Original Article
Treatment of vertebrobasilar fusiform aneurysms with Pipeline embolization device
Interventional Neuroradiology 2015, Vol. 21(4) 434–440 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1591019915590068 ine.sagepub.com
Osama Ahmed, Christopher Storey, Piyush Kalakoti, Jai Deep Thakur, Shihao Zhang, Anil Nanda, Bharat Guthikonda and Hugo Cuellar
Abstract Object: Treatment of complex intracranial aneurysms with Pipeline embolization device (PED) (ev3/Covidien Vascular Therapies) has gained recent popularity. One application of PEDs that is not well described in the literature is the utility and long-term safety in treatment of vertebrobasilar fusiform (VBF) aneurysms. Despite the advancements in endovascular therapy, VBF aneurysms continue to challenging pathology. The authors provide long-term follow-up of VBF aneurysms treated with PEDs. Methods: We retrospectively reviewed four patients that were treated at Louisiana State University Health Sciences Center in Shreveport with PEDs for VBFs from 2012 to 2014. Each patient was discussed in a multidisciplinary setting between neurosurgeons and neurointerventionalists. Each patient underwent platelet function tests to ensure responsiveness to anti-platelet agents and was treated by one neurointerventionalist (HC). All patients were placed on aspirin and Plavix and were confirmed for therapeutic response prior to discharge. Results: Follow-up ranged from 12 to 25 months, with a mean of 14.25 months. Two cases presented with a recurrence after the initial treatment, both of which required subsequent treatment. Of the four patients treated, one patient developed hemiparesis and three died. Conclusion: Despite reports describing successful treatment of VBF aneurysms with PEDs, delayed complications after obliteration and remodeling can occur. We describe our institutional experience of VBFs treated with PEDs. Treatment of holobasilar fusiform aneurysms may carry a worse prognosis after treatment. Further long-term follow-up will provide a better understanding of this pathology.
Keywords Fusiform aneurysm, vertebrobasilar aneurysm, flow diverting stent, endovascular treatment
Introduction Treatment of complex intracranial aneurysms with Pipeline embolization device (PED) (ev3/Covidien Vascular Therapies) has gained recent popularity. One application of PEDs that is not well described in the literature is the utility and long-term safety in treatment of vertebrobasilar fusiform (VBF) aneurysms. Despite the advancements in endovascular therapy, VBF aneurysms continue to represent a challenging pathology. The anatomic aspects and large number of perforators complicate endovascular treatment of these lesions. The need for anti-platelet therapy post treatment is an additional risk factor. The incidence of VBF aneurysms ranges from 0.06 to 5.8%.1 Presenting symptoms of this pathology include ischemic strokes (especially of the brainstem), hydrocephalus, cranial nerve palsies, and subarachnoid hemorrhage.1,2 Incidence of subarachnoid hemorrhage from this disease is approximately 2.2 per 1000-person years.3
There are several case reports and a few case series describing the use of PEDs in the treatment of VBF aneurysms.4–12 There are even fewer studies with long-term follow-up and outcome. We report four cases treated with PEDs for VBF aneurysms and provide follow-up.
Methods We retrospectively reviewed four patients who were treated at Louisiana State University Health Sciences
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA Corresponding author: Hugo Cuellar, Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA. Email: [email protected]
Ahmed et al. Center in Shreveport with PEDs for VBF aneurysms from January 2012 to January 2014. Each presenting patient was discussed in a multidisciplinary setting between neurosurgeons and neurointerventionalists. Each patient underwent platelet function tests to ensure responsiveness to anti-platelet agents. All patients were treated by one neurointerventionalist (HC) under general anesthesia. All patients were placed on anti-platelet therapy at least 5 days prior to intervention. One patient was not placed on Plavix pre-procedurally because the symptoms remained stable. All patients were treated for the fusiform aneurysm due to unresolved mass effect or persistent symptoms despite medical therapy. There was no intraprocedural anticoagulation administered since every patient was on anti-platelet therapy prior to the procedure. Every patient was placed on Aspirin 325 mg and Plavix 75 mg after the procedure. P2Y12 Plavix assay was confirmed for therapeutic response on every patient prior to discharge. Patients that showed complete obliteration of the aneurysm and resolution of their symptoms were advised to stop Plavix 6 months after the procedure. Follow-up assessment of the aneurysm was achieved with an angiogram.
Results The average age of our study population was 62.75 years. Eighty percent of the patients were male. Follow-up ranged from 12 to 25 months with a mean of 14.25 months. The details of each case are presented in Table 1. The average pre-operative modified Rankin Score (mRS) was 2.5 and the post-operative mRS was 5.5. We report a 25% morbidity and 75% mortality rate. An average of 4.5 PEDs was used per aneurysm and 5.25 stents per aneurysm. Two cases presented with a recurrence which required subsequent treatment (Cases 1 and 3). Case 1 presented with migration and disruption of the telescoping PED construct 25 months after initial treatment due to growth of the aneurysm. The patient stopped taking Plavix 6 months after the procedure due to complete obliteration and resolution of the symptoms. The same patient presented with ischemic insult 19 months after stopping Plavix. Case 3 had evidence of endoleak and aneurysm growth that required retreatment. Both cases which required retreatment died. Other than Case 1, all patients remained on 325 mg of aspirin and 75 mg of Plavix.
Discussion The natural history of VBFs continues to present a moribund pathology. Despite technological advancements in surgical and endovascular technique, treatment options do not improve upon the natural history. The incidence of VBFs range from 0.6 to 5.8%, while the 5-year mortality rate ranges from 23% to 35%.1,13 The incidence of SAH from VBFs is 2.2/1000 person years; however, the risk of cerebral
435 ischemia is much higher.2 The incidence of cerebral ischemia increases from 6.1%, 17.3%, to 25.4% at 1, 5, and 10-year period, respectively.14 There are several hypotheses which explain the pathogenesis of fusiform aneurysms. Fusiform aneurysm could be due to a congenital anomaly, arterial dissection, reticular fiber deficiency in the muscular layer, degeneration of the arterial wall due to hypertension, or mechanical injury by post-stenotic turbulence.3,15–18 Lipid deposition in the intima and muscular layer causing atrophy may lead to tortuosity of the vessel due to increases in intraluminal pressure. Sluggish blood flow in a dilated artery may predispose the aneurysm to thrombosis development.19 Before the advent and advancement of endovascular technology, VBF aneurysms were treated medically or surgically. With fusiform aneurysms that do not have a significant mass effect but are causing ischemia, medical management is considered the first line of treatment. If there is mass effect on neural structures with concurrent ischemic changes or if there is persistent ischemia despite anti-platelet therapy, surgical intervention may be warranted. Historically, surgical treatment consisted of three treatment options described by Drake et al: flow reduction with poor posterior collaterals via Hunterian ligation, flow reversal with adequate collaterals, trapping with mural hematoma decompression.20 Surgical outcomes have varied widely in the literature. Kalani et al. described a series of complex vertebrobasilar aneurysms that underwent flow reduction with an overall mortality rate of approximately 45%.21 In comparison to our mortality rate with endovascular treatment, successful treatment of this pathology continues to elude neurosurgeons. Despite the exponential advancements in endovascular technology, VBF aneurysms continue to be one of the most formidable lesions for neurosurgeons. The first flow diverting stent commercially available, the Silk stent, was used to treat a wide range of pathology with varied success.22 Subsequently, the PED received approval by the Food and Drug Administration in 2011. Flow diverting stents work by reconstructing the parent artery and preventing high velocity blood flow into the aneurysm. The stagnant blood in the aneurysm sac thrombosis. This eliminates the aneurysm sac from normal circulation and decreases the risk of rupture. A second mechanism for aneurysm obliteration is that the stent mesh provides a scaffold for neointimal growth, thus isolating the aneurysm from circulation. Unfortunately, flow diverting stents present with their own set of complications when used for VBFs. With the use of stents, there is an inherent risk of thrombus development. The neointimal growth can potentially occlude perforators off the parent artery. With holobasilar fusiform aneurysms, a single stent deployment will not divert flow across the entire length of the pathology. For this reason, a telescoping construct of several stents is usually needed. This is likely to decrease
56
67
56
72
Coils
no
no
no
yes
1
2
3
4
Case No
1
2
3
4
1 (3 Neuroform stents)
8
3
6
No of PEDs
Male
Male
Male
Male
Gender
N/A
Incomplete
Incomplete
N/A
Aspirin 325 mg and Plavix 75 mg Aspirin 325 mg and Plavix 75 mg
Aspirin 325 mg and Plavix 75 mg
Post-procedural antiplatelets
Occlusion of aneurysm
Complete
Mass effect
Persistent TIAs
Persistent TIAs
Persistent TIAs
Reason for treatment
Leg weakness
Dizziness, numbness
Dizziness, nausea, emesis Slurred speech
Initial symptoms
4
2
6
6
4
6
2
2
Post-mRS
Holobasilar and right vertebral artery Holobasilar and bilateral vertebral arteries
Holobasilar artery and left VB junction Holobasilar artery
Aneurysm Location
Pre-mRS
Aspirin 81 mg and Meclizine Aspirin 81 mg and Plavix 75 mg Aspirin 81 mg and Plavix 75 mg Aspirin 81 mg and Plavix 75 mg
Pre-procedural medications
VB – vertebrobasilar, TIA – transient ischemic attacks, * - Neuroform stent, mRS – modified Rankin Scale.
Age
Case No
Table 1. Four patients treated with PEDs for VBFs.
N/A
Yes
No
Yes
Retreatment
33 30
11.9 82
10 35
4.5 3
Dimensions of aneurysm (mm)
Thrombosis, recurrence, failed construct, ischemia, death Ischemia, right hemiparesis Mass effect, hemiparesis, recurrence, death Ischemia, death
Complication
4.75 25 (5), 5 35 (2), 5 20 4.5 30 (3)*, 4.5 35
4.75 25, 5 35, 5 16
4 35
Dimensions of stents (mm)
436 Interventional Neuroradiology 21(4)
Ahmed et al.
437
Table 2. Summary of publications on treatment of VBF aneurysms with PEDs.
Authors
# of patients Avg # with fusiform of PEDs/ Occlusion of Complications Morbidity Mortality aneurysm aneurysm (# of patients) (%) (%) aneurysm
Fiorella et al.6,23 2
3
Yes
Yes (1)
Yes (50%) Yes (50%)
Narata et al.8 Ducruet et al.5 Tan et al.12 Chalouhi et al.4 Siddiqui et al.10
2 1 1 3 7
3 2 6 – 4.85
Yes Yes Yes Yes
No No No No Yes (5)
No No No No Yes (14%)
No No No No Yes
Gong et al.7 Nelson et al.9 Szikora et al.11 Ertl et al.26
1 1 1 1
1 3.5 5 6
Yes Yes Yes No
No No No Yes
No No No No
No No No Yes
the porosity of the stent and lead to complications related to perforator occlusion. Another uncertainty that lies with flow diverting stents is the use of antiplatelet agents. There is no established guidelines on the administration or combination of antiplatelet agents. In this study, all patients were placed on 81 mg aspirin and 75 mg Plavix before the procedure. After the procedure, 325 mg aspirin and 75 mg Plavix were continued indefinitely except for one patient that exhibited resolution of their preprocedural symptoms. There is a paucity of literature describing the utility, safety, and efficacy of PEDs in the treatment of VBF aneurysms. Fiorella et al. reported the first use of PED in two patients with VBF aneurysms.6 One patient had a combination of Multilink Vision stent (Abbott Vascular, Abbott Park, IL), Neuroform stent (Boston Scientific, Fremont, CA), and PED. The other patient had three PEDs placed.6 After nearly a two year followup, Fiorella et al. reported one of the patients developed complete occlusion of the fusiform aneurysm and parent artery causing ischemic strokes.23 As PEDs have gained popularity in treatment of VBF aneurysms, several reports have described their outcomes (Table 2).4,5,7,8,12,13,24–26 Several larger studies incorporate posterior circulation aneurysms of multiple locations but do not discuss VBF aneurysms as a separate entity.5,13,27 Because of the paucity of literature in treatment of VBF aneurysms and PEDs, it is difficult to generalize the safety and efficacy of its use. The largest series of VBF aneurysms is by Siddiqui et al.,10 who retrospectively reviewed 26 patients treated with PEDs. Of the 26 patients, seven were treated for fusiform vertebrobasilar aneurysms. The authors reported a 57% mortality rate with only one patient (14%) being completely asymptomatic after treatment of VBFs. Each fusiform aneurysm required an average of 4.86 PEDs, with two requiring nine PEDs.10
Follow-up period
Description of complication
12–28 months Thrombosis of parent artery, brainstem stroke 6–9 months – 6 months – 6 months – 5.5 months – (57%) – Ischemic stroke, SAH 6 months – – – 6 months – (100%) 17 months Brainstem compression
Our average number of PEDs per aneurysm was almost 4 (3.8). One patient required a maximum of eight PEDs. One important finding is that patients with holobasilar aneurysms faired far worse than segmental fusiform aneurysms, with holobasilar aneurysms having a mRS of 5 or 6 in 75% of the patients. Chalouhi et al. reported seven posterior circulation aneurysms treated with PEDs,4 of which three were fusiform. Two out of the three patients achieved complete occlusion of the fusiform aneurysm. There were no reported complications or mortalities. The average follow-up was 5.5 months.4 Shapiro et al. published a systematic review of VBF aneurysms.28 Four hundred and forty cases were included in this study. Seventy percent of the patients were male, which coincides with our study (80% male). There was a 66% incidence of hypertension and 41% incidence of smoking. All of our cases had a past medical history of hypertension. The authors determined the overall mortality rate was 43% with a 7.1 year follow-up. We encountered a higher mortality rate with treatment in our case series. Shapiro et al. analyzed outcomes in subpopulations of hemorrhage, ischemic stroke, mass effect, and growth.28 The authors discovered that patients presenting with symptoms due to mass effect or growth of aneurysm with serial imaging were poor prognostic factors. All of the patients in our case series presented due to mass effect, TIA/stroke, and refractory to medical therapy. Two of our four patients had aneurysm regrowth after treatment. We suspect an intrinsic component to a subset of VBF aneurysms that lead to a poorer outcome is likely. Despite achieving successful PED placement and obliteration of the aneurysm, two cases presented with recurrence/growth. Krings et al. suggests partially thrombosed aneurysms repeatedly bleed into the vessel wall,29 causing enhancement of the wall (see Figure 1(e)). Hemorrhage into the vessel wall is also
438 associated with adjacent brain edema.29 With patent perforators off the aneurysm, continuous blood flow could explain the recurrence/growth we encountered in Cases 1 and 3 despite achieving radiographic obliteration of the aneurysm. To overcome this, sacrifice of the perforators off the basilar trunk would lead to catastrophic injury. If the fusiform aneurysm extends to involve the vertebral arteries, sacrifice of a vertebral artery may limit the number of patent perforators, thus possibly decreasing the risk of recurrence. This was attempted in Case 4, but immediate ischemic insult prevented the authors from observing the risk of long-term recurrence. With treatment mortality rates after treatment higher than the reported natural history, one must
Interventional Neuroradiology 21(4) question the safety of PED for VBF aneurysms. Because of the naturally long length of a holobasilar fusiform aneurysm, a telescoping construct decreases the porosity of the stents. Due to the high number of perforating branches off the basilar trunk, the chances of perforator occlusion increases, thus leading to ischemic injury. The blood supply to the perforators’ and aneurysm’s vasa vasorum may contribute to aneurysm regrowth, which explains aneurysm recurrence on angiography despite achieving obliteration after treatment. One limitation of this study is the small patient population reported. This study population was performed at a single institution under a single neuroradiologist. Another limitation is although every patient presented with a holobasilar fusiform aneurysm, there
Figure 1. (a) Lateral view of the initial angiogram showing a right VB junction aneurysm extending to the distal third of the basilar artery. (b) MRI T1 weighted image showing a fusiform aneurysm with compression of the brainstem. (c) A 3 month follow-up angiogram shows a partially thrombosed fusiform aneurysm. (d) A 10 month follow-up angiogram with development of endoleaks at the proximal and distal ends with growth of the aneurysm. (e) A 10 month CT angiogram shows hypervascularity at the periphery of the aneurysm that was not present on the initial CT angiogram, suggestive of blood flow to the vasa vasorum. This could be responsible for growth of the aneurysm. (f) Diffusion-weighted image showing ischemic changes in the brainstem.
Ahmed et al. is some heterogeneity in the diseases treated. Some fusiform aneurysms were localized to the basilar artery while some extended to the vertebrobasilar junction. It is unknown if Case 3 died due to complications related to treatment or natural causes, which could alter our mortality rate. There is no established protocol on the use of antiplatelet agents, which could contribute to the risk of ischemia after stent deployment.
Conclusion The immediate risk of treating VBF aneurysms is evident in our case series. Despite reports describing successful treatment of this moribund disease process with PEDs, delayed complications after obliteration and remodeling of the aneurysm can occur. Holobasilar fusiform aneurysms may be more difficult to treat due to the length and need of a telescoping construct. Medical management in holobasilar fusiform aneurysms may lead to better outcomes than intervention. We advocate careful consideration and long-term follow-up despite successful obliteration of the VBF aneurysm. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest None declared.
Notes This study or portions of this study have been presented at our institutional research symposium. References 1. Titlic M, Tonkic A, Jukic I, et al. Clinical manifestations of vertebrobasilar dolichoectasia. Bratisl Leka´rske Listy 2008; 109: 528–530. 2. Passero SG, Calchetti B and Bartalini S. Intracranial bleeding in patients with vertebrobasilar dolichoectasia. Stroke 2005; 36: 1421–1425. 3. Nijensohn DE, Saez RJ and Reagan TJ. Clinical significance of basilar artery aneurysms. Neurology 1974; 24: 301–305. 4. Chalouhi N, Tjoumakaris S, Dumont AS, et al. Treatment of posterior circulation aneurysms with the pipeline embolization device. Neurosurgery 2013; 72: 883–889. 5. Ducruet AF, Crowle RW, Albuquerque FC, et al. Reconstructive endovascular treatment of a ruptured vertebral artery dissecting aneurysm using the Pipeline embolization device. J Neurointerventional Surg 2013; 5: e20. 6. Fiorella D, Woo HH, Albuquerque FC, et al. Definitive reconstruction of circumferential, fusiform intracranial aneurysms with the pipeline embolization device. Neurosurgery 2008; 62: 1115–1120. 7. Gong D, Yan B, Dowling R, et al. Successful treatment of growing basilar artery dissecting aneurysm by pipeline flow diversion embolization device. J Stroke Cerebrovasc Dis 2014; 23: 1713–1716.
439 8. Narata AP, Yilmaz H, Schaller K, et al. Flow-diverting stent for ruptured intracranial dissecting aneurysm of vertebral artery. Neurosurgery 2012; 70: 982–988. 9. Nelson PK, Lylyk P, Szikora I, et al. The pipeline embolization device for the intracranial treatment of aneurysms trial. Am J Neuroradiol 2011; 32: 34–40. 10. Siddiqui AH, Abla AA, Kan P, et al. Panacea or problem: flow diverters in the treatment of symptomatic large or giant fusiform vertebrobasilar aneurysms. J Neurosurg 2012; 116: 1258–1266. 11. Szikora I, Berentei Z, Kulcsar Z, et al. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the pipeline embolization device. Am J Neuroradiol 2010; 31: 1139–1147. 12. Tan LA, Moftakhar R and Lopes DK. Treatment of a ruptured vertebrobasilar fusiform aneurysm using pipeline embolization device. J Cerebrovasc Endovasc Neurosurg 2013; 15: 30–33. 13. Cruz JP, O’Kelly C, Kelly M, et al. Pipeline embolization device in aneurysmal subarachnoid hemorrhage. Am J Neuroradiol 2013; 34: 271–276. 14. Flemming KD, Wiebers DO, Brown Jr, RD, et al. The natural history of radiographically defined vertebrobasilar nonsaccular intracranial aneurysms. Cerebrovasc Dis 2005; 20: 270–279. 15. Anson JA, Lawton MT and Spetzler RF. Characteristics and surgical treatment of dolichoectatic and fusiform aneurysms. J Neurosurg 1996; 84: 185–193. 16. Hegedu¨s K. Ectasia of the basilar artery with special reference to possible pathogenesis. Surg Neurol 1985; 24: 463–469. 17. Shokunbi M, Vinters H and Kaufmann J. Fusiform intracranial aneurysm. Clinicopathological features. Surg Neurol 1988; 29: 263–270. 18. Van Donselaar CA, Stefanko SZ, van der Kwast TH, et al. Basilar artery giant fusiform aneurysms caused by congenital defect of the internal elastic lamina and media. Clin Neuropathol 1988; 7: 68–72. 19. Echiverri HC, Rubino FA, Gupta SR, et al. Fusiform aneurysm of the vertebrobasilar arterial system. Stroke 1989; 20: 1741–1747. 20. Drake CG and Peerless SJ. Giant fusiform intracranial aneurysms: review of 120 patients treated surgically from 1965 to 1992. J Neurosurg 1997; 87: 141–162. 21. Kalani MYS, Zabramski JM, Nakaji P, et al. Bypass and flow reduction for complex basilar and vertebrobasilar junction aneurysms. Neurosurgery 2012; 72: 763–775. 22. Cirillo L, Leonardi M, Dallolio M, et al. Complications in the treatment of intracranial aneurysms with silk stents: an analysis of 30 consecutive patients. Interv Neuroradiol 2012; 18: 413–425. 23. Fiorella D, Hsu D, Woo HH, et al. Very late thrombosis of a pipeline embolization device construct: case report. Neurosurgery 2010; 67: onsE313–onsE314. 24. Munich SA, Tan LA, Keigher KM, et al. The Pipeline embolization device for the treatment of posterior circulation fusiform aneurysms: lessons learned at a single institution. J Neurosurg 2014; 121: 1077–1084. 25. Phillips TJ, Wenderoth JD, Phatouros CC, et al. Safety of the pipeline embolization device in treatment of posterior circulation aneurysms. Am J Neuroradiol 2012; 33: 1225–1231.
440 26. Ertl L, Holtmannspotter M, Patzig H, et al. Use of flow-diverting devices in fusiform vertebrobasilar giant aneurysms: a report and periprocedural course and long-term follow-up. Am J Neuroradiol 2014; 35: 1346–1352. 27. Meckel S, McAuliffe W, Fiorella D, et al. Endovascular treatment of complex aneurysms at the vertebrobasilar junction with flow-diverting stents: initial experience. Neurosurgery 2013; 73: 386–394. 28. Shapiro M, Becske T, Riina HA, et al. Non-saccular vertebrobasilar aneurysms and dolichoectasia: a
Interventional Neuroradiology 21(4) systematic literature review. J Neurointerv Surg 2014; 6: 389–393. 29. Krings T, Alvarez H, Reinacher P, et al. Growth and rupture mechanism of partially thrombosed aneurysms. Interv Neuroradiol 2007; 13: 117–126. 30. Raphaeli D, Collignon L, De Witte O, et al. Endovascular treatment of posterior circulation fusiform aneurysms: single-center experience in 31 patients. Neurosurgery 2011; 69: 274–283.
Treatment of vertebrobasilar fusiform aneurysms with Pipeline embolization device
Interventional Neuroradiology 2015, Vol. 21(4) 434–440 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1591019915590068 ine.sagepub.com
Osama Ahmed, Christopher Storey, Piyush Kalakoti, Jai Deep Thakur, Shihao Zhang, Anil Nanda, Bharat Guthikonda and Hugo Cuellar
Abstract Object: Treatment of complex intracranial aneurysms with Pipeline embolization device (PED) (ev3/Covidien Vascular Therapies) has gained recent popularity. One application of PEDs that is not well described in the literature is the utility and long-term safety in treatment of vertebrobasilar fusiform (VBF) aneurysms. Despite the advancements in endovascular therapy, VBF aneurysms continue to challenging pathology. The authors provide long-term follow-up of VBF aneurysms treated with PEDs. Methods: We retrospectively reviewed four patients that were treated at Louisiana State University Health Sciences Center in Shreveport with PEDs for VBFs from 2012 to 2014. Each patient was discussed in a multidisciplinary setting between neurosurgeons and neurointerventionalists. Each patient underwent platelet function tests to ensure responsiveness to anti-platelet agents and was treated by one neurointerventionalist (HC). All patients were placed on aspirin and Plavix and were confirmed for therapeutic response prior to discharge. Results: Follow-up ranged from 12 to 25 months, with a mean of 14.25 months. Two cases presented with a recurrence after the initial treatment, both of which required subsequent treatment. Of the four patients treated, one patient developed hemiparesis and three died. Conclusion: Despite reports describing successful treatment of VBF aneurysms with PEDs, delayed complications after obliteration and remodeling can occur. We describe our institutional experience of VBFs treated with PEDs. Treatment of holobasilar fusiform aneurysms may carry a worse prognosis after treatment. Further long-term follow-up will provide a better understanding of this pathology.
Keywords Fusiform aneurysm, vertebrobasilar aneurysm, flow diverting stent, endovascular treatment
Introduction Treatment of complex intracranial aneurysms with Pipeline embolization device (PED) (ev3/Covidien Vascular Therapies) has gained recent popularity. One application of PEDs that is not well described in the literature is the utility and long-term safety in treatment of vertebrobasilar fusiform (VBF) aneurysms. Despite the advancements in endovascular therapy, VBF aneurysms continue to represent a challenging pathology. The anatomic aspects and large number of perforators complicate endovascular treatment of these lesions. The need for anti-platelet therapy post treatment is an additional risk factor. The incidence of VBF aneurysms ranges from 0.06 to 5.8%.1 Presenting symptoms of this pathology include ischemic strokes (especially of the brainstem), hydrocephalus, cranial nerve palsies, and subarachnoid hemorrhage.1,2 Incidence of subarachnoid hemorrhage from this disease is approximately 2.2 per 1000-person years.3
There are several case reports and a few case series describing the use of PEDs in the treatment of VBF aneurysms.4–12 There are even fewer studies with long-term follow-up and outcome. We report four cases treated with PEDs for VBF aneurysms and provide follow-up.
Methods We retrospectively reviewed four patients who were treated at Louisiana State University Health Sciences
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA Corresponding author: Hugo Cuellar, Department of Neurosurgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA. Email: [email protected]
Ahmed et al. Center in Shreveport with PEDs for VBF aneurysms from January 2012 to January 2014. Each presenting patient was discussed in a multidisciplinary setting between neurosurgeons and neurointerventionalists. Each patient underwent platelet function tests to ensure responsiveness to anti-platelet agents. All patients were treated by one neurointerventionalist (HC) under general anesthesia. All patients were placed on anti-platelet therapy at least 5 days prior to intervention. One patient was not placed on Plavix pre-procedurally because the symptoms remained stable. All patients were treated for the fusiform aneurysm due to unresolved mass effect or persistent symptoms despite medical therapy. There was no intraprocedural anticoagulation administered since every patient was on anti-platelet therapy prior to the procedure. Every patient was placed on Aspirin 325 mg and Plavix 75 mg after the procedure. P2Y12 Plavix assay was confirmed for therapeutic response on every patient prior to discharge. Patients that showed complete obliteration of the aneurysm and resolution of their symptoms were advised to stop Plavix 6 months after the procedure. Follow-up assessment of the aneurysm was achieved with an angiogram.
Results The average age of our study population was 62.75 years. Eighty percent of the patients were male. Follow-up ranged from 12 to 25 months with a mean of 14.25 months. The details of each case are presented in Table 1. The average pre-operative modified Rankin Score (mRS) was 2.5 and the post-operative mRS was 5.5. We report a 25% morbidity and 75% mortality rate. An average of 4.5 PEDs was used per aneurysm and 5.25 stents per aneurysm. Two cases presented with a recurrence which required subsequent treatment (Cases 1 and 3). Case 1 presented with migration and disruption of the telescoping PED construct 25 months after initial treatment due to growth of the aneurysm. The patient stopped taking Plavix 6 months after the procedure due to complete obliteration and resolution of the symptoms. The same patient presented with ischemic insult 19 months after stopping Plavix. Case 3 had evidence of endoleak and aneurysm growth that required retreatment. Both cases which required retreatment died. Other than Case 1, all patients remained on 325 mg of aspirin and 75 mg of Plavix.
Discussion The natural history of VBFs continues to present a moribund pathology. Despite technological advancements in surgical and endovascular technique, treatment options do not improve upon the natural history. The incidence of VBFs range from 0.6 to 5.8%, while the 5-year mortality rate ranges from 23% to 35%.1,13 The incidence of SAH from VBFs is 2.2/1000 person years; however, the risk of cerebral
435 ischemia is much higher.2 The incidence of cerebral ischemia increases from 6.1%, 17.3%, to 25.4% at 1, 5, and 10-year period, respectively.14 There are several hypotheses which explain the pathogenesis of fusiform aneurysms. Fusiform aneurysm could be due to a congenital anomaly, arterial dissection, reticular fiber deficiency in the muscular layer, degeneration of the arterial wall due to hypertension, or mechanical injury by post-stenotic turbulence.3,15–18 Lipid deposition in the intima and muscular layer causing atrophy may lead to tortuosity of the vessel due to increases in intraluminal pressure. Sluggish blood flow in a dilated artery may predispose the aneurysm to thrombosis development.19 Before the advent and advancement of endovascular technology, VBF aneurysms were treated medically or surgically. With fusiform aneurysms that do not have a significant mass effect but are causing ischemia, medical management is considered the first line of treatment. If there is mass effect on neural structures with concurrent ischemic changes or if there is persistent ischemia despite anti-platelet therapy, surgical intervention may be warranted. Historically, surgical treatment consisted of three treatment options described by Drake et al: flow reduction with poor posterior collaterals via Hunterian ligation, flow reversal with adequate collaterals, trapping with mural hematoma decompression.20 Surgical outcomes have varied widely in the literature. Kalani et al. described a series of complex vertebrobasilar aneurysms that underwent flow reduction with an overall mortality rate of approximately 45%.21 In comparison to our mortality rate with endovascular treatment, successful treatment of this pathology continues to elude neurosurgeons. Despite the exponential advancements in endovascular technology, VBF aneurysms continue to be one of the most formidable lesions for neurosurgeons. The first flow diverting stent commercially available, the Silk stent, was used to treat a wide range of pathology with varied success.22 Subsequently, the PED received approval by the Food and Drug Administration in 2011. Flow diverting stents work by reconstructing the parent artery and preventing high velocity blood flow into the aneurysm. The stagnant blood in the aneurysm sac thrombosis. This eliminates the aneurysm sac from normal circulation and decreases the risk of rupture. A second mechanism for aneurysm obliteration is that the stent mesh provides a scaffold for neointimal growth, thus isolating the aneurysm from circulation. Unfortunately, flow diverting stents present with their own set of complications when used for VBFs. With the use of stents, there is an inherent risk of thrombus development. The neointimal growth can potentially occlude perforators off the parent artery. With holobasilar fusiform aneurysms, a single stent deployment will not divert flow across the entire length of the pathology. For this reason, a telescoping construct of several stents is usually needed. This is likely to decrease
56
67
56
72
Coils
no
no
no
yes
1
2
3
4
Case No
1
2
3
4
1 (3 Neuroform stents)
8
3
6
No of PEDs
Male
Male
Male
Male
Gender
N/A
Incomplete
Incomplete
N/A
Aspirin 325 mg and Plavix 75 mg Aspirin 325 mg and Plavix 75 mg
Aspirin 325 mg and Plavix 75 mg
Post-procedural antiplatelets
Occlusion of aneurysm
Complete
Mass effect
Persistent TIAs
Persistent TIAs
Persistent TIAs
Reason for treatment
Leg weakness
Dizziness, numbness
Dizziness, nausea, emesis Slurred speech
Initial symptoms
4
2
6
6
4
6
2
2
Post-mRS
Holobasilar and right vertebral artery Holobasilar and bilateral vertebral arteries
Holobasilar artery and left VB junction Holobasilar artery
Aneurysm Location
Pre-mRS
Aspirin 81 mg and Meclizine Aspirin 81 mg and Plavix 75 mg Aspirin 81 mg and Plavix 75 mg Aspirin 81 mg and Plavix 75 mg
Pre-procedural medications
VB – vertebrobasilar, TIA – transient ischemic attacks, * - Neuroform stent, mRS – modified Rankin Scale.
Age
Case No
Table 1. Four patients treated with PEDs for VBFs.
N/A
Yes
No
Yes
Retreatment
33 30
11.9 82
10 35
4.5 3
Dimensions of aneurysm (mm)
Thrombosis, recurrence, failed construct, ischemia, death Ischemia, right hemiparesis Mass effect, hemiparesis, recurrence, death Ischemia, death
Complication
4.75 25 (5), 5 35 (2), 5 20 4.5 30 (3)*, 4.5 35
4.75 25, 5 35, 5 16
4 35
Dimensions of stents (mm)
436 Interventional Neuroradiology 21(4)
Ahmed et al.
437
Table 2. Summary of publications on treatment of VBF aneurysms with PEDs.
Authors
# of patients Avg # with fusiform of PEDs/ Occlusion of Complications Morbidity Mortality aneurysm aneurysm (# of patients) (%) (%) aneurysm
Fiorella et al.6,23 2
3
Yes
Yes (1)
Yes (50%) Yes (50%)
Narata et al.8 Ducruet et al.5 Tan et al.12 Chalouhi et al.4 Siddiqui et al.10
2 1 1 3 7
3 2 6 – 4.85
Yes Yes Yes Yes
No No No No Yes (5)
No No No No Yes (14%)
No No No No Yes
Gong et al.7 Nelson et al.9 Szikora et al.11 Ertl et al.26
1 1 1 1
1 3.5 5 6
Yes Yes Yes No
No No No Yes
No No No No
No No No Yes
the porosity of the stent and lead to complications related to perforator occlusion. Another uncertainty that lies with flow diverting stents is the use of antiplatelet agents. There is no established guidelines on the administration or combination of antiplatelet agents. In this study, all patients were placed on 81 mg aspirin and 75 mg Plavix before the procedure. After the procedure, 325 mg aspirin and 75 mg Plavix were continued indefinitely except for one patient that exhibited resolution of their preprocedural symptoms. There is a paucity of literature describing the utility, safety, and efficacy of PEDs in the treatment of VBF aneurysms. Fiorella et al. reported the first use of PED in two patients with VBF aneurysms.6 One patient had a combination of Multilink Vision stent (Abbott Vascular, Abbott Park, IL), Neuroform stent (Boston Scientific, Fremont, CA), and PED. The other patient had three PEDs placed.6 After nearly a two year followup, Fiorella et al. reported one of the patients developed complete occlusion of the fusiform aneurysm and parent artery causing ischemic strokes.23 As PEDs have gained popularity in treatment of VBF aneurysms, several reports have described their outcomes (Table 2).4,5,7,8,12,13,24–26 Several larger studies incorporate posterior circulation aneurysms of multiple locations but do not discuss VBF aneurysms as a separate entity.5,13,27 Because of the paucity of literature in treatment of VBF aneurysms and PEDs, it is difficult to generalize the safety and efficacy of its use. The largest series of VBF aneurysms is by Siddiqui et al.,10 who retrospectively reviewed 26 patients treated with PEDs. Of the 26 patients, seven were treated for fusiform vertebrobasilar aneurysms. The authors reported a 57% mortality rate with only one patient (14%) being completely asymptomatic after treatment of VBFs. Each fusiform aneurysm required an average of 4.86 PEDs, with two requiring nine PEDs.10
Follow-up period
Description of complication
12–28 months Thrombosis of parent artery, brainstem stroke 6–9 months – 6 months – 6 months – 5.5 months – (57%) – Ischemic stroke, SAH 6 months – – – 6 months – (100%) 17 months Brainstem compression
Our average number of PEDs per aneurysm was almost 4 (3.8). One patient required a maximum of eight PEDs. One important finding is that patients with holobasilar aneurysms faired far worse than segmental fusiform aneurysms, with holobasilar aneurysms having a mRS of 5 or 6 in 75% of the patients. Chalouhi et al. reported seven posterior circulation aneurysms treated with PEDs,4 of which three were fusiform. Two out of the three patients achieved complete occlusion of the fusiform aneurysm. There were no reported complications or mortalities. The average follow-up was 5.5 months.4 Shapiro et al. published a systematic review of VBF aneurysms.28 Four hundred and forty cases were included in this study. Seventy percent of the patients were male, which coincides with our study (80% male). There was a 66% incidence of hypertension and 41% incidence of smoking. All of our cases had a past medical history of hypertension. The authors determined the overall mortality rate was 43% with a 7.1 year follow-up. We encountered a higher mortality rate with treatment in our case series. Shapiro et al. analyzed outcomes in subpopulations of hemorrhage, ischemic stroke, mass effect, and growth.28 The authors discovered that patients presenting with symptoms due to mass effect or growth of aneurysm with serial imaging were poor prognostic factors. All of the patients in our case series presented due to mass effect, TIA/stroke, and refractory to medical therapy. Two of our four patients had aneurysm regrowth after treatment. We suspect an intrinsic component to a subset of VBF aneurysms that lead to a poorer outcome is likely. Despite achieving successful PED placement and obliteration of the aneurysm, two cases presented with recurrence/growth. Krings et al. suggests partially thrombosed aneurysms repeatedly bleed into the vessel wall,29 causing enhancement of the wall (see Figure 1(e)). Hemorrhage into the vessel wall is also
438 associated with adjacent brain edema.29 With patent perforators off the aneurysm, continuous blood flow could explain the recurrence/growth we encountered in Cases 1 and 3 despite achieving radiographic obliteration of the aneurysm. To overcome this, sacrifice of the perforators off the basilar trunk would lead to catastrophic injury. If the fusiform aneurysm extends to involve the vertebral arteries, sacrifice of a vertebral artery may limit the number of patent perforators, thus possibly decreasing the risk of recurrence. This was attempted in Case 4, but immediate ischemic insult prevented the authors from observing the risk of long-term recurrence. With treatment mortality rates after treatment higher than the reported natural history, one must
Interventional Neuroradiology 21(4) question the safety of PED for VBF aneurysms. Because of the naturally long length of a holobasilar fusiform aneurysm, a telescoping construct decreases the porosity of the stents. Due to the high number of perforating branches off the basilar trunk, the chances of perforator occlusion increases, thus leading to ischemic injury. The blood supply to the perforators’ and aneurysm’s vasa vasorum may contribute to aneurysm regrowth, which explains aneurysm recurrence on angiography despite achieving obliteration after treatment. One limitation of this study is the small patient population reported. This study population was performed at a single institution under a single neuroradiologist. Another limitation is although every patient presented with a holobasilar fusiform aneurysm, there
Figure 1. (a) Lateral view of the initial angiogram showing a right VB junction aneurysm extending to the distal third of the basilar artery. (b) MRI T1 weighted image showing a fusiform aneurysm with compression of the brainstem. (c) A 3 month follow-up angiogram shows a partially thrombosed fusiform aneurysm. (d) A 10 month follow-up angiogram with development of endoleaks at the proximal and distal ends with growth of the aneurysm. (e) A 10 month CT angiogram shows hypervascularity at the periphery of the aneurysm that was not present on the initial CT angiogram, suggestive of blood flow to the vasa vasorum. This could be responsible for growth of the aneurysm. (f) Diffusion-weighted image showing ischemic changes in the brainstem.
Ahmed et al. is some heterogeneity in the diseases treated. Some fusiform aneurysms were localized to the basilar artery while some extended to the vertebrobasilar junction. It is unknown if Case 3 died due to complications related to treatment or natural causes, which could alter our mortality rate. There is no established protocol on the use of antiplatelet agents, which could contribute to the risk of ischemia after stent deployment.
Conclusion The immediate risk of treating VBF aneurysms is evident in our case series. Despite reports describing successful treatment of this moribund disease process with PEDs, delayed complications after obliteration and remodeling of the aneurysm can occur. Holobasilar fusiform aneurysms may be more difficult to treat due to the length and need of a telescoping construct. Medical management in holobasilar fusiform aneurysms may lead to better outcomes than intervention. We advocate careful consideration and long-term follow-up despite successful obliteration of the VBF aneurysm. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest None declared.
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