- Department of Radiology, Graduate School of Medicine, University of Tennessee Medical Center Knoxville, Knoxville, Tennessee, USA
- Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA
Correspondence Address:
Gavin W. Britz
Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA
DOI:10.4103/2152-7806.109194
Copyright: © 2013 Ferrell AS This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Ferrell AS, Britz GW. Developments on the horizon in the treatment of neurovascular problems. Surg Neurol Int 19-Mar-2013;4:
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Abstract
The field of Interventional Neuroradiology and Endovascular Neurosurgery has seen much technical advancement in the past two decades, which has brought the specialty from its infancy as an alternative therapy to the current standing as near standard of care for many complex neurovascular pathologies. This past year is no exception with flow diverting stents and stent retriever devices aiming to make their mark on advanced treatments for intracranial aneurysms and ischemic stroke, respectively. This review article will focus on the development of these technologies, current data supporting their advantages and limitations, and a brief expert opinion on where these technologies may take the field in the next few years.
Keywords: Cerebral aneurysm, flow diversion, ischemic stroke, stent retriever
CEREBRAL ANEURYSM TREATMENT
Percutaneous treatment of intracranial aneurysms began with electrothrombosis in 1941 and subsequently progressed to the use of various pushable coils and detachable balloons, all of which were difficult to safely control and produced suboptimal, incomplete results.[
The most recent development in the field of endovascular therapy for the treatment of intracranial aneurysms in the past several years is the concept of flow diversion. Flow-diverting stents are flexible, self-expanding stents delivered by a standard microcatheter. These stents have significantly expanded metal surface area coverage compared with traditional stents marketed for intracranial use such as Neuroform® (Stryker Neurovascular, Freemont, CA) or Enterprise™ (Cordis, Miami Lakes, Florida). This coverage area gives the device an extremely low porosity, which when placed within a vessel harboring an aneurysm that preferentially redirects flow through the parent vessel, limits aneurysm inflow, and ultimately results in aneurysm thrombosis. In effect these devices create endoluminal parent vessel reconstruction by altering hemodynamics and by induction of complex biological responses, which result in neointimilization, factors which collectively aim to heal the diseased segment of the vessel and the aneurysm ostia.[
Initial experience with these stents has been greatly received as deployment seems to be technically achievable in the majority of cases (although this requires a learning curve above that seen with traditional intracranial stents), they result in a high percentage of complete aneurysm occlusion, and to date have acceptable complication rates. Initially approved and marketed for the treatment of wide necked, complex aneurysms with limited therapeutic options, these devices are increasingly being used for the treatment of more traditional aneurysms.
Two flow diverting stents are currently being used internationally, the Pipeline™ Embolization Device (PED; ev3, Irvine, California, USA) and the Silk stent (BALT Extrusion, Montmorency, France). The PED became the first available device in the United States when it received approval from the FDA on April 6, 2011 for the endovascular treatment of adults (age 22 and above) with large or giant wide-necked intracranial aneurysms of the internal carotid artery (ICA) from the petrous to superior hypophyseal segments.
The PED is composed of 48 braided strands of woven wire mesh containing 25% platinum and 75% cobalt–nickel alloy[
In PITA only two (6.5%) periprocedural strokes occurred giving the device a similar safety profile to that seen with standard stent-assisted coil embolization of intracranial aneurysms.[
Not all series have demonstrated as high of a safety profile, however. In the Budapest experience, clinical complications were seen in 4 of 18 (22.2%) patients.[
With placement of any intracranial stent, routine antiplatelet therapy is used to prevent peri-procedural thromboembolic complications. Given the increased metal surface of flow diverting stents much attention has been given to the adequate use and monitoring of antiplatelet drugs, although there is no current standard agreement on type, dose, or duration of therapy.[
One obvious initial concern of the device given the increased “metal burden” is that significant in-stent stenosis would be observed on follow-up angiograms. PITA demonstrated no evidence of significant in-stent stenosis (≥50%) by conventional angiography at 180 days.[
One important concept regarding the mechanism of action of flow diverting stents relies on the idea that branch vessels with outflow will be preserved when the stent covers their ostia while the target aneurysm, which by nature does not have an outflow channel, will undergo progressive thrombosis. In clinical practice to date, this hypothesis seems only partially accurate. In the Budapest experience, a total of 28 visual side branches were covered with at least one PED. One ophthalmic artery was immediately nonvisualized on completion angiography and resulted in retinal branch occlusion. Two additional ophthalmic arteries (each covered by multiple devices) were found to be occluded at 6-month follow-up angiography, although both were clinically silent.[
There has been much enthusiasm for the use of flow diverters to treat giant and fusiform aneurysms involving the vertebrobasilar circulation. The natural history of these lesions is dismal with a reported mortality rate of approximately 30% and to date both surgical and endovascular solutions to these lesions remain fraught with potential devastating complications.[
So where do we stand with flow diversion? What is the future? Although many staunch supporters of the device would like to see this to be the cure for all treatments for intracranial aneurysms, it is doubtful this will happen. As with all technical advancements in surgery or the endovascular world each step forward is faced with a smaller step back. It seems likely that flow diverting stents will make a huge impact on the treatment of wide necked large and giant aneurysms of the ICA. These devices seem to work extremely well for these lesions with potentially shorter procedural times and possibly lower costs for the larger aneurysms in which a traditional stent with numerous coils would be required to achieve an acceptable treatment.[
Many positive attributes of flow diverting technology exist. One of the major drawbacks of traditional endovascular therapy as compared to surgical clipping is that complete, durable occlusion is achieved in a significantly lower percentage of patients. Following endovascular therapy many lesions are only partially treated or present later with recurrences. This is particularly true for large (≥10 mm) and wide-necked aneurysms, which often require numerous retreatments and long-term imaging surveillance.[
Until we understand the hemodynamic effect of the device on branch and perforating vessels more clearly, use of flow diversion in the vertebrobasilar circulation, the middle cerebral artery bifurcation, and within the anterior communicating artery complex remains to be seen. As of now we have acceptable treatment options both surgically and with endovascular means for these lesions. Until we are sure of the safety profile of the device in these regions, the potential risks seem to outweigh the benefits over established treatments. As with prior technical advancements, it is likely that flow diverting stents will take their place in the interventionalist's armetarium for a specific, albeit potentially large, subset of intracranial aneurysms. This being said traditional endovascular approaches as well as surgical therapies will retain their role. Indeed in our future it is doubtful there will be a “fix all” device for the treatment of intracranial aneurysms.
ISCHEMIC STROKE
The restoration of blood flow by vessel recanalization has been shown in the literature to improve outcome and reduce mortality in the setting of acute ischemic stroke;[
Attempts to prove the effectiveness and adequacy of IA rt-PA and various mechanical thrombectomy devices as compared to IV therapy for use in acute ischemic stroke has seen many ups and downs in the past decade. The past year has been no different with one potentially major step forward and another backwards with regards to mechanical thrombectomy. On April 18, 2012 the Interventional Management of Stroke (IMS) III independent data monitoring board recommended to place the IMS III trial on hold due to interim analysis showing a very low likelihood of ultimately demonstrating a difference between the two treatment arms. IMS III was a randomized multi-center, open-label clinical trial designed to determine if a combination of intravenous tissue plasminogen activator (IV rt-PA) and an approved IA therapy (an FDA approved mechanical thrombectomy device and/or IA rt-PA) was superior to IV rt-PA alone.[
However, a little over 2 months before halted enrollment in IMS III was announced, the promising preliminary results of the SWIFT (Solitaire with the intention for thrombectomy) trial were presented at the International Stroke Conference in New Orleans on February 3, 2012. SWIFT was an open label, randomized, blinded, multi-center trial evaluating the effectiveness of the Solitaire™ FR Revascularization Device (ev3 Inc., Irvine, CA, USA) against the Merci Retriever® (Concentric Medical/Stryker Neurovascular, Mountain View, CA, USA) for mechanical revascularization of large vessel occlusions in the setting of acute ischemic stroke. The Solitaire™ FR device is an intracranial stent, initially marketed for use in aneurysm embolization, which demonstrated promising results from preliminary trials abroad for use as a mechanical clot retriever for ischemic stroke.[
The SWIFT trial indeed did support these hopes, showing a significantly higher recanalization rate without symptomatic intracranial hemorrhage (SICH) of the Soltaire™ FR Revascularization Device compared with the Merci® Retriever (61% vs. 24%) in the final report published online August 26, 2012.[
At least six additional stent retriever devices have entered premarket testing since the early results of high recanalization rates with Solitaire™ were released.[
So where do we go and what do we do with these conflicting results? The data from IMS III is sound and convincing. With previously available mechanical devices IMS III makes a compelling argument that a combination of IV and IA therapy is not superior to IV therapy alone. However, several main counterpoints must be considered. IMS III was designed to evaluate combination therapy. The trial did not select for IV rt-PA failures, which are often large vessel occlusions for which endovascular therapy is currently considered most useful.[
Second, given the recent results of the SWIFT trial it must be noted that the majority of IMS III was completed without the use of stent retriever devices. The Solitaire™ device was incorporated into IMS III as the device was approved; however, this occurred late enough that at the time of interim analysis <1% of interventional cases were performed using the new stent retriever technology.[
Stent retrievers will likely positively impact the success of mechanical thrombectomy for acute ischemic stroke. It is doubtful, however, in the author's opinion, that they will truly revolutionize the field, making IA interventions for stroke akin to that seen for acute coronary occlusion. Despite accruing data that mechanical devices give higher rates of recanalization than IV rt-PA there has been difficulty in demonstrating a concurrent improvement in patient outcomes.[
Indeed the key clinical factor driving the field currently and likely into the future, is the overall poor success of other available treatment options for ischemic stroke, most specifically the relative limited efficacy of IV rt-PA.[
As a final point one cannot discuss the current limitations of acute ischemic stroke intervention without addressing patient specific considerations and time window constraints. Although there are roughly 795,000 strokes in the United States each year[
References
1. Akbari SH, Reynolds MR, Kadkhodayan Y, Cross DT, Moran CJ. Hemorrhagic complications after prasugrel (Effient) therapy for vascular neurointerventional procedures. J Neurointerv Surg. 2012. p.
2. Baker WL, Colby JA, Tongbram V, Talati R, Silverman IE, White CM. Neurothrombectomy devices for the treatment of acute ischemic stroke: State of the evidence. Ann Internal Med. 2011. 154: 243-52
3. Brinjikji W, Rabinstein AA, Kallmes DF, Cloft HJ. Patient outcomes with endovascular embolectomy therapy for acute ischemic stroke: A study of the national inpatient sample: 2006 to 2008. Stroke. 2011. 42: 1648-52
4. Brisman JL, Song JK, Newell DW. Cerebral aneurysms. N Engl J Med. 2006. 355: 928-39
5. Broussalis E, Trinka E, Hitzl W, Wallner A, Chroust V, Killer-Oberpfalzer M. Comparison of Stent-Retriever Devices versus the Merci Retriever for Endovascular Treatment of Acute Stroke. AJNR Am J Neuroradiol. 2012. p.
6. Buonamici P, Marcucci R, Migliorini A, Gensini GF, Santini A, Paniccia R. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007. 49: 2312-7
7. Castano C, Dorado L, Guerrero C, Millan M, Gomis M, Perez de la Ossa N. Mechanical thrombectomy with the Solitaire AB device in large artery occlusions of the anterior circulation: A pilot study. Stroke. 2010. 41: 1836-40
8. Chitale R, Gonzalez LF, Randazzo C, Dumont AS, Tjoumakaris S, Rosenwasser R. Single center experience with pipeline stent: Feasibility, technique and complications. Neurosurgery. 2012. 71: 679-91
9. Cloft HJ, Rabinstein A, Lanzino G, Kallmes DF. Intra-arterial stroke therapy: An assessment of demand and available work force. AJNR Am J Neuroradiol. 2009. 30: 453-8
10. Colby GP, Lin LM, Paul AR, Huang J, Tamargo RJ, Coon AL. Cost comparison of endovascular treatment of anterior circulation aneurysms with the pipeline embolization device versus stent-assisted coiling. Neurosurgery. 2012. 71: 944-8
11. Debrun G, Lacour P, Caron JP, Hurth M, Comoy J, Keravel Y. Detachable balloon and calibrated-leak balloon techniques in the treatment of cerebral vascular lesions. J Neurosurg. 1978. 49: 635-49
12. Deutschmann HA, Wehrschuetz M, Augustin M, Niederkorn K, Klein GE. Long-term 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
13. Dorn F, Stehle S, Lockau H, Zimmer C, Liebig T. Endovascular treatment of acute intracerebral artery occlusions with the solitaire stent: Single-centre experience with 108 recanalization procedures. Cerebrovasc Dis. 2012. 34: 70-7
14. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: A randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999. 282: 2003-11
15. Gianturco C, Anderson JH, Wallace S. Mechanical devices for arterial occlusion. Am J Roentgenol Radium Ther Nucl Med. 1975. 124: 428-35
16. Gorelick PB. Assessment of stent retrievers in acute ischaemic stroke. Lancet. 2012. 380: 1208-10
17. Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008. 359: 1317-29
18. Hampton T, Walsh D, Tolias C, Fiorella D. Mural destabilization after aneurysm treatment with a flow-diverting device: A report of two cases. J Neurointerv Surg. 2011. 3: 167-71
19. Harrigan M.editorsHandbook of cerebrovascular disease and neurointerventional technique. New York: Springer; 2012. p.
20. Harrigan MR, Deveikis JP.editorsHandbook of cerebrovascular disease and neurointerventional technique. Dordecht, New York: Humana Press; 2009. p.
21. Hieshima GB, Grinnell VS, Mehringer CM. A detachable balloon for therapeutic transcatheter occlusions. Radiology. 1981. 138: 227-8
22. Jones GM, Twilla JD, Hoit DA, Arthur AS. Prevention of stent thrombosis with reduced dose of prasugrel in two patients undergoing treatment of cerebral aneurysms with pipeline embolisation devices. BMJ Case Rep. 2012. p.
23. Jones GM, Twilla JD, Hoit DA, Arthur AS. Prevention of stent thrombosis with reduced dose of prasugrel in two patients undergoing treatment of cerebral aneurysms with pipeline embolisation devices. J Neurointerv Surg. 2012. p.
24. Khatri P, Hill MD, Palesch YY, Spilker J, Jauch EC, Carrozzella JA. Methodology of the Interventional Management of Stroke III Trial. Int J Stroke. 2008. 3: 130-7
25. Koh JS, Lee SJ, Ryu CW, Kim HS. Safety and efficacy of mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke: A systematic review. Neurointervention. 2012. 7: 1-9
26. Leung GK, Tsang AC, Lui WM. Pipeline embolization device for intracranial aneurysm: A Systematic Review. Clin Neuroradiol. 2012. 22: 295-303
27. Lubicz B, Collignon L, Raphaeli G, De Witte O. Pipeline flow-diverter stent for endovascular treatment of intracranial aneurysms: Preliminary experience in 20 patients with 27 aneurysms. World Neurosurg. 2011. 76: 114-9
28. Luessenhop AJ, Velasquez AC. Observations on the tolerance of the intracranial arteries to catheterization. J Neurosurg. 1964. 21: 85-91
29. Lylyk P, Miranda C, Ceratto R, Ferrario A, Scrivano E, Luna HR. Curative endovascular reconstruction of cerebral aneurysms with the pipeline embolization device: The Buenos Aires experience. Neurosurgery. 2009. 64: 632-42
30. McAuliffe W, Wycoco V, Rice H, Phatouros C, Singh TJ, Wenderoth J. Immediate and midterm results following treatment of unruptured intracranial aneurysms with the pipeline embolization device. AJNR Am J Neuroradiol. 2012. 33: 164-70
31. Meyers PM, Schumacher HC, Connolly ES, Heyer EJ, Gray WA, Higashida RT. Current status of endovascular stroke treatment. Circulation. 2011. 123: 2591-601
32. Miteff F, Faulder KC, Goh AC, Steinfort BS, Sue C, Harrington TJ. Mechanical thrombectomy with a self-expanding retrievable intracranial stent (Solitaire AB): Experience in 26 patients with acute cerebral artery occlusion. AJNR Am J Neuroradiol. 2011. 32: 1078-81
33. Mordasini P, Brekenfeld C, Byrne JV, Fischer U, Arnold M, Heldner MR. Technical feasibility and application of mechanical thrombectomy with the solitaire FR Revascularization device in acute basilar artery occlusion. AJNR Am J Neuroradiol. 2013. 34: 159-63
34. Morgenstern LB, Staub L, Chan W, Wein TH, Bartholomew LK, King M. Improving delivery of acute stroke therapy: The TLL Temple Foundation Stroke Project. Stroke. 2002. 33: 160-6
35. Mpotsaris A, Bussmeyer M, Loehr C, Oelerich M, Buchner H, Weber W. Mechanical thrombectomy in severe acute stroke: Preliminary results of the Solitaire stent. J Neurol Neurosurg Psychiatry. 2012. 83: 117-8
36. Mullan S, Raimondi AJ, Dobben G, Vailati G, Hekmatpanah J. Electrically induced thrombosis in intracranial aneurysms. J Neurosurg. 1965. 22: 539-47
37. 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. 2011. 32: 34-40
38. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): A randomised trial. Lancet. 2012. 380: 1231-40
39. O’Kelly CJ, Spears J, Chow M, Wong J, Boulton M, Weill A. Canadian Experience with the Pipeline Embolization Device for Repair of Unruptured Intracranial Aneurysms. AJNR Am J Neuroradiol. 2012. p.
40. Prabhakaran S, Wells KR, Lee VH, Flaherty CA, Lopes DK. Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol. 2008. 29: 281-5
41. 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
42. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: A meta-analysis. Stroke. 2007. 38: 967-73
43. Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O. The importance of size: Successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke. 2011. 42: 1775-7
44. Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007. 38: 948-54
45. Saver J, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG. SOLITAIRE FR with the Intention for Thrombectomy (SWIFT) Study. International Stroke Conference, New Orleans; 2012. p.
46. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): A randomised, parallel-group, non-inferiority trial. Lancet. 2012. 380: 1241-9
47. Siddiqui AH, Abla AA, Kan P, Dumont TM, Jahshan S, Britz GW. Panacea or problem: Flow diverters in the treatment of symptomatic large or giant fusiform vertebrobasilar aneurysms. J Neurosurg. 2012. 116: 1258-66
48. Stampfl S, Hartmann M, Ringleb PA, Haehnel S, Bendszus M, Rohde S. Stent placement for flow restoration in acute ischemic stroke: A single-center experience with the Solitaire stent system. AJNR Am J Neuroradiol. 2011. 32: 1245-8
49. Szikora I, Berentei Z, Kulcsar Z, Marosfoi M, Vajda ZS, Lee W. Treatment of intracranial aneurysms by functional reconstruction of the parent artery: The Budapest experience with the pipeline embolization device. AJNR Am J Neuroradiol. 2010. 31: 1139-47
50. . Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995. 333: 1581-7
51. Tomsick TA, Khatri P, Jovin T, Demaerschalk B, Malisch T, Demchuk A. Equipoise among recanalization strategies. Neurology. 2010. 74: 1069-76
52. van Rooij WJ, Sluzewski M. Perforator infarction after placement of a pipeline flow-diverting stent for an unruptured A1 aneurysm. AJNR Am J Neuroradiol. 2010. 31: E43-4
53. Wijdicks EF, Kallmes DF, Manno EM, Fulgham JR, Piepgras DG. Subarachnoid hemorrhage: Neurointensive care and aneurysm repair. Mayo Clin Proc. 2005. 80: 550-9
54. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007. 357: 2001-5
55. Writing Group M, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S. Heart disease and stroke statistics-2010 update: A report from the American Heart Association. Circulation. 2010. 121: e46-215
56. Zaidat OO, Lazzaro MA, Gupta R, Yavagal DR, Rasmussen PA, Hirsch JA. Interventional Management of Stroke III Trial: Establishing the foundation. J Neurointerv Surg. 2012. 4: 235-7