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Patency of the posterior communicating artery after flow diversion treatment of internal carotid artery aneurysms
Clinical Neurology and Neurosurgery 120 (2014) 84–88
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Patency of the posterior communicating artery after flow diversion treatment of internal carotid artery aneurysms Waleed Brinjikji a,∗ , Giuseppe Lanzino a,b , Harry J. Cloft a,b , David F. Kallmes a,b a b
Department of Radiology, Mayo Clinic, Rochester, USA Department of Neurosurgery, Mayo Clinic, Rochester, USA
a r t i c l e
i n f o
Article history: Received 26 January 2014 Received in revised form 20 February 2014 Accepted 23 February 2014 Available online 3 March 2014 Keywords: Aneurysm Intervention Flow diverter Stroke Endovascular
a b s t r a c t Background and purpose: Cerebral aneurysm treatment with the Pipeline Embolization Device (PED) often mandates device placement across the ostia of arteries of the Circle of Willis. We determined the patency rates of the posterior communicating artery (Pcomm) after placement across its ostium a PED and studied neurologic outcomes in these patients. Methods: We analyzed, retrospectively, a consecutive series of patients in whom a PED was placed across the ostium of Pcomm while treating the target aneurysm. Pcomm arterial flow after PED placement was graded on a 3-point scale at post-operative angiography and follow-up angiography. Data on pretreatment aneurysm rupture status, concomitant coiling, number of PEDs used, and neurologic status at follow-up were collected. Results: Eleven patients with 13 aneurysms were included in this study. All patients had an ipsilateral posterior cerebral artery arising from the basilar artery (P1). In the immediate post-procedural setting, four patients (36%) had diminished Pcomm flow rates. After a mean follow-up of 12.6 ± 6.7 months, three Pcomm arteries (27%) were occluded and two Pcomm arteries (18%) had diminished flow. Of patients with diminished flow/occluded Pcomm at follow-up, 80% (4/5) had diminished flow at initial post-procedure angiography compared to none of the six patients without diminished/occluded flow immediately post treatment. No patients suffered new neurologic symptoms at follow-up. Conclusions: Approximately one half of Pcomm arteries demonstrated occlusion or decreased flow at follow-up if the ostia are covered with a flow diversion device. Covering the Pcomm ostium in patients with a P1 did not result in any neurologic deficits. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Flow diverter devices such as the Pipeline Embolic Device (PED, eV3/Covidien, Irvine, CA) are increasingly being used in the embolization of intracranial aneurysms as both alternatives and adjuncts to endovascular coiling [1–4]. The PED is approved in the United States for treatment of intracranial aneurysms of the internal carotid artery proximal to the origin of the posterior communicating artery (Pcomm). However, these devices are being increasingly used in locations other than the proximal intracranial internal carotid artery (ICA). Histologic studies have demonstrated that after disrupting flow into the aneurysmal sac, flow diverters result in aneurysmal thrombosis and eventual sealing of the
aneurysm ostium through neointimal proliferation across device struts [5]. Computation fluid dynamic studies have demonstrated that upon deployment of flow diverters, mean intra-aneurysmal flow velocities and wall shear stress are significantly reduced resulting in aneurysmal occlusion [6]. While flow diverters limit aneurysmal blood flow, blood flow into large vessels and perforating vessels covered by the device is generally preserved [5]. While many in vitro and experimental models have demonstrated longterm patency rates of branch vessels covered by PED, the long term patency of major branch vessels is not well established [7–9]. In this study we assessed the immediate and long term patency rates of the Pcomm artery in patients following the placement of a PED across the Pcomm artery ostium.
2. Methods ∗ Corresponding author at: Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, 55901, USA. Tel.: +1 2489779168; fax: +1 2489779168. E-mail address: [email protected] (W. Brinjikji). http://dx.doi.org/10.1016/j.clineuro.2014.02.018 0303-8467/© 2014 Elsevier B.V. All rights reserved.
After Institutional Review Board approval, we retrospectively examined a consecutive series of patients undergoing treatment
W. Brinjikji et al. / Clinical Neurology and Neurosurgery 120 (2014) 84–88
of intracranial aneurysms with the PED in which the PED was placed across the ostium of the Pcomm artery from January 2011 to June 2012. Inclusion criteria were the following: (1) Patients >18 years old, (2) PED placed across the ostium of the Pcomm artery for treatment of a wide-necked or large/giant aneurysm, (3) follow-up clinical exam and angiogram at 6 months. Patients who did not receive follow-up were excluded from analysis. All patients in this study were included in the International Retrospective Study of Pipeline Embolization Device (IntrePED) Registry (ClinicalTrials.gov Identifier: NCT01558102) which is assessing the post-market safety and efficacy of Pipeline embolization in the treatment of intracranial aneurysms. All patients undergoing treatment were premedicated with aspirin and clopidogrel and full anticoagulation was maintained during the procedure (target activated clotting time between 250 and 300 s). Following the procedure, patients were maintained on dual antiplatelet therapy for 3 months. After 3 months, clopidogrel was discontinued and aspirin was continued indefinitely. This antiplatelet regimen was the same in all patients and no platelet responsiveness studies were used in these cases. All of the procedures were performed with the patient under general anesthesia. A bi- or triaxial access technique and, in all cases, a Marksman (ev3) microcatheter, were used to obtain distal access past the segment of the vessel harboring the target aneurysm. Pipeline Embolization Devices were sized to match the maximum diameter of the target vessel. One or multiple devices were used at the discretion of the operators to maximize the changes of complete aneurysm occlusion and/or to ensure adequate coverage of the aneurysm neck and of a segment of parent artery proximal and distal to it. Digital subtraction angiography was performed at two frames per section prior to and following placement of the PED. Determination of Pcomm artery patency was made for each patient immediately after the original procedure and at the followup angiography obtained furthest from the initial procedure by a blinded investigator. A note was also made of any subjectively determined change in flow patterns (slowing of angiographic flow after PED deployment and/or at follow-up). Pcomm artery patency was scored on a three point scale: (1) patent: similar filling of the Pcomm when comparing pre- and post-treatment angiograms, (2) diminished flow but patent: decreased or delayed filling of Pcomm when comparing pre-and post-treatment angiograms, (3) occluded: no filling of the Pcomm on post-treatment angiograms. All patients underwent a detailed clinical examination before the procedure, immediately after the procedures, the following day and at each corresponding follow-up angiogram. In addition to Pcomm artery patency, patient age, gender, aneurysm rupture status, aneurysm occlusion at follow-up (complete = no flow within the aneurysm, near complete = minimal (<10%) residual flow and incomplete ≥ 10% residual flow), aneurysm maximum size, the use of concomitant coiling, previous coiling, and the presence, symmetry and size of the ipsilateral first segment of the posterior cerebral artery (P1) and Pcomm arteries were assessed. Asymmetry was defined as ipsilateral P1 or Pcomm segment <50% size in diameter of the contralateral P1 or Pcomm respectively.
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3. Results 3.1. Patient and aneurysm characteristics A total of 11 patients (9 women and 2 men) with 13 aneurysms were included in this study. Mean patient age was 52.0 ± 11.6 years (range 32–68). Aneurysm sizes ranged from 2 mm to 27 mm with a mean of 11.7 ± 7.8 mm. Eleven aneurysms were unruptured and two were previously ruptured. The two ruptured aneurysms were treated with coil embolization in the acute phase and staged Pipeline placement after patients had recovered from the acute subarachnoid hemorrhage (SAH). One patient had concomitant coiling and six patients had prior coiling of the treated aneurysm. Initially, one PED was placed in nine patients and two PEDs were placed in two patients. One patient had a recurrence which was treated with an additional pipeline (Fig. 1), thus, in total, three patients had two PEDs placed. At last follow-up, nine aneurysms (81.8%) demonstrated complete or near-complete occlusion, one aneurysm (9.1%) demonstrated incomplete occlusion and did not receive further treatment and one aneurysm (9.1%) recurred and required further treatment with an additional PED which did not affect Pcomm patency. Of the two patients with incomplete occlusion, one patient had incorporation of a large Pcomm into the aneurysm. 3.2. Angiographic and clinical results A summary of angiographic and clinical data for the eleven patients included in this study is provided in Table 1. Representative cases are provided in Figs. 1 and 2. Following placement of the PED across the ostium of the Pcomm artery, seven patients (64%) had a patent Pcomm artery on initial post-treatment angiography while four patients (36%) had diminished flow but the Pcomm artery remained patent Follow-up times ranged from 6 to 26 months with a mean follow-up of 12.6 ± 6.7 months. No patient was lost to follow-up. On follow-up examination, six patients (55%) had a patent Pcomm artery. All six of these patients had patent Pcomm arteries on initial post-procedural angiogram. Two patients had diminished flow (18%) in patent Pcomm arteries. Both of these latter patients had diminished but patent Pcomm arteries on initial post-procedural angiogram. Three patients (27%) had occluded Pcomm arteries at follow up. Of these patients, at immediate post treatment angiography one had a patent Pcomm artery, and two had diminished flow. One patient had fibromuscular dysplasia and on the last follow-up angiogram demonstrated complete occlusion of the internal carotid artery proximal to the PED stent. In this patient the Pcomm filled in a retrograde fashion following vertebral artery injection. One of the three patients also had a vertebral artery injection which demonstrated no evidence of retrograde Pcomm flow. No patients had new neurologic symptoms on follow-up examination. All patients had an ipsilateral P1 segment present on the initial angiogram. The P1 segment was symmetric or larger than the contralateral P1 in 8 patients (72%). Asymmetry was seen in 3 (27%) cases. The size of the ipsilateral Pcomm artery was greater than or equal to the size of the contralateral Pcomm artery in 10 cases (90.9%). 3.3. Determinants of Pcomm patency
2.1. Statistical analysis Summary statistics are presented for all data available using means ± standard deviations for continuous variables and frequency tabulations for categorical variables. All statistical analyses were performed using JMP 9.0.
Mean ipsilateral Pcomm artery size was 1.7 ± 0.6 mm for patients with Pcomm arterial occlusion at follow-up compared to 1.9 ± 0.7 mm for patients without occlusion. Mean ipsilateral Pcomm artery size was 1.7 ± 0.7 mm for patients with diminished flow or occlusion at follow-up compared to 2.0 ± 0.6 mm for patients with patent Pcomm arterial flow. The ipsilateral Pcomm
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Table 1 Patient characteristics and PCOM patency. Aneurysm location
Aneurysm size (mm)
Number of PEDs
Concomitant coiling
Prior coiling
Postprocedure PCOM patency
PCOM patency at follow-up
Length of follow-up (months)
Aneurysm occlusion at follow-up
P1 size (mm)
P1 symmetry
Pcomm size (mm)
Pcomm symmetry
1
U
PCOM
27
1 + 1 on follow-up
Yes
No
Patent
Patent
26
1
A
2
S
2
R
3
2
No
No
Patent
Occluded
26
3
S
2
S
3
U
18
1
No
Yes
Patent
Patent
12
2
S
2
S
4 5
U U
Anterior choroidal Superior hypophyseal PCOM PCOM
17 16
1 1
No No
Yes Yes
Patent Patent
Patent Patent
12 6
2 1
S A
2 3
S S
6
U
8
1
No
No
2.5
S
10
1
No
No
Diminished but patent Patent
S
U
Diminished but patent Patent
2
7
2
A
2
S
8
U
3, 9, 2
2
No
No
Patent
Patent
9
R
Superior hypophyseal Supraclinoid ICA 3 aneurysms, supraclinoid ICA ICA terminus
Recurrence, retreated with additional Pipeline Near complete Near complete Complete Near complete Near complete Incomplete
21
1
No
Yes
10
U
PCOM
5
1
No
No
Diminished but patent Occluded
11
R
PCOM
13
1
No
Yes
Diminished but patent Diminished but patent Diminished but patent
Occluded
12
PCOM: posterior communicating artery; ICA: internal carotid artery; U: unruptured; R: ruptured; A: asymmetric; S: symmetric.
6 6 13
Complete
3
S
1
Absent
9
Complete
3
S
1
S
13
Near complete Near complete
2
S
2
S
3
S
1
S
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Aneurysm rupture status
Patient number
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Fig. 1. Case example: Aneurysm recurrence and patent Pcomm patient 1 with a 27 mm Pcomm aneurysm. (a) The Pcomm ostium is incorporated in the aneurysm in this patient. (b) Immediately after coiling and PED treatment, post-operative images demonstrate decreased intraaneurysmal flow and a patent Pcomm. (c) The Pcomm remained patent 13 months after initial treatment. (d) Due to increased aneurysm filling, at 24 months, the aneurysm was retreated with an additional PED, (e) 2 months after the second treatment, the aneurysm demonstrates persistent filling with a patent Pcomm.
artery was similar in size or larger than the contralateral Pcomm artery in all 11 cases. Mean ipsilateral P1 size was 2.7 ± 0.6 mm for patients with occlusion at follow-up compared to 2.0 ± 0.8 mm for patients without occlusion. Mean ipsilateral P1 size was 2.6 ± 0.5 mm for patients with diminished flow or occlusion at follow-up compared to 1.8 ± 0.8 mm for patients with normal flow. P1 artery symmetry was not associated with Pcomm occlusion. Of patients with occluded Pcomm at follow-up, 67% (2/3) had diminished flow at initial post-procedure angiography compared to 25.0% (2/8) in patients without occlusion (P = 0.49). Of patients with diminished flow/occluded Pcomm at follow-up, 80.0% (4/5) had diminished flow at initial post-procedure angiography compared to 0.0% (0/6) of patients without diminished/occluded flow. Of the patients treated with two PEDs, one patient had occlusion of the Pcomm on follow-up (33.3%) and two patients had patent Pcomm arteries on follow-up (66.6%). Of the patients treated with one PED, two patients had occlusion of the Pcomm on followup (25.0%), two had diminished flow (25.0%) and four had patent Pcomm arteries (50.0%). 4. Discussion Our current study demonstrated that about one half of Pcomm arteries covered with flow diversion devices will undergo occlusion
or will show diminished flow compared to baseline. In no cases was Pcomm occlusion associated with clinical symptoms, however, and all patients in this case series had a patent P1 segment seen on angiography at baseline. While size and symmetry of the ipsilateral P1 were not significantly associated with Pcomm occlusion rates, there was a trend toward patients with larger and ipsilateral P1s having diminished flow immediately after placement. Initial post-angiographic Pcomm flow was significantly associated with diminished flow/occlusion in the long-term. These findings are important because they demonstrate that placement of a flow diverter at a major vessel branch can lead to branch occlusion, but in the setting of adequate collateral circulation, results in no new neurologic symptoms. Previous clinical, animal and computational studies have examined the propensity for branch artery occlusion following flow-diversion implantation [5,7,10,11]. Kallmes et al. found that upon occlusion of lumbar branch vessels in the rabbit aorta with overlapping flow-diversion devices, these perforating vessels remained patent on follow-up [12,13]. While a device placed across the origin of a perforating vessel (traditionally consider endvessels with no distal collaterals) may maintain flow across the ostium of the small perforator due to a pressure gradient across its ostium, the same is not true when larger vessels like the ophthalmic artery and the Pcomm (which often have significant distal collateral potential) are covered by these devices. In such cases the
Fig. 2. Occluded Pcomm at post-op and at follow-up patient 10 with a 5 mm Pcomm aneurysm. (a) The Pcomm artery ostium is incorporated in the aneurysm in this patient. (b) Upon deployment of a PED, diminished flow was demonstrated in the Pcomm. (c) After 7 months of follow-up, the Pcomm remains occluded.
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pressure gradient across the device struts is not enough to maintain patent flow due to the opposing effect of the distal collateral flow which creates a neutral gradient and angiographic occlusion. This usually does not result in clinical symptoms because of the collateral potential which in turn is most likely the main mechanism responsible for the phenomenon of angiographic occlusion. In a similar analysis, Puffer et al. examined ophthalmic artery patency rates following flow-diverter placement and found that nearly 25% of ophthalmic arteries are occluded on long-term follow-up [14]. This rate of occlusion is similar to our rate of approximately 27%. In a meta-analysis of outcomes of flow-diverter treatment, Brinjikji et al. found a perforator infarction rate of 3% with many perforator infarctions occur in the posterior circulation where collateral flow is limited [1]. There are several technical considerations that one must consider when treating aneurysms close to large branches with flow diverters. In cases where there are large branches incorporated into the neck or base of an aneurysm, deployment of flow diverters is controversial and often times does not result in aneurysm occlusion. This could be secondary to the aneurysm filling in a retrograde fashion from the covered vessel. Specifically, in the case of Pcomm aneurysms, this would be due to a P1-Pcomm endoleak. In such situations, one must consider whether treatment techniques such as flow-diverter with concomitant coiling or balloon assisted coiling would be helpful. Stent-assisted coiling was the primary alternative to flowdiverter therapy for the patients included in our study. Prior studies have compared outcomes of stent-assisted coiling and flow diversion for the treatment of both small and large aneurysms. In a study comparing stent-assisted coiling and flow diversion for small aneurysms, Chalouhi et al. found similar clinical and angiographic outcomes between the two treatment modalities [15]. Chalouhi et al. also found that flow diversion was associated with significantly higher occlusion rates and similar complication rates compared to coiling of large unruptured aneurysms [16]. Lanzino et al. found that flow diverter treatment of paraclinoid aneurysms resulted in higher rates of complete occlusion and similar rates of morbidity compared to coiling. Overall, these studies suggest that flow diverter treatment yields superior angiographic outcomes with similar complication rates when compared to coiling and stent assisted coiling of anterior circulation aneurysms [17]. Our study was limited by the relatively small number of treated aneurysms which diminishes our power to detect differences between groups. For this reason, we did not perform any statistical comparisons in our study. Currently, no grading system for vessel patency following flow-diverter therapy exists. Thus, our three point grading system has not been validated. Furthermore, lack of angiographic opacification of a vessel may not indicate complete absence of flow through the vessel. On follow-up angiography, most patients did not necessarily have injections of the posterior circulation arteries, thus filling of the Pcomm from the posterior circulation could not be appreciated. All patients in our series had a P1 branch and thus did not experience any neurological symptoms as a result of this occlusion; thus, it remains unclear whether patients without a P1 branch would develop Pcomm occlusions at as high a rate as in our series or if these patients would be more predisposed to developing neurological symptoms. The presence of a P1 may have increased the rate of Pcomm occlusion as the flow-diverter may have caused some decreased inflow and the distal supply of the Pcomm from the P1 may have overtaken the supply. With a
mean follow-up of approximately 13 months, this may not have been enough time to determine the long-term patency of Pcomm in these patients. Platelet responsiveness, a potentially important factor in determine arterial patency following PED placement, was not examined in this study. 5. Conclusions Approximately one half of Pcomm arteries were occluded or demonstrated decreased flow at follow-up when the ostia were covered with a flow diversion device. Occlusion of Pcomm in patients with a P1 did not result in any neurologic symptoms. Larger studies examining long-term angiographic outcomes, neurologic sequelae and vessel patency following flow-diverter deployment across vessel ostia are needed. References [1] Brinjikji W, Murad MH, Lanzino G, Cloft HJ, Kallmes DF. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013;44:442–7. [2] Deutschmann HA, Wehrschuetz M, Augustin M, Niederkorn K, Klein GE. Longterm follow-up after treatment of intracranial aneurysms with the Pipeline Embolization Device: results from a single center. AJNR Am J Neuroradiol 2012;33:481–6. [3] Fischer S, Vajda Z, Aguilar Perez M, Schmid E, Hopf N, Bazner H, et al. Pipeline embolization device (PED) for neurovascular reconstruction: initial experience in the treatment of 101 intracranial aneurysms and dissections. Neuroradiology 2012;54:369–82. [4] Saatci I, Yavuz K, Ozer C, Geyik S, Cekirge HS. Treatment of intracranial aneurysms using the pipeline flow-diverter embolization device: a singlecenter experience with long-term follow-up results. AJNR Am J Neuroradiol 2012;33:1436–46. [5] D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke 2011;42:2363–8. [6] Kulcsar Z, Augsburger L, Reymond P, Pereira VM, Hirsch S, Mallik AS, et al. Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis. Acta Neurochir (Wien) 2012;154:1827–34. [7] Geremia G, Haklin M, Brennecke L. Embolization of experimentally created aneurysms with intravascular stent devices. AJNR Am J Neuroradiol 1994;15:1223–31. [8] Lieber BB, Livescu V, Hopkins LN, Wakhloo AK. Particle image velocimetry assessment of stent design influence on intra-aneurysmal flow. Ann Biomed Eng 2002;30:768–77. [9] Trager AL, Sadasivan C, Seong J, Lieber BB. Correlation between angiographic and particle image velocimetry quantifications of flow diverters in an in vitro model of elastase-induced rabbit aneurysms. J Biomech Eng 2009;131:034506. [10] Appanaboyina S, Mut F, Löhner R, Scrivano E, Miranda C, Lylyk P, et al. Computational modelling of blood flow in side arterial branches after stenting of cerebral aneurysms. Int J Comput Fluid Dyn 2008;22:669–76. [11] Seong J, Wakhloo AK, Lieber BB. In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm model in rabbit. J Biomech Eng 2007;129:863–72. [12] Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 2007;38:2346–52. [13] Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30:1153–8. [14] Puffer RC, Kallmes DF, Cloft HJ, Lanzino G. Patency of the ophthalmic artery after flow diversion treatment of paraclinoid aneurysms. J Neurosurg 2012;116:892–6. [15] 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;45:54–8. [16] Chalouhi N, Tjoumakaris S, Starke RM, Gonzalez LF, Randazzo C, Hasan D, et al. Comparison of flow diversion and coiling in large unruptured intracranial saccular aneurysms. Stroke 2013;44:2150–4. [17] Lanzino G, Crobeddu E, Cloft HJ, Hanel R, Kallmes DF. Efficacy and safety of flow diversion for paraclinoid aneurysms: a matched-pair analysis compared with standard endovascular approaches. AJNR Am J Neuroradiol 2012;33:2158–61.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Patency of the posterior communicating artery after flow diversion treatment of internal carotid artery aneurysms Waleed Brinjikji a,∗ , Giuseppe Lanzino a,b , Harry J. Cloft a,b , David F. Kallmes a,b a b
Department of Radiology, Mayo Clinic, Rochester, USA Department of Neurosurgery, Mayo Clinic, Rochester, USA
a r t i c l e
i n f o
Article history: Received 26 January 2014 Received in revised form 20 February 2014 Accepted 23 February 2014 Available online 3 March 2014 Keywords: Aneurysm Intervention Flow diverter Stroke Endovascular
a b s t r a c t Background and purpose: Cerebral aneurysm treatment with the Pipeline Embolization Device (PED) often mandates device placement across the ostia of arteries of the Circle of Willis. We determined the patency rates of the posterior communicating artery (Pcomm) after placement across its ostium a PED and studied neurologic outcomes in these patients. Methods: We analyzed, retrospectively, a consecutive series of patients in whom a PED was placed across the ostium of Pcomm while treating the target aneurysm. Pcomm arterial flow after PED placement was graded on a 3-point scale at post-operative angiography and follow-up angiography. Data on pretreatment aneurysm rupture status, concomitant coiling, number of PEDs used, and neurologic status at follow-up were collected. Results: Eleven patients with 13 aneurysms were included in this study. All patients had an ipsilateral posterior cerebral artery arising from the basilar artery (P1). In the immediate post-procedural setting, four patients (36%) had diminished Pcomm flow rates. After a mean follow-up of 12.6 ± 6.7 months, three Pcomm arteries (27%) were occluded and two Pcomm arteries (18%) had diminished flow. Of patients with diminished flow/occluded Pcomm at follow-up, 80% (4/5) had diminished flow at initial post-procedure angiography compared to none of the six patients without diminished/occluded flow immediately post treatment. No patients suffered new neurologic symptoms at follow-up. Conclusions: Approximately one half of Pcomm arteries demonstrated occlusion or decreased flow at follow-up if the ostia are covered with a flow diversion device. Covering the Pcomm ostium in patients with a P1 did not result in any neurologic deficits. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Flow diverter devices such as the Pipeline Embolic Device (PED, eV3/Covidien, Irvine, CA) are increasingly being used in the embolization of intracranial aneurysms as both alternatives and adjuncts to endovascular coiling [1–4]. The PED is approved in the United States for treatment of intracranial aneurysms of the internal carotid artery proximal to the origin of the posterior communicating artery (Pcomm). However, these devices are being increasingly used in locations other than the proximal intracranial internal carotid artery (ICA). Histologic studies have demonstrated that after disrupting flow into the aneurysmal sac, flow diverters result in aneurysmal thrombosis and eventual sealing of the
aneurysm ostium through neointimal proliferation across device struts [5]. Computation fluid dynamic studies have demonstrated that upon deployment of flow diverters, mean intra-aneurysmal flow velocities and wall shear stress are significantly reduced resulting in aneurysmal occlusion [6]. While flow diverters limit aneurysmal blood flow, blood flow into large vessels and perforating vessels covered by the device is generally preserved [5]. While many in vitro and experimental models have demonstrated longterm patency rates of branch vessels covered by PED, the long term patency of major branch vessels is not well established [7–9]. In this study we assessed the immediate and long term patency rates of the Pcomm artery in patients following the placement of a PED across the Pcomm artery ostium.
2. Methods ∗ Corresponding author at: Department of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, 55901, USA. Tel.: +1 2489779168; fax: +1 2489779168. E-mail address: [email protected] (W. Brinjikji). http://dx.doi.org/10.1016/j.clineuro.2014.02.018 0303-8467/© 2014 Elsevier B.V. All rights reserved.
After Institutional Review Board approval, we retrospectively examined a consecutive series of patients undergoing treatment
W. Brinjikji et al. / Clinical Neurology and Neurosurgery 120 (2014) 84–88
of intracranial aneurysms with the PED in which the PED was placed across the ostium of the Pcomm artery from January 2011 to June 2012. Inclusion criteria were the following: (1) Patients >18 years old, (2) PED placed across the ostium of the Pcomm artery for treatment of a wide-necked or large/giant aneurysm, (3) follow-up clinical exam and angiogram at 6 months. Patients who did not receive follow-up were excluded from analysis. All patients in this study were included in the International Retrospective Study of Pipeline Embolization Device (IntrePED) Registry (ClinicalTrials.gov Identifier: NCT01558102) which is assessing the post-market safety and efficacy of Pipeline embolization in the treatment of intracranial aneurysms. All patients undergoing treatment were premedicated with aspirin and clopidogrel and full anticoagulation was maintained during the procedure (target activated clotting time between 250 and 300 s). Following the procedure, patients were maintained on dual antiplatelet therapy for 3 months. After 3 months, clopidogrel was discontinued and aspirin was continued indefinitely. This antiplatelet regimen was the same in all patients and no platelet responsiveness studies were used in these cases. All of the procedures were performed with the patient under general anesthesia. A bi- or triaxial access technique and, in all cases, a Marksman (ev3) microcatheter, were used to obtain distal access past the segment of the vessel harboring the target aneurysm. Pipeline Embolization Devices were sized to match the maximum diameter of the target vessel. One or multiple devices were used at the discretion of the operators to maximize the changes of complete aneurysm occlusion and/or to ensure adequate coverage of the aneurysm neck and of a segment of parent artery proximal and distal to it. Digital subtraction angiography was performed at two frames per section prior to and following placement of the PED. Determination of Pcomm artery patency was made for each patient immediately after the original procedure and at the followup angiography obtained furthest from the initial procedure by a blinded investigator. A note was also made of any subjectively determined change in flow patterns (slowing of angiographic flow after PED deployment and/or at follow-up). Pcomm artery patency was scored on a three point scale: (1) patent: similar filling of the Pcomm when comparing pre- and post-treatment angiograms, (2) diminished flow but patent: decreased or delayed filling of Pcomm when comparing pre-and post-treatment angiograms, (3) occluded: no filling of the Pcomm on post-treatment angiograms. All patients underwent a detailed clinical examination before the procedure, immediately after the procedures, the following day and at each corresponding follow-up angiogram. In addition to Pcomm artery patency, patient age, gender, aneurysm rupture status, aneurysm occlusion at follow-up (complete = no flow within the aneurysm, near complete = minimal (<10%) residual flow and incomplete ≥ 10% residual flow), aneurysm maximum size, the use of concomitant coiling, previous coiling, and the presence, symmetry and size of the ipsilateral first segment of the posterior cerebral artery (P1) and Pcomm arteries were assessed. Asymmetry was defined as ipsilateral P1 or Pcomm segment <50% size in diameter of the contralateral P1 or Pcomm respectively.
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3. Results 3.1. Patient and aneurysm characteristics A total of 11 patients (9 women and 2 men) with 13 aneurysms were included in this study. Mean patient age was 52.0 ± 11.6 years (range 32–68). Aneurysm sizes ranged from 2 mm to 27 mm with a mean of 11.7 ± 7.8 mm. Eleven aneurysms were unruptured and two were previously ruptured. The two ruptured aneurysms were treated with coil embolization in the acute phase and staged Pipeline placement after patients had recovered from the acute subarachnoid hemorrhage (SAH). One patient had concomitant coiling and six patients had prior coiling of the treated aneurysm. Initially, one PED was placed in nine patients and two PEDs were placed in two patients. One patient had a recurrence which was treated with an additional pipeline (Fig. 1), thus, in total, three patients had two PEDs placed. At last follow-up, nine aneurysms (81.8%) demonstrated complete or near-complete occlusion, one aneurysm (9.1%) demonstrated incomplete occlusion and did not receive further treatment and one aneurysm (9.1%) recurred and required further treatment with an additional PED which did not affect Pcomm patency. Of the two patients with incomplete occlusion, one patient had incorporation of a large Pcomm into the aneurysm. 3.2. Angiographic and clinical results A summary of angiographic and clinical data for the eleven patients included in this study is provided in Table 1. Representative cases are provided in Figs. 1 and 2. Following placement of the PED across the ostium of the Pcomm artery, seven patients (64%) had a patent Pcomm artery on initial post-treatment angiography while four patients (36%) had diminished flow but the Pcomm artery remained patent Follow-up times ranged from 6 to 26 months with a mean follow-up of 12.6 ± 6.7 months. No patient was lost to follow-up. On follow-up examination, six patients (55%) had a patent Pcomm artery. All six of these patients had patent Pcomm arteries on initial post-procedural angiogram. Two patients had diminished flow (18%) in patent Pcomm arteries. Both of these latter patients had diminished but patent Pcomm arteries on initial post-procedural angiogram. Three patients (27%) had occluded Pcomm arteries at follow up. Of these patients, at immediate post treatment angiography one had a patent Pcomm artery, and two had diminished flow. One patient had fibromuscular dysplasia and on the last follow-up angiogram demonstrated complete occlusion of the internal carotid artery proximal to the PED stent. In this patient the Pcomm filled in a retrograde fashion following vertebral artery injection. One of the three patients also had a vertebral artery injection which demonstrated no evidence of retrograde Pcomm flow. No patients had new neurologic symptoms on follow-up examination. All patients had an ipsilateral P1 segment present on the initial angiogram. The P1 segment was symmetric or larger than the contralateral P1 in 8 patients (72%). Asymmetry was seen in 3 (27%) cases. The size of the ipsilateral Pcomm artery was greater than or equal to the size of the contralateral Pcomm artery in 10 cases (90.9%). 3.3. Determinants of Pcomm patency
2.1. Statistical analysis Summary statistics are presented for all data available using means ± standard deviations for continuous variables and frequency tabulations for categorical variables. All statistical analyses were performed using JMP 9.0.
Mean ipsilateral Pcomm artery size was 1.7 ± 0.6 mm for patients with Pcomm arterial occlusion at follow-up compared to 1.9 ± 0.7 mm for patients without occlusion. Mean ipsilateral Pcomm artery size was 1.7 ± 0.7 mm for patients with diminished flow or occlusion at follow-up compared to 2.0 ± 0.6 mm for patients with patent Pcomm arterial flow. The ipsilateral Pcomm
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Table 1 Patient characteristics and PCOM patency. Aneurysm location
Aneurysm size (mm)
Number of PEDs
Concomitant coiling
Prior coiling
Postprocedure PCOM patency
PCOM patency at follow-up
Length of follow-up (months)
Aneurysm occlusion at follow-up
P1 size (mm)
P1 symmetry
Pcomm size (mm)
Pcomm symmetry
1
U
PCOM
27
1 + 1 on follow-up
Yes
No
Patent
Patent
26
1
A
2
S
2
R
3
2
No
No
Patent
Occluded
26
3
S
2
S
3
U
18
1
No
Yes
Patent
Patent
12
2
S
2
S
4 5
U U
Anterior choroidal Superior hypophyseal PCOM PCOM
17 16
1 1
No No
Yes Yes
Patent Patent
Patent Patent
12 6
2 1
S A
2 3
S S
6
U
8
1
No
No
2.5
S
10
1
No
No
Diminished but patent Patent
S
U
Diminished but patent Patent
2
7
2
A
2
S
8
U
3, 9, 2
2
No
No
Patent
Patent
9
R
Superior hypophyseal Supraclinoid ICA 3 aneurysms, supraclinoid ICA ICA terminus
Recurrence, retreated with additional Pipeline Near complete Near complete Complete Near complete Near complete Incomplete
21
1
No
Yes
10
U
PCOM
5
1
No
No
Diminished but patent Occluded
11
R
PCOM
13
1
No
Yes
Diminished but patent Diminished but patent Diminished but patent
Occluded
12
PCOM: posterior communicating artery; ICA: internal carotid artery; U: unruptured; R: ruptured; A: asymmetric; S: symmetric.
6 6 13
Complete
3
S
1
Absent
9
Complete
3
S
1
S
13
Near complete Near complete
2
S
2
S
3
S
1
S
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Aneurysm rupture status
Patient number
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Fig. 1. Case example: Aneurysm recurrence and patent Pcomm patient 1 with a 27 mm Pcomm aneurysm. (a) The Pcomm ostium is incorporated in the aneurysm in this patient. (b) Immediately after coiling and PED treatment, post-operative images demonstrate decreased intraaneurysmal flow and a patent Pcomm. (c) The Pcomm remained patent 13 months after initial treatment. (d) Due to increased aneurysm filling, at 24 months, the aneurysm was retreated with an additional PED, (e) 2 months after the second treatment, the aneurysm demonstrates persistent filling with a patent Pcomm.
artery was similar in size or larger than the contralateral Pcomm artery in all 11 cases. Mean ipsilateral P1 size was 2.7 ± 0.6 mm for patients with occlusion at follow-up compared to 2.0 ± 0.8 mm for patients without occlusion. Mean ipsilateral P1 size was 2.6 ± 0.5 mm for patients with diminished flow or occlusion at follow-up compared to 1.8 ± 0.8 mm for patients with normal flow. P1 artery symmetry was not associated with Pcomm occlusion. Of patients with occluded Pcomm at follow-up, 67% (2/3) had diminished flow at initial post-procedure angiography compared to 25.0% (2/8) in patients without occlusion (P = 0.49). Of patients with diminished flow/occluded Pcomm at follow-up, 80.0% (4/5) had diminished flow at initial post-procedure angiography compared to 0.0% (0/6) of patients without diminished/occluded flow. Of the patients treated with two PEDs, one patient had occlusion of the Pcomm on follow-up (33.3%) and two patients had patent Pcomm arteries on follow-up (66.6%). Of the patients treated with one PED, two patients had occlusion of the Pcomm on followup (25.0%), two had diminished flow (25.0%) and four had patent Pcomm arteries (50.0%). 4. Discussion Our current study demonstrated that about one half of Pcomm arteries covered with flow diversion devices will undergo occlusion
or will show diminished flow compared to baseline. In no cases was Pcomm occlusion associated with clinical symptoms, however, and all patients in this case series had a patent P1 segment seen on angiography at baseline. While size and symmetry of the ipsilateral P1 were not significantly associated with Pcomm occlusion rates, there was a trend toward patients with larger and ipsilateral P1s having diminished flow immediately after placement. Initial post-angiographic Pcomm flow was significantly associated with diminished flow/occlusion in the long-term. These findings are important because they demonstrate that placement of a flow diverter at a major vessel branch can lead to branch occlusion, but in the setting of adequate collateral circulation, results in no new neurologic symptoms. Previous clinical, animal and computational studies have examined the propensity for branch artery occlusion following flow-diversion implantation [5,7,10,11]. Kallmes et al. found that upon occlusion of lumbar branch vessels in the rabbit aorta with overlapping flow-diversion devices, these perforating vessels remained patent on follow-up [12,13]. While a device placed across the origin of a perforating vessel (traditionally consider endvessels with no distal collaterals) may maintain flow across the ostium of the small perforator due to a pressure gradient across its ostium, the same is not true when larger vessels like the ophthalmic artery and the Pcomm (which often have significant distal collateral potential) are covered by these devices. In such cases the
Fig. 2. Occluded Pcomm at post-op and at follow-up patient 10 with a 5 mm Pcomm aneurysm. (a) The Pcomm artery ostium is incorporated in the aneurysm in this patient. (b) Upon deployment of a PED, diminished flow was demonstrated in the Pcomm. (c) After 7 months of follow-up, the Pcomm remains occluded.
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pressure gradient across the device struts is not enough to maintain patent flow due to the opposing effect of the distal collateral flow which creates a neutral gradient and angiographic occlusion. This usually does not result in clinical symptoms because of the collateral potential which in turn is most likely the main mechanism responsible for the phenomenon of angiographic occlusion. In a similar analysis, Puffer et al. examined ophthalmic artery patency rates following flow-diverter placement and found that nearly 25% of ophthalmic arteries are occluded on long-term follow-up [14]. This rate of occlusion is similar to our rate of approximately 27%. In a meta-analysis of outcomes of flow-diverter treatment, Brinjikji et al. found a perforator infarction rate of 3% with many perforator infarctions occur in the posterior circulation where collateral flow is limited [1]. There are several technical considerations that one must consider when treating aneurysms close to large branches with flow diverters. In cases where there are large branches incorporated into the neck or base of an aneurysm, deployment of flow diverters is controversial and often times does not result in aneurysm occlusion. This could be secondary to the aneurysm filling in a retrograde fashion from the covered vessel. Specifically, in the case of Pcomm aneurysms, this would be due to a P1-Pcomm endoleak. In such situations, one must consider whether treatment techniques such as flow-diverter with concomitant coiling or balloon assisted coiling would be helpful. Stent-assisted coiling was the primary alternative to flowdiverter therapy for the patients included in our study. Prior studies have compared outcomes of stent-assisted coiling and flow diversion for the treatment of both small and large aneurysms. In a study comparing stent-assisted coiling and flow diversion for small aneurysms, Chalouhi et al. found similar clinical and angiographic outcomes between the two treatment modalities [15]. Chalouhi et al. also found that flow diversion was associated with significantly higher occlusion rates and similar complication rates compared to coiling of large unruptured aneurysms [16]. Lanzino et al. found that flow diverter treatment of paraclinoid aneurysms resulted in higher rates of complete occlusion and similar rates of morbidity compared to coiling. Overall, these studies suggest that flow diverter treatment yields superior angiographic outcomes with similar complication rates when compared to coiling and stent assisted coiling of anterior circulation aneurysms [17]. Our study was limited by the relatively small number of treated aneurysms which diminishes our power to detect differences between groups. For this reason, we did not perform any statistical comparisons in our study. Currently, no grading system for vessel patency following flow-diverter therapy exists. Thus, our three point grading system has not been validated. Furthermore, lack of angiographic opacification of a vessel may not indicate complete absence of flow through the vessel. On follow-up angiography, most patients did not necessarily have injections of the posterior circulation arteries, thus filling of the Pcomm from the posterior circulation could not be appreciated. All patients in our series had a P1 branch and thus did not experience any neurological symptoms as a result of this occlusion; thus, it remains unclear whether patients without a P1 branch would develop Pcomm occlusions at as high a rate as in our series or if these patients would be more predisposed to developing neurological symptoms. The presence of a P1 may have increased the rate of Pcomm occlusion as the flow-diverter may have caused some decreased inflow and the distal supply of the Pcomm from the P1 may have overtaken the supply. With a
mean follow-up of approximately 13 months, this may not have been enough time to determine the long-term patency of Pcomm in these patients. Platelet responsiveness, a potentially important factor in determine arterial patency following PED placement, was not examined in this study. 5. Conclusions Approximately one half of Pcomm arteries were occluded or demonstrated decreased flow at follow-up when the ostia were covered with a flow diversion device. Occlusion of Pcomm in patients with a P1 did not result in any neurologic symptoms. Larger studies examining long-term angiographic outcomes, neurologic sequelae and vessel patency following flow-diverter deployment across vessel ostia are needed. References [1] Brinjikji W, Murad MH, Lanzino G, Cloft HJ, Kallmes DF. Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis. Stroke 2013;44:442–7. [2] Deutschmann HA, Wehrschuetz M, Augustin M, Niederkorn K, Klein GE. Longterm follow-up after treatment of intracranial aneurysms with the Pipeline Embolization Device: results from a single center. AJNR Am J Neuroradiol 2012;33:481–6. [3] Fischer S, Vajda Z, Aguilar Perez M, Schmid E, Hopf N, Bazner H, et al. Pipeline embolization device (PED) for neurovascular reconstruction: initial experience in the treatment of 101 intracranial aneurysms and dissections. Neuroradiology 2012;54:369–82. [4] Saatci I, Yavuz K, Ozer C, Geyik S, Cekirge HS. Treatment of intracranial aneurysms using the pipeline flow-diverter embolization device: a singlecenter experience with long-term follow-up results. AJNR Am J Neuroradiol 2012;33:1436–46. [5] D’Urso PI, Lanzino G, Cloft HJ, Kallmes DF. Flow diversion for intracranial aneurysms: a review. Stroke 2011;42:2363–8. [6] Kulcsar Z, Augsburger L, Reymond P, Pereira VM, Hirsch S, Mallik AS, et al. Flow diversion treatment: intra-aneurismal blood flow velocity and WSS reduction are parameters to predict aneurysm thrombosis. Acta Neurochir (Wien) 2012;154:1827–34. [7] Geremia G, Haklin M, Brennecke L. Embolization of experimentally created aneurysms with intravascular stent devices. AJNR Am J Neuroradiol 1994;15:1223–31. [8] Lieber BB, Livescu V, Hopkins LN, Wakhloo AK. Particle image velocimetry assessment of stent design influence on intra-aneurysmal flow. Ann Biomed Eng 2002;30:768–77. [9] Trager AL, Sadasivan C, Seong J, Lieber BB. Correlation between angiographic and particle image velocimetry quantifications of flow diverters in an in vitro model of elastase-induced rabbit aneurysms. J Biomech Eng 2009;131:034506. [10] Appanaboyina S, Mut F, Löhner R, Scrivano E, Miranda C, Lylyk P, et al. Computational modelling of blood flow in side arterial branches after stenting of cerebral aneurysms. Int J Comput Fluid Dyn 2008;22:669–76. [11] Seong J, Wakhloo AK, Lieber BB. In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm model in rabbit. J Biomech Eng 2007;129:863–72. [12] Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 2007;38:2346–52. [13] Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30:1153–8. [14] Puffer RC, Kallmes DF, Cloft HJ, Lanzino G. Patency of the ophthalmic artery after flow diversion treatment of paraclinoid aneurysms. J Neurosurg 2012;116:892–6. [15] 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;45:54–8. [16] Chalouhi N, Tjoumakaris S, Starke RM, Gonzalez LF, Randazzo C, Hasan D, et al. Comparison of flow diversion and coiling in large unruptured intracranial saccular aneurysms. Stroke 2013;44:2150–4. [17] Lanzino G, Crobeddu E, Cloft HJ, Hanel R, Kallmes DF. Efficacy and safety of flow diversion for paraclinoid aneurysms: a matched-pair analysis compared with standard endovascular approaches. AJNR Am J Neuroradiol 2012;33:2158–61.