- 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
Gavin W. Britz
Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA
DOI:10.4103/2152-7806.109194Copyright: © 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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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.
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[
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