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Original research
A2, M2, P2 aneurysms and beyond: results of treatment with pipeline embolization device in 65 patients
  1. Christopher T Primiani1,
  2. Zeguang Ren1,
  3. Peter Kan2,
  4. Ricardo Hanel3,
  5. Vitor Mendes Pereira4,
  6. Wai Man Lui5,
  7. Nitin Goyal6,
  8. Lucas Elijovich6,
  9. Adam S Arthur6,
  10. David M Hasan7,
  11. Santiago Ortega-Gutierrez8,
  12. Edgar A Samaniego8,
  13. Ajit S Puri9,
  14. Anna L Kuhn10,
  15. Kirill Orlov10,
  16. Dmitry Kislitsin10,
  17. Anton Gorbatykh10,
  18. Muhammad Waqas11,
  19. Elad I Levy11,
  20. Adnan H Siddiqui11,
  21. Maxim Mokin1
  1. 1 Department of Neurosurgery, University of South Florida, Tampa, Florida, USA
  2. 2 Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
  3. 3 Department of Lyerly Neurosurgery, Baptist Neurological Institute, Jacksonville, Florida, USA
  4. 4 Division of Neuroradiology, University Health Network - Toronto Western Hospital, Toronto, Ontario, Canada
  5. 5 Division of Neurosurgery, Department of Surgery, The University of Hong Kong, Hong Kong, Hong Kong
  6. 6 Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee, USA
  7. 7 Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA
  8. 8 Department of Neurology, University of Iowa, Iowa City, Iowa, USA
  9. 9 Department of Radiology, University of Massachusetts, Worcester, Massachusetts, USA
  10. 10 Department of Neurosurgery, Meshalkin National Medical Research Center, Novosibirsk, Russia
  11. 11 Department of Neurosurgery, University at Buffalo, Buffalo, New York, USA
  1. Correspondence to Dr Maxim Mokin, Department of Neurosurgery, University of South Florida, Tampa, Florida, USA ; mokin{at}


Background Intracranial aneurysms located in the distal vessels are rare and remain a challenge to treat through surgical or endovascular interventions.

Objective To describe a multicenter approach with flow diversion using the pipeline embolization device (PED) for treatment of distal intracranial aneurysms.

Methods Cases of distal intracranial aneurysms defined as starting on or beyond the A2 anterior cerebral artery, M2 middle cerebral artery, and P2 posterior cerebral artery segments were included in the final analysis.

Results 65 patients with distal aneurysms treated with the PED were analyzed. Median aneurysm size at the largest diameter was 7.0 mm, 60% were of a saccular morphology, and 9/65 (13.8%) patients presented in the setting of acute rupture. Angiographic follow-up data were available for 53 patients, with a median follow-up time of 6 months: 44/53 (83%) aneurysms showed complete obliteration, 7/53 (13.2%) showed reduced filling, and 2/53 (3%) showed persistent filling. There was no association between patient characteristics, including aneurysm size (P=0.36), parent vessel diameter (P=0.27), location (P=0.81), morphology (P=0.63), ruptured status on admission (P=0.57), or evidence of angiographic occlusion at the end of the embolization procedure (P=0.49). Clinical outcome data were available for 60/65 patients: 95% (57/60) had good clinical outcome (modified Rankin Scale score of 0–2) at 3 months.

Conclusions This large multicenter study of patients with A2, M2, and P2 distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves.

  • aneurysm
  • angiography
  • artery
  • blood flow
  • device

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The pipeline embolization device (PED; Medtronic, Irvine, California, USA) is currently the most widely used flow diversion device for the treatment of brain aneurysms.1 Its on-label indications are large or giant wide neck intracranial aneurysms in the internal carotid artery from the petrous to the superior hypophyseal segments; however, the PED has been increasingly used for other anatomical locations. A review of the literature on the off-label use of the PED described its use for the treatment of acutely ruptured aneurysms, posterior circulation aneurysms, small aneurysms, including blister aneurysms, aneurysms with fusiform and dissecting morphologies, and distally located aneurysms.2

Distal aneurysms of intracranial arteries are rare and can be difficult to treat with either surgical (including clipping, bypass, and trapping) or traditional endovascular approaches (primary coiling, balloon assisted coiling, or stent assisted coiling) because of its non-saccular morphology, poorly defined margins, various underlying etiologies, such as infectious or dissections, and involvement of side branches.3 4 Several studies attempted to investigate the safety and efficacy of the PED for the treatment of distal aneurysms; however, most cases included in these series were limited to the aneurysms located at the A1 anterior cerebral artery (ACA) or M1 middle cerebral artery (MCA) segments.2 5–7 Utilization of the PED for the treatment of distally located intracranial aneurysms remains largely unknown and underrepresented in the literature. Here we review a multicenter experience with the PED exclusively for distally located aneurysms (on or beyond A2, M2, and P2 arterial segments).


Study design

The study was approved by the local institutional review board at each participating center for retrospective data collection and review. Consecutive cases of distal intracranial aneurysms treated with the PED between January 2011 and December 2017 at nine centers were included in this study. Distal aneurysms were defined as aneurysms on or beyond the A2 ACA, M2 MCA, and P2 posterior cerebral artery (PCA) anatomical segments according to the previously proposed classification.3 Cases of aneurysms originating from proximal segments of the ACA, MCA, or PCA were excluded. Cases that utilized other types of flow diverters as the primary treatment strategy were also excluded. Treatment of distal aneurysms was based on operator preference, including timing of the procedure, choice and number of devices, administration and dose of antiplatelet agents, and post-procedure care.


Baseline and post-procedural imaging studies, including CT, MRI, and DSA were reviewed by local investigators at each participating site and were not adjudicated by a central core laboratory. The following data were collected: patient demographic data, aneurysm characteristics, clinical presentation, procedural details and complications, and follow-up results of radiographic studies and functional outcomes. Clinical outcome was measured using the modified Rankin Scale (mRS) score. A mRS score of 0–2 was considered a good clinical outcome.

Statistical analysis

Statistical analyses included the χ2 test, Fisher’s exact test, one way ANOVA, and multivariate analysis, performed using SPSS (IBM SPSS Statistics for Windows, V.24, IBM Corp, Armonk, New York, USA) and GraphPad Prism (V.7.99, GraphPad Software, La Jolla, California, USA). For all statistical analyses, P<0.05 was considered statistically significant.


There were a total of 65 patients with distal aneurysms treated with the PED. The average number of aneurysms treated at each center was 7.2 (range 4–12). Baseline clinical and imaging characteristics of these cases are shown in tables 1 and 2. There was a significant difference in the distribution of the aneurysms based on morphology and location (P=0.001). MCA M2 aneurysm was the most commonly treated lesion (28/65, 43.1%), represented mainly by M2 fusiform and saccular aneurysms (13 cases (20%) and 13 cases (20%), respectively). ACA A3 aneurysms were the second most common aneurysm type (16/65 (24.6%)) in our cohort; of these, 13 were saccular (20%).

Table 1

Baseline clinical and radiographic data of 65 patients with distal aneurysms treated with the pipeline embolization device

Table 2

Distribution of aneurysms based on morphology and location

The median and mean aneurysm size at its largest diameter was 7.0 mm and 7.8 mm, respectively. We found that 58.5% of aneurysms were saccular, 29.2% fusiform, and 12.3% had a dissecting morphology. The median parent vessel diameter was 2.4 mm, and parent artery <2.5 mm in diameter was present in 55% of cases. Nine of 65 (13.8%) patients presented in a setting of acute aneurysm rupture. Five of 56 unruptured aneurysms in our series were symptomatic due to a focal mass effect, or as a source of embolic stroke. Treatment with a single PED was performed in 57 (87.7%) cases, two devices were used in 5 patients, and three devices were used in 1 patient in our cohort. Adjunct treatment was performed in 8 (13.5%) cases: coiling (n=6) and use of other stents for optimized PED support or wall apposition (n=2). Intraprocedural complications (table 3) were reported in five patients (7.7%).

Table 3

Aneurysm occlusion status at angiographic follow-up

Angiographic follow-up data were available for 53 patients with median and mean follow-up times of 6 months and 11.6 months, respectively. Overall, 83.0% of aneurysms (44/53) showed complete obliteration (figure 1), 13.2% (7/53) showed reduced filling, and 3.8% (2/53) showed persistent robust filling at angiographic follow-up. Aneurysm occlusion status based on aneurysm location and morphology is summarized in table 3. ACA aneurysms achieved complete occlusion in 18/21 (85.7%), MCA aneurysms in 19/24 (79.2%), and PCA aneurysms in 7/8 (87.5%) cases; the difference was not significant (P=0.81). Similar rates of occlusion were found depending on the aneurysm type (P=0.63); dissecting aneurysms achieved complete occlusion in 5/5 (100%), fusiform in 13/15 (86.7%), and saccular in 26/33 (78.8%) cases. There was no association between age (P=0.20), sex (P=0.13), aneurysm size (P=0.36), parent vessel diameter (P=0.27), ruptured status on admission (P=0.57), or evidence of immediate angiographic occlusion at the end of the embolization procedure (P=0.49) on the results of final angiographic outcome on follow-up imaging.

Figure 1

Treatment of P3 aneurysm with the pipeline embolization device (PED). A patient with a history of vein of Galen malformation treated with prior embolization was found to have a growing right posterior cerebral artery (PCA) aneurysm during evaluation for worsening headaches. (A) Anteroposterior and (B) lateral views, vertebral artery injection, showing a right P3 PCA aneurysm (arrows). Note the dysplastic appearance of multiple intracranial vessels and robust right posterior communicating segment. (C) Anteroposterior view, right internal carotid artery injection, and (D) unsubtracted image, 6 month follow-up study showing successful treatment of the right P3 aneurysm with 2.75×18 mm PED (arrows). Mild in-stent stenosis is present without residual filling of the aneurysm.

Retreatment procedures were performed in four patients in our cohort, including the two patients that had unchanged filling status of aneurysm on follow-up imaging. Two patients were found to have occlusion of the PED and parent vessel (figure 2), and three patients had occlusion of a side branch on follow-up imaging; all five patients remained clinically asymptomatic. Clinical 3 month follow-up data were available for 60 of 65 patients; 95% of patients (57/60) had a good clinical outcome (mRS 0–2) at 3 months. Good clinical outcome was statistically different based on the presence of intraoperative or postoperative complications (two thirds of patients with a poor clinical outcome had an operative related complication, P=0.010).

Figure 2

Treatment of M3 aneurysm with the pipeline embolization device (PED) and subsequent in-stent occlusion. A patient was found to have a 14 mm M3 aneurysm during evaluation for infective endocarditis and headaches. (A) Lateral view, standard, and (B) high magnification, left internal carotid artery injection showing M3 segment aneurysm. Treatment with 3×20 mm PED was performed. (C, D) Lateral views, left internal carotid artery injection, 12 month follow-up demonstrating complete aneurysm obliteration. There is occlusion of the PED and parent M3 branch (arrows). The patient remained clinically asymptomatic.

In patients with unruptured aneurysm only, the rate of good clinical outcome was 50/52 (96%). Four of five patients with intraprocedural and immediate post-procedural complications in our dataset were from an unruptured aneurysm (one patient with mRS 0, one patient with mRS 1 at 3 months, one found to have extension of stroke on follow-up with no new neurological deficits, and one patient died after hematoma evacuation). A summary of the complications is shown in table 4.

Table 4

Complications associated with treatment of distal aneurysms using the pipeline embolization device

Complication rates based on patient presentation, aneurysm location, and aneurysm morphology are summarized in table 5. There was no significant difference in patients with intraoperative or postoperative complications grouped by aneurysm location (P=0.761), morphology (P=0.197), or initial presentation (P=0.174). M2 aneurysm location accounted for three out of five intraoperative and post-procedural complications (10.7% of total M2 aneurysms) with P2 location accounting for the remaining two patients (22.2% of total P2 aneurysms). Complications by morphology included one patient with dissection, two fusiform, and two saccular aneurysms. Nine patients presented with aneurysm ruptured, and one resulted in in-stent thrombosis complication (11%).

Table 5

Complication rates by patient presentation, aneurysm location, and aneurysm morphology


The definition of distal aneurysm is not clearly standardized among the neurointerventional community. Most studies describing the endovascular treatment of aneurysms with the PED denote aneurysms beyond the circle of Willis as distal. In these studies, the majority of aneurysms were located at A1 and M1 anatomical segments.5 8 9 In our study, we only included cases with aneurysms beginning at or beyond A2, M2, or P2 posterior anatomical segments according to the previously proposed nomenclature for segmental anatomy of such lesions.3 The safety and efficacy of the PED for the treatment of aneurysms at A2, M2, P2, and more distal segments are poorly understood due to the rarity of these lesions and scarce description in the literature. The overall compete angiographic occlusion of aneurysm on follow-up imaging was achieved in 83% of cases, and only 6% of cases required re-treatment. A similar range of complete angiographic occlusion and good clinical outcomes can be found in previously published literature describing cases of distal aneurysms treated with the PED.5 7 10–12 In our series, 95% of patients at follow-up had a good clinical outcome. With intention to treat analysis, which usually applies to prospective studies rather than retrospective series, the rate of good outcome was calculated at 81.5%. The rate of procedure related complications was 7.7%, consisting of in-stent thrombosis and early post-procedural hemorrhagic events (tables 4 and 5).

There are several possible explanations for these high technical success rates documented in our series. First, continuous improvement in device and catheter technology, such as the introduction of the second generation PED (PED Flex), Phenom microcatheter (Medtronic), and new distal access catheters with improved target lesion access and treatment are especially critical for distally located aneurysms. Second, our increasing knowledge of the optimal use of antiplatelet agents (including intravenous agents for emergent cases) may contribute to lowering risks for thrombotic and hemorrhagic complications. Finally, increasing operator experience with the PED and recognition of its technical limitations may lead to optimal patient selection.

Surgical treatment of distal aneurysms remains a valuable treatment option; however, its safety profile, patient selection, and optimal microsurgical approaches are not well defined. Rodriguez-Hernandez et al described their outcome of 100 distal aneurysms treated with surgical management; clipping was the most common approach (72%), followed by trapping (15%), and a combination of trapping plus bypass (13%; mainly for MCA aneurysms).3 Angiographically, complete occlusion was achieved in 91% of aneurysms. Surgical mortality was 2.9% and clinical worsening was observed in 17% of patients. However, direct comparison of these results with our cohort should be performed with caution due to the differences in patient populations. For example, in our cohort, 86% of patients had unruptured aneurysms versus only 60% in the surgical cohort.

Given the rarity of distal aneurysms, differences in surgical approaches based on aneurysm location and morphology, a randomized trial of endovascular versus surgical management in the future is unlikely. For this study, we initially considered comparing and calculating how many patients could be eligible for surgical treatment. However, this task was unable to be completed due to differences in surgical techniques and operator preferences from the dual trained endovascular neurosurgeons among our author group. Further research and discussion regarding surgical versus endovascular treatment modalities for the treatment of distal aneurysms are warranted.

An interesting observation in our series was the findings of two patients with complete occlusion of the parent vessel and the PED on follow-up imaging. Both patients remained asymptomatic throughout the procedure and follow-up. This phenomenon of gradual asymptomatic parent artery occlusion after treatment with the PED (termed ‘tourniquet-like occlusion’) was previously described by Srinivasan et al.13 The study reported three cases with complete occlusion and two cases of >50% in-stent stenosis. The frequency of complete occlusion with the PED was estimated to occur in 1% of cases. The authors speculated that small parent vessel diameter, pre-existing stenosis, fusiform pathology, and the use of multiple devices were the risk factors.

Our study has several limitations. It is a retrospective study, which limits the accuracy of case reporting. The study included multiple treatment sites, and the results did not account for the differences in perioperative protocols and treatment techniques. Imaging results were not adjudicated by a central core laboratory, angiographic follow-up data were not available in 18% of patients, and 8% of patients were lost to clinical follow-up.


This large multicenter study of patients with A2, M2, P2, and distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves.



  • Contributors MM: study concept and design. MM and CTP wrote the manuscript. MM and CTP performed the statistical analysis. All authors participated in data collection, edited the manuscript, and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The study was approved by the local institutional review board at each participating center for retrospective data collection and review.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data was presented in this paper.