Use of a Flow Re-direction Endoluminal Device (FRED) for Wide-neck Large/Giant Cerebral Aneurysms

Transcription

1 DOI: /jnet.ra-diverter Use of a Flow Re-direction Endoluminal Device (FRED) for Wide-neck Large/Giant Cerebral Aneurysms Yuji Matsumaru, Tatsuo Amano, and Masayuki Sato Objective: There are some reports concerning the effectiveness of flow-diverter (FD) stents for untreatable cerebral aneurysm by conventional surgery and endovascular treatment. Treatment with a Pipeline embolization device, one of the original FD stents, has just started in Japan. We report herewith our initial experience of Flow Re-direction Endoluminal Device (FRED), which is a new FD with unique double layer structures, for wide-neck large or giant cerebral aneurysms. Materials and Methods: This report is part of a clinical trial for the approval of FRED in Japan with permission of the Institutional Review Board of Toranomon Hospital. Between October 2014 and January 2015, we treated six aneurysms in six patients with FRED including three cavernous and three paraclinoid aneurysms, three asymptomatic and three symptomatic aneurysms, four large and two giant aneurysms. Results: All patients were treated with single FRED without any coils. There were no transient ischemic attack, no stroke and no death in peri- and post-operative periods. One patient s preexisting eye symptom temporarily worsened. Followup angiography at 6 months showed no filling (O Kelly Marotta scale: D) in two patients, entry remnant (OKM scale C) in two patients, and subtotal filling (OKM scale B) in two patients. Conclusion: Treatments using FRED were achieved without any severe complication. Clinical trials will continue to demonstrate its safety and efficacy for complex aneurysms. Keywords flow diverter stent, aneurysm, endovascular treatment, flow re-direction endoluminal device Introduction A flow-diverter stent (FD) decreases intra-aneurysmal blood flow, causes thrombosis, and induces endothelium formation for healing when inserted into a parent blood vessel at the aneurysmal neck. 1) The metal content is higher than that of standard assisting stents for aneurysms, and the porosity is lower. The Pipeline Embolization Device (PED; Medtronic, Dublin, Ireland) is a first-generation device, and, internationally, it has commonly been used. Several studies have reported its usefulness for the management of cerebral aneurysms that are difficult to treat using standard methods. 2 9) The Flow-Redirection Endoluminal Device Department of Neurological Endovascular Therapy, Toranomon Hospital, Tokyo, Japan Received: February 8, 2016; Accepted: July 19, 2016 Corresponding author: Yuji Matsumaru. Department of Neurological Endovascular Therapy, Toranomon Hospital, Toranomon, Minato-ku, Tokyo , Japan yujimatsumaru@me.com 2016 The Editorial Committee of Journal of Neuroendovascular Therapy. All rights reserved. (FRED; MicroVention, Tustin, California, U.S.A.) is a second-generation FD. It is characterized by a 2-layer structure consisting of high-porosity outer and low-porosity inner layers ) To introduce this product in Japan, a clinical trial involving four institutions in Japan has been conducted since In Toranomon Hospital, the trial was started after its protocol was approved by the Ethics Review Board, and is currently being conducted. In this study, we report the characteristics of the FRED and our experience regarding its initial use. Subjects and Methods Indication criteria In this trial, indication criteria included aneurysmal sites, such as an area from the petrous part of the internal carotid artery to the A1 region of the anterior cerebral artery or M1 region of the middle cerebral artery, as well as the intracranial vertebral and basilar arteries, a proximal/distal parent blood vessel diameter of 2.5 to 5.0 mm, a neck diameter of 4 mm with a maximum diameter of 10 mm, fusiform aneurysms requiring treatment, and aneurysms that may recur when 1

2 Matsumaru Y, et al. the FRED at an aneurysm-adjacent area, an aneurysm measuring <50% of the entire length can be recaptured, facilitating additional insertion to an adequate position. Fig. 1 Flow Re-direction Endoluminal Device (FRED). selecting conventional treatment methods despite a maximum diameter of 7 to 9.9 mm. Furthermore, we excluded patients with subarachnoid hemorrhage within 60 days. FRED The FRED is an FD for treating cerebral aneurysms (Fig. 1). It is a nitinol wire-braided stent, with a closed cell design. It dilates by unsheathing a stent from a delivery catheter (self-dilation-type stent). It is characterized by a 2-layer structure: a low-porosity (high metal content) inner-layer stent consisting of 48 nitinol wires and a high-porosity (low metal content) outer-layer stent consisting of 16 nitinol wires. The 2-layer structure is located at the center of the FRED, and 4- to 8-mm areas at both ends consist of the outer layer alone. The inner layer is primarily responsible for blood flow-modifying effects, and the outer layer is responsible for stent-wall apposition and inner-layer support. Therefore, the effective length of this device refers to the length of the inner layer, but not to the entire length. Each layer is fixed by a spindle tantalum wire net. Furthermore, the visibility of tantalum wire is favorable, facilitating the visual recognition of the state of stent development and insertion under fluoroscopy. Both ends are dilated in a flare state, differing from those of the PED. At both ends, four radio-opaque markers are present. In this trial, FREDs with five different diameters (3.5, 4.0, 4.5, 5.0, and 5.5 mm) were prepared so that they were matched to blood vessels measuring 2.5 to 5.5 mm in diameter. The effective length of the FRED ranges from 7 to 39 mm in an open state, but is elongated in thinner blood vessels. The FRED is attached to a delivery wire with a radioopaque end tip and proximal-end marker at the end. It can be inserted into a microcatheter (Headway 27, Microvention) with a lumen diameter of inches. Even when developing Methods Clopidogrel at 75 mg and aspirin at 100 mg were administered for 1 week prior to endovascular treatment. During treatment, systemic heparinization was performed. Under general anesthesia, a 5F distal access-guiding catheter (SOFIA, Microvention) was inserted into the petrous or cavernous part of the internal carotid artery through the femoral artery and a 5F long introducer sheath (Fubuki guiding sheath, Asahi Intec, Aichi, Japan). Angiography with a biplane angiograph (Allura xper 20/20, Philips Healthcare, Best, Netherlands) and subsequent 3-dimensional rotatory angiography were performed. The vascular diameter was measured on Work Station (XtraVision Workstation, Philips Healthcare). The FRED diameter was selected based on the vascular diameter of the proximal aneurysm, and the FRED length was selected so that its effective length was 4 mm or more from the proximal and distal ends of the aneurysm. In the lumen, a microcatheter (Headway 27, Microvention) proceeded to a distal position where the end tip of the FRED could be safely developed, and, subsequently, the FRED was inserted into the microcatheter, and placed at the site of insertion. The microcatheter was unsheathed, and, after the flare region was developed, the valve of a Y connector was loosened, and the delivery wire of the FRED was pushed and unsheathed so that the microcatheter was spontaneously pushed back. Based on the state of a tantalum wire visually recognized under fluoroscopy, the FRED was developed over a sufficient time so that it stuck to a blood vessel. When a favorable wall apposition was not achieved due to unfavorable FRED development, the delivery wire was further pushed to develop the FRED. However, in some cases, FRED development was achieved by drawing and additionally pushing the delivery wire. After FRED insertion, standard angiography and cone-beam CT with the continuous arterial injection of a diluted contrast medium through a guiding catheter were performed to confirm the states of FRED development and apposition to blood vessels. When development or apposition was insufficient, a balloon catheter (Scepter C, Microvention) was carefully guided into the FRED, and dilated. At the site of puncture, hemostasis was performed using a device for hemostasis (Angio-Seal, St. Jude Medical, St. Paul, Minnesota, U.S.A.), and heparin was continuously administered for 48h. Therapy with an antiplatelet drug was also continued. Observation of the embolic 2

3 Use of a Flow Re-direction Endoluminal Device (FRED) for Wide-neck Large/Giant Cerebral Aneurysms A B C D E F Fig. 2 Case 1: 65-year-old female presented with left oculomotor nerve palsy caused by unruptured large partially thrombosed left paraclinoid aneurysm (A) treated with FRED (B). The wall apposition of the FRED was confirmed by cone-beam CT with diluted contrast (C). The angiogram just after the treatment shows the stagnation of the contrast in the aneurysm with eclipse sign (D, E). Follow-up angiogram after 6 months shows complete occlusion of the aneurysm (OKM scale D). FRED: flow re-direction endoluminal device state of the aneurysm using angiography was scheduled after 6 and 12 months. Results Treatment with the FRED was performed for six patients (six aneurysms) between October 2014 and January 2015 (Figs. 2 4). The details are shown in Table 1. The mean age was 63.5 years (58 72 years). All patients were female. They had unruptured aneurysms. The sites consisted of the cavernous part of the internal carotid artery in three patients and para-floor superior process of the internal carotid artery in three. In three patients, the aneurysms were symptomatic: ocular movement disorder. Four patients had large aneurysms measuring 10 to 25 mm and two had giant aneurysms. All aneurysms were classified as wide-neck type, measuring 4 mm. All lesions were saccular aneurysms. In three patients, partial intra-aneurysmal thrombosis was observed. In all patients, the FRED could be guided/inserted into a target vessel while covering the target aneurysm s neck. Furthermore, a single stent was used in all patients, and there was no concurrent use of a coil. The FREDs used are shown in Table 2. In two patients, wall apposition immediately after insertion was unfavorable, and the FRED was dilated using a balloon catheter. The intra-aneurysmal retention of a contrast medium immediately after treatment, that is, eclipse sign, 6) was observed in all patients. In five, the FRED was placed at the origin of the ophthalmic artery, but there were no changes on ophthalmic artery angiography immediately after insertion in any patient. During the perioperative period, there was no TIA, stroke, or death. Angiographic findings 6 months after treatment were evaluated as no filling (OKM D) in two patients, entry remnant (OKM C) in two, and subtotal filling (OKM B) in two using the O Kelly Marotta (OKM) scale. 13) Of the five patients in whom the FRED was placed at the origin of the ophthalmic artery, the ophthalmic artery was occluded in one. However, a collateral pathway from the external carotid artery was observed (Fig. 3), and there were no signs. In one patient with a symptomatic aneurysm, the deterioration of ocular symptoms was noted, but has gradually reduced. During follow-up, there was no TIA, stroke, or death. 3

4 Journal of Neuroendovascular Therapy Advance Published Date: November 9, 2016 Matsumar u Y, et al. ɩ B C Fig. 3 Case 4: 60-year-old female with the symptom of right oculomotor nerve palsy by right cavernous giant partially thrombosed aneurysm (A) treated with FRED. The follow-up angiogram at 6 months shows the entry remnant (OKM scale C) of the aneurysm and occlusion of the right ophthalmic artery (B). Right external carotid injection shows the right ophthalmic artery (C: arrow heads). FRED: flow re-direction endoluminal device A B C D E F Fig. 4 Case 6: 72-year-old female with the symptom of right oculomotor and abducens nerve palsy by right cavernous giant partially thrombosed aneurysm (A) treated with FRED. Proximal end of implanted RRED shows incomplete wall apposition (B: arrow heads). Then, the proximal portion of FRED is dilated with balloon catheter, and the contrast stagnates in the aneurysm (C E). The follow-up angiogram at 6 months still shows the subtotal filling (OKM scale B) (F). FRED: flow re-direction endoluminal device 4

5 Use of a Flow Re-direction Endoluminal Device (FRED) for Wide-neck Large/Giant Cerebral Aneurysms Table 1 Characteristics of patients treated with FRED Case Age/sex Symptom Morphology of aneurysms Location Intra-aneurysmal thrombosis Maximum diameter Neck diameter Proximal vessel size Distal vessel size 1 65F IIIrd n palsy Saccular Lt. Paraclinoid Partially thrombosed 12.5 mm 4.2 mm 4.1 mm 3.5 mm 2 58F No Saccular Rt. Paraclinoid No 14.4 mm 4.2 mm 4.7 mm 4.0 mm 3 71F No Saccular Rt. Cavernous No 15.4 mm 10 mm 4.8 mm 4.9 mm 4 60F IIIrd n palsy Saccular Rt. Cavernous Partially thrombosed 34 mm 18 mm 4.7 mm 6.5 mm * 5 65F No Saccular Rt. Paraclinoid No 10.3 mm 6.2 mm 4.1 mm 3.7 mm 6 72F IIIrd & VIth n palsy Saccular Rt. Cavernous Partially thrombosed 26 mm 5.6 mm 4.9 mm 4.1 mm The vessel is flattened. The size is maximum diameter. FRED: flow re-direction endoluminal device Table 2 Results of the treatment with FRED Used FRED (mm) Post dilatation with balloon Eclipse sign just after the procedure Jail of the ophthalmic artery OKM scale at 6 months Patency of the ophthalmic artery in follow-up Adverse events No + + D + No No + + C + No No + - B + No No + + C - No Yes + + D + No Yes + + B + Transient worsening of cranial nerve palsy O Kelly Marotta scale. FRED: flow re-direction endoluminal device 5

6 Matsumaru Y, et al. Discussion The FRED was certified as a CE-Mark product, and has been primarily used in Europe. Diaz et al. inserted the FRED to treat 14 aneurysms, and reported that there were no perioperative complications, and that recapture through partial development was possible. 14) Poncyljusz et al. indicated that there were no perioperative complications in eight FRED-inserted patients. According to them, complete occlusion was achieved in all five who underwent postoperative angiography, but asymptomatic thrombosis was noted in 1. 12) Kocer et al. selected the FRED for 33 patients (37 aneurysms), and reported that the incidence of perioperative complications was 3%, and that complete occlusion was achieved in 80% after 4 to 6 months and in 100% after 7 to 12 months. 10) All cerebral aneurysms treated with the FRED in our hospital were large or giant wide-neck-type aneurysms. In most patients, partial thrombosis was noted, and radical treatment by surgical clipping or conventional coil embolization, with a low incidence of complications, was considered difficult. In all patients, FRED insertion was possible, and there was no TIA, stroke, or death related to this procedure, suggesting its safety. Angiography after 6 months confirmed complete occlusion (OKM scale D) in 33% and a slightly contrastenhanced, neck-adjacent area (OKM scale C) in 33%. With respect to FRED experience, Kocer et al. reported that the complete occlusion rate increased with the course. 10) The occlusion rate may increase in the further follow-up period. The FRED is characterized by a 2-layer structure. The low-porosity inner layer reduces aneurysmal blood flow, being responsible for blood flow changes. The high-porosity outer layer is responsible for vascular apposition and innerlayer support. The outer layer is longer than the inner layer by 3 mm each at both ends. Therefore, at the site of FRED insertion involving the outer layer alone, the risk of penetrating branch occlusion may be low. Kocer et al. speculated that, as only the outer layer is adjacent to the inside of a catheter, catheter resistance might reduce, facilitating delivery. 10) Based on our experience, the FRED could be more readily inserted into a catheter compared with the PED, although this was based on subjective evaluation. Wall apposition was favorably achieved by sufficiently pushing/developing the FRED. In two patients, proximal-end dilation was unfavorable, but the proximal end could be readily dilated using a balloon catheter. Furthermore, a spindle tantalum wire facilitated observation of the state of stent dilation. Diaz et al. also reported its favorable visibility under fluoroscopy. 14) We placed the FRED at the origin of the ocular artery in five patients. After 6 months, its occlusion and a sufficient collateral pathway from the external carotid artery were confirmed in one. However, there were no signs associated with this finding. Kocer et al. placed the FRED at the origin of the ophthalmic artery in 28 patients, and reported that there was no occlusion on subsequent angiography, and that a transient ischemic symptom occurred in one. 10) Several studies indicated that PED insertion at the origin of the ophthalmic artery did not frequently cause occlusion of the ophthalmic artery or clinical ocular symptoms. 15,16) On the other hand, a study reported that detailed ophthalmological examination of 28 patients in whom the PED was inserted showed ophthalmological complications in 39.3% even in the absence of signs; caution is needed. 17) With respect to changes in stent morphology after FRED insertion, Kocer et al. reported stent foreshortening the day after treatment in one patient. They indicated the following reasons: the stent diameter was smaller than the diameter of the major blood vessel, and the stent dilated at the neck region after insertion due to a wide-neck-type aneurysm. As a braded stent shortens on dilation, its size and length must be selected, considering this. Furthermore, Kocer et al. reported shortening of both ends or one end of a stent, that is, fish mouth phenomenon, in four patients during follow-up. Although the etiology was unclear, a first-generation FRED was used in all patients with this phenomenon. They indicated that there was no such phenomenon in patients in whom a secondgeneration FRED, in which the diameter of wire used for a stent in the outer layer was improved to a slightly thick wire (similar to the LVIS stent (Microvention)), was used. In our patients, the modified second-generation FRED was used, and there was no such phenomenon. Kocer et al. recommended that a stent size matched to the diameter of a proximal blood vessel should be selected to prevent endoleak. 10) Blood vessels are thinner at a distal area, and a stent size greater than the distal vascular diameter may be selected. They also reported that, when the difference was 1 mm or greater, stent dilation and wall apposition were affected. The number of our patients was small, and the followup period was short. Therefore, the efficacy of this device remains to be confirmed. However, the FRED could be readily guided, and its visibility under fluoroscopy was favorable. In addition, wall apposition was favorable, facilitating recapture. Furthermore, there were no ischemic or hemorrhagic complications based on our experience, suggesting the usefulness of this device. However, further follow-up and clinical experience accumulation may be necessary. 6

7 Use of a Flow Re-direction Endoluminal Device (FRED) for Wide-neck Large/Giant Cerebral Aneurysms Conclusion The FRED is a new FD with a 2-layer structure, consisting of high-porosity outer and low-porosity inner layers. It is easy to guide/insert the FRED in/into a catheter, and wall apposition is favorable, facilitating recapture during insertion. Based on our experience, FRED insertion was possible in all patients, and there were no complications; this device may be safe. To evaluate its efficacy, future follow-up and case accumulation may be necessary. Disclosure Statement The main author received lecture s fees from Terumo Corporation, Medtronic, and Johnson & Johnson K.K. There is no conflict of interest for the other co-authors. References 1) Taussky P, Tawk RG, Miller DA, et al: New therapies for unruptured intracranial aneurysms. Neurol Clin 2013; 31: ) Becske T, Kallmes DF, Saatci I, et al: Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013; 267: ) Byrne JV, Beltechi R, Yarnold JA, et al: Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study. PLoS One 2010; 5: e ) Kallmes DF, Hanel R, Lopes D, et al: International retrospective study of the pipeline embolization device: a multicenter aneurysm treatment study. AJNR Am J Neuroradiol 2015; 36: ) Lubicz B, Collignon L, Raphaeli G, et al: Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 2010; 41: ) Lylyk P, Miranda C, Ceratto R, et al: Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery 2009; 64: ; discussion ) McAuliffe W, Wycoco V, Rice H, et al: Immediate and midterm results following treatment of unruptured intracranial aneurysms with the pipeline embolization device. AJNR Am J Neuroradiol 2012; 33: ) Nelson PK, Lylyk P, Szikora I, et al: The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011; 32: ) Yu SC, Kwok CK, Cheng PW, et al: Intracranial aneurysms: midterm outcome of pipeline embolization device a prospective study in 143 patients with 178 aneurysms. Radiology 2012; 265: ) Kocer N, Islak C, Kizilkilic O, et al: Flow Re-direction Endoluminal Device in treatment of cerebral aneurysms: initial experience with short-term follow-up results. J Neurosurg 2014; 120: ) Mohlenbruch MA, Herweh C, Jestaedt L, et al: The FRED flow-diverter stent for intracranial aneurysms: clinical study to assess safety and efficacy. AJNR Am J Neuroradiol 2015; 36: ) Poncyljusz W, Sagan L, Safranow K, et al: Initial experience with implantation of novel dual layer flow-diverter device FRED. Wideochir Inne Tech Maloinwazyjne 2013; 8: ) O kelly CJ, Krings T, Fiorella D, et al: A novel grading scale for the angiographic assessment of intracranial aneurysms treated using flow diverting stents. Interv Neuroradiol 2010; 16: ) Diaz O, Gist TL, Manjarez G, et al: Treatment of 14 intracranial aneurysms with the FRED system. J Neurointerv Surg 2014; 6: ) Durst CR, Starke RM, Clopton D, et al: Endovascular treatment of ophthalmic artery aneurysms: ophthalmic artery patency following flow diversion versus coil embolization. J Neurointerv Surg 2016; 8: ) Vedantam A, Rao VY, Shaltoni HM, et al: Incidence and clinical implications of carotid branch occlusion following treatment of internal carotid artery aneurysms with the pipeline embolization device. Neurosurgery 2015; 76: ; discussion ) Rouchaud A, Leclerc O, Benayoun Y, et al: Visual outcomes with flow-diverter stents covering the ophthalmic artery for treatment of internal carotid artery aneurysms. AJNR Am J Neuroradiol 2015; 36: