- Email: [email protected]
Flow Diversion for Intracranial Aneurysms: Optimally Defining and Evolving a New Tool and Approach
Perspectives Commentary on: SILK Flow-Diverting Device for Intracranial Aneurysms by Binning et al. pp. 477.E1-477.E6.
Bernard R. Bendok, M.D. Associate Professor of Neurological Surgery and Radiology Northwestern University Feinberg School of Medicine
Flow Diversion for Intracranial Aneurysms: Optimally Defining and Evolving a New Tool and Approach Bernard R. Bendok and Salah G. Aoun
A
s the diversity and sophistication of tools to treat intracranial aneurysms has expanded, the potential to achieve excellent outcomes for a greater number of patients is increasingly feasible. As the options have expanded, however, decision making has become more complex. Although results have been improved by the use of surgical and endovascular techniques in a complementary fashion, certain aneurysms continue to be frustrating to treat with either technique because of high morbidity associated with treatment, significant recurrence issues, or expected poor outcomes. Certain fusiform aneurysms, dissecting aneurysms, giant petrous and cavernous aneurysms, and other select complex giant aneurysms fall into this category. The observation that sidewall aneurysms in animal models thrombose when a stent is placed across their orifice (17, 18) led to a quest to develop flow-diverting stents (FDs) that could potentially be used as a standalone treatment for otherwise difficult-to-treat aneurysms. Hemodynamic studies have suggested that FDs have the potential to promote aneurysmal thrombosis by disrupting aneurysmal inflow and outflow jets, thus potentially reducing flow velocity and turbulence as well as wall shear stress (5, 6, 13). Although contrast can typically still be observed in the aneurysmal lumen after stenting, factors that contribute to progressive growth or rupture are thought to be reduced. It should be duly noted that these encouraging observations may overlook potential negative sequelae because aneurysmal rupture has been reported after stent placement (4, 12). Animal experiments have added additional insights on how FDs may work (4, 13). First, thrombus formation can occur immediately or within weeks, which can potentially disrupt intra-aneurysmal flow and can progress towards complete obliteration (5, 12, 19). Second, during the months after stent placement, the tines can become endothelialized, providing a physiological ex-
Key words 䡲 Endovascular 䡲 Flow diversion 䡲 Large aneurysm 䡲 SILK stent
Abbreviations and Acronyms FDs: Flow-diverting stents PED: Pipeline embolization device SFD: SILK flow diverter
WORLD NEUROSURGERY 76 [5]: 401-404, NOVEMBER 2011
clusion of the aneurysm and allowing the thrombus to resorb (5, 6, 13). Electron microscopy images in a rabbit model have revealed that the neoendothelialization process within the stent seems to spare perforators (13). Conversely, neointimal overgrowth has been hypothesized as a contributing factor to perforator stroke in human subjects (8). Two FDs devices are currently available for commercial use: the Pipeline embolization device (PED; Chestnut Medical Technologies, Menlo Park, CA) in Europe and the United States, and the SILK FD (SFD; Balt Extrusion, Montmorency, France) in Europe only. The PED is a woven tube of 48 wires of platinum and cobalt-chromium alloy. It provides 30%-35% area coverage of the inner vascular surface, approximately three times as much as non-FDs, and can be retrieved up until the final phases of deployment (9, 11, 14). The device was approved by the U.S. Food and Drug Administration on April 6, 2011, for the treatment of large or giant wide-necked intracranial aneurysms in the cavernous and paraclinoid regions of the internal carotid artery. The SFD is a braided cylinder of 48 filaments of nickel-titanium and platinum alloy. It provides 35%-55% vascular surface coverage and can be retrieved or repositioned up until 80%-90% deployment (2, 10). It has not yet received U.S. Food and Drug Administration approval but is available for commercial use in Europe and other countries. Data regarding both stents remain fairly sparse and relatively short term with regards to follow-up. The results of four clinical studies are available to date on the PED (Table 1) (11, 13, 14). Reported technical success rates are high (⬎95%) (9, 11). Periprocedural complications (0%-6.5%) include stent malposition, aneurysm rupture, transient hemiparesis, and acute stroke. Although immediate angiographic aneurysm obliteration rates are low (8%-22%) (7, 13), complete aneurysm occlusion rates at the 12-month follow-up are high (93.3%-95.2%). Reported mor-
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA To whom correspondence should be addressed: Bernard R. Bendok, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 76, 5:401-404. DOI: 10.1016/j.wneu.2011.06.048
www.WORLDNEUROSURGERY.org
401
402
4% 8% 49% (0-80 weeksMedian⫽ 119 days)/72% Small:18 Large:37 Giant: 15 n⫽0 14% SFD ⫹ coiling; 14% SFD only 70/70 Published - 2010 Silk Registry results: Byrne et al.
y y y
Saccular: 63% Anterior circulation: 71% Neck ⬎ 4mm: 54%
15% 4% 69% (6 and 12 months)/ 82.8% Small:18 Large:12 Giant: 4 n ⫽ 9 (26.5%) SFD only 29/34 Published - 2010
www.SCIENCEDIRECT.com
Silk Flow Diverter (SFD)
Prospective Study in 29 patients With 34 Aneurysms Lubicz et al.
y y y
Saccular: 56% Anterior circulation: 85% Wide-necked: 50%
5.6% major stroke or neurological death 95.2% at 12 months/not available Large:85 Giant: 22 n ⫽ 8 (7.4%) 0.9% PED ⫹ coiling; 99.1% PED only 108/110? The PUFS Study
Preliminary results released – Not yet published
y
All wide-necked or fusiform
6.5% 93.3% at 6 months/97% Anterior circulation: 93.6% Neck ⱖ4 : 71% Small:20 Large: 9 Giant: 2 n ⫽ 12 (38.7%) 51.6% PED ⫹ coiling; 48.4% PED only Published -2011 The PITA trial
31/31
y y
0%
0% 5.5% 94.4% of patients at 6 months/100% All wide-necked Small: 5 Large:10 Giant: 4 n ⫽ 1 (5%) 18/19 Published - 2010 The Budapest Experience
47% PED ⫹ coiling; 53% PED only
y
No major complications (stroke or death) were encountered 56% at 3 months/79% 93% at 6 months/53% 95% at 12 months/34% Saccular: 87% Anterior circulation: 87.3% All wide-necked Small:33 Large:22 Giant: 8 n ⫽ 23 (37%) 53/63 Published - 2009 Pipeline Embolization Device (PED)
The Buenos Aires Experience
PED ⫹ coiling
y y y
Mortality Aneurysm Characteristics Flow Diverter
Study
Status Publication Date
Table 1. Results of Clinical Studies on PED and SFD
Number of Patients/ Number of Aneurysms
Treatment Modality
Number of Previously Treated Aneurysms
Aneurysm Size, n
Complete Angiographic Occlusion Rate at Follow-up/Follow-up Rate
Permanent Major Morbidity
PERSPECTIVES
bidity and mortality in the PED series ranges from 0% to 6.5% at 12 months. No radiographic recurrences were observed. Of note, no significant data are available beyond 12 months. Fewer data are currently available regarding the SFD (Table 1) (2, 10). Two main studies have been published: The SILK Registry by Byrne et al. (2) and a prospective study of 29 patients with 34 aneurysms by Lubicz et al (10). In the SILK Registry reported technical success rates were high (90%-96%). Immediate procedural morbidity and mortality were 1.4% and 2.9%, respectively (2). Immediate postprocedural complete occlusion rates were low (10%-11.8%) but increased to 49% at the latest follow-up (median, 119 days). Reported mortality and morbidity rates were 8% and 4%, respectively. In the Lubicz et al. (10) study, complete occlusion rates reach 69% at 6-12 months’ follow-up, with 4% mortality and 15% morbidity. Despite these promising results, a number of concerns still remain. Thus far, there is a legitimate reluctance to use these stents in the acute phase after subarachnoid hemorrhage. The need for dual antiplatelet therapy for prolonged periods is also a potential limitation. It is in fact not yet clear how long antiplatelet therapy will be needed for these stents (12). Another concern is the rare but serious reports of delayed aneurysm rupture (7, 15). Antiplatelets prevent fibrin deposition and clot maturation from a highly cellular and biologically active red thrombus to a wellorganized white thrombus. This is potentially significant because fibrin can prevent proteolytic enzymes released by the clot from actively eroding the arterial wall (15). On the basis of this theoretical concern, additional coiling after stent placement is thought to promote white thrombus formation and stability and to decrease the risk of rupture; in an urgent field safety notice released on March 2010, Balt Extrusion announced that because of a number of case fatalities after SILK implantation, they did not have sufficient evidence at the time to promote their device as standalone endovascular treatment. Instead, they declared that “The SILK is intended for endovascular occlusion with the use of coils in the aneurysmal sac” (1). Other possible mechanisms for early and delayed aneurysmal rupture include disturbed intravascular hemodynamics and increased intra-aneurysmal pressure (3, 12). Clearly this potential complication needs to be better understood. The inability to reaccess the aneurysm without special techniques makes it all the more worrisome. Thromboembolic risks and parent artery occlusion are additional concerns. Reported occlusion rates vary between 4.9% and 10% (19, 21), and in-stent thrombosis has been observed as late as 23 months after stent placement (5). Klisch et al. (7) reported on two patients who suffered from acute stent thrombosis within two weeks of clopidogrel discontinuation, one year after the endovascular procedure. Histologic studies have raised questions regarding the ability of endothelial cells to cover the metallic stent tines, which might explain the increased propensity for thrombus formation and may require a longer and even indefinite duration of antiaggregant treatment (4, 7). One issue that may theoretically be worrisome regarding thromboembolism is the propensity of needing multiple overlapping stents to achieve stasis within an aneurysm. Metallic strut superposition may provide an additional obstacle to endothelial cell colonization and drive the need for longer antiaggregant administration. Parent artery stenosis is another possible compli-
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.06.048
PERSPECTIVES
cation, with reported rates as high as 27.5% in the series of Lubicz et al. (10). An additional concern is the potential for short-term or delayed perforator or side branch occlusion because this is another possible mechanism for stroke after FDs placement. Although the incidence for this complication is not yet known, it has been documented in the literature (9, 12, 16, 20) and is thought to be more likely related to poor collateral supply and neo-intimal overgrowth rather than direct vessel obstruction by the stent tines (21). The need for overlapping stents may increase the risk of this potential complication. In the current study, Binning et al. report the first two cases of intracranial aneurysm treatment using the SFD in the United States. The first patient was a 50-year-old woman who presented with right-sided weakness and a 25-mm carotid artery aneurysm. She did not tolerate balloon test occlusion of the left internal carotid artery and was not considered a good candidate for endovascular coiling because of mass effect issues. She also refused open surgical treatment. A SILK stent was uneventfully placed after the appropriate perioperative antiaggregant medications were administered. The stent was positioned from her left middle cerebral artery to her left internal carotid artery. Immediate intra-aneurysmal stasis was observed. After an episode of violent coughing, she spontaneously ruptured an intercostal artery and became hemodynamically unstable. Anticoagulants and antiaggregants were discontinued. The patient subsequently experienced subarachnoid and intraventricular hemorrhage, as well as in-stent thrombosis. She later developed a middle cerebral artery infarct. At her two-month follow-up she was aphasic with a right-sided hemiplegia. What lessons can be learned from this case are not entirely clear, but one must bare several issues in mind. First, this aneurysm clearly has good surgical solutions, although they too carry risk. Second, the origin of the A1 off the base of the aneurysm makes this vessel vulnerable to thromboembolism. There is in fact delayed filling noted in the A1 (Figure 3A in Binning et al.’s article). Third, antiplatelet therapy carries low but real risk for hemorrhagic
REFERENCES 1. Balt Extrusion, Urgent Field Safety Notice, March 2010. Available at: http://www.mhra.gov.uk/Safety information/Safetywarningsalertsandrecalls/field safetynotices/FieldSafetyNoticesformedicaldevices/ CON076109. Accessed July 15, 2011. 2. Byrne JV, Beltechi R, Yarnold JA, Birks J, Kamran M: Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study. PLoS One 5:9, 2010. 3. Cebral JR, Mut F, Raschi M, Scrivano E, Ceratto R, Lylyk P, Putman CM: Aneurysm rupture following treatment with flow-diverting stents: computational hemodynamics analysis of treatment. AJNR Am J Neuroradiol 32:27-33, 2011. 4. Fiorella D: Curative cerebrovascular reconstruction with the Pipeline embolization device: the emergence of definitive endovascular therapy for intracranial aneurysms. J Neurointervent Surg 1:56-65, 2009. 5. Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK: Very late thrombosis of a pipeline embolization de-
complications which can be difficult to control. Management of the hemorrhagic complications often requires cessation and reversal of antiplatelet and anticoagulant therapy which expose the stent to thrombosis. Fourth, this aneurysm ruptured, and the phenomenon remains poorly understood. Increasing evidence indicates that this a real risk with FDs. It has been suggested that placement of several coils in the aneurysm may reduce this complication, but that remains theoretical. The second patient was a 75-year-old man with progressive walking difficulty and gait instability. Imaging revealed a thrombosed fusiform aneurysm of the vertebrobasilar junction that did not have reasonable traditional surgical nor interventional options. He received dual antiplatelet treatment, and two SILK devices were placed through his dominant left vertebral artery, resulting in immediate stasis. His hospital course was uneventful. Follow-up at 2 and 12 months revealed complete aneurysm remodeling with no in-stent stenosis or aneurysm filling. The patient improved clinically, living independently and ambulating with a cane. Early follow-up suggests his has been a successful application of FDs, but further follow-up is needed. We congratulate the authors for creatively and responsibly using new tools in ways that have the potential to improve outcomes. We appreciate their honest presentation of complications. Without staring these complications in the eye, we will not have the vision to improve our decision making, strategies, and technologies. FDs appear to be a promising addition to the expanding therapeutic arsenal for intracranial aneurysms. Much remains to be learned, however, about their safety and efficacy. This mandates rigorous trials with long-term follow-up. Until more data become available, caution should be exercised in their use. The use of FDs for aneurysms that can be safely treated surgically or interventionally cannot yet be justified outside of clinical trials. Until better data emerge, the current indications for FDs remain aneurysms, which have no better solutions as judged by skilled and thoughtful practitioners.
vice construct: case report. Neurosurgery 67(3 Suppl Operative):onsE313-314; discussion onsE314, 2010. 6. Ionita CN, Paciorek AM, Dohatcu A, Hoffmann KR, Bednarek DR, Kolega J, Levy EI, Hopkins LN, Rudin S, Mocco JD: The asymmetric vascular stent: efficacy in a rabbit aneurysm model. Stroke 40:959-965, 2009. 7. Klisch J, Turk A, Turner R, Woo HH, Fiorella D: Very late thrombosis of flow-diverting constructs after the treatment of large fusiform posterior circulation aneurysms. AJNR Am J Neuroradiol 32:627-632, 2011. 8. Kulcsar Z, Ernemann U, Wetzel SG, Bock A, Goericke S, Panagiotopoulos V, Forsting M, Ruefenacht DA, Wanke I: High-profile flow diverter (silk) implantation in the basilar artery: efficacy in the treatment of aneurysms and the role of the perforators. Stroke 41:1690-1696, 2010. 9. Lylyk P, Miranda C, Ceratto R, Ferrario A, Scrivano E, Luna HR, Berez AL, Tran Q, Nelson PK, Fiorella D: Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device:
WORLD NEUROSURGERY 76 [5]: 401-404, NOVEMBER 2011
the Buenos Aires experience. Neurosurgery 64: 632-642; discussion 642-633; quiz N636, 2009. 10. Lubicz B, Collignon L, Raphaeli G, Pruvo JP, Bruneau M, De Witte O, Leclerc X: Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 41:2247-2253, 2010. 11. Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D: The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol. 32:34-40, 2011. 12. Pierot L: Flow diverter stents in the treatment of intracranial aneurysms: where are we? J Neuroradiol 38:40-46, 2011. 13. Sadasivan C, Cesar L, Seong J, Rakian A, Hao Q, Tio FO, Wakhloo AK, Lieber BB: An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model. Stroke 40:952-958, 2009. 14. Szikora I, Berentei Z, Kulcsar Z, Marosfoi M, Vajda ZS, Lee W, Berez A, Nelson PK: Treatment of intra-
www.WORLDNEUROSURGERY.org
403
PERSPECTIVES
cranial aneurysms by functional reconstruction of the parent artery: the Budapest experience with the pipeline embolization device. AJNR Am J Neuroradiol 31:1139-1147, 2010.
17. Wakhloo AK, Lanzino G, Lieber BB, Hopkins LN: Stents for intracranial aneurysms: the beginning of a new endovascular era? Neurosurgery 43:377-379, 1998.
15. Turowski B, Macht S, Kulcsar Z, Hanggi D, Stummer W: Early fatal hemorrhage after endovascular cerebral aneurysm treatment with a flow diverter (SILK-Stent): do we need to rethink our concepts? Neuroradiology 53:37-41, 2011.
18. Wakhloo AK, Tio FO, Lieber BB, Schellhammer F, Graf M, Hopkins LN: Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response. AJNR Am J Neuroradiol 16:1043-1051, 1995.
16. van Rooij WJ, Sluzewski M: Perforator infarction after placement of a pipeline flow-diverting stent for an unruptured A1 aneurysm. AJNR Am J Neuroradiol 31:E43-E44, 2010.
19. Walcott BP, Pisapia JM, Nahed BV, Kahle KT, Ogilvy CS: Early experience with flow diverting endoluminal stents for the treatment of intracranial aneurysms. J Clin Neurosci 18:891-894, 2011.
20. Wanke I, Forsting M: Stents for intracranial widenecked aneurysms: more than mechanical protection. Neuroradiology 50:991-998, 2008. 21. Wong GK, Kwan MC, Ng RY, Yu SC, Poon WS: Flow diverters for treatment of intracranial aneurysms: Current status and ongoing clinical trials. J Clin Neurosci 18:737-740, 2011. Citation: World Neurosurg. (2011) 76, 5:401-404. DOI: 10.1016/j.wneu.2011.06.048 Journal homepage: www.WORLDNEUROSURGERY.org
404
www.SCIENCEDIRECT.com
Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.06.048
Bernard R. Bendok, M.D. Associate Professor of Neurological Surgery and Radiology Northwestern University Feinberg School of Medicine
Flow Diversion for Intracranial Aneurysms: Optimally Defining and Evolving a New Tool and Approach Bernard R. Bendok and Salah G. Aoun
A
s the diversity and sophistication of tools to treat intracranial aneurysms has expanded, the potential to achieve excellent outcomes for a greater number of patients is increasingly feasible. As the options have expanded, however, decision making has become more complex. Although results have been improved by the use of surgical and endovascular techniques in a complementary fashion, certain aneurysms continue to be frustrating to treat with either technique because of high morbidity associated with treatment, significant recurrence issues, or expected poor outcomes. Certain fusiform aneurysms, dissecting aneurysms, giant petrous and cavernous aneurysms, and other select complex giant aneurysms fall into this category. The observation that sidewall aneurysms in animal models thrombose when a stent is placed across their orifice (17, 18) led to a quest to develop flow-diverting stents (FDs) that could potentially be used as a standalone treatment for otherwise difficult-to-treat aneurysms. Hemodynamic studies have suggested that FDs have the potential to promote aneurysmal thrombosis by disrupting aneurysmal inflow and outflow jets, thus potentially reducing flow velocity and turbulence as well as wall shear stress (5, 6, 13). Although contrast can typically still be observed in the aneurysmal lumen after stenting, factors that contribute to progressive growth or rupture are thought to be reduced. It should be duly noted that these encouraging observations may overlook potential negative sequelae because aneurysmal rupture has been reported after stent placement (4, 12). Animal experiments have added additional insights on how FDs may work (4, 13). First, thrombus formation can occur immediately or within weeks, which can potentially disrupt intra-aneurysmal flow and can progress towards complete obliteration (5, 12, 19). Second, during the months after stent placement, the tines can become endothelialized, providing a physiological ex-
Key words 䡲 Endovascular 䡲 Flow diversion 䡲 Large aneurysm 䡲 SILK stent
Abbreviations and Acronyms FDs: Flow-diverting stents PED: Pipeline embolization device SFD: SILK flow diverter
WORLD NEUROSURGERY 76 [5]: 401-404, NOVEMBER 2011
clusion of the aneurysm and allowing the thrombus to resorb (5, 6, 13). Electron microscopy images in a rabbit model have revealed that the neoendothelialization process within the stent seems to spare perforators (13). Conversely, neointimal overgrowth has been hypothesized as a contributing factor to perforator stroke in human subjects (8). Two FDs devices are currently available for commercial use: the Pipeline embolization device (PED; Chestnut Medical Technologies, Menlo Park, CA) in Europe and the United States, and the SILK FD (SFD; Balt Extrusion, Montmorency, France) in Europe only. The PED is a woven tube of 48 wires of platinum and cobalt-chromium alloy. It provides 30%-35% area coverage of the inner vascular surface, approximately three times as much as non-FDs, and can be retrieved up until the final phases of deployment (9, 11, 14). The device was approved by the U.S. Food and Drug Administration on April 6, 2011, for the treatment of large or giant wide-necked intracranial aneurysms in the cavernous and paraclinoid regions of the internal carotid artery. The SFD is a braided cylinder of 48 filaments of nickel-titanium and platinum alloy. It provides 35%-55% vascular surface coverage and can be retrieved or repositioned up until 80%-90% deployment (2, 10). It has not yet received U.S. Food and Drug Administration approval but is available for commercial use in Europe and other countries. Data regarding both stents remain fairly sparse and relatively short term with regards to follow-up. The results of four clinical studies are available to date on the PED (Table 1) (11, 13, 14). Reported technical success rates are high (⬎95%) (9, 11). Periprocedural complications (0%-6.5%) include stent malposition, aneurysm rupture, transient hemiparesis, and acute stroke. Although immediate angiographic aneurysm obliteration rates are low (8%-22%) (7, 13), complete aneurysm occlusion rates at the 12-month follow-up are high (93.3%-95.2%). Reported mor-
Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA To whom correspondence should be addressed: Bernard R. Bendok, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 76, 5:401-404. DOI: 10.1016/j.wneu.2011.06.048
www.WORLDNEUROSURGERY.org
401
402
4% 8% 49% (0-80 weeksMedian⫽ 119 days)/72% Small:18 Large:37 Giant: 15 n⫽0 14% SFD ⫹ coiling; 14% SFD only 70/70 Published - 2010 Silk Registry results: Byrne et al.
y y y
Saccular: 63% Anterior circulation: 71% Neck ⬎ 4mm: 54%
15% 4% 69% (6 and 12 months)/ 82.8% Small:18 Large:12 Giant: 4 n ⫽ 9 (26.5%) SFD only 29/34 Published - 2010
www.SCIENCEDIRECT.com
Silk Flow Diverter (SFD)
Prospective Study in 29 patients With 34 Aneurysms Lubicz et al.
y y y
Saccular: 56% Anterior circulation: 85% Wide-necked: 50%
5.6% major stroke or neurological death 95.2% at 12 months/not available Large:85 Giant: 22 n ⫽ 8 (7.4%) 0.9% PED ⫹ coiling; 99.1% PED only 108/110? The PUFS Study
Preliminary results released – Not yet published
y
All wide-necked or fusiform
6.5% 93.3% at 6 months/97% Anterior circulation: 93.6% Neck ⱖ4 : 71% Small:20 Large: 9 Giant: 2 n ⫽ 12 (38.7%) 51.6% PED ⫹ coiling; 48.4% PED only Published -2011 The PITA trial
31/31
y y
0%
0% 5.5% 94.4% of patients at 6 months/100% All wide-necked Small: 5 Large:10 Giant: 4 n ⫽ 1 (5%) 18/19 Published - 2010 The Budapest Experience
47% PED ⫹ coiling; 53% PED only
y
No major complications (stroke or death) were encountered 56% at 3 months/79% 93% at 6 months/53% 95% at 12 months/34% Saccular: 87% Anterior circulation: 87.3% All wide-necked Small:33 Large:22 Giant: 8 n ⫽ 23 (37%) 53/63 Published - 2009 Pipeline Embolization Device (PED)
The Buenos Aires Experience
PED ⫹ coiling
y y y
Mortality Aneurysm Characteristics Flow Diverter
Study
Status Publication Date
Table 1. Results of Clinical Studies on PED and SFD
Number of Patients/ Number of Aneurysms
Treatment Modality
Number of Previously Treated Aneurysms
Aneurysm Size, n
Complete Angiographic Occlusion Rate at Follow-up/Follow-up Rate
Permanent Major Morbidity
PERSPECTIVES
bidity and mortality in the PED series ranges from 0% to 6.5% at 12 months. No radiographic recurrences were observed. Of note, no significant data are available beyond 12 months. Fewer data are currently available regarding the SFD (Table 1) (2, 10). Two main studies have been published: The SILK Registry by Byrne et al. (2) and a prospective study of 29 patients with 34 aneurysms by Lubicz et al (10). In the SILK Registry reported technical success rates were high (90%-96%). Immediate procedural morbidity and mortality were 1.4% and 2.9%, respectively (2). Immediate postprocedural complete occlusion rates were low (10%-11.8%) but increased to 49% at the latest follow-up (median, 119 days). Reported mortality and morbidity rates were 8% and 4%, respectively. In the Lubicz et al. (10) study, complete occlusion rates reach 69% at 6-12 months’ follow-up, with 4% mortality and 15% morbidity. Despite these promising results, a number of concerns still remain. Thus far, there is a legitimate reluctance to use these stents in the acute phase after subarachnoid hemorrhage. The need for dual antiplatelet therapy for prolonged periods is also a potential limitation. It is in fact not yet clear how long antiplatelet therapy will be needed for these stents (12). Another concern is the rare but serious reports of delayed aneurysm rupture (7, 15). Antiplatelets prevent fibrin deposition and clot maturation from a highly cellular and biologically active red thrombus to a wellorganized white thrombus. This is potentially significant because fibrin can prevent proteolytic enzymes released by the clot from actively eroding the arterial wall (15). On the basis of this theoretical concern, additional coiling after stent placement is thought to promote white thrombus formation and stability and to decrease the risk of rupture; in an urgent field safety notice released on March 2010, Balt Extrusion announced that because of a number of case fatalities after SILK implantation, they did not have sufficient evidence at the time to promote their device as standalone endovascular treatment. Instead, they declared that “The SILK is intended for endovascular occlusion with the use of coils in the aneurysmal sac” (1). Other possible mechanisms for early and delayed aneurysmal rupture include disturbed intravascular hemodynamics and increased intra-aneurysmal pressure (3, 12). Clearly this potential complication needs to be better understood. The inability to reaccess the aneurysm without special techniques makes it all the more worrisome. Thromboembolic risks and parent artery occlusion are additional concerns. Reported occlusion rates vary between 4.9% and 10% (19, 21), and in-stent thrombosis has been observed as late as 23 months after stent placement (5). Klisch et al. (7) reported on two patients who suffered from acute stent thrombosis within two weeks of clopidogrel discontinuation, one year after the endovascular procedure. Histologic studies have raised questions regarding the ability of endothelial cells to cover the metallic stent tines, which might explain the increased propensity for thrombus formation and may require a longer and even indefinite duration of antiaggregant treatment (4, 7). One issue that may theoretically be worrisome regarding thromboembolism is the propensity of needing multiple overlapping stents to achieve stasis within an aneurysm. Metallic strut superposition may provide an additional obstacle to endothelial cell colonization and drive the need for longer antiaggregant administration. Parent artery stenosis is another possible compli-
WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.06.048
PERSPECTIVES
cation, with reported rates as high as 27.5% in the series of Lubicz et al. (10). An additional concern is the potential for short-term or delayed perforator or side branch occlusion because this is another possible mechanism for stroke after FDs placement. Although the incidence for this complication is not yet known, it has been documented in the literature (9, 12, 16, 20) and is thought to be more likely related to poor collateral supply and neo-intimal overgrowth rather than direct vessel obstruction by the stent tines (21). The need for overlapping stents may increase the risk of this potential complication. In the current study, Binning et al. report the first two cases of intracranial aneurysm treatment using the SFD in the United States. The first patient was a 50-year-old woman who presented with right-sided weakness and a 25-mm carotid artery aneurysm. She did not tolerate balloon test occlusion of the left internal carotid artery and was not considered a good candidate for endovascular coiling because of mass effect issues. She also refused open surgical treatment. A SILK stent was uneventfully placed after the appropriate perioperative antiaggregant medications were administered. The stent was positioned from her left middle cerebral artery to her left internal carotid artery. Immediate intra-aneurysmal stasis was observed. After an episode of violent coughing, she spontaneously ruptured an intercostal artery and became hemodynamically unstable. Anticoagulants and antiaggregants were discontinued. The patient subsequently experienced subarachnoid and intraventricular hemorrhage, as well as in-stent thrombosis. She later developed a middle cerebral artery infarct. At her two-month follow-up she was aphasic with a right-sided hemiplegia. What lessons can be learned from this case are not entirely clear, but one must bare several issues in mind. First, this aneurysm clearly has good surgical solutions, although they too carry risk. Second, the origin of the A1 off the base of the aneurysm makes this vessel vulnerable to thromboembolism. There is in fact delayed filling noted in the A1 (Figure 3A in Binning et al.’s article). Third, antiplatelet therapy carries low but real risk for hemorrhagic
REFERENCES 1. Balt Extrusion, Urgent Field Safety Notice, March 2010. Available at: http://www.mhra.gov.uk/Safety information/Safetywarningsalertsandrecalls/field safetynotices/FieldSafetyNoticesformedicaldevices/ CON076109. Accessed July 15, 2011. 2. Byrne JV, Beltechi R, Yarnold JA, Birks J, Kamran M: Early experience in the treatment of intra-cranial aneurysms by endovascular flow diversion: a multicentre prospective study. PLoS One 5:9, 2010. 3. Cebral JR, Mut F, Raschi M, Scrivano E, Ceratto R, Lylyk P, Putman CM: Aneurysm rupture following treatment with flow-diverting stents: computational hemodynamics analysis of treatment. AJNR Am J Neuroradiol 32:27-33, 2011. 4. Fiorella D: Curative cerebrovascular reconstruction with the Pipeline embolization device: the emergence of definitive endovascular therapy for intracranial aneurysms. J Neurointervent Surg 1:56-65, 2009. 5. Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK: Very late thrombosis of a pipeline embolization de-
complications which can be difficult to control. Management of the hemorrhagic complications often requires cessation and reversal of antiplatelet and anticoagulant therapy which expose the stent to thrombosis. Fourth, this aneurysm ruptured, and the phenomenon remains poorly understood. Increasing evidence indicates that this a real risk with FDs. It has been suggested that placement of several coils in the aneurysm may reduce this complication, but that remains theoretical. The second patient was a 75-year-old man with progressive walking difficulty and gait instability. Imaging revealed a thrombosed fusiform aneurysm of the vertebrobasilar junction that did not have reasonable traditional surgical nor interventional options. He received dual antiplatelet treatment, and two SILK devices were placed through his dominant left vertebral artery, resulting in immediate stasis. His hospital course was uneventful. Follow-up at 2 and 12 months revealed complete aneurysm remodeling with no in-stent stenosis or aneurysm filling. The patient improved clinically, living independently and ambulating with a cane. Early follow-up suggests his has been a successful application of FDs, but further follow-up is needed. We congratulate the authors for creatively and responsibly using new tools in ways that have the potential to improve outcomes. We appreciate their honest presentation of complications. Without staring these complications in the eye, we will not have the vision to improve our decision making, strategies, and technologies. FDs appear to be a promising addition to the expanding therapeutic arsenal for intracranial aneurysms. Much remains to be learned, however, about their safety and efficacy. This mandates rigorous trials with long-term follow-up. Until more data become available, caution should be exercised in their use. The use of FDs for aneurysms that can be safely treated surgically or interventionally cannot yet be justified outside of clinical trials. Until better data emerge, the current indications for FDs remain aneurysms, which have no better solutions as judged by skilled and thoughtful practitioners.
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the Buenos Aires experience. Neurosurgery 64: 632-642; discussion 642-633; quiz N636, 2009. 10. Lubicz B, Collignon L, Raphaeli G, Pruvo JP, Bruneau M, De Witte O, Leclerc X: Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 41:2247-2253, 2010. 11. Nelson PK, Lylyk P, Szikora I, Wetzel SG, Wanke I, Fiorella D: The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol. 32:34-40, 2011. 12. Pierot L: Flow diverter stents in the treatment of intracranial aneurysms: where are we? J Neuroradiol 38:40-46, 2011. 13. Sadasivan C, Cesar L, Seong J, Rakian A, Hao Q, Tio FO, Wakhloo AK, Lieber BB: An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model. Stroke 40:952-958, 2009. 14. Szikora I, Berentei Z, Kulcsar Z, Marosfoi M, Vajda ZS, Lee W, Berez A, Nelson PK: Treatment of intra-
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18. Wakhloo AK, Tio FO, Lieber BB, Schellhammer F, Graf M, Hopkins LN: Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response. AJNR Am J Neuroradiol 16:1043-1051, 1995.
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20. Wanke I, Forsting M: Stents for intracranial widenecked aneurysms: more than mechanical protection. Neuroradiology 50:991-998, 2008. 21. Wong GK, Kwan MC, Ng RY, Yu SC, Poon WS: Flow diverters for treatment of intracranial aneurysms: Current status and ongoing clinical trials. J Clin Neurosci 18:737-740, 2011. Citation: World Neurosurg. (2011) 76, 5:401-404. DOI: 10.1016/j.wneu.2011.06.048 Journal homepage: www.WORLDNEUROSURGERY.org
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WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2011.06.048