Accepted Manuscript Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients Jay Vachhani, MD, Christopher Nickele, MD, Lucas Elijovich, MD, Paul Klimo, MD, MPH, Adam S. Arthur, MD, MPH PII: S1878-8750(16)30908-1 DOI: 10.1016/j.wneu.2016.09.078 Reference: WNEU 4618 To appear in: World Neurosurgery Received Date: 14 July 2016 Accepted Date: 19 September 2016 Please cite this article as: Vachhani J, Nickele C, Elijovich L, Klimo P, Arthur AS, Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients, World Neurosurgery (2016), doi: 10.1016/ j.wneu.2016.09.078. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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. ACCEPTED MANUSCRIPT Title: Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients Authors: Jay Vachhani1,2; Christopher Nickele1,2; Lucas Elijovich1,2,3; Paul Klimo1,2; Adam S. Arthur1,2 M AN U Corresponding Author: Adam Arthur, MD, MPH Semmes-Murphey Neurologic and Spine Institute 6325 Humphreys Blvd Memphis TN, 38120 Phone:(901) 522-7700 Fax: (901) 259-0132 Email: aarthur@semmes-murphey.com SC RI PT Affiliations: 1. Semmes-Murphey Neurologic and Spine Institute, Memphis TN 2. Department of Neurosurgery University of Tennessee Health Sciences Center, Memphis TN 3. Department of Neurology, University of Tennessee Health Sciences Center, Memphis TN TE D Academic Degrees: Jay Vachhani, MD; Christopher Nickele, MD; Lucas Elijovich, MD; Paul Klimo, MD, MPH; Adam S. Arthur, MD, MPH Key Words: Flow Diversion; Pediatric; Intracranial; Aneurysm AC C EP Abbreviations: ACA=Anterior Cerebral Artery; GOS=Glasgow Outcome Score; KID=Kids’ Inpatient Database; MRA=magnetic resonance angiogram; MRI=magnetic resonance imaging; mRS=modified Rankin Scale score; PA=Posterior-Anterior; PED=Pipeline Embolization Device 1 ACCEPTED MANUSCRIPT ABSTRACT Intracranial flow diversion has gained increasing popularity since the approval of the Pipeline Embolization Device (PED). Although it is only approved for use in adult patients, the RI PT PED has been used to treat aneurysms in pediatric patients. We present the first reported case of the use of a PED in a pediatric patient to treat an unusual fusiform distal anterior cerebral artery aneurysm. A 12-year-old female presented with new onset seizures and was found to have an SC incidental distal left anterior cerebral artery aneurysm. Initially, this was managed conservatively, but follow-up imaging performed 4 months after presentation demonstrated M AN U enlargement of the aneurysm. The patient underwent endovascular embolization of her aneurysm with a Pipeline Embolization Device. This was successfully performed and the patient recovered from the procedure with no neurologic deficits. Follow-up digital subtraction angiography and magnetic resonance angiography at 6 and 12 months, respectively, showed complete occlusion of the aneurysm. The authors also reviewed the literature on flow diversion for treatment of TE D pediatric intracranial aneurysms. AC C EP Word count: 165 (250 limit) 2 ACCEPTED MANUSCRIPT INTRODUCTION Intracranial flow diversion has gained increasing popularity since the approval of the Pipeline Embolization Device (PED; Medtronic Neurovascular, Minneapolis, MN) for treatment RI PT of large, giant, or wide necked aneurysms of the internal carotid artery. At present, the PED system is the sole Food and Drug Administration approved flow diverter available in the United States, although several others are under study. The PED consists of a braided mesh cylinder of SC platinum and cobalt microfilaments that provide 30–35% metal surface coverage at nominal expansion. This high surface area coverage disrupts blood flow into the aneurysm and promotes M AN U aneurysm thrombosis, but is porous enough to preserve the patency of normal branch vessels (8). Although it is only approved for use in adult patients, the PED has been used to treat aneurysms in pediatric patients (10, 15). A recent case report has also demonstrated successful embolization of distal anterior circulation aneurysms with the PED (13). We present the first TE D reported case of the use of a PED in a pediatric patient to treat an unusual fusiform distal anterior cerebral artery (ACA) aneurysm. EP CASE REPORT History and Examination AC C A 12-year-old girl presented with a new onset seizure and was found to have an aneurysm on magnetic resonance imaging (MRI). A subsequent cerebral angiogram showed a fusiform aneurysm of the left A2 segment of the anterior cerebral artery. A repeat angiogram performed 4 months later showed significant growth in the aneurysm and she was subsequently referred to our center (Fig. 1). 3 ACCEPTED MANUSCRIPT Endovascular Treatment with Flow Diversion The patient was placed under general anesthesia in the angiography suite. A 6 French Raabe sheath (Cook Medical, Bloomington, IN) was inserted into the right common femoral RI PT artery and advanced into the left internal carotid artery over a 4 French Berenstein catheter and Terumo Glidewire. A 3-D digital subtraction angiography run with separate workspace reconstruction was performed in the left internal carotid artery. This showed a fusiform SC aneurysm of the distal left anterior cerebral artery that measures 6.2 mm at its widest point (Fig. 2). M AN U Heparin was administered to the patient until the activated clotting time was measured to be 273. A Synchro 2 microwire (Striker, Kalamazoo, MI) was used to select the left anterior cerebral artery through a Marksman microcatheter (Medtronic Neurovascular, Minneapolis, MN) placed through a Navien support catheter (Medtronic Neurovascular, Minneapolis, MN). Once TE D the left anterior cerebral artery distal to the aneurysm was selected, a 2.5 x 20 mm PED was deployed distal to the aneurysm up to the midpoint of the aneurysm. The Marksman catheter was advanced through the PED and an additional 2.75 x 20 mm PED was deployed, overlapping the EP proximal portion of the first stent into the proximal left anterior cerebral artery. A digital subtraction angiography run at the end of the case showed appropriate placement of the devices, AC C with overlapping PEDs through the central portion of the fusiform aneurysm. The patient awoke from the procedure with no neurologic deficits. She was discharged home on postoperative day 1. Postoperative Follow-Up 4 ACCEPTED MANUSCRIPT The patient returned for a follow-up cerebral angiogram and magnetic resonance angiogram 6 months and 12 months after her initial embolization, respectively, which showed no residual filling of the aneurysm, nor any parent vessel stenosis. Her clopidogrel was discontinued RI PT and she remained on aspirin only. Her headaches dissipated over 3 months and she has remained neurologically intact with no further seizures off anti-epileptic drugs (Figs 3 and 4). SC DISCUSSION Pediatric intracranial aneurysms are rare and thought to represent less than 5% of all M AN U intracranial aneurysms (9). Historically, these aneurysms have been treated with open surgical techniques, such as clip reconstruction, trapping, or vessel occlusion with or without bypass. Endovascular treatments are generally not FDA-approved for usage in pediatric patients, and there is concern as to how endovascular devices will fare in growing cerebral arteries. Kalani et TE D al. reported 27 pediatric patients with 29 aneurysms treated with surgical cerebral revascularization techniques at the Barrow Neurologic Institute (11). They reported complete aneurysm obliteration in 24 of 29 (82.7%) aneurysms with a Glasgow Outcome Score (GOS) of EP 4 or 5 in 26 out of 27 (96.3%) patients. Although there was no perioperative mortality, the perioperative morbidity did include 4 strokes, 1 infection, 1 iliac pseudoaneurysm, 1 unilateral AC C blindness onset, and 1 neck hematoma (11). Over the past 2 decades, the rate of endovascular treatment for pediatric aneurysms has increased significantly. Alawi et al. analyzed the Kids’ Inpatient Database (KID) and found a statistically significant increase in the rate of endovascular coiling from 1998 to 2009 (2). Less than 10 coiling operations were performed from 1998 to 2000, which increased to 395 from 2007 to 2009. The rate of clipping remained unchanged from 49 in the first period to 48 in the last 5 ACCEPTED MANUSCRIPT period. The overall morbidity and mortality was significantly higher with clipping, 30.37% and 6.09%, respectively, than with coiling, 15.68% and 1.65%, respectively (p<0.05) (2). Flow diversion has gained increasing popularity since the publication of the Pipeline for RI PT Uncoilable or Failed Aneurysms Trial (4). Although there have been no large studies evaluating the efficacy of flow diversion in pediatric patients, case reports and small case series have shown promise (Table 1) (5, 12). The literature on endovascular flow diversion for the treatment of SC pediatric aneurysms shows 19 patients with 21 aneurysms treated with either PEDs (17), Silk flow-diverting devices (3; Balt Extrusion, Montmorency, France), or Surpass aneurysm M AN U embolization systems (1; Striker, Kalamazoo, MI). The median age of the patient was 11 with a slight female predominance (10 to 9). Complete aneurysm occlusion was seen in 14 patients and incomplete aneurysm occlusion in 5. Only 1 of the 5 patients with incomplete aneurysm occlusion required an additional treatment with a superficial temporal artery to middle cerebral TE D artery bypass, followed by parent vessel occlusion. Of the 16 patients with clinical follow-up data, 11 had a modified Rankin Scale score (mRS) of 0 or GOS score of 5, 3 had a mRS of 2, 1 had a GOS of 4, and 1 had a GOS of 3 (1, 3, 5-7, 10, 12-15, 17, 19). Vargas and colleagues EP described a saccular A2 aneurysm in an 8-year-old male treated with PED. Unfortunately, the 8month follow-up angiogram showed asymptomatic occlusion of the parent vessel with distal AC C collateral filling (17). To the authors’ knowledge, this is the first reported case of a growing fusiform distal ACA aneurysm in a child successfully treated with flow diversion. The natural history of fusiform intracranial aneurysms is not well known. Sacho and colleagues recently published their data on the natural history and outcome after treatment of unruptured fusiform cerebral aneurysms in adults. Of the 96 nonatherosclerotic aneurysms that were followed, only 8 showed signs of enlargement on follow-up angiography. Having a 6 ACCEPTED MANUSCRIPT symptomatic presentation was the only risk factor that had a statistically significant association with aneurysmal growth. In addition, all the aneurysms in the growth group were greater than or equal to 7 mm in size upon presentation (16). Yasui and colleagues performed a retrospective RI PT review of 4 adult patients with incidentally found fusiform vertebrobasilar artery aneurysms. They found that the 2 patients whose aneurysms grew shared similar angiographic findings. Aneurysms in the growth group had irregular walls and a gentle slope of the fusiform dilation. turbulent flow with thrombus formation (18). SC MRI showed high and intermediate signal intensity in addition to normal flow voids, suggesting M AN U We do not advocate the unrestrained usage of flow diversion for the treatment of all aneurysms diagnosed in pediatric (or adult) patients. This treatment carries significant risk, and in many cases, this risk may exceed the natural history risks that may be anticipated for an untreated aneurysm. In this case, we felt that the natural history risk of a growing, symptomatic TE D fusiform aneurysm was high. It seemed that vessel sacrifice would entail a high risk of neurologic deficit, and other measures to preserve vessel patency, such as stent-assisted coiling CONCLUSION EP or clipping with bypass, also carried serious risks. AC C We present an unusual case of a growing fusiform distal ACA aneurysm in a child successfully treated with a PED. Historically, pediatric intracranial aneurysms have been treated surgically. To the authors’ best knowledge, the literature on the treatment of pediatric aneurysms treated with flow diversion shows 19 patients with 21 aneurysms. Overall, 14 out of 19 patients (74%) showed complete occlusion of their aneurysms with parent vessel preservation. One of the 5 patients with incomplete aneurysm occlusion required intracranial bypass with parent vessel 7 ACCEPTED MANUSCRIPT occlusion. Larger, prospective studies to determine the optimal treatment for pediatric intracranial aneurysms may not be feasible nor applicable to all cases. RI PT DISCLOSURE The authors received no financial or material sources of support for this report. Drs. Vachhani, Nickele, and Klimo have no financial relationships to disclose. Dr. SC Elijovich has served as a consultant for Codman, Medtronic/Covidien, and Stryker. Dr. Arthur has served as a consultant for Codman, Medtronic, Microvention, Penumbra, Sequent, Siemens, ACKNOWLEDGMENTS M AN U Stryker; and has received research support from Siemens and Sequent. The authors wish to thank Andrew J. Gienapp, BA (Department of Medical Education, TE D Methodist University Hospital, Memphis, TN and Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN) for technical and copy editing, preparation of AC C EP the manuscript and figures for publishing, and publication assistance with this manuscript. 8 ACCEPTED MANUSCRIPT REFERENCES 1. Abla AA, Zaidi HA, Crowley RW, Britz GW, McDougall CG, Albuquerque FC, Spetzler RF: Optic chiasm compression from mass effect and thrombus formation following RI PT unsuccessful treatment of a giant supraclinoid ICA aneurysm with the Pipeline device: open surgical bailout with STA-MCA bypass and parent vessel occlusion. J Neurosurg Pediatr 14:31-37, 2014. Alawi A, Edgell RC, Elbabaa SK, Callison RC, Khalili YA, Allam H, Alshekhlee A: SC 2. Treatment of cerebral aneurysms in children: analysis of the Kids' Inpatient Database. J 3. M AN U Neurosurg Pediatr 14:23-30, 2014. Appelboom G, Kadri K, Hassan F, Leclerc X: Infectious aneurysm of the cavernous carotid artery in a child treated with a new-generation of flow-diverting stent graft: case report. Neurosurgery 66:E623-624; discussion E624, 2010. Becske T, Kallmes DF, Saatci I, McDougall CG, Szikora I, Lanzino G, Moran CJ, Woo TE D 4. HH, Lopes DK, Berez AL, Cher DJ, Siddiqui AH, Levy EI, Albuquerque FC, Fiorella DJ, Berentei Z, Marosfoi M, Cekirge SH, Nelson PK: Pipeline for uncoilable or failed 5. EP aneurysms: results from a multicenter clinical trial. Radiology 267:858-868, 2013. Burrows AM, Zipfel G, Lanzino G: Treatment of a pediatric recurrent fusiform middle 6. AC C cerebral artery (MCA) aneurysm with a flow diverter. J Neurointerv Surg 5:e47, 2013. 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Ikeda DS, Marlin ES, Shaw A, Powers CJ: Successful endovascular reconstruction of a recurrent giant middle cerebral artery aneurysm with multiple telescoping flow diverters in a pediatric patient. Pediatr Neurosurg 50:88-93, 2015. Kalani MY, Elhadi AM, Ramey W, Nakaji P, Albuquerque FC, McDougall CG, TE D 11. Zabramski JM, Spetzler RF: Revascularization and pediatric aneurysm surgery. J Neurosurg Pediatr 13:641-646, 2014. Kan P, Mokin M, Puri AS, Wakhloo AK: Successful treatment of a giant pediatric EP 12. fusiform basilar trunk aneurysm with surpass flow diverter. J Neurointerv Surg 2015. Lin N, Lanzino G, Lopes DK, Arthur AS, Ogilvy CS, Ecker RD, Dumont TM, Turner AC C 13. RDt, Gooch MR, Boulos AS, Kan P, Snyder KV, Levy EI, Siddiqui AH: Treatment of Distal Anterior Circulation Aneurysms With the Pipeline Embolization Device: A US Multicenter Experience. Neurosurgery 2015. 10 ACCEPTED MANUSCRIPT 14. Lubicz B, Collignon L, Raphaeli G, Pruvo JP, Bruneau M, De Witte O, Leclerc X: Flowdiverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 41:2247-2253, 2010. Navarro R, Brown BL, Beier A, Ranalli N, Aldana P, Hanel RA: Flow diversion for RI PT 15. complex intracranial aneurysms in young children. J Neurosurg Pediatr 15:276-281, 2015. Sacho RH, Saliou G, Kostynskyy A, Menezes R, Tymianski M, Krings T, Radovanovic I, SC 16. Terbrugge K, Rinkel GJ, Willinsky R: Natural history and outcome after treatment of 17. M AN U unruptured intradural fusiform aneurysms. Stroke 45:3251-3256, 2014. Vargas SA, Diaz C, Herrera DA, Dublin AB: Intracranial Aneurysms in Children: The Role of Stenting and Flow-Diversion. J Neuroimaging 2015. 18. Yasui T, Komiyama M, Iwai Y, Yamanaka K, Nishikawa M, Morikawa T: Evolution of TE D incidentally-discovered fusiform aneurysms of the vertebrobasilar arterial system: neuroimaging features suggesting progressive aneurysm growth. Neurol Med Chir (Tokyo) 41:523-527; discussion 528, 2001. EP Zarzecka A, Gory B, Turjman F: Implantation of two flow diverter devices in a child with a giant, fusiform vertebral artery aneurysm: case report. Pediatr Neurol 50:185-187, 2014. AC C 19. 11 ACCEPTED MANUSCRIPT FIGURE LEGENDS Figure 1. Posterior-Anterior (PA) and lateral projections of a left internal carotid artery injection, prior to treatment (A and B). This demonstrated the aneurysm in the A2 segment of RI PT the left anterior cerebral artery, with a full 360-degree loop in the aneurysmal portion of the vessel. Two oblique projections of the left internal carotid injection (C and D). Note the largest portion of the fusiform aneurysm (black arrow) and proximal anterior cerebral (single SC arrowhead) and distal anterior cerebral artery (double arrowhead). M AN U Figure 2. The same 2 oblique projections of the left anterior cerebral artery aneurysm immediately after placement of 2 pipeline flex devices within the fusiform aneurysmal segment (A and B). Again the fusiform aneurysm (black arrow) and the proximal (single arrowhead) and TE D distal (double arrowhead) vessel are marked. Figure 3. Slightly different oblique angles evaluating the treatment of the aneurysm, at 6 month follow up. Right internal carotid injection shows remodeling of the fusiform aneurysm (black EP arrow) with mild intimal hyperplasia, consistent across the length of the stent construct (A). Left internal carotid injection with the proximal (single arrowhead) and distal (double arrowhead) AC C anterior cerebral artery marked (B). Figure 4: Follow-up magnetic resonance angiogram (MRA) images. 3D reconstructed images (A) show the 360 loop of the stent construct (black arrow) filling well and widely patent. The axial images (B) show the proximal and distal ends of the stent construct (white arrows). 12 ACCEPTED MANUSCRIPT TABLES Age Sex Location Type Treatment Appelboom 20103 10 F ICA Saccular Silk 12 F Basilar 5 F Basilar 7 M Vertebrobasilar Burrows 20135 15 M Cinar 20136 8 F Zarzecka 201319 15 F Abla 20141 10 M Ikeda 201510 12 F Kan 201512 16 M 16 Lin 201513 PED Dissecting PED Dissecting PED M2 Fusiform PED ICA Saccular PED Vertebrobasilar Fusiform PED ICA Fusiform PED M2 Fusiform PED Basilar Fusiform Surpass M M2 Fusiform PED M A2 Dissecting PED F Basilar Dissecting/Fusiform Silk F ICA Saccular Silk F Vertebrobasilar and ICA Saccular x 2 PED x 2 4 M ICA Saccular PED 8 M A2 Saccular PED 9 M Basilar and ICA Fusiform x 2 PED x 2 12 F A2 Fusiform PED 13 Lubicz 201514 17 10 Vargas 201517 Current Case 11 AC C Navarro 201515 M AN U SC Dissecting EP de Barros Faria 20117 RI PT Source TE D Table 1. Patient and Treatment Characteristics from Reports in the Literature Abbreviations: ICA= Internal Carotid Artery; PED=Pipeline Embolization Device AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT HIGHLIGHTS: Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients Pediatric intracranial aneurysms are rare and have been historically treated with open RI PT • surgical techniques • At present, the PED system is the sole FDA-approved flow diverter, and even though it aneurysms in some pediatric patients The literature on the treatment of pediatric aneurysms treated with flow diversion (only M AN U • SC has only been approved for use in adult patients, the PED has been used to treat 19 patients) shows 14 of 19 patients (74%) with complete occlusion of their aneurysms with parent vessel preservation Our report is an unusual case of a growing fusiform distal ACA aneurysm in a child EP TE D successfully treated with a PED. AC C • ACCEPTED MANUSCRIPT Title: Flow Diversion for Treatment of Growing A2 Aneurysm in a Child: Case Report and Review of Flow Diversion for Intracranial Aneurysms in Pediatric Patients AC C EP TE D M AN U SC RI PT Abbreviations: ACA=Anterior Cerebral Artery; GOS=Glasgow Outcome Score; KID=Kids’ Inpatient Database; MRA=magnetic resonance angiogram; MRI=magnetic resonance imaging; mRS=modified Rankin Scale score; PA=Posterior-Anterior; PED=Pipeline Embolization Device