Microsurgical Management of Intracranial Aneurysms after Failed Flow Diversion

Journal Pre-proof Microsurgical Management of Intracranial Aneurysms after Failed Flow Diversion Nnenna Mbabuike, MD, Sophia Shakur, MD, Kelly Gassie, MD, Visish Srinivasan, MD, Justin Mascitelli, MD, Adib Abla, MD, Edward Duckworth, MD, Peter Kan, MD, Georgios A. Zenonos, MD, Clemens Schirmer, MD, Fady T. Charbel, MD, Evandro de Olivera, MD, Jacques J. Morcos, MD, Michael Lawton, MD, Rabih G. Tawk;, MD PII:

S1878-8750(19)32277-6

DOI:

https://doi.org/10.1016/j.wneu.2019.08.121

Reference:

WNEU 13157

To appear in:

World Neurosurgery

Received Date: 10 June 2019 Revised Date:

15 August 2019

Accepted Date: 16 August 2019

Please cite this article as: Mbabuike N, Shakur S, Gassie K, Srinivasan V, Mascitelli J, Abla A, Duckworth E, Kan P, Zenonos GA, Schirmer C, Charbel FT, de Olivera E, Morcos JJ, Lawton M, Tawk; RG, Microsurgical Management of Intracranial Aneurysms after Failed Flow Diversion, World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.08.121. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.

Microsurgical Management of Intracranial Aneurysms after Failed Flow Diversion

Nnenna Mbabuike, MD1; Sophia Shakur, MD2; Kelly Gassie, MD1; Visish Srinivasan, MD3; Justin Mascitelli, MD4; Adib Abla MD6; Edward Duckworth, MD3; Peter Kan, MD3; Georgios A. Zenonos, MD8, Clemens Schirmer, MD5; Fady T. Charbel, MD2; Evandro de Olivera MD1,7; Jacques J. Morcos, MD8, Michael Lawton, MD4; Rabih G. Tawk; MD1

1

Department of Neurosurgery, Mayo Clinic Florida

2

Department of Neurosurgery, University of Illinois College of Medicine at Chicago

3

Department of Neurosurgery, Baylor College of Medicine

4

Department of Neurosurgery, Barrow Neurological Institute

5

Department of Neurosurgery, Geisinger Medical Center

6

Department of Neurosurgery, University of California San Francisco

7

Institute of Neurological Sciences, Sao Paolo

8

Department of Neurosurgery, University of Miami

Corresponding Author: Rabih G. Tawk, MD Department of Neurosurgery Mayo Clinic Florida Jacksonville, FL 32224 904-953-6594 [email protected]

Running Title: Microsurgery for Aneurysms after Failed Flow Diversion Keywords: microsurgery, operative, treatment, bailout, aneurysms, flow diversion

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Abstract

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Introduction: Flow diversion has become increasingly popular for treatment of cerebral

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aneurysms over the last few years. There has been an increasing number of patients with

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aneurysms who have failed flow diversion, with paucity in the literature of salvage treatment for

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these challenging cases.

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Methods: We present a multi-center series of 13 aneurysms that failed treatment with flow

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diversion and were treated subsequently with open surgery. We also present a review of the

10

literature regarding operative management of aneurysms following unsuccessful treatment with

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flow diversion.

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Results: Twelve patients with 13 aneurysms were included in this study. All patients had surgery

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after flow diversion for persistent aneurysm filling, mass effect, or aneurysm rupture. Patients

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were treated with aneurysm clipping and parent vessel reconstruction, decompression of the

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aneurysm mass, occlusion of proximal flow to the aneurysm or aneurysm trapping with or

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without extracranial-intracranial (EC-IC) artery bypass.

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Conclusions: Aneurysms that fail flow diversion present a variety of unique and challenging

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management situations that will likely be encountered with increased frequency given the

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popularity of flow diversion. Microsurgical bailout options require an individualized care that is

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tailored to the underlying pathology, patient characteristics, and surgical expertise.

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Running Title: Microsurgery for Aneurysms after Failed Flow Diversion

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Keywords: microsurgery, operative, treatment, bailout, aneurysms, flow diversion 1

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Introduction Treatment of intracranial aneurysms with flow diversion (FD) has increased

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exponentially since the approval of Pipeline Embolization Device (PED) by the FDA in 2011.1

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FD constituted a paradigm shift in the treatment of large and giant aneurysms of the proximal

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internal carotid artery (ICA) with occlusion rates of 86.8% at 12 months follow-up.1 The use of

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PED has been expanded outside FDA-approved indications to small and distal aneurysms and

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posterior circulation aneurysms. As with any new treatment modality, aneurysm cases that failed

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to obliterate or lesions that continued to grow after treatment have been emerging sporadically

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and they present unique challenging situations. A growing number of lessons continue to be

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learned in regards to FD1 and there is a paucity of literature addressing the management of these

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aneurysms after failure of FD. In particular, while most cases of failed treatment have been

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addressed with endovascular methods1 there are only few reported cases that have undergone

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surgery as a salvage therapy or a bailout option5-9. In this series, we present 13 cases from 8 tertiary care academic centers of open surgical

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treatment for aneurysms that failed treatment with FD. We share the lessons that we have learned

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along with a review of the literature.

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Methods

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Databases from 8 tertiary centers were reviewed and cases with intracranial aneurysms

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treated with FD from 2011 to 2019 were identified. Failure of FD was defined as 1) aneurysms

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that failed to obliterate after 2 years from treatment, 2) aneurysms that continued to grow after

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FD, and 3) aneurysms that ruptured after FD. Only aneurysms that were treated with open

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microsurgical techniques were included in this study, while aneurysms that were retreated with

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endovascular techniques and patients who died from PED complications without being retreated

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were excluded. The goal was to explore the variable reasons for these failures along with a

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collective experience regarding microsurgical management of these conditions. The collected

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data included basic patient demographics, aneurysm size, aneurysm location, antiplatelet therapy,

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time of rescue surgery, surgical bailout method, symptoms at time of rescue surgery, use of

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balloon occlusion test, and bypass surgery. An online literature search was also performed to identify reported cases of aneurysms

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that had failed FD and were subsequently treated with open surgery. Online databases including

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PubMed and Medline were searched for keywords ‘pipeline’, ‘flow diversion’, ‘failure’,

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‘surgery’, ‘rescue, ‘bailout’, and ‘operative.’ The search included all studies between January

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2011 and June 2019. The review was limited to publications written in English and included

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observational case series and individual case reports. Relevant data from the retrieved studies

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was collected including basic demographics, aneurysm type, initial treatment, time of rescue

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surgery, and methods of rescue surgery.

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Results

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Case Series The series included 8 women and 5 men with an average age of 56 years (Table 1). Eight

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patients had unruptured intracranial aneurysms of the anterior circulation, two patients had a

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large fusiform vertebrobasilar aneurysm, and one had a giant basilar trunk aneurysm. One patient

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had left ICA terminus aneurysm with delayed rupture after previous treatment with FD. One

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patient was a previously ruptured supraclinoidal aneurysm originally treated with PED, and with

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progressive enlargement after two treatments with PED. Eleven cases had previous treatment

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with PED, one case had treatment with the flow re-direction endoluminal device (FRED), and

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one case had treatment with Derivos. All patients had treatment with dual antiplatelet therapy

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using aspirin (ASA) and Clopidogrel (Plavix). Six patients were symptomatic at the time of the

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rescue surgery either from the mass effect associated with the aneurysm or from decreased blood

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flow to the intracranial circulation distal to the flow diverter. The earliest time point of rescue

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surgery following placement of the flow diverter was at 6 weeks and the latest was at 3 years.

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A balloon test occlusion (BTO) was performed on 3 patients prior to surgery (Table 1).

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The operative method for rescue of these failed aneurysms included: microsurgical clipping of

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the aneurysm in 6/13 (one with superficial temporal artery (STA) to middle cerebral artery

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(MCA) bypass), aneurysm trapping in 3/13 (2/13 had thrombectomy of the aneurysm with

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Cavitron Ultrasonic Aspirator (CUSA), decompression of aneurysm fundus for relief of mass

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effect from the aneurysm on adjacent structures in 2/13, proximal ligation of the ICA with

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double barrel STA-MCA bypass in 1/13, and a common carotid to posterior cerebral artery

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bypass using a radial artery interposition graft with bilateral vertebral artery endovascular

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occlusion, one preceding and one following the bypass (Table 1). An endoscope was used in 2

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cases to assist with microsurgical clip ligation and for verification of clip position and patency of

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adjacent vessels and perforators (Table 1).

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Illustrative Cases

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Case 1

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A 65-year-old woman with incidental left posterior communicating artery (PCOM)

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aneurysm (5 x 4mm with a broad neck) underwent treatment with PED (4.5 x 14mm; Figure 1 A,

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B). Follow-up MRAs showed persistent aneurysm filling and at 18 months upon presentation to

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us diagnostic cerebral angiogram demonstrated persistent aneurysm filling measuring 4.8 x

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3mm. The aneurysm had a wide neck and was based mostly on the PCOM. Therefore, the neck

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was not completely covered by the PED (Figure 2). Allcock’s test demonstrated a true left fetal

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PCA as there was no filling of the left posterior cerebral artery (PCA) from vertebral injection

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with ipsilateral carotid compression. The patient had no symptoms at that time, but upon review

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of her old angiograms, there was evidence of aneurysm growth and decision was made to

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proceed with microsurgical clip reconstruction.

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Intraoperatively, microdissection and exposure of the ICA, PCOM origin, and the

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aneurysm superficial surface were uneventful. Mobilization of the ICA to explore the vasculature

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and perforators behind it was difficult and the vessel was very stiff due to the presence of the

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PED intraluminally. A 30-degree endoscope was used to assist with deep dissection and visualize

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the deep portion of the PCOM and the perforators in preparation for aneurysm clip ligation. The

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aneurysm was secured with a combination of a fenestrated clip around the ICA to control the

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proximal neck and a straight clip to obliterate the dome (Figure 3). The endoscope was used after

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clipping to verify the location of the clip blades across the aneurysm as the ICA could not be

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mobilized for optimal visualization. Video angiography with ICG confirmed patency of the ICA

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and PCOM with complete aneurysm obliteration. The patient tolerated the procedure well and

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had an uneventful postoperative course. Follow-up catheter angiogram at 3 months confirmed

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complete aneurysm obliteration and patency of the ICA and PCOM.

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Case 2

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A 68-year-old man was found with a left intraparenchymal hemorrhage following his

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presentation with acute neurological decline (Figure 4A, B). The patient had a history of a giant

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left ICA terminus aneurysm and left PCOM aneurysm that were treated with coil assisted PED

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embolization elsewhere (Figure 4C, D). This was performed 5 months prior to his presentation

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and reportedly, the patient’s postoperative course was complicated by a stroke with right-sided

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weakness. Catheter angiography demonstrated patency of both aneurysms. The source of the

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patient’s hemorrhage was thought to be the left ICA terminus aneurysm, which filled in

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retrograde fashion via the left A1 segment (Figure 4D). Endovascular embolization of the

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recurrent left ICA terminus aneurysm could not be performed and decision was made to pursue

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microsurgical treatment with proximal vessel occlusion. The left A1 segment was occluded just

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proximal to the aneurysm neck with a single aneurysm clip via a right-sided lateral supraorbital

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craniotomy. Postoperative angiogram showed no filling of the left ICA terminus aneurysm

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(Figure 5A). A routine follow-up catheter angiogram revealed recurrence of the aneurysm with filling

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via the PED in the left ICA (Figure 5B). Consequently, the decision was made to proceed with

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definitive treatment. Baseline left M1 flow was 99 mL/min as measured with NOVA

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(Noninvasive Optimal Vessel Analysis software; VasSol, Inc., River Forest, IL) (Figure 5C).2 A

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STA-MCA bypass was performed for flow replacement using the flow-assisted surgical

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technique (FAST).3,4 The STA cut flow was measured at 89 mL/min, bypass flow was 75

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mL/min, and cut flow index was 0.84. The left M1 segment was occluded with a single

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aneurysm clip and flow measurements showed that the bypass replaced the M1 flow sufficiently.

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The left ICA terminus aneurysm was then dissected and directly clipped and this was followed

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by clipping of the PCOM aneurysm. Postoperative angiogram demonstrated occlusion of both

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aneurysms (Figure 6A) and patency of the bypass. The patient had an uneventful recovery and

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was discharged to rehabilitation. At last follow-up, 3 years after surgery, the patient had mild

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right arm weakness. Angiogram showed no aneurysms and a patent bypass (Figure 6C).

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Review of the Literature An online literature search of PubMed and Medline identified five reports representing

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five cases detailing open surgical treatment of an aneurysm that has failed PED treatment

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between June 2013 and June 2019 (Table 2)5-9. Four cases had anterior circulation aneurysms

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and 1 had a PCA aneurysm5. Three cases had placement of one PED and the other 2 had multiple devices6,7. The

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timing of the rescue surgery ranged between day 1 and 9 months post-operatively.6,9 Failure in

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two cases was attributed to technical complications: 1) failure of the proximal PED to deploy5,

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and 2) foreshortening of the distal end of the device into the aneurysm dome8. In one case,

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failure of the PED was attributed to the anatomic relationship and the proximity between the

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ophthalmic artery and the aneurysm 9. The remaining cases involved progressive mass effect

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with persistent filling of the aneurysm after treatment with FD6,8. Three cases involved a bypass

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of the parent vessel and one involved trapping and excision of the aneurysm7. All cases except

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two reported extraction of the PED from the parent vessel in the acute phase (3 months or less)

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after PED placement, prior to endothelialization of the PED.

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Discussion The results of treatment of complex aneurysms with FD have led to a broad adoption of

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this technique. A pooled analysis of 3 large PED studies demonstrated 75% aneurysm occlusion

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at 180 days and 84% at 1 year 11. Recent data from a prospective cohort reported a cure rate of

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93% with no major or minor hemorrhagic or ischemic events at 3 years10. With the increased

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utilization of this technique, emerging reports are surfacing regarding its limitations and we

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continue to witness a refinement in selection of cases suitable for this technology. Factors associated with PED failure include persistent flow in the aneurysm related to the

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transmural flow through PED mesh,9,12-14inadequate aneurysm coverage in complex aneurysms,

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proximal and/or distal endoleak from poor wall apposition, and pre-existing stents.1,15 While

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these factors are being elucidated with emerging reports, there is no established rescue solutions

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for failed PED cases. Due to the small pores of the PED lattice, the device can’t be crossed with microcatheters

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and the endovascular options for treatment of persistent aneurysms after PED are limited to

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placement of additional flow diverters or endovascular sacrifice of the parent vessel. While these

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options are reasonable, they are not sufficient in certain cases with persistent or growing mass

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effect from the aneurysm or in cases with aneurysm re-rupture. Overall, the microsurgical options after FD failure include: 1) aneurysm clipping with

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parent vessel reconstruction, with or without removal of the device, 2) aneurysm trapping with or

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without extracranial-intracranial bypass, 3) proximal parent vessel occlusion with or without

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bypass, 4) aneurysm wrapping, and 5) debulking to alleviate mass effect from the aneurysm

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mass. Surgery on failed PED needs to be individualized to each patient with special

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consideration to the distinctive clinical and technical factors that an implanted PED involves.

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Therefore, the decision on how to treat aneurysms after failed FD cannot be made on scientific

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grounds alone and factors that need to be considered for microsurgical treatment are summarized

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in Table 3 and discussed below.

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While aneurysm obliteration with reconstruction of parent vessel should be considered,

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this may not be feasible when a flow diverter is obstructing the parent vessel lumen or when the

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device is deployed in a suboptimal fashion across the aneurysm neck.5,7 Therefore, surgery on

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failed PED needs to be individualized to each patient with special consideration to the cause and

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timing of the failure.

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Time Interval to Surgery after Failed FD

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In regards to timing, several risks are specific to the time interval between the

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implantation and failure. In the acute phase, patients are typically on dual antiplatelet therapy for

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at least 3 months until the device is covered with endothelium. In Case 3, dual antiplatelet

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therapy was discontinued 24 hours prior to surgery and the patient received platelets during

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surgery in response to excessive bleeding. In Case 7, dual anticoagulation was discontinued 1

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week prior to surgery and the patient had a stroke following decompression despite implantation

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of the devices 6 months prior to surgery. Therefore, we believe that patients with multiple

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devices and/or patients with devices implanted in the posterior circulation especially for fusiform

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aneurysms are at particularly high risk for thromboembolic complications when discontinuing

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antiplatelet agents. Next, extraction of the device may be considered in bailout surgery for PED failure and

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this depends largely on time interval since implantation and the cause of PED failure. Over time

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the incorporated device begins to affects the mobility, flexibility, and compliance of the vessel in

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response to surgical manipulation. Patients with parent vessel occlusion from thrombosis or with

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suboptimal deployment of the PED should be considered for extraction of the flow diverter and

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vascular reconstruction in the acute phase before the device becomes adherent to the vessel

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walls. Three of the five reported cases had extraction of the flow diverter5,7,8 and two of these

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had technical failures of the PED.7,8

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Device extraction is facilitated through dissection of the aneurysm fundus and removal of

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the device from the parent vessel. Early data suggests that flow diverters have earlier and thicker

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neointimal formation and endothelialization than flexible stents.17 In rabbit external iliac arteries

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(diameter, 2.67±0.07 mm), planimetric time-course analysis disclosed <20% endothelialization

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at 4 days, <40% at 7 days, and near-complete endothelialization at 28 days. Based on this data,

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the potential for damaging the parent vessel during removal would likely be significant beyond

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3-4 days and should probably be avoided and replaced with deconstructive strategies with flow

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replacement.17

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Deconstructive versus Reconstructive Surgical Options

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Surgical considerations unique to surgery after failed FD may involve the use of a

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deconstructive (i.e., vessel sacrifice) versus reconstructive (i.e., aneurysm repair) surgical

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procedures. BTO of the parent vessel, reported in 3 cases, 5,7,8 is helpful in the decision-making

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process and can be combined with a hypotensive challenge to increase the test sensitivity. When

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patients fail BTO, a bypass for flow replacement with a large bypass graft or a double-barrel

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STA is required to prevent ischemic complications16; and this can be followed by aneurysm

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clipping or trapping during the same procedure. We encourage completion of a BTO when considering surgery as it helps predict the

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safety of parent vessel sacrifice when vascular reconstruction cannot be performed and needs to

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be converted to vascular deconstruction. This is demonstrated in Case 3 (Table 1) as the

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aneurysm could not be reconstructed due to the location of the proximal neck within the

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cavernous sinus and the fragility of aneurysm walls with excessive bleeding. This is also

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highlighted in Case 13 (Table 1) in the treatment of a vertebrobasilar aneurysm including the use

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of a radial graft for the external carotid artery (ECA)-PCA bypass. Two of the reported cases6,8

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had STA-MCA bypass in conjunction with proximal cervical ICA occlusion in one case and

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aneurysm clipping in the other (Table 2). Both the second illustrative case and the case reported

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by Bowers et al8 discuss the location of proximal occlusion in combination with a bypass

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procedure. Other structural points for deciding on repair versus sacrifice include the presence of

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significant branches or perforators within the affected segment. Maintaining patency of these

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branches is crucial to prevent ischemic complications. In addition, the friability of the aneurysm

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walls can make the application of an aneurysm clip technically challenging. This can be related

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to thrombosis that needs to be evacuated first to allow closure of the clip blades. Other

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challenges in direct clip application are related to the extreme fragility of the aneurysm with

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largely inflamed and hemorrhagic walls that can shear easily with closure of the clip blades.

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Clinical Considerations for Surgery after Failed FD

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Persistence or worsening of mass effect from the aneurysm represents another type of

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failed FD that requires surgery. Although this is not related to the device itself, there are 2

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possible presentations with different etiologies. The first presentation occurs in the acute phase

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and is mostly related to thrombus formation within the aneurysm resulting in worsening of the

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mass effect. The second presentation is related to an increase in the aneurysm mass even without

262

filling of the aneurysm with contrast on vascular imaging and can occur in a delayed fashion

263

(Cases 6,7, 8, and 9) and could be related to mural wall destabilization causing delayed

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spontaneous aneurysm growth.16,18 In conjunction with the literature review, this series highlights the need for refinement in

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our understanding of the pathophysiological changes induced by FD, especially in aneurysms

267

that continue to grow producing signs and symptoms related to mass effect. Although the deficit

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can be attributed solely to an increase in the mass effect of the aneurysm after thrombosis,19-23

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massive cerebral edema after thrombosis of intracranial aneurysms has been reported.21,23 The

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development of vasa vasorum has been reported as a mechanism for aneurysm enlargement

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despite angiographic complete occlusion24. A new intra-aneurysmal thrombus has also been

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associated with abrupt onset of neurological signs and symptoms even without aneurysm

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enlargement.25 Residual aneurysm filling and expansion of thrombus can result in inflammatory

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changes and worsening of the symptoms related to mass effect. 13

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Furthermore, FD should be carefully considered in patients presenting with visual

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changes. Compared to other cranial nerves, the optic nerves and chiasm are likely more

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susceptible to mass effect.26 The importance of vision highlights the complexity of treating

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similar patients in daily practice and patients who decline or fail to demonstrate early and steady

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improvement in vision should be considered for direct surgical decompression without delay.

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Alternatively, indirect decompression of the optic chiasm can be achieved by untethering the

281

optic nerve with incision of the falciform ligament without resection of the aneurysm thrombus 6.

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In our series (Table 1), Cases 3, 6, and 7 had mass effect and Case 3 had visual loss from

283

pressure on the optic apparatus. All aneurysms were opened and thrombectomy was performed

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to achieve direct decompression and relief of the mass effect.

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Technical Considerations for Surgery after Failed FD Technical challenges are commonly encountered during surgery after failed FD and are

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related to the physical characteristics of intracranial vessels with implanted devices. Based on

289

our observations, the vessels become difficult to manipulate and mobilize in order to visualize

290

the deep parts of the aneurysm, perforators, and adjacent branches beyond the direct line of sight.

291

The use of ICG is valuable to demonstrate vascular patency as flow can be seen through the

292

mesh of these devices. We found the use of angled endoscopes valuable for visualization of the

293

clip blades and perforators to compensate for the decreased compliance of these vessels and we

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used a 30-degree endoscope in illustrative Cases 1 and 5. Intraoperative angiography can also be

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helpful when ICG cannot visualize deep portions of the aneurysm and adjacent vessels. The application of a temporary clip over intracranial vessels with implanted devices and

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ability to obtain proximal control poses another technical challenge due to the changes in the

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vascular compliance and potential for permanent deformities and flow alterations. In an

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experimental study with repeated clip applications, Neuroform and Enterprise stents returned to

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their original configuration and diameter, whereas the PED was irreversibly deformed.27 In the

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study by Bell et al, while the initial clip application to the PED did not result in flow arrest, the

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second single clip application did. The PED were also irreversibly deformed after the

303

experimental protocol with an average luminal diameter reduction of 26.85%.25

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Closure of the clips and getting flow arrest for proximal control is difficult due to

305

stiffness from the incorporated flow diverters. In Case 3 (Table 1) temporary clip application was

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performed over the ICA with 2 overlapping PEDs and the vessel was noted to be deformed when

307

the temporary clip was removed and replaced by a permanent clip. However, the vessel remained

308

patent with an oval deformity across its circumference. Devices implanted within the ICA often

309

extend proximally and extradurally and exposure of the cervical ICA should be considered to

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achieve proximal control and proximal ligation when needed. Thus, preparing the neck for

311

accessing the cervical ICA should be considered when the proximal aneurysm neck extends to

312

the paraclinoidal segment and access to the cervical carotid can be used for temporary occlusion

313

and proximal control or for permanent occlusion and vessel sacrifice. Furthermore, an alternative

314

to applying a temporary clip, when the exposed proximal vessel is “occupied” with a PED, is to

315

use temporary cardiac arrest with IV Adenosine, at the exact moment of the permanent clip

316

application, as was done in case #12 (Table 1).

317

In short, this case series discusses the microsurgical options for aneurysms failing FD and

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the specific influential factors that need to be considered during surgery. While this cases series

320

represents a multi-institutional collective contribution with the largest number of cases reported

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in one study, this is still a relatively small sample size and this topic needs further investigation.

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In addition, the study is limited by the retrospective data collection and inherent selection bias.

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Furthermore, it is important to realize that this study has not addressed the subgroup of patients

324

who have failed PED treatment and have either suffered death or morbidity from the failure, or

325

were retreated with alternative endovascular methods. Future studies will be integral in

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establishing an algorithm that can be applied in these unique cases.

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Conclusion The steadfast use of FD for treatment of complex aneurysms has been met with great

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success. However, a broad spectrum of challenging conditions is being seen when these devices

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fail to achieve aneurysm obliteration. In this case series we demonstrate that intracranial

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aneurysms failing flow diversion may be retreated with microsurgical intervention as a viable

333

option. To do so one must consider several contributing factors including: time interval since

334

failure, use of BTO to determine the feasibility of a reconstructive or deconstructive aneurysm

335

repair, necessity of decompression of the aneurysmal fundus, and the clinical implications of the

336

discontinuation of antiplatelet therapy in these patients. Technically, vessels incorporating flow

337

diverters have decreased compliance and persistent aneurysms have very fragile walls.

338

Aneurysm clipping with parent vessel reconstruction is challenging and trapping of the involved

339

segment with or without bypass seems to be safe and effective. Nonetheless, specific patient

340

phenotypes require individualized management given their broad spectrum of clinical

341

manifestations.

342

References

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native donor flow sufficiency. Neurosurgery. 2016;78(3):332-341. 5. Ding D, Liu KC. Microsurgical extraction of a malfunctioned pipeline embolization

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Sep;15(3):241-5. 6. Abla AA, Zaidi HA, Crowley RW, Britz GW, McDougall CG, Albuquerque FC, Spetzler

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unsuccessful treatment of a giant supraclinoid ICA aneurysm with the Pipeline device:

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open surgical bailout with STA-MCA bypass and parent vessel occlusion. J Neurosurg

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Pediatr. 2014 Jul;14(1):31-7 7. Ding D, Starke RM, Liu KC. Microsurgical strategies following failed endovascular

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aneurysm. J Cerebrovasc Endovasc Neurosurg. 2014 Mar;16(1):26-31 8. Bowers CA, Taussky P, Park MS, Neil JA, Couldwell WT. Rescue microsurgery with

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9. Gressot LV, Patel AJ, Srinivasan VM, Arthur A, Kan P, Duckworth EA. An

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Treatments Should Be Considered. World Neurosurg. 2016 Sep;93:486 10. Becske T, Potts MB, Shapiro M, Kallmes DF, Brinjikji W, Saatci I, McDougall CG,

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2016 Oct 28:1-6. 12. Kan P, Srinivasan VM, Mbabuike N, Tawk RG, Ban VS, Welch BG, Mokin M, Mitchell

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BD, Puri A, Binning MJ, Duckworth E. Aneurysms with persistent patency after

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treatment with the Pipeline Embolization Device. J Neurosurg. 2016 Sep 16:1-5. 13. Daou B, Valle-Giler EP, Chalouhi N, Starke RM, Tjoumakaris S, Hasan D, Rosenwasser

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RH, Hebert R, Jabbour P. Patency of the posterior communicating artery following

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single institution experience. Neuroradiology. 2016 Mar;58(3):267-75. 16. Cherian J, Srinivasan V, Kan P, Duckworth EAM. Double-Barrel Superficial Temporal

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Neurosurg (Hagerstown). 2018 Mar 1;14(3):288-294. 17. Matsuda Y, Chung J, Lopes DK: Analysis of neointima development in flow diverters

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using optical coherence tomography imaging Journal of NeuroInterventional

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Jun;3(2):167-71. doi: 10.1136/jnis.2010.002873 19. Aoki N. Partially thrombosed aneurysm presenting as the sudden onset of bitemporal

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21. Heros RC, Kolluri S. Giant intracranial aneurysms presenting with massive cerebral

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edema. Neurosurgery. 1984 Oct;15(4):572-7

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22. Pozzati E, Nuzzo G, Gaist G. Giant aneurysm of the pericallosal artery. Case report. J

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aneurysms. J Neurol Neurosurg Psychiatry. 1982 Nov;45(11):1040-7.

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vertebral artery after complete endovascular occlusion and trapping: the role of vasa

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vasorum. Case report. J Neurosurg. 2003 Feb;98(2):407-13. 25. Halbach VV, Higashida RT, Dowd CF, Barnwell SL, Fraser KW, Smith TP, Teitelbaum

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GP, Hieshima GB. The efficacy of endosaccular aneurysm occlusion in alleviating

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neurological deficits produced by mass effect. J Neurosurg. 1994 Apr;80(4):659-66 26. Tawk RG, Villalobos HJ, Levy EI, Hopkins LN. Surgical decompression and coil

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removal for the recovery of vision after coiling and proximal occlusion of a clinoidal

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segment aneurysm: technical case report. Neurosurgery. 2006 Jun;58(6):E1217

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27. Bell RS, Bank WO, Armonda RA, Vo AH, Kerber CW. Can a self-expanding aneurysm

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stent be clipped? Emergency proximal control options for the vascular neurosurgeon.

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Neurosurgery. 2011 Apr;68(4):1056-62.

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Figures

429 430

Figure 1. Case 1. A: Angiogram Lateral view showing Left fetal PCOM aneurysm PED

431

placement. B: Lateral unsubstracted view showing the device with red arrows pointing out the

432

proximal and distal ends. Aneurysm clip is noted from previous clipping of contralateral MCA

433

aneurysm.

434

Figure 2. Case 1. Angiogram Lateral views showing progressive growth over time and

435

persistence of Left PCOM aneurysm after flow diversion.

436

Figure 3. Case 1. CTA sagittal cut showing a fenestrated aneurysm clip around the ICA with

437

implanted PED

438

Figure 4. Case 2: A. Computed tomography and B. magnetic resonance imaging T2 sequence

439

upon admission showing the hemorrhage and aneurysm mass with surrounding edema. C.

440

Unsubstracted angiogram showing PED across the neck of previously coiled left ICA terminus

441

aneurysm and posterior communicating artery aneurysm. D. Preoperative angiogram displaying

442

retrograde filling of left ICA terminus aneurysm via left A1 segment.

443

Figure 5. Case 2: A. Postoperative angiogram after clip occlusion of left A1 segment. B.

444

Follow-up angiogram 2 months later revealing persistent aneurysm filling. C. Baseline NOVA

445

showing left M1 flow (99 mL/min). D. Left M1 and E. STA-MCA intraoperative flow

446

measurement with a flow probe. F. Intraoperative view of the PED within the left ICA and

447

MCA in relation to the aneurysm.

448 449

Figure 6. Case 2: A. Postoperative lateral angiogram after trapping of the aneurysm with distal

450

bypass. The bypass is filling the MCA and the ICA distal to the PCOM and the ICA is now

451

ending in the PCOM. B. Postoperative NOVA showing the bypass filling the LMCA. C. Follow-

452

up angiogram lateral view showing obliteration of both aneurysms.

453

Figure 7. Case 4. Right ICA angiogram showing a right supraclinoid aneurysm of the

454

communicating segment in the AP (A) and Lateral (B) views. C: Right carotid angiogram

455

demonstrates patent STA-MCA bypass following surgery for persistent aneurysm. D & E: Left

20

Mbabuike

456

ICA angiogram demonstrates contralateral filling of MCA with aneurysm obliteration after

457

proximal ligation of right ICA.

458

Figure 8. Case 6. A&B: 3-D angiogram left ICA showing the left ophthalmic artery aneurysm.

459

C: Left ICA angiogram following the initial primary coil embolization of the aneurysm in 2008.

460

D: Follow up MRA in 2011 with demonstration of thrombus within the aneurysm fundus. E:

461

MRA in 2012 after retreatment of aneurysm using stent-assisted coil embolization. F: MRA in

462

2013 demonstrating aneurysm enlargement. G: CTA head in 2013 after placement of PED. H:

463

MRA in 2016 demonstrating progressive aneurysm enlargement despite flow diversion. I: MRA

464

in 2016 after craniotomy for decompression of aneurysm fundus

465

Figure 9. Case 7. This patient developed progressive symptoms of dysphagia, vertigo, and facial

466

paralysis over 4 years. Serial imaging demonstrated an enlarging fusiform aneurysmal dilatation

467

with partial thrombosis of the left vertebral and basilar arteries (dimensions 71.4 x 8.7 mm) (A &

468

B). A Derivo flow diverting stent measuring 6 x 50 mm was deployed followed by two devices 6

469

x 50mm and 6x 40mm) for complete aneurysm coverage along the basilar and the V4 segment of

470

the left vertebral artery as shown on unsubstracted view (C).

471

Figure 10. The patient continued to have worsening of symptoms and MRI with contrast showed

472

the thrombosed portion of the aneurysm causing brainstem compression in axial and sagittal

473

views (A & B).

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Figure 11. A & B: MRI with contrast axial cuts after partial thrombectomy of the aneurysm for

475

decompression of the brainstem. Acute ischemia of the right PICA-AICA territory is seen as a

476

hypointense lesion of the right cerebellar hemisphere with mass effect and effacement of the 4th

477

ventricle.

478

21

Table 1. Cases of Surgical Treatment of Aneurysms Following Failed Flow Diversion Case

1

2

3

Patient Age/Gender

65/F

68/M

47/F

Aneurysm Type

Left PCOM1 aneurysm

Left ICA terminus aneurysm and left PCOM aneurysm

Left PCOM1 aneurysm

4

42/F

Right supraclinoid aneurysm of the communicating segment

5

56/F

Left Ventral ICA aneurysm

Aneurysm Size (greatest dimension)

Initial Treatment

Antiplatelet Therapy

5 mm

PED2

ASA/Plavix

42 mm

PED assisted coil embolization

ASA/Plavix

27 mm

PEDx2

ASA/Plavix

Time of Rescue of Surgery (post op)

Balloon Occlusion Test

Symptomatic at Time of Rescue Surgery

18 months

Yes

No

Aneurysm clipping with endoscopic assistance

5 months

No

No

Clipping of both aneurysms with STA-MCA bypass

Yes

Yes, mass effect on optic apparatus

Aneurysm trapping with ligation of cervical ICA3 and clipping of ophthalmic artery and ICA proximal to PCOM

Proximal ligation of supraclinoid ICA and double Barrel STA5MCA6 bypass

Aneurysm clipping with endoscopic assistance

6 weeks

11 mm

FRED4

ASA/Plavix

10 months

No

Yes, decreased flow into the MCA distal to the flow diverter with poor reserve on CTP with Diamox challenge

7mm

PED

ASA/Plavix

2 years and 5 months

No

No

Rescue Surgery

Primary Coil Embolization followed by Enterprise stent-assisted coil embolization followed by PED placement

No

Yes, mass effect from aneurysm fundus

6 months

No

Yes, mass effect on the pons and midbrain

ASA/Plavix

>6 months

No

No

PED and Coil Embolization

ASA/Plavix

>6 months

No

Bilateral 6th nerve palsies, quadriplegia

78/F

Left ophthalmic aneurysm

7

55/M

Fusiform Left vertebrobasilar aneurysm

71mm x 8.7 mm

Derivo Flow Diversion x 3

ASA/Plavix

8

48/M

Left posterior cerebral artery aneurysm

19mm

PED

40/M

Fusiform basilar trunk aneurysm

40mm x 35mm x 32mm

6

9

19 mm

ASA/Plavix

48 / F

Left periophthalmic aneurysm

9.1 mm

PED x 2

ASA/Plavix

1 year and 2 months

No

No

Decompression of aneurysm mass for relief of mass effect via a far lateral craniotomy Aneurysm trapping without bypass and thrombectomy with CUSA7 via an orbitozygomatic craniotomy Aneurysm trapping without bypass and thrombectomy with CUSA via a far lateral approach Aneurysm clipping

58 / F

Right Ophthalmic Aneurysm

5.1 mm

PED x 2

ASA / Plavix

2 years and 6 months

No

No

Aneurysm clipping

48 / F

Right Supraclinoidal ICA

7mm (at the time of surgical management)

PED x 2

ASA / Plavix

4 months

No

No

Aneurysm clipping (with Adenosine cardiac arrest)

10

11

12

3 years

Decompression of aneurysm fundus for relief of mass effect

68 /M 13

Right Vertebrobasilar

6 cm

PED

ASA / Plavix

1

>6 months

Yes

Mass Effect on Brainstem

ECA- PCA bypass, and bilateral VA endovascular occlusion

PCOM= Posterior Communicating Artery 2 PED= Pipeline Embolization Device 3 ICA= Internal Cerebral Artery 4 FRED= flow redirection device 5STA= Superficial Temporal Artery 6MCA= Middle Cerebral Artery 7CUSA = Cavitron Ultrasonic Aspirator, 8CCAPCA = Common carotid artery to posterior cerebral artery, 9VA = vertebral artery

Table 2. Literature Review for Surgical Treatment of Failed Flow Diversion5-9 Author, Year

No. of Cases

Ding et al, 20135

6

Abla, 2014

Ding et al, 20147

1

1

1

Age/Gender Aneurysm Type

59/F

Right MCA1 bifurcation aneurysm

10/M

Left ICA3 supraclinoid aneurysm

51/M

Initial Surgery

PED2

PED x 7

Time of Rescue Surgery after implantation of PED

Post op Day 1

9 months

Left PCA5 aneurysm

PED x 2

3 months

Right ICA terminus aneurysm

PED

Postop Day 3

Right Ophthalmic Aneurysm

PED

9 months

Symptomatic at Time of Rescue Surgery

Left sided hemiparesis due to thrombus in M1 segment from thrombosis of PED

Progressive visual deficit

Temporal hemianopsia of the right eye due to occlusion of proximal PED and left PCA

58/F Bowers et al, 20158

1

Gressot et al, 20169

1

1

50/F

Thunderclap headache, vertigo and nausea/emesis

Asymptomatic

Rescue Surgery Microsurgical extraction of PED through open aneurysm dome; Excess aneurysm dome resected without parent vessel reconstruction due to friable vessels STA4-MCA bypass with cervical ICA occlusion ETV6 + Microsurgical extraction of proximal PED with trapping and excision of aneurysm STA-MCA bypass with saphenous vein graft; Aneurysm Trapping and Microsurgical extraction of PED Aneurysm clipping for persistent aneurysm filling

MCA= Middle Cerebral Artery 2 PED= Pipeline Embolization Device 3 ICA= Internal Cerebral Artery 4 STA= Superficial Temporal Artery 5 PCA= Posterior Cerebral Artery 6 ETV= Endoscopic Third Ventriculostomy









Table 3. Factors to Consider in Microsurgical Treatment of Aneurysms Failing Flow Diversion In cases where the ability to complete vascular reconstruction is questionable, BTO can be helpful in determining the need for revascularization when considering parent vessel sacrifice or deconstructive procedures with trapping Persistent aneurysm enlargement despite placement of FD1 may require decompression of the aneurysm fundus especially if adjacent to the optic apparatus Vessels harboring PED become stiff and noncompliant and are difficult to mobilize intraoperatively Endoscopic assistance improves visualization of perforators and the position of the aneurysm clip Extraction of the PED beyond the acute phase (> 3 months) should be avoided due to endothelization of the device and risk of vascular wall injury Discontinuing dual antiplatelet therapy in the acute phase prior to surgery poses a high risk of thromboembolic and ischemic complications 1 FD= Flow Diversion

Abbreviations Balloon test occlusion (BTO) Cavitron Ultrasonic Aspirator (CUSA) External carotid artery (ECA) Flow diversion (FD) Flow-assisted surgical technique (FAST) Internal carotid artery (ICA) Middle cerebral artery (MCA) bypass NOVA (Noninvasive Optimal Vessel Analysis) Pipeline Embolization Device (PED) Posterior cerebral artery (PCA) Posterior communicating artery (PCOM) Superficial temporal artery (STA)

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: