Review
Endovascular treatment of complex intracranial aneurysms by pipeline flow-diverter embolization device: a single-center experience Fatih Keskin1, Fatih Erdi1, Bulent Kaya1, Necdet Poyraz2, Suat Keskin2, Erdal Kalkan1, Orhan Ozbek3, Osman Koc4 1
Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurosurgery, Konya, Turkey, Necmettin Erbakan University, Meram Faculty of Medicine, Department of Radiology, Konya, Turkey, 3 Necmettin Erbakan University, Meram Faculty of Medicine, Department of Interventional Radiology, Konya, Turkey, 4Necmettin Erbakan University, Meram Faculty of Medicine, Department of Interventional Neuroradiology, Konya, Turkey 2
Objective: Endovascular coil embolization has become an effective treatment modality for most intracranial aneurysms. However, complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide necked aneurysm, or small aneurysm that are unsuitable for coil embolization are still deterrent to be treated. Flow diversion is a novel concept that is applied in the treatment of these complex intracranial aneurysms. Method: We review the results and important features of 25 aneurysms in 24 patients who underwent endovascular treatment by using the pipeline flow-diverter embolization device. Result: At 6 month follow-up, all aneurysms (100%) showed total occlusion in our series. Only one patient who had giant vertebrobasilar aneurysm experienced major complication related to endovascular treatment. Discussion: We suggest that parent artery reconstruction via flow diversion with the PED is a valid and safe treatment modality. Keywords: Endovascular, Flow-diverter, Pipeline, Embolization, Complex, Aneurysm
Introduction Endovascular coil embolization has become an effective treatment modality for most of the intracranial aneurysms.1 Complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide necked aneurysms, and small aneurysm that are unsuitable for coil embolization are still to be deterrent to treat with either surgical or endovascular technique due to their high morbidity and mortality. These aneurysms also have significant recurrence rates and poor outcomes.2,3 Flow diversion is a novel technique that is utilized in the treatment of these complex intracranial aneurysms. The pipeline embolization device (PED) is a flow diverter (FD) that has gained significant attention recently.4–7
Preliminary results of FDs that were applied in large and wide-necked or fusiform aneurysms were promising.8–10 In addition, evidence regarding the indications of FDs for small aneurysms, which are not amenable to standard coiling techniques, including blister-like aneurysms and the aneurysms with high procedural rupture risk, has started to accumulate.4,11,12 The current literature on the use of flow diversion for the treatment of these challenging aneurysms is limited to small case series or subgroup analyses from large series.8 In this current study, we report in detail our experience at a single center using the PED for the endovascular treatment of these aneurysms. In addition, we discuss the main features of this new technique in the light of the relevant literature.
Methods Correspondence to: Fatih Erdi, Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurosurgery, 42080 Akyokus/Meram, Konya, Turkey. Email: [email protected]
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/1743132814Y.0000000450
The University Institutional Review Board approved the study protocol of this study.
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Endovascular treatment of aneurysms via PED
A retrospective review of 24 patients who underwent endovascular treatment at our institution with the PED (ev3 Neurovascular, Irvine, CA, USA) between April 2012 and December 2013 was performed. Angiograms and procedure notes of the 24 cases were reviewed. Aneurysms are categorized based on digital subtraction angiography (DSA), as well as computed tomography (CT) angiography and magnetic resonance (MR) angiography. Clinical data, including the presence of subarachnoid hemorrhage (SAH), which was classified on CT scan with the Fisher Grade13 and angiographic data, were collected at the time of the procedure and at 6 months thereafter. If the patient refused follow-up angiography, the aneurysm was evaluated by means of CT angiography. Aneurysm size and location were recorded, and the change in size was noted using followup angiography or CT angiography. The presence of new contrast stasis after PED placement was noted. The average modified Rankin score (mRS) on admission and at last follow-up visit was recorded and compared.14 The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other neurological disabilities.14
The Modified Rankin Scale The scale runs from 0 to 6, running from perfect health without symptoms to death. 0 – No symptoms. 1 – No significant disability. Able to carry out all usual activities, despite some symptoms. 2 – Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 – Moderate disability. Requires some help, but able to walk unassisted. 4 – Moderately severe disability. Unable to attend to own bodily needs without assistance and unable to walk unassisted. 5 – Severe disability. Requires constant nursing care and attention, bedridden, and incontinent. 6 – Dead.
N N N N N
Table 1 Patient characteristics Sex Male 10 Female 14 Age (year) 49.92 (range 21–89 years) Presentation SAH 4 Headache 6 Cranial nerve palsy 1 Incidental 11 Follow-up after prior treatment 2 SAH grade* Grade 1 0 Grade 2 1 Grade 3 4 Grade 4 1 ** mRS (average) Prior to treatment 0.91 Last follow-up 0.58 Improved 10 patient Stable 12 patient Worsened 2 patient SAH: subarachnoid hemorrhage; mRS: modified Rankin score. According to Fisher SAH grading scale.13 ** According to modified Rankin score.14
*
discovered during their prior elective radiological investigations. The average mRS on admission was 0.91 and it was 0.58 at the last follow-up. The mean clinical followup duration was 8.6 months (range 2–22 months). At presentation, 23 (95.83%) out of 24 patients had a mRS of 2 or lower; the remaining 1 patient (4.16%) had a mRS of 3. At follow-up, 23 (95.83%) out of 24 patients had a mRS of 2 or lower, and 1 (4.16%) had a mRS of 4. When we compare mRS on admission to last follow-up, 10 patients improved (41.6%), 12 patients remained stable (50%), and 2 patients worsened (8.3%).
Aneurysm characteristics The details of treated aneurysms are listed in Table 2. Some examples of our cases are provided in Figs. 1A– F, 2 A–D, 3A–D, and 4A–C.
N N
Table 2 Aneurysm characteristics
Patient characteristics Twenty-five aneurysms were treated in 24 patients (10 men and 14 women) (Table 1). Twenty-one aneurysms were unruptured and four aneurysms were ruptured. The mean age was 49.9 years (range 21–89 years). All patients underwent endovascular treatment. Four patients presented with SAH and one patient with third cranial nerve palsy due to compressive effect. Six patients presented primarily with severe headache (without SAH). Two patients had been treated with coil embolization due to ruptured middle cerebral artery (MCA) and ICA aneurysms previously. These patients were retreated with PED subsequently because of regrowth of their aneurysms. Other patients had incidental aneurysms that were
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Ruptured Unruptured
4 21
Location Extradural Intradural
3 22
ICA Petrous segment Cavernous segment Ophthalmic segment MCA Vertebrobasilar
23 3 15 5 1 1
Size ,10 mm 10–25 mm .25 mm
8 10 7
MCA: middle cerebral artery.
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Figure 1 Preoperative computed tomography (CT) shows Fisher grade 3 subarachnoid hemorrhage (SAH) (A). Preoperative angiography depicts a wide necked small (3 mm) aneurysm originating from the left ICA anterior choroidal artery (B). Postoperative angiography images after pipeline embolization device (PED) delivery are seen in (C) and (D). Follow-up angiography at 6 months demonstrates total occlusion of the aneurysm (E,F).
Twenty-three internal carotid artery (92%), one MCA, and one vertebrobasilar artery aneurysms were treated by using PED. One patient had two aneurysms, one ruptured and one unruptured, each were treated by PED (bilateral ICA aneurysms). Two previously coiled ruptured aneurysms in different patients: one MCA and one ICA aneurysm treated with PED owing to regrowth of related aneurysms. The size of aneurysms was measured as ,10 mm in eight aneurysms, 10–25 mm in ten aneurysms, and .25 mm in seven aneurysms. Overall 3 aneurysms were extradural and other 22 aneurysms were intradural. There were 3 ICA petrous segment aneurysms, 15 ICA cavernous segment aneurysms, and 5 ICA ophthalmic segment aneurysms. The vertebrobasilar aneurysm was fusiform whereas other aneurysms were saccular in our cases.
Procedure Antiplatelet regimen Premedication with 75 mg of clopidogrel (Plavix; Sanofiaventis, Istanbul, Turkey) and 100 mg of aspirin was started 5–7 days prior to the procedure. If antiplatelet premedication was not done on the day before treatment, patients were premedicated with a loading dose of clopidogrel (300 mg) and aspirin (100 mg).
Overall 21 patients received 75 mg Clopidogrel and 100 mg aspirin as premedication and four patients were premedicated with a loading dose. Daily dual antiplatelet therapy was continued after procedure for 6 months (clopidogrel, 75 mg; aspirin, 100 mg) followed by aspirin alone daily for an additional 12 months. All patients received heparin during the procedure with an activated clotting time maintained at 2–2.5 times baseline.
Device quantity Delivery of the PEDs was successful in all cases without any technique-related complication. There was no significant in-stent thrombosis or thrombotic complication that required lysis intra-operatively. One patient underwent two procedures for different aneurysms. One patient had two PEDs placed in the same session (ICA aneurysm). Another one patient underwent placement of four PEDs in the same procedure (vertebrobasilar aneurysm). Multiple devices were placed in an overlapping fashion.
Complications Twenty-three out of 24 patients had no procedure related complications (95.8%). Transient ischemic attack, minor stroke, or other temporary symptoms were not seen after the treatment in any of our cases.
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In one patient who has vertebrobasilar aneurysm experienced a major complication related to endovascular treatment. In this patient, a small ischemic area on the anterior surface of medulla oblongata developed probably due to perforating vessel obstruction covered by the PED. This patient deteriorated at postoperative fourth hour and developed left sided hemiplegia. Preoperative mRS of this patient was 3 points at baseline and raised to 4. The patient is currently stable without any additional deterioration. One patient with an ICA aneurysm stopped taking antiplatelet therapy against medical advice at 2 months and her ICA PED became occluded. The patient had no symptoms; hence the antiplatelet therapy was not prescribed again. The patient has been under follow-up for 22 months without any problem.
Angiographic outcomes Immediate angiographic results Immediate angiographic results are graded based on contrast stasis within the aneurysm.12 Mild stasis is defined as contrast visualized in the aneurysm until the late arterial phase. Moderate stasis is defined as contrast visualized in the aneurysm until the capillary phase. Pronounced stasis is defined as contrast visualized in the aneurysm until the venous phase. Twenty aneurysms showed pronounced stasis, two aneurysms complete occlusion, and the other three aneurysms showed none, mild, or moderate stasis immediately after PED placement. Long term results At 6 month following the procedure, all aneurysms (100%) showed total occlusion. Total occlusion was confirmed with angiography in 11 aneurysms and with CT angiography in 14 aneurysms. CT angiography was performed if the patient refused to undergo follow-up angiography. The details of the angiographic results are listed in Table 3.
Discussion Flow diverters have been introduced into the armamentarium for aneurysm treatment recently.7 These devices are tubular stent-like implants with low porosity. Two working mechanisms of FDs were Table 3 Angiographic results Immediate angiographic results* None Mild stasis Moderate stasis Pronounced stasis Complete occlusion Follow-up results at 6 months Complete occlusion confirmed with angiography Complete occlusion confirmed with CT angiography
1 1 1 20 2 11 14
*Immediate angiographic results are graded based on contrast stasis within the aneurysm.
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identified as flow redirection and tissue overgrowth.7 In the beginning two FDs were clinically available: PED (ev3 Neurovascular, Irvine, CA, USA) and Silk (Balt, Montmorency, France). Other devices including Surpass (Stryker, Fremont, CA, USA), FRED (Microvention, Tustin, CA, USA),7 and p64 Flow Modulation Device (Phenox, Bochum, Germany) have recently been introduced. Preliminary clinical experience with FDs was mostly reported in relatively small single-center or multicenter retrospective series.7,9,15 The results of these studies showed an excellent feasibility of the treatment with acceptable periprocedural complications as well as morbidity and mortality rates and a high efficiency.7 The exact indications for flow diversion are yet to be fully established but growing clinical experience shows that FDs are mainly used in complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide-neck aneurysms, multiple aneurysms within a segmental diseased artery, and recanalized aneurysms after previous coiling.2,3,7 The common denominator of these aneurysms is their high morbidity associated with treatment and significant recurrence issues and poor outcomes irrespective of the treatment type, be it surgical or endovascular.2,3 Recently, Kulcsa´r et al. extended the indications of FDs to small aneurysms that are untreatable by standard coiling technique including blister-like aneurysms and the aneurysm that have high rupture risk during aneurysm access or coil placement.4,11,12 We treated eight small aneurysms (,10 mm) with PED in this series. Two of them were 2 and 3 mm sized (Fig. 1B) wide necked aneurysms and another one was a 3 mm blister type ICA aneurysm (Fig. 3A). In our cases, small ICA aneurysms showed pronounced occlusion immediately after PED delivery (Figs. 1C and 3B) and any procedure related complication was not seen. Similar to our results, Lin et al.12 concluded that treatment of small ICA aneurysms with PED is safe and associated with a high early angiographic success rate. Monteith et al.8 concluded that endovascular treatment of fusiform aneurysms with flow diversion appears to be safe and effective; however, the absolute risk of perforator occlusion in the regions of the MCA and basilar trunk was undetermined. Seven large or giant aneurysms (two examples of giant aneurysms can be seen at Figs. 2 and 4) were treated in our series including one fusiform type vertebrobasilar aneurysm. The only major complication occurred in a patient who had a fusiform vertebrobasilar aneurysm. Monteith et al. treated eight vertebrobasilar aneurysms, four of which were fusiform aneurysms. They reported one perforator infarction with resultant permanent neurological
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Figure 2 Preoperative angiography shows a wide-necked, giant (20 mm), unruptured aneurysm in the right ICA ophthalmic segment (A). Postoperative angiography images after pipeline embolization device (PED) delivery are seen in (B) and (C). Control angiography at 12 months demonstrates total occlusion of the aneurysm (D).
deficit after PED delivery.8 They proposed that the ischemic complications in the basilar trunk and MCA may be owing to using overlapping multiple devices and easy occlusion of the small perforators in these regions. This latter observation was in line with our experience with the patient in whom major complication (stroke) occurred after placement of four PEDs in an overlapping fashion during a single procedure. The main potential complications of FDs are nearly same with other endovascular techniques used for aneurysm repair.7,8 Thromboembolic events and intra-operative rupture are among major complications.7 Although the risk of intraoperative rupture is reduced because of lack of endosaccular manipulations, the risk of thromboembolic events is higher as compared with standard coiling or balloon-assisted coiling (BAC) due to the fact that FDs are placed in the parent artery. To prevent thromboembolic events, the use of preoperative and postoperative single or
dual antiplatelet treatment is currently recommended.7 In our series, all patients received dual antiplatelet therapy except one and no thromboembolic event occurred during the follow-up period. Flow diverters have some unique complications, which are not observed with standard coiling or BAC, i.e. delayed aneurysm rupture and remote parenchymal hematoma development.7,16,17 We did not observe any delayed aneurysm rupture or remote parenchymal hematoma in our patient group. Another important point about the FDs is the patency of the perforating arteries and side branches covered by the device.7 Kulcsar et al. treated 12 basilar artery aneurysms with FDs.11 In their follow-up, small symptomatic lesions related to small perforator occlusion was determined in two patients.11 In our cases, one patient who has fusiform vertebrobasilar aneurysm developed left sided hemiparalysis 4 hours after the procedure most probably related to occlusion of perforators.
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Figure 3 Preoperative angiography of a small (3 mm), ruptured blister type, lobulated, aneurysm located at the ICA supraclinoid segment (A). Postoperative angiography immediately after pipeline embolization device (PED) delivery (B,C). Control angiography at 6 months shows total occlusion of the aneurysm (D).
In addition, an exceptional complication was reported by Fiorella et al. as very late (23 months after procedure) thrombosis of FDs. Thus, long-term follow-up is warranted in these patients.7,18 Our mean clinical follow-up duration was 8.6 months and additional data were collected. We routinely start and continue antiplatelet therapy for 12 months. Our aneurysm occlusion rate for PED is 100% at 6 months with a very low major complication rate with just one patient. Murthy et al. stated about 80% aneurysm occlusion rate at 6 months with a complication rate of 16% in their systematic review on the clinical outcomes of PED with a total of 13 studies, with 905 patients.19 We think our overall results
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are favorable and in agreement with the current literature. Our study has some limitations. First, in order to evaluate the exact radiographic and clinical improvement with use of FD and associated complications, larger studies with long-term follow-up are required. We experienced an additional limitation with CT angiography. We used CT angiography mandatorily in 14 aneurysms for follow-up due to patients’ refusal of angiography. Computed tomography angiography has some limitations for revealing a complete follow-up data. It is not as accurate as conventional angiography in assessing residual filling of the aneurysm and it has a lower level of overall detail.
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Figure 4 Preoperative magnetic resonance (MR) angiography shows partially thrombosed right petro-cavernosus ICA aneurysm (A). Preoperative angiography demonstrates a giant saccular wide-necked, unruptured aneurysm of the right ICA petro-cavernosus segment (B). Near complete occlusion can be seen immediately after the procedure (C).
Conclusion Treatment of vertebrobasilar fusiform aneurysms via PED poses some difficulties due primarily to complex structure of these aneurysms. In our series, we experienced major complication in a case of vertebrobasilar fusiform aneurysm. In order to evaluate the exact effectiveness of PED and associated complications in these aneurysms, larger studies with longterm follow-up are required. Our results showed that aneurysms (,10 mm) treated with PED were totally occluded in all cases (100%) without any complication. According to the results of current study, parent artery reconstruction via flow diversion with the PED is a valid and safe treatment modality with low morbidity for wide necked complex aneurysms and the aneurysms, which are not amenable for standard coiling procedures including small aneurysms.
Disclaimer Statements Contributors Fatih Keskin and Erdal Kalkan contributed in planning. Fatih Erdi contributed in writing. Bu¨lent Kaya, Necdet Poyraz, and Suat Keskin contributed in editing. Osman Koc performed angiography. Funding Conflicts of interest Ethics approval The manuscript to be published was shown to the identifiable patient.
References 1 Won YS, Rho MH, Kim BM, Park HJ, Kwag HJ, Chung EC. Various techniques of stent-assisted coil embolization of widenecked or fusiform middle cerebral artery aneurysms: initial and mid-term results. J Korean Neurosurg Soc. 2013;53(5):274–80. 2 Bendok BR, Aoun SG. Flow diversion for intracranial aneurysms: optimally defining and evolving a new tool and approach. World Neurosurg. 2011;76(5):401–4. 3 Byrne JV, Beltechi R, Yarnold JA, Birks J, Kamran M. Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study. PLoS One. 2010;5(9):e12492.
4 Chalouhi N, Starke RM, Yang S, Bovenzi CD, Tjoumakaris S, Hasan D, et al. Extending the indications of flow diversion to small, unruptured, saccular aneurysms of the anterior circulation. Stroke. 2014;45(1):54–8. 5 Pistocchi S, Blanc R, Bartolini B, Piotin M. Flow diverters at and beyond the level of the circle of Willis for the treatment of intracranial aneurysms. Stroke. 2012;43:1032–8. 6 D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke. 2011;42:2363–8. 7 Pierot L, Wakhloo AK. Endovascular treatment of intracranial aneurysms: current status. Stroke. 2013;44:2046–54. 8 Monteith SJ, Tsimpas A, Dumont AS, Tjoumakaris S, Gonzalez LF, Rosenwasser RH, et al. Endovascular treatment of fusiform cerebral aneurysms with the pipeline embolization device. J Neurosurg. doi: 10.3171/2013.12.JNS13945 [published online January 24, 2014]. 9 Lylyk P, Miranda C, Ceratto R, Ferrario A, Scrivano E, Luna HR, et al. Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery. 2009;64:632–43. 10 Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D. The pipeline embolization device for the intracranial treatment of aneurysms trial. Am J Neuroradiol. 2011;32:34–40. 11 Kulcsa´r Z, Wetzel SG, Augsburger L, Gruber A, Wanke I, Ru¨fenacht DA. Effect of flow diversion treatment on very small ruptured aneurysms. Neurosurgery. 2010;67(3):789–93. 12 Lin LM, Colby GP, Kim JE, Huang J, Tamargo RJ, Coon AL. Immediate and follow-up results for 44 consecutive cases of small (,10 mm) internal carotid artery aneurysms treated with the pipeline embolization device. Surg Neurol Int. 2013;4:114. 13 Fisher C, Kistler J, Davis J. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980;6(1):1–9. 14 Van Swieten J, Koudstaal P, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604–7. 15 Berge J, Biondi A, Machi P, Brunel H, Pierot L, Gabrillarques J, et al. Flow-diverter silk stent for the treatment of intracranial aneurysms: 1-year follow-up in a multicenter study. Am J Neuroradiol. 2012;33:1150–5. 16 Turowski B, Macht S, Kulcsar Z, Ha¨nngi D, Stummer W. Early fatal hemorrhage after endovascular cerebral aneurysm treatment with a flow diverter (SILK-Stent). Neuroradiology. 2011;53:37–41. 17 Cebral JR, Mut F, Raschi M, Scrivano E, Ceratto R, Lylyk P, et al. Aneurysm rupture following treatment with flowdiverting stents: computational hemodynamics analysis of treatment. Am J Neuroradiol. 2011;32:27–33. 18 Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK. Very late thrombosis of a pipeline embolization device construct: case report. Neurosurgery. 2010;67(3 Suppl operative):onsE313–4 [discussion on sE314]. 19 Murthy SB, Shah S, Venkatasubba Rao CP, Bershad EM, Suarez JI. Treatment of unruptured intracranial aneurysms with the pipeline embolization device. J Clin Neurosci. 2014; 21(1):6–11.
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Endovascular treatment of complex intracranial aneurysms by pipeline flow-diverter embolization device: a single-center experience Fatih Keskin1, Fatih Erdi1, Bulent Kaya1, Necdet Poyraz2, Suat Keskin2, Erdal Kalkan1, Orhan Ozbek3, Osman Koc4 1
Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurosurgery, Konya, Turkey, Necmettin Erbakan University, Meram Faculty of Medicine, Department of Radiology, Konya, Turkey, 3 Necmettin Erbakan University, Meram Faculty of Medicine, Department of Interventional Radiology, Konya, Turkey, 4Necmettin Erbakan University, Meram Faculty of Medicine, Department of Interventional Neuroradiology, Konya, Turkey 2
Objective: Endovascular coil embolization has become an effective treatment modality for most intracranial aneurysms. However, complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide necked aneurysm, or small aneurysm that are unsuitable for coil embolization are still deterrent to be treated. Flow diversion is a novel concept that is applied in the treatment of these complex intracranial aneurysms. Method: We review the results and important features of 25 aneurysms in 24 patients who underwent endovascular treatment by using the pipeline flow-diverter embolization device. Result: At 6 month follow-up, all aneurysms (100%) showed total occlusion in our series. Only one patient who had giant vertebrobasilar aneurysm experienced major complication related to endovascular treatment. Discussion: We suggest that parent artery reconstruction via flow diversion with the PED is a valid and safe treatment modality. Keywords: Endovascular, Flow-diverter, Pipeline, Embolization, Complex, Aneurysm
Introduction Endovascular coil embolization has become an effective treatment modality for most of the intracranial aneurysms.1 Complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide necked aneurysms, and small aneurysm that are unsuitable for coil embolization are still to be deterrent to treat with either surgical or endovascular technique due to their high morbidity and mortality. These aneurysms also have significant recurrence rates and poor outcomes.2,3 Flow diversion is a novel technique that is utilized in the treatment of these complex intracranial aneurysms. The pipeline embolization device (PED) is a flow diverter (FD) that has gained significant attention recently.4–7
Preliminary results of FDs that were applied in large and wide-necked or fusiform aneurysms were promising.8–10 In addition, evidence regarding the indications of FDs for small aneurysms, which are not amenable to standard coiling techniques, including blister-like aneurysms and the aneurysms with high procedural rupture risk, has started to accumulate.4,11,12 The current literature on the use of flow diversion for the treatment of these challenging aneurysms is limited to small case series or subgroup analyses from large series.8 In this current study, we report in detail our experience at a single center using the PED for the endovascular treatment of these aneurysms. In addition, we discuss the main features of this new technique in the light of the relevant literature.
Methods Correspondence to: Fatih Erdi, Necmettin Erbakan University, Meram Faculty of Medicine, Department of Neurosurgery, 42080 Akyokus/Meram, Konya, Turkey. Email: [email protected]
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/1743132814Y.0000000450
The University Institutional Review Board approved the study protocol of this study.
Neurological Research
2014
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000
NO .
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Keskin et al.
Endovascular treatment of aneurysms via PED
A retrospective review of 24 patients who underwent endovascular treatment at our institution with the PED (ev3 Neurovascular, Irvine, CA, USA) between April 2012 and December 2013 was performed. Angiograms and procedure notes of the 24 cases were reviewed. Aneurysms are categorized based on digital subtraction angiography (DSA), as well as computed tomography (CT) angiography and magnetic resonance (MR) angiography. Clinical data, including the presence of subarachnoid hemorrhage (SAH), which was classified on CT scan with the Fisher Grade13 and angiographic data, were collected at the time of the procedure and at 6 months thereafter. If the patient refused follow-up angiography, the aneurysm was evaluated by means of CT angiography. Aneurysm size and location were recorded, and the change in size was noted using followup angiography or CT angiography. The presence of new contrast stasis after PED placement was noted. The average modified Rankin score (mRS) on admission and at last follow-up visit was recorded and compared.14 The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other neurological disabilities.14
The Modified Rankin Scale The scale runs from 0 to 6, running from perfect health without symptoms to death. 0 – No symptoms. 1 – No significant disability. Able to carry out all usual activities, despite some symptoms. 2 – Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 – Moderate disability. Requires some help, but able to walk unassisted. 4 – Moderately severe disability. Unable to attend to own bodily needs without assistance and unable to walk unassisted. 5 – Severe disability. Requires constant nursing care and attention, bedridden, and incontinent. 6 – Dead.
N N N N N
Table 1 Patient characteristics Sex Male 10 Female 14 Age (year) 49.92 (range 21–89 years) Presentation SAH 4 Headache 6 Cranial nerve palsy 1 Incidental 11 Follow-up after prior treatment 2 SAH grade* Grade 1 0 Grade 2 1 Grade 3 4 Grade 4 1 ** mRS (average) Prior to treatment 0.91 Last follow-up 0.58 Improved 10 patient Stable 12 patient Worsened 2 patient SAH: subarachnoid hemorrhage; mRS: modified Rankin score. According to Fisher SAH grading scale.13 ** According to modified Rankin score.14
*
discovered during their prior elective radiological investigations. The average mRS on admission was 0.91 and it was 0.58 at the last follow-up. The mean clinical followup duration was 8.6 months (range 2–22 months). At presentation, 23 (95.83%) out of 24 patients had a mRS of 2 or lower; the remaining 1 patient (4.16%) had a mRS of 3. At follow-up, 23 (95.83%) out of 24 patients had a mRS of 2 or lower, and 1 (4.16%) had a mRS of 4. When we compare mRS on admission to last follow-up, 10 patients improved (41.6%), 12 patients remained stable (50%), and 2 patients worsened (8.3%).
Aneurysm characteristics The details of treated aneurysms are listed in Table 2. Some examples of our cases are provided in Figs. 1A– F, 2 A–D, 3A–D, and 4A–C.
N N
Table 2 Aneurysm characteristics
Patient characteristics Twenty-five aneurysms were treated in 24 patients (10 men and 14 women) (Table 1). Twenty-one aneurysms were unruptured and four aneurysms were ruptured. The mean age was 49.9 years (range 21–89 years). All patients underwent endovascular treatment. Four patients presented with SAH and one patient with third cranial nerve palsy due to compressive effect. Six patients presented primarily with severe headache (without SAH). Two patients had been treated with coil embolization due to ruptured middle cerebral artery (MCA) and ICA aneurysms previously. These patients were retreated with PED subsequently because of regrowth of their aneurysms. Other patients had incidental aneurysms that were
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Size ,10 mm 10–25 mm .25 mm
8 10 7
MCA: middle cerebral artery.
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Figure 1 Preoperative computed tomography (CT) shows Fisher grade 3 subarachnoid hemorrhage (SAH) (A). Preoperative angiography depicts a wide necked small (3 mm) aneurysm originating from the left ICA anterior choroidal artery (B). Postoperative angiography images after pipeline embolization device (PED) delivery are seen in (C) and (D). Follow-up angiography at 6 months demonstrates total occlusion of the aneurysm (E,F).
Twenty-three internal carotid artery (92%), one MCA, and one vertebrobasilar artery aneurysms were treated by using PED. One patient had two aneurysms, one ruptured and one unruptured, each were treated by PED (bilateral ICA aneurysms). Two previously coiled ruptured aneurysms in different patients: one MCA and one ICA aneurysm treated with PED owing to regrowth of related aneurysms. The size of aneurysms was measured as ,10 mm in eight aneurysms, 10–25 mm in ten aneurysms, and .25 mm in seven aneurysms. Overall 3 aneurysms were extradural and other 22 aneurysms were intradural. There were 3 ICA petrous segment aneurysms, 15 ICA cavernous segment aneurysms, and 5 ICA ophthalmic segment aneurysms. The vertebrobasilar aneurysm was fusiform whereas other aneurysms were saccular in our cases.
Procedure Antiplatelet regimen Premedication with 75 mg of clopidogrel (Plavix; Sanofiaventis, Istanbul, Turkey) and 100 mg of aspirin was started 5–7 days prior to the procedure. If antiplatelet premedication was not done on the day before treatment, patients were premedicated with a loading dose of clopidogrel (300 mg) and aspirin (100 mg).
Overall 21 patients received 75 mg Clopidogrel and 100 mg aspirin as premedication and four patients were premedicated with a loading dose. Daily dual antiplatelet therapy was continued after procedure for 6 months (clopidogrel, 75 mg; aspirin, 100 mg) followed by aspirin alone daily for an additional 12 months. All patients received heparin during the procedure with an activated clotting time maintained at 2–2.5 times baseline.
Device quantity Delivery of the PEDs was successful in all cases without any technique-related complication. There was no significant in-stent thrombosis or thrombotic complication that required lysis intra-operatively. One patient underwent two procedures for different aneurysms. One patient had two PEDs placed in the same session (ICA aneurysm). Another one patient underwent placement of four PEDs in the same procedure (vertebrobasilar aneurysm). Multiple devices were placed in an overlapping fashion.
Complications Twenty-three out of 24 patients had no procedure related complications (95.8%). Transient ischemic attack, minor stroke, or other temporary symptoms were not seen after the treatment in any of our cases.
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In one patient who has vertebrobasilar aneurysm experienced a major complication related to endovascular treatment. In this patient, a small ischemic area on the anterior surface of medulla oblongata developed probably due to perforating vessel obstruction covered by the PED. This patient deteriorated at postoperative fourth hour and developed left sided hemiplegia. Preoperative mRS of this patient was 3 points at baseline and raised to 4. The patient is currently stable without any additional deterioration. One patient with an ICA aneurysm stopped taking antiplatelet therapy against medical advice at 2 months and her ICA PED became occluded. The patient had no symptoms; hence the antiplatelet therapy was not prescribed again. The patient has been under follow-up for 22 months without any problem.
Angiographic outcomes Immediate angiographic results Immediate angiographic results are graded based on contrast stasis within the aneurysm.12 Mild stasis is defined as contrast visualized in the aneurysm until the late arterial phase. Moderate stasis is defined as contrast visualized in the aneurysm until the capillary phase. Pronounced stasis is defined as contrast visualized in the aneurysm until the venous phase. Twenty aneurysms showed pronounced stasis, two aneurysms complete occlusion, and the other three aneurysms showed none, mild, or moderate stasis immediately after PED placement. Long term results At 6 month following the procedure, all aneurysms (100%) showed total occlusion. Total occlusion was confirmed with angiography in 11 aneurysms and with CT angiography in 14 aneurysms. CT angiography was performed if the patient refused to undergo follow-up angiography. The details of the angiographic results are listed in Table 3.
Discussion Flow diverters have been introduced into the armamentarium for aneurysm treatment recently.7 These devices are tubular stent-like implants with low porosity. Two working mechanisms of FDs were Table 3 Angiographic results Immediate angiographic results* None Mild stasis Moderate stasis Pronounced stasis Complete occlusion Follow-up results at 6 months Complete occlusion confirmed with angiography Complete occlusion confirmed with CT angiography
1 1 1 20 2 11 14
*Immediate angiographic results are graded based on contrast stasis within the aneurysm.
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identified as flow redirection and tissue overgrowth.7 In the beginning two FDs were clinically available: PED (ev3 Neurovascular, Irvine, CA, USA) and Silk (Balt, Montmorency, France). Other devices including Surpass (Stryker, Fremont, CA, USA), FRED (Microvention, Tustin, CA, USA),7 and p64 Flow Modulation Device (Phenox, Bochum, Germany) have recently been introduced. Preliminary clinical experience with FDs was mostly reported in relatively small single-center or multicenter retrospective series.7,9,15 The results of these studies showed an excellent feasibility of the treatment with acceptable periprocedural complications as well as morbidity and mortality rates and a high efficiency.7 The exact indications for flow diversion are yet to be fully established but growing clinical experience shows that FDs are mainly used in complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide-neck aneurysms, multiple aneurysms within a segmental diseased artery, and recanalized aneurysms after previous coiling.2,3,7 The common denominator of these aneurysms is their high morbidity associated with treatment and significant recurrence issues and poor outcomes irrespective of the treatment type, be it surgical or endovascular.2,3 Recently, Kulcsa´r et al. extended the indications of FDs to small aneurysms that are untreatable by standard coiling technique including blister-like aneurysms and the aneurysm that have high rupture risk during aneurysm access or coil placement.4,11,12 We treated eight small aneurysms (,10 mm) with PED in this series. Two of them were 2 and 3 mm sized (Fig. 1B) wide necked aneurysms and another one was a 3 mm blister type ICA aneurysm (Fig. 3A). In our cases, small ICA aneurysms showed pronounced occlusion immediately after PED delivery (Figs. 1C and 3B) and any procedure related complication was not seen. Similar to our results, Lin et al.12 concluded that treatment of small ICA aneurysms with PED is safe and associated with a high early angiographic success rate. Monteith et al.8 concluded that endovascular treatment of fusiform aneurysms with flow diversion appears to be safe and effective; however, the absolute risk of perforator occlusion in the regions of the MCA and basilar trunk was undetermined. Seven large or giant aneurysms (two examples of giant aneurysms can be seen at Figs. 2 and 4) were treated in our series including one fusiform type vertebrobasilar aneurysm. The only major complication occurred in a patient who had a fusiform vertebrobasilar aneurysm. Monteith et al. treated eight vertebrobasilar aneurysms, four of which were fusiform aneurysms. They reported one perforator infarction with resultant permanent neurological
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Figure 2 Preoperative angiography shows a wide-necked, giant (20 mm), unruptured aneurysm in the right ICA ophthalmic segment (A). Postoperative angiography images after pipeline embolization device (PED) delivery are seen in (B) and (C). Control angiography at 12 months demonstrates total occlusion of the aneurysm (D).
deficit after PED delivery.8 They proposed that the ischemic complications in the basilar trunk and MCA may be owing to using overlapping multiple devices and easy occlusion of the small perforators in these regions. This latter observation was in line with our experience with the patient in whom major complication (stroke) occurred after placement of four PEDs in an overlapping fashion during a single procedure. The main potential complications of FDs are nearly same with other endovascular techniques used for aneurysm repair.7,8 Thromboembolic events and intra-operative rupture are among major complications.7 Although the risk of intraoperative rupture is reduced because of lack of endosaccular manipulations, the risk of thromboembolic events is higher as compared with standard coiling or balloon-assisted coiling (BAC) due to the fact that FDs are placed in the parent artery. To prevent thromboembolic events, the use of preoperative and postoperative single or
dual antiplatelet treatment is currently recommended.7 In our series, all patients received dual antiplatelet therapy except one and no thromboembolic event occurred during the follow-up period. Flow diverters have some unique complications, which are not observed with standard coiling or BAC, i.e. delayed aneurysm rupture and remote parenchymal hematoma development.7,16,17 We did not observe any delayed aneurysm rupture or remote parenchymal hematoma in our patient group. Another important point about the FDs is the patency of the perforating arteries and side branches covered by the device.7 Kulcsar et al. treated 12 basilar artery aneurysms with FDs.11 In their follow-up, small symptomatic lesions related to small perforator occlusion was determined in two patients.11 In our cases, one patient who has fusiform vertebrobasilar aneurysm developed left sided hemiparalysis 4 hours after the procedure most probably related to occlusion of perforators.
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Figure 3 Preoperative angiography of a small (3 mm), ruptured blister type, lobulated, aneurysm located at the ICA supraclinoid segment (A). Postoperative angiography immediately after pipeline embolization device (PED) delivery (B,C). Control angiography at 6 months shows total occlusion of the aneurysm (D).
In addition, an exceptional complication was reported by Fiorella et al. as very late (23 months after procedure) thrombosis of FDs. Thus, long-term follow-up is warranted in these patients.7,18 Our mean clinical follow-up duration was 8.6 months and additional data were collected. We routinely start and continue antiplatelet therapy for 12 months. Our aneurysm occlusion rate for PED is 100% at 6 months with a very low major complication rate with just one patient. Murthy et al. stated about 80% aneurysm occlusion rate at 6 months with a complication rate of 16% in their systematic review on the clinical outcomes of PED with a total of 13 studies, with 905 patients.19 We think our overall results
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are favorable and in agreement with the current literature. Our study has some limitations. First, in order to evaluate the exact radiographic and clinical improvement with use of FD and associated complications, larger studies with long-term follow-up are required. We experienced an additional limitation with CT angiography. We used CT angiography mandatorily in 14 aneurysms for follow-up due to patients’ refusal of angiography. Computed tomography angiography has some limitations for revealing a complete follow-up data. It is not as accurate as conventional angiography in assessing residual filling of the aneurysm and it has a lower level of overall detail.
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Figure 4 Preoperative magnetic resonance (MR) angiography shows partially thrombosed right petro-cavernosus ICA aneurysm (A). Preoperative angiography demonstrates a giant saccular wide-necked, unruptured aneurysm of the right ICA petro-cavernosus segment (B). Near complete occlusion can be seen immediately after the procedure (C).
Conclusion Treatment of vertebrobasilar fusiform aneurysms via PED poses some difficulties due primarily to complex structure of these aneurysms. In our series, we experienced major complication in a case of vertebrobasilar fusiform aneurysm. In order to evaluate the exact effectiveness of PED and associated complications in these aneurysms, larger studies with longterm follow-up are required. Our results showed that aneurysms (,10 mm) treated with PED were totally occluded in all cases (100%) without any complication. According to the results of current study, parent artery reconstruction via flow diversion with the PED is a valid and safe treatment modality with low morbidity for wide necked complex aneurysms and the aneurysms, which are not amenable for standard coiling procedures including small aneurysms.
Disclaimer Statements Contributors Fatih Keskin and Erdal Kalkan contributed in planning. Fatih Erdi contributed in writing. Bu¨lent Kaya, Necdet Poyraz, and Suat Keskin contributed in editing. Osman Koc performed angiography. Funding Conflicts of interest Ethics approval The manuscript to be published was shown to the identifiable patient.
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4 Chalouhi N, Starke RM, Yang S, Bovenzi CD, Tjoumakaris S, Hasan D, et al. Extending the indications of flow diversion to small, unruptured, saccular aneurysms of the anterior circulation. Stroke. 2014;45(1):54–8. 5 Pistocchi S, Blanc R, Bartolini B, Piotin M. Flow diverters at and beyond the level of the circle of Willis for the treatment of intracranial aneurysms. Stroke. 2012;43:1032–8. 6 D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke. 2011;42:2363–8. 7 Pierot L, Wakhloo AK. Endovascular treatment of intracranial aneurysms: current status. Stroke. 2013;44:2046–54. 8 Monteith SJ, Tsimpas A, Dumont AS, Tjoumakaris S, Gonzalez LF, Rosenwasser RH, et al. Endovascular treatment of fusiform cerebral aneurysms with the pipeline embolization device. J Neurosurg. doi: 10.3171/2013.12.JNS13945 [published online January 24, 2014]. 9 Lylyk P, Miranda C, Ceratto R, Ferrario A, Scrivano E, Luna HR, et al. Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: the Buenos Aires experience. Neurosurgery. 2009;64:632–43. 10 Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D. The pipeline embolization device for the intracranial treatment of aneurysms trial. Am J Neuroradiol. 2011;32:34–40. 11 Kulcsa´r Z, Wetzel SG, Augsburger L, Gruber A, Wanke I, Ru¨fenacht DA. Effect of flow diversion treatment on very small ruptured aneurysms. Neurosurgery. 2010;67(3):789–93. 12 Lin LM, Colby GP, Kim JE, Huang J, Tamargo RJ, Coon AL. Immediate and follow-up results for 44 consecutive cases of small (,10 mm) internal carotid artery aneurysms treated with the pipeline embolization device. Surg Neurol Int. 2013;4:114. 13 Fisher C, Kistler J, Davis J. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery. 1980;6(1):1–9. 14 Van Swieten J, Koudstaal P, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604–7. 15 Berge J, Biondi A, Machi P, Brunel H, Pierot L, Gabrillarques J, et al. Flow-diverter silk stent for the treatment of intracranial aneurysms: 1-year follow-up in a multicenter study. Am J Neuroradiol. 2012;33:1150–5. 16 Turowski B, Macht S, Kulcsar Z, Ha¨nngi D, Stummer W. Early fatal hemorrhage after endovascular cerebral aneurysm treatment with a flow diverter (SILK-Stent). Neuroradiology. 2011;53:37–41. 17 Cebral JR, Mut F, Raschi M, Scrivano E, Ceratto R, Lylyk P, et al. Aneurysm rupture following treatment with flowdiverting stents: computational hemodynamics analysis of treatment. Am J Neuroradiol. 2011;32:27–33. 18 Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK. Very late thrombosis of a pipeline embolization device construct: case report. Neurosurgery. 2010;67(3 Suppl operative):onsE313–4 [discussion on sE314]. 19 Murthy SB, Shah S, Venkatasubba Rao CP, Bershad EM, Suarez JI. Treatment of unruptured intracranial aneurysms with the pipeline embolization device. J Clin Neurosci. 2014; 21(1):6–11.
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