Neuroradiology DOI 10.1007/s00234-014-1339-x
INTERVENTIONAL NEURORADIOLOGY
Flow diversion for complex middle cerebral artery aneurysms Mario Zanaty & Nohra Chalouhi & Stavropoula I. Tjoumakaris & L. Fernando Gonzalez & Robert Rosenwasser & Pascal Jabbour
Received: 9 November 2013 / Accepted: 30 January 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction This study aims to evaluate the safety and efficacy of flow diversion for treatment of large and complex middle cerebral artery (MCA) aneurysms. Methods We conducted a retrospective review of the clinical charts of all patients who underwent Pipeline Embolization Device (PED) placement for aneurysm at our institution from October 2010 to October 2013. We included ten patients, of which five had large MCA aneurysms and three had giant ones. Fusiform unruptured aneurysms represented seven of all ten aneurysms. Angiographic and clinical follow-up were available for all patients mostly between 7 and 12 months. Results We had no technical complications, one periprocedural morbidity, and no mortality. On followup, we had no hemorrhagic complications, no aneurysms rupture, and only one clinically significant thromboembolic event in a patient who discontinued antiplatelet therapy against medical advice. One patient had completely occluded his diseased vessel but remained asymptomatic. The overall complication rate is 3/10. On follow-up, complete occlusion occurred in seven patients (7/9). Conclusion PED treatment for large, giant, and bifurcation MCA aneurysms was feasible, with satisfying M. Zanaty : N. Chalouhi : S. I. Tjoumakaris : L. F. Gonzalez : R. Rosenwasser : P. Jabbour Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, PA, USA P. Jabbour (*) Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University Hospital, 901 Walnut Street 3rd Floor, Philadelphia, PA 19107, USA e-mail: [email protected]
complete occlusion rate, no mortality, and reasonable morbidity rate. Keywords Pipeline Embolization Device . Flow diversion technique . Large middle cerebral artery aneurysm . Bifurcation aneurysm . Complex middle cerebral artery aneurysm
Introduction Middle cerebral artery (MCA) aneurysms represent the third most common cause of subarachnoid hemorrhage (SAH) and almost one fifth of unruptured aneurysms (UAs) [1]. Those arising from bifurcation represent 85 % of all MCA aneurysms. They tend to be widenecked and incorporate one or more branch vessels. The risk of occluding branch vessels as well as the risk of coil herniation has classically favored microsurgery over endovascular intervention. Technique such as stentassisted coiling (SAC), balloon remodeling, and Ystenting with or without coiling have been employed for the treatment of MCA aneurysms, but results remains suboptimal [2]. Hence, we opted for flow diversion as an alternative endovascular treatment. The Pipeline Embolization Device (PED) is a dedicated flow diverter used for treating aneurysms of various sizes and shapes. Experiences with the device have been mostly limited to aneurysms arising from the internal carotid artery. Little data exists on the safety and efficacy of PED in MCA aneurysms. Although other flow diversion devices exist in the market, the majority of the available data is on the use of PED, and it is the only FDA-approved flow diverter in the USA; the other flow diverters can be used in the context of a trial. Therefore off-label use is only allowed with PED.
Neuroradiology
Methodology
Results
Study design and population selection
Participants
We conducted a retrospective review of the clinical charts of all patients who underwent PED placement for MCA aneurysms at our institution from January 2011 to October 2013. Ten patients were identified and constituted the study population. For MCA aneurysms, surgical clipping is the first-line option at our institution except for older patients and those with multiple comorbidities. Patients with aneurysms deemed difficult to clip are considered candidates for endovascular management. Patient with recurrent aneurysms following previous surgical clipping were also considered eligible for endovascular treatment with PED. We grouped the patients together in three groups according to their aneurysm locations: those with aneurysms involving the MCA bifurcation, where side branch occlusion is of major concern; those with M1 aneurysms, where the treatment risk is mainly occluding the lenticulostriate arteries; and those with aneurysms involving M2 and beyond, where the flexibility of the PED device is critical.
Ten patients underwent PED placement for ten cerebral aneurysms. Demographic and clinical data are given in Table 1. Mean age was 47.5 years, and 6/10 of our patients were older than 50 years. Six out of ten (6/10) patients were male. Two out of ten (2/10) patients had already undergone microsurgical clipping. Seven out of ten (7/10) aneurysms were fusiform, including a large dissecting one. In total, we had two small (25 mm) aneurysms. On average, the mean measured aneurysm diameter was 15.5 mm. We treated 5/10 of aneurysms with only one PED/aneurysm and another 4/10 with two PED/ aneurysm; in the latter cases, more devices were needed for sufficient neck coverage. Three PED were required to treat a giant wide-necked (30×10 mm) aneurysm. Therefore, on average, 1.60 PED was used per aneurysm.
Treatment Patients were loaded with 75 mg/day of clopidogrel and 81 mg/day of aspirin for at least 10 days before the intervention. Clopidogrel assay were checked, and clopidogrel dosage was adjusted until a platelet inhibition greater than 30 % was achieved before the procedure. Patients who exhibited resistance to clopidogrel were switched to prasugrel. Dual antiplatelet therapy was envisioned for at least 6 months followed by life-long monotherapy of 81 mg aspirin. Periprocedural angiographic evaluation/procedural assessment The dimensions of the aneurysms were obtained through 3-D reconstructions of the initial rotational angiogram. The PED was sized according to the width of the inflow vessel to avoid any endoleak. PED embolization was classified as achieving complete stasis, significant stasis, or no disruption of inflow jet based on a perioperative angiogram.
Outcomes We successfully managed to treat all ten aneurysms without any technical failure. One patient (1/10) had a periprocedural complication. In this patient, PED treatment was uneventful but antiplatelet drugs (APD) had to be stopped before colonoscopy, and the patient developed a right MCA stroke. Antiplatelet therapy was then resumed and the patient rapidly improved. This patient’s mRs was 1 at discharge. Clinical follow-up was available for all patients with a mean followup of 7.55 months. Most of our patients were evaluated between 7 and 12 months, and 2/10 had their last follow-up after 12 months. Only one patient did not have an angiogram follow-up yet because he was recently treated. At the last follow-up, 7/10 of our patients had a mRs of 0, while 2/10 had a mRs of 1, and only 1/10 had a mRs of 3. This was a Table 1 Demographic and clinical characteristics Age
Median=60.5 years
Gender
Male=60 % Female=40 % Median=15 mm Small=20 % Large=50 % Giant=30 % Fusiform=70 % Saccular=30 %
Size Proportion of size
Follow-up/angiographic outcomes Patients were evaluated in the hospital for periprocedural complications. After discharge, patients were scheduled for clinical follow-up and routine invasive or noninvasive angiographic imaging. Follow-up were done at one or more of the following periods: 3–6, 6–12, and >12 months. Modified Rankin scale (mRs) was obtained at the latest follow-up visit.
Form Follow-up Previously treateda a
The previous treatment was microsurgery only
20 %
Neuroradiology Table 2 Outcomes
Percentage
Periprocedural mortality
Periprocedural morbidity
Long-term morbidity
Long-term mortality
Complete occlusion
0%
10 %
20 %
0%
70 %
patient who stopped APD against medical advice and developed a complete M1 occlusion. We had no periprocedural mortality. One of the patients had a complete occlusion of his diseased vessel on his latest follow-up, but was completely asymptomatic. All patients have undergone digital subtraction catheter angiography for angiographic follow-up. Complete occlusion occurred in 6/9 patients and 2/9 patients had a near-complete occlusion (Table 2), including one broad-based giant trifurcation aneurysm involving M1 and both M2. Only one patient (1/9) had an incomplete occlusion, but his latest follow-up was at 3 months. Subgroup description Both the patients with distal MCA aneurysms (M2 and beyond) had a complete aneurysm occlusion. One of the patients had a complete aneurysm occlusion of his severely diseased vessel as reported previously. Three out of the five patients with M1 aneurysms had a complete aneurysm occlusion, and the remaining two had a near-complete occlusion. The patient who stopped APD without medical advice has obstructed his diseased vessel with the lenticulostriate arteries. Of the patients with MCA aneurysms, one had a complete aneurysm occlusion and another had a near-complete occlusion. We have no follow-up yet on the third patient. In this group, we had no complications except for the patient who stopped his APD for colonoscopy. We have four illustrative cases (Figs. 1, 2, 3, and 4; Table 3).
Discussion Background The PED (Covidien, Irvine, CA, USA) is a microcatheterdelivered, self-expanding, and cylindrical stent composed of a mesh of 48 individual cobalt chromium and platinum strands [26]. It has a low porosity, high metal coverage, and is specifically designed for flow diversion. Based on the existing data, PED has been shown efficacious in wide-necked (>4 mm), large and giant, complex aneurysms [3, 4]. It has also been used for small saccular aneurysms and recurrent aneurysms after coiling or even after stenting, but with a lesser efficacy. In a recent study, PED achieved higher occlusion rate, fewer recanalization rate, and similar morbidity and mortality than traditional coiling [5]. The results of PED are also comparable to SAC [6] and balloon-assisted embolization [7] in wideneck aneurysm. However, data on the efficacy and safety of PED in MCA aneurysms is limited. For MCA bifurcation aneurysms, it is postulated that treatment with PED will necessarily jail one limb of the bifurcation. Furthermore, if the occlusion is not successful, the only remaining endovascular option is to use another stent, which would put further risk on the jailed limb. SAC has been used for wide-necked and complex cerebral aneurysms [8, 9]. An alternative technique of SAC has been widely accepted, where two stents in a Y configuration (Y stenting) are deployed to help maintain branching artery patency while treating bifurcation aneurysms [10]. Fargen et al.
Fig. 1 a–c A 65-year-old patient with a right-sided dissecting M3 aneurysm (a). The patient was treated by embolization with PED 205×18 and PED 2.5×14 (b). Six-month follow-up showed complete occlusion of the diseased M3 vessel, but he was completely asymptomatic (c)
Neuroradiology Fig. 2 a–d A 26-year-old patient with a fusiform 5×4.7 mm M3 aneurysm (a–b). The patient has undergone embolization with PED 2.5×12. Nineteen-month follow-up shows 100 % occlusion of the aneurysm and remodeling of the vessel (c–d)
Fig. 3 a–d A 28-year-old male with a 6-mm fusiform left MCA bifurcation aneurysm (a). The aneurysm was treated first by clipping. Three years later, follow-up angiography showed a large recurrence of the MCA aneurysm, 12×12 mm that was treated by embolization with 2.5× 16 and 2.5×18 Pipeline stent (b). Eighteen-month follow-up angiography shows a stable 90–95 % occlusion of the aneurysm (c–d)
Neuroradiology
Fig. 4 a–e A 68-year-old patient with a partially thrombosed left giant middle cerebral artery aneurysm involving both of M2s and measuring approximately 27 mm in diameter (a). The patient underwent clipping (b)
then embolization with pipeline (c). Follow-up shows significant improvement with minimal filling (d–e)
[9] reported a multicenter series of Y stenting of bifurcation aneurysms with relatively low periprocedural complications, low recurrence rate, and favorable occlusion rate. Only two of the bifurcation aneurysms treated were located in the MCA. SAC still faces the problem of thromboembolic events as it ranges from 4 to 8 % [8, 9, 11]. One of the mechanisms that contribute to aneurysm occlusion is an uncharacterized flow diversion effect [9, 12–14], justifying the use of PED if it can be done safely. In clinical studies, Yavuz et al. [15] reported
the only case series that focuses on PED treatment for MCA aneurysms. Twenty-one MCA bifurcation aneurysms and four distal MCA aneurysms were successfully treated with a complete occlusion rate of 84 % (21/25) on the latest follow-up (3– 30 months) [15]. The author recommended that the follow-up should take place at 6 months. They had no procedural mortality and reported a SAH as the only periprocedural complication. They had a single thromboembolic event that happened after discontinuation of Plavix. Branch occlusion rate
Table 3 Outcomes Location
Size Shape (mm)
M1
15.8
Number of PED
Periprocedural Follow-up complication complication
3/5 Saccular 1.60 PED (8 PED 0/5 2/5 Fusiform for 5 aneurysms)
MCA bifurcation 16.67 3/3 Fusiform 1.67 PED (5 PED 0/3 for 3 aneurysms) M2 and beyond
13.00 2/2 Fusiform 1.5 PED (3 PED 0/2 for 2 aneurysms)
Mortality mRS at Occlusion at latest F/u latest follow-up
1/5: 0/5 Stopped APD and complete M1 occlusion 1/3: stopped APD 0/3 and developed an MCA stroke 1/2: Complete M3 occlusion 0/2
PED Pipeline Embolization Device, mRS modified Rankin Scale, APD antiplatelet drug
0.8
3/5 complete 2/5 near complete
0.5
1/3 Complete 1/3 Incomplete 1/3 No follow-up 2/2 Complete
0
Neuroradiology
was less than expected, as 12 branches out of 22 remained patent, six other had reduced filling, and only three were occluded but without any symptoms. Finally, a single device was used in all but two patients. Our experience In PED treatment, the main periprocedural and postprocedural complications are hemorrhagic and thromboembolic events [16]. They are in part explained by the variability in response to antiplatelet treatment [17]. However, early and delayed aneurysm ruptures [13, 14, 18–20] and distal ipsilateral hemorrhage [11, 19, 21–24] are complications that are probably specific to flow diversion. We had three thromboembolic events, two of which were related to specific circumstances where APDs were discontinued. The third event was an asymptomatic complete vessel occlusion of a previously severe diseased vessel. All those who remained on dual antiplatelet therapy experienced no complications. We did not have any hemorrhagic complication or aneurysm rupture. We have observed that many of the aneurysms that had a near-complete occlusion at 3–6 months have progressed to full occlusion on future follow-up. In total, 50 % of the patients with complete occlusion had a near-complete occlusion before 6 months. The only patient with incomplete occlusion at last follow-up in our study was evaluated at 3 months; therefore, his aneurysm might progress to a higher occlusion rate on future follow-up. In contrast to the study of Yavuz et al. where most of the aneurysms were small, most of the aneurysms (8/10) treated in our study were large and complex MCA aneurysms. This is related to the fact that microsurgery is the primary option for this subgroup of aneurysms. Darsaut et al., in their laboratory investigations of flow diversion on canines, showed that flow diverter devices (FDDs) failed to occlude curved sidewall aneurysms and bifurcation aneurysms at 3 or 6 months [25]. The reasons were device deformation and migration into the aneurysm, incomplete neointimal growth, and adjunctive flow to the aneurysm by branches. The authors also found that the lower the porosity, the higher the chance of occlusion at the cost of an increased risk of thrombosis of jailed branches and parent arteries. The difference between the findings in their preclinical research and those of the clinical studies may be explained by several hypotheses. First, the follow-up in the laboratory experience occurred mostly at 3 months, which is shorter than the follow-up in most of the clinical studies and premature for a final assessment of occlusion. As it has been shown in our experience, many of the aneurysms that were incompletely occluded at 3 months have subsequently progressed to full occlusion. Secondly, a large proportion of FDDs used in the lab study were found deformed and migrated on autopsy. This has lead to incomplete coverage of the neck with gaps in
neointimal growth [25]. In our series, careful preventive measures, such as using longer device and avoiding dragging and stretching of the PED, were taken not to deform the device and achieving complete coverage with good wall apposition [26]. Finally, the last reason for treatment failure in their experience was the presence of branch flow that prevented the exclusion of the aneurysm from the circulation.
Limitations The major limitations of our case series are the retrospective design and the small number given the difficult set of criteria for patient inclusion. The results, far from being generalizable, seem encouraging for future use of flow diversion in MCA aneurysms. Given the specific indications, PED can be safely and efficaciously used. Careful manipulation of the device and complete neck-coverage seem crucial for successful treatment.
Conclusion In this flow-diversion era, evidence so far has shown that flow diversion success depends mainly on the type of aneurysm. Careful patient selection along with technical skills seems to be the key to success. However, data that supports the use of PED in the treatment of MCA aneurysms is piling up. The next step in evaluating the safety and usefulness of this approach would be a trial involving a larger sample of patients.
Conflict of interest PJ consults for Covidien.
References 1. International Study of Unruptured Intracranial Aneurysms Investigators (1998) Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1339: 1725–1733 2. Chalouhi N, Jabbour P, Singhal S, Drueding R, Starke RM, Dalyai RT, Tjoumakaris S, Gonzalez LF, Dumont AS, Rosenwasser R, Randazzo CG (2013) Stent-assisted coiling of intracranial aneurysms: predictors of complications, recanalization, and outcome in 508 cases. Stroke 44(5):1348–1353 3. Leung GKK, Tsang ACO, Lui WM (2012) Pipeline embolization device for intracranial aneurysm: a systematic review. Clin Neuroradiol 22:295–303 4. Briganti F, Napoli M, Tortora F, Solari D, Bergui M, Boccardi E, Cagliari E, Castellan L, Causin F, Ciceri E, Cirillo L, De Blasi R, Delehaye L, Di Paola F, Fontana A, Gasparotti R, Guidetti G, Divenuto I, Iannucci G, Isalberti M, Leonardi M, Lupo F, Mangiafico S, Manto A, Menozzi R, Muto M, Nuzzi NP, Papa R, Petralia B, Piano M, Resta M, Padolecchia R, Saletti A, Sirabella G, Bolgè LP (2012) Italian multicenter experience with flow-diverter devices for intracranial unruptured aneurysm treatment with
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periprocedural complications—a retrospective data analysis. Neuroradiology 54:1145–1152 Chalouhi N, Tjoumakaris S, Starke RM, Gonzalez LF, Randazzo C, Hasan D, McMahon JF, Singhal S, Moukarzel LA, Dumont AS, Rosenwasser R, Jabbour P (2013) Comparison of flow diversion and coiling in large unruptured intracranial saccular aneurysms. Stroke 44:2150–2154 Bodily KD, Cloft HJ, Lanzino G, Fiorella DJ, White PM, Kallmes DF (2011) Stent-assisted coiling in acutely ruptured intracranial aneurysms: a qualitative, systematic review of the literature. AJNR Am J Neuroradiol 32(7):1232–1236 Shapiro M, Babb J, Becske T, Nelson PK (2008) Safety and efficacy of adjunctive balloon remodeling during endovascular treatment of intracranial aneurysms: a literature review. AJNR Am J Neuroradiol 29(9):1777–1781 Fiorella D, Albuquerque FC, Woo H, Rasmussen PA, Masaryk TJ, McDougall CG (2010) Neuroform stent assisted aneurysm treatment: evolving treatment strategies, complications and results of long term follow-up. J Neurointerv Surg 2(1):16–22 Fargen KM, Hoh BL, Welch BG, Pride GL, Lanzino G, Boulos AS, Carpenter JS, Rai A, Veznedaroglu E, Ringer A, Rodriguez-Mercado R, Kan P, Siddiqui A, Levy EI, Mocco J (2012) Long-term results of enterprise stent-assisted coiling of cerebral aneurysms. Neurosurgery 71(2):239–244 Chow MM, Woo HH, Masaryk TJ, Rasmussen PA (2004) A novel endovascular treatment of a wide-necked basilar apex aneurysm by using a Y-configuration, double-stent technique. AJNR Am J Neuroradiol 25(3):509–512 Chalouhi N, Jabbour P, Gonzalez LF, Dumont AS, Rosenwasser R, Starke RM, Gordon D, Hann S, Tjoumakaris S (2012) Safety and efficacy of endovascular treatment of basilar tip aneurysms by coiling with and without stent assistance: a review of 235 cases. Neurosurgery 71(4):785–794 Cekirge HS, Yavuz K, Geyik S, Saatci I (2011) A novel “Y” stent flow diversion technique for the endovascular treatment of bifurcation aneurysms without endosaccular coiling. AJNR Am J Neuroradiol 32(7):1262–1268 Lawson MF, Newman WC, Chi YY, Mocco JD, Hoh BL (2011) Stent-associated flow remodeling causes further occlusion of incompletely coiled aneurysms. Neurosurgery 69(3): 598–603 Piotin M, Blanc R, Spelle L, Mounayer C, Piantino R, Schmidt PJ, Moret J (2010) Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 41(1):110–115
15. Yavuz K, Geyik S, Saatci I, Cekirge HS (2013) Endovascular treatment of middle cerebral artery aneurysms with flow modification with the use of the pipeline embolization device. AJNR Am J Neuroradiol. doi:10.3174/ajnr.A3692 16. De Vries J, Boogaarts J, Van Norden A, Wakhloo AK (2013) New generation of flow diverter (surpass) for unruptured intracranial aneurysms: a prospective single-center study in 37 patients. Stroke 44: 1567–1577 17. Lee DH, Arat A, Morsi H, Shaltoni H, Harris JR, Mawad ME (2008) Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol 29:1389–1394 18. Fargen KM, Velat GJ, Lawson MF, Mocco J, Hoh BL (2012) Review of reported complications associated with the pipeline embolization device. World Neurosurg 77(3–4):403–404 19. Babiker MH, Gonzalez L, Ryan J, Albuquerque F, Collins D, Elvikis A, Frakes DH (2012) Influence of stent configuration on cerebral aneurysm fluid dynamics. J Biomech 45(3):440–447 20. Bendok BR, Parkinson RJ, Hage ZA, Adel JG, Gounis MJ (2007) The effect of vascular reconstruction device-assisted coiling on packing density, effective neck coverage, and angiographic outcome: an in vitro study. Neurosurgery 61(4):835–840 21. Kulcsár Z, Houdart E, Bonafé A, Parker G, Millar J, Goddard AJ, Renowden S, Gál G, Turowski B, Mitchell K, Gray F, Rodriguez M, van den Berg R, Gruber A, Desal H, Wanke I, Rüfenacht DA (2011) Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR Am J Neuroradiol 32 (1):20–25 22. Byrne JV, Szikora I (2012) Flow diverters in the management of intracranial aneurysms: a review. EJMINT 1225000057 23. Rohde S, Bendszus M, Hartmann M, Hähnel S (2010) Treatment of a wide-necked aneurysm of the anterior cerebral artery using two enterprise stents in “Y”-configuration stenting technique and coil embolization: a technical note. Neuroradiology 52(3):231–235 24. Chalouhi N, Dumont AS, Hasan D, Tjoumakaris S, Gonzalez LF, Starke RM, Dalyai R, El Moursi S, Rosenwasser R, Jabbour P (2012) Is packing density important in stent-assisted coiling? Neurosurgery 71(2):386–387 25. Darsaut TE, Bing F, Salazkin I, Gevry G, Raymond J (2012) Flow diverters failing to occlude experimental bifurcation or curved sidewall aneurysms: an in vivo study in canines. J Neurosurg 117:37–44 26. Chalouhi N, Tjoumakaris SI, Gonzalez LF, Hasan D, Pema PJ, Gould G, Rosenwasser RH, Jabbour PM (2013) Spontaneous delayed migration/shortening of the pipeline embolization device: report of 5 Cases. AJNR Am J Neuroradiol 34(12):2326–2330
INTERVENTIONAL NEURORADIOLOGY
Flow diversion for complex middle cerebral artery aneurysms Mario Zanaty & Nohra Chalouhi & Stavropoula I. Tjoumakaris & L. Fernando Gonzalez & Robert Rosenwasser & Pascal Jabbour
Received: 9 November 2013 / Accepted: 30 January 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction This study aims to evaluate the safety and efficacy of flow diversion for treatment of large and complex middle cerebral artery (MCA) aneurysms. Methods We conducted a retrospective review of the clinical charts of all patients who underwent Pipeline Embolization Device (PED) placement for aneurysm at our institution from October 2010 to October 2013. We included ten patients, of which five had large MCA aneurysms and three had giant ones. Fusiform unruptured aneurysms represented seven of all ten aneurysms. Angiographic and clinical follow-up were available for all patients mostly between 7 and 12 months. Results We had no technical complications, one periprocedural morbidity, and no mortality. On followup, we had no hemorrhagic complications, no aneurysms rupture, and only one clinically significant thromboembolic event in a patient who discontinued antiplatelet therapy against medical advice. One patient had completely occluded his diseased vessel but remained asymptomatic. The overall complication rate is 3/10. On follow-up, complete occlusion occurred in seven patients (7/9). Conclusion PED treatment for large, giant, and bifurcation MCA aneurysms was feasible, with satisfying M. Zanaty : N. Chalouhi : S. I. Tjoumakaris : L. F. Gonzalez : R. Rosenwasser : P. Jabbour Department of Neurosurgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience, Philadelphia, PA, USA P. Jabbour (*) Division of Neurovascular Surgery and Endovascular Neurosurgery, Department of Neurological Surgery, Thomas Jefferson University Hospital, 901 Walnut Street 3rd Floor, Philadelphia, PA 19107, USA e-mail: [email protected]
complete occlusion rate, no mortality, and reasonable morbidity rate. Keywords Pipeline Embolization Device . Flow diversion technique . Large middle cerebral artery aneurysm . Bifurcation aneurysm . Complex middle cerebral artery aneurysm
Introduction Middle cerebral artery (MCA) aneurysms represent the third most common cause of subarachnoid hemorrhage (SAH) and almost one fifth of unruptured aneurysms (UAs) [1]. Those arising from bifurcation represent 85 % of all MCA aneurysms. They tend to be widenecked and incorporate one or more branch vessels. The risk of occluding branch vessels as well as the risk of coil herniation has classically favored microsurgery over endovascular intervention. Technique such as stentassisted coiling (SAC), balloon remodeling, and Ystenting with or without coiling have been employed for the treatment of MCA aneurysms, but results remains suboptimal [2]. Hence, we opted for flow diversion as an alternative endovascular treatment. The Pipeline Embolization Device (PED) is a dedicated flow diverter used for treating aneurysms of various sizes and shapes. Experiences with the device have been mostly limited to aneurysms arising from the internal carotid artery. Little data exists on the safety and efficacy of PED in MCA aneurysms. Although other flow diversion devices exist in the market, the majority of the available data is on the use of PED, and it is the only FDA-approved flow diverter in the USA; the other flow diverters can be used in the context of a trial. Therefore off-label use is only allowed with PED.
Neuroradiology
Methodology
Results
Study design and population selection
Participants
We conducted a retrospective review of the clinical charts of all patients who underwent PED placement for MCA aneurysms at our institution from January 2011 to October 2013. Ten patients were identified and constituted the study population. For MCA aneurysms, surgical clipping is the first-line option at our institution except for older patients and those with multiple comorbidities. Patients with aneurysms deemed difficult to clip are considered candidates for endovascular management. Patient with recurrent aneurysms following previous surgical clipping were also considered eligible for endovascular treatment with PED. We grouped the patients together in three groups according to their aneurysm locations: those with aneurysms involving the MCA bifurcation, where side branch occlusion is of major concern; those with M1 aneurysms, where the treatment risk is mainly occluding the lenticulostriate arteries; and those with aneurysms involving M2 and beyond, where the flexibility of the PED device is critical.
Ten patients underwent PED placement for ten cerebral aneurysms. Demographic and clinical data are given in Table 1. Mean age was 47.5 years, and 6/10 of our patients were older than 50 years. Six out of ten (6/10) patients were male. Two out of ten (2/10) patients had already undergone microsurgical clipping. Seven out of ten (7/10) aneurysms were fusiform, including a large dissecting one. In total, we had two small (25 mm) aneurysms. On average, the mean measured aneurysm diameter was 15.5 mm. We treated 5/10 of aneurysms with only one PED/aneurysm and another 4/10 with two PED/ aneurysm; in the latter cases, more devices were needed for sufficient neck coverage. Three PED were required to treat a giant wide-necked (30×10 mm) aneurysm. Therefore, on average, 1.60 PED was used per aneurysm.
Treatment Patients were loaded with 75 mg/day of clopidogrel and 81 mg/day of aspirin for at least 10 days before the intervention. Clopidogrel assay were checked, and clopidogrel dosage was adjusted until a platelet inhibition greater than 30 % was achieved before the procedure. Patients who exhibited resistance to clopidogrel were switched to prasugrel. Dual antiplatelet therapy was envisioned for at least 6 months followed by life-long monotherapy of 81 mg aspirin. Periprocedural angiographic evaluation/procedural assessment The dimensions of the aneurysms were obtained through 3-D reconstructions of the initial rotational angiogram. The PED was sized according to the width of the inflow vessel to avoid any endoleak. PED embolization was classified as achieving complete stasis, significant stasis, or no disruption of inflow jet based on a perioperative angiogram.
Outcomes We successfully managed to treat all ten aneurysms without any technical failure. One patient (1/10) had a periprocedural complication. In this patient, PED treatment was uneventful but antiplatelet drugs (APD) had to be stopped before colonoscopy, and the patient developed a right MCA stroke. Antiplatelet therapy was then resumed and the patient rapidly improved. This patient’s mRs was 1 at discharge. Clinical follow-up was available for all patients with a mean followup of 7.55 months. Most of our patients were evaluated between 7 and 12 months, and 2/10 had their last follow-up after 12 months. Only one patient did not have an angiogram follow-up yet because he was recently treated. At the last follow-up, 7/10 of our patients had a mRs of 0, while 2/10 had a mRs of 1, and only 1/10 had a mRs of 3. This was a Table 1 Demographic and clinical characteristics Age
Median=60.5 years
Gender
Male=60 % Female=40 % Median=15 mm Small=20 % Large=50 % Giant=30 % Fusiform=70 % Saccular=30 %
Size Proportion of size
Follow-up/angiographic outcomes Patients were evaluated in the hospital for periprocedural complications. After discharge, patients were scheduled for clinical follow-up and routine invasive or noninvasive angiographic imaging. Follow-up were done at one or more of the following periods: 3–6, 6–12, and >12 months. Modified Rankin scale (mRs) was obtained at the latest follow-up visit.
Form Follow-up Previously treateda a
The previous treatment was microsurgery only
20 %
Neuroradiology Table 2 Outcomes
Percentage
Periprocedural mortality
Periprocedural morbidity
Long-term morbidity
Long-term mortality
Complete occlusion
0%
10 %
20 %
0%
70 %
patient who stopped APD against medical advice and developed a complete M1 occlusion. We had no periprocedural mortality. One of the patients had a complete occlusion of his diseased vessel on his latest follow-up, but was completely asymptomatic. All patients have undergone digital subtraction catheter angiography for angiographic follow-up. Complete occlusion occurred in 6/9 patients and 2/9 patients had a near-complete occlusion (Table 2), including one broad-based giant trifurcation aneurysm involving M1 and both M2. Only one patient (1/9) had an incomplete occlusion, but his latest follow-up was at 3 months. Subgroup description Both the patients with distal MCA aneurysms (M2 and beyond) had a complete aneurysm occlusion. One of the patients had a complete aneurysm occlusion of his severely diseased vessel as reported previously. Three out of the five patients with M1 aneurysms had a complete aneurysm occlusion, and the remaining two had a near-complete occlusion. The patient who stopped APD without medical advice has obstructed his diseased vessel with the lenticulostriate arteries. Of the patients with MCA aneurysms, one had a complete aneurysm occlusion and another had a near-complete occlusion. We have no follow-up yet on the third patient. In this group, we had no complications except for the patient who stopped his APD for colonoscopy. We have four illustrative cases (Figs. 1, 2, 3, and 4; Table 3).
Discussion Background The PED (Covidien, Irvine, CA, USA) is a microcatheterdelivered, self-expanding, and cylindrical stent composed of a mesh of 48 individual cobalt chromium and platinum strands [26]. It has a low porosity, high metal coverage, and is specifically designed for flow diversion. Based on the existing data, PED has been shown efficacious in wide-necked (>4 mm), large and giant, complex aneurysms [3, 4]. It has also been used for small saccular aneurysms and recurrent aneurysms after coiling or even after stenting, but with a lesser efficacy. In a recent study, PED achieved higher occlusion rate, fewer recanalization rate, and similar morbidity and mortality than traditional coiling [5]. The results of PED are also comparable to SAC [6] and balloon-assisted embolization [7] in wideneck aneurysm. However, data on the efficacy and safety of PED in MCA aneurysms is limited. For MCA bifurcation aneurysms, it is postulated that treatment with PED will necessarily jail one limb of the bifurcation. Furthermore, if the occlusion is not successful, the only remaining endovascular option is to use another stent, which would put further risk on the jailed limb. SAC has been used for wide-necked and complex cerebral aneurysms [8, 9]. An alternative technique of SAC has been widely accepted, where two stents in a Y configuration (Y stenting) are deployed to help maintain branching artery patency while treating bifurcation aneurysms [10]. Fargen et al.
Fig. 1 a–c A 65-year-old patient with a right-sided dissecting M3 aneurysm (a). The patient was treated by embolization with PED 205×18 and PED 2.5×14 (b). Six-month follow-up showed complete occlusion of the diseased M3 vessel, but he was completely asymptomatic (c)
Neuroradiology Fig. 2 a–d A 26-year-old patient with a fusiform 5×4.7 mm M3 aneurysm (a–b). The patient has undergone embolization with PED 2.5×12. Nineteen-month follow-up shows 100 % occlusion of the aneurysm and remodeling of the vessel (c–d)
Fig. 3 a–d A 28-year-old male with a 6-mm fusiform left MCA bifurcation aneurysm (a). The aneurysm was treated first by clipping. Three years later, follow-up angiography showed a large recurrence of the MCA aneurysm, 12×12 mm that was treated by embolization with 2.5× 16 and 2.5×18 Pipeline stent (b). Eighteen-month follow-up angiography shows a stable 90–95 % occlusion of the aneurysm (c–d)
Neuroradiology
Fig. 4 a–e A 68-year-old patient with a partially thrombosed left giant middle cerebral artery aneurysm involving both of M2s and measuring approximately 27 mm in diameter (a). The patient underwent clipping (b)
then embolization with pipeline (c). Follow-up shows significant improvement with minimal filling (d–e)
[9] reported a multicenter series of Y stenting of bifurcation aneurysms with relatively low periprocedural complications, low recurrence rate, and favorable occlusion rate. Only two of the bifurcation aneurysms treated were located in the MCA. SAC still faces the problem of thromboembolic events as it ranges from 4 to 8 % [8, 9, 11]. One of the mechanisms that contribute to aneurysm occlusion is an uncharacterized flow diversion effect [9, 12–14], justifying the use of PED if it can be done safely. In clinical studies, Yavuz et al. [15] reported
the only case series that focuses on PED treatment for MCA aneurysms. Twenty-one MCA bifurcation aneurysms and four distal MCA aneurysms were successfully treated with a complete occlusion rate of 84 % (21/25) on the latest follow-up (3– 30 months) [15]. The author recommended that the follow-up should take place at 6 months. They had no procedural mortality and reported a SAH as the only periprocedural complication. They had a single thromboembolic event that happened after discontinuation of Plavix. Branch occlusion rate
Table 3 Outcomes Location
Size Shape (mm)
M1
15.8
Number of PED
Periprocedural Follow-up complication complication
3/5 Saccular 1.60 PED (8 PED 0/5 2/5 Fusiform for 5 aneurysms)
MCA bifurcation 16.67 3/3 Fusiform 1.67 PED (5 PED 0/3 for 3 aneurysms) M2 and beyond
13.00 2/2 Fusiform 1.5 PED (3 PED 0/2 for 2 aneurysms)
Mortality mRS at Occlusion at latest F/u latest follow-up
1/5: 0/5 Stopped APD and complete M1 occlusion 1/3: stopped APD 0/3 and developed an MCA stroke 1/2: Complete M3 occlusion 0/2
PED Pipeline Embolization Device, mRS modified Rankin Scale, APD antiplatelet drug
0.8
3/5 complete 2/5 near complete
0.5
1/3 Complete 1/3 Incomplete 1/3 No follow-up 2/2 Complete
0
Neuroradiology
was less than expected, as 12 branches out of 22 remained patent, six other had reduced filling, and only three were occluded but without any symptoms. Finally, a single device was used in all but two patients. Our experience In PED treatment, the main periprocedural and postprocedural complications are hemorrhagic and thromboembolic events [16]. They are in part explained by the variability in response to antiplatelet treatment [17]. However, early and delayed aneurysm ruptures [13, 14, 18–20] and distal ipsilateral hemorrhage [11, 19, 21–24] are complications that are probably specific to flow diversion. We had three thromboembolic events, two of which were related to specific circumstances where APDs were discontinued. The third event was an asymptomatic complete vessel occlusion of a previously severe diseased vessel. All those who remained on dual antiplatelet therapy experienced no complications. We did not have any hemorrhagic complication or aneurysm rupture. We have observed that many of the aneurysms that had a near-complete occlusion at 3–6 months have progressed to full occlusion on future follow-up. In total, 50 % of the patients with complete occlusion had a near-complete occlusion before 6 months. The only patient with incomplete occlusion at last follow-up in our study was evaluated at 3 months; therefore, his aneurysm might progress to a higher occlusion rate on future follow-up. In contrast to the study of Yavuz et al. where most of the aneurysms were small, most of the aneurysms (8/10) treated in our study were large and complex MCA aneurysms. This is related to the fact that microsurgery is the primary option for this subgroup of aneurysms. Darsaut et al., in their laboratory investigations of flow diversion on canines, showed that flow diverter devices (FDDs) failed to occlude curved sidewall aneurysms and bifurcation aneurysms at 3 or 6 months [25]. The reasons were device deformation and migration into the aneurysm, incomplete neointimal growth, and adjunctive flow to the aneurysm by branches. The authors also found that the lower the porosity, the higher the chance of occlusion at the cost of an increased risk of thrombosis of jailed branches and parent arteries. The difference between the findings in their preclinical research and those of the clinical studies may be explained by several hypotheses. First, the follow-up in the laboratory experience occurred mostly at 3 months, which is shorter than the follow-up in most of the clinical studies and premature for a final assessment of occlusion. As it has been shown in our experience, many of the aneurysms that were incompletely occluded at 3 months have subsequently progressed to full occlusion. Secondly, a large proportion of FDDs used in the lab study were found deformed and migrated on autopsy. This has lead to incomplete coverage of the neck with gaps in
neointimal growth [25]. In our series, careful preventive measures, such as using longer device and avoiding dragging and stretching of the PED, were taken not to deform the device and achieving complete coverage with good wall apposition [26]. Finally, the last reason for treatment failure in their experience was the presence of branch flow that prevented the exclusion of the aneurysm from the circulation.
Limitations The major limitations of our case series are the retrospective design and the small number given the difficult set of criteria for patient inclusion. The results, far from being generalizable, seem encouraging for future use of flow diversion in MCA aneurysms. Given the specific indications, PED can be safely and efficaciously used. Careful manipulation of the device and complete neck-coverage seem crucial for successful treatment.
Conclusion In this flow-diversion era, evidence so far has shown that flow diversion success depends mainly on the type of aneurysm. Careful patient selection along with technical skills seems to be the key to success. However, data that supports the use of PED in the treatment of MCA aneurysms is piling up. The next step in evaluating the safety and usefulness of this approach would be a trial involving a larger sample of patients.
Conflict of interest PJ consults for Covidien.
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