design, heterogeneity in PED delivery systems employed, and variable follow-up times.

Conclusion

Pipeline embolization of distal PICA aneurysms is feasible in certain cases, though operator experience is important for these procedures given the technical challenges to this approach. Further study in large patient samples is necessary to confirm these findings and define rates of safety and efficacy for this off-label application of PED.

IRB approval number

202001107