Treatment of a complex intracranial aneurysm with a flow diverter
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.263266
Source of Support: None, Conflict of Interest: None
The introduction of Guglielmi detachable coils in 1991, and the subsequent validation of their effectiveness by the seminal International Subarachnoid Aneurysm Trial (ISAT) trial,, ended the therapeutic monopoly of the microsurgical clipping procedure. Coil embolization, however, had certain limitations with a few challenging aneurysm morphologies like a blister aneurysm, an aneurysm near arterial branches, an aneurysm with arterial branches arising from within its wall, a cavernous sinus aneurysm, and a giant and dysplastic aneurysm.
The flow diverter, an endovascular device had been developed in the years 2006-2007. It 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.,,
Coil embolization has been practiced for a far longer period. Numerous trials, studies and meta-analysis have demonstrated their safety and efficacy as well as their limitations in managing aneurysms with various morphologies.,,,, Surprisingly, only one randomized study exists that compared the safety and effectiveness of the flow diversion (pipeline embolization device [PED]) to coil embolization for the treatment of coilable wide-necked internal carotid artery (ICA) aneurysms (the Complete Occlusion of Coilable Aneurysms [COCOA] Study). It enrolled only 13 patients between 2008 and 2015 and was then terminated, presumably owing to a poor patient recruitment.
What is a complex aneurysm? Is it just a perception? So far, no standardized definition for a complex aneurysm exists that unequivocally distinguishes it from a standard aneurysm. Since flow diverters are specifically designed for aneurysms with a complex morphology, with a wide necked configuration, and with a large or giant size, evolving a comprehensive definition that clearly differentiates between a “standard” and “complex” intracranial aneurysm is vital to the proper selection of the management modality of aneurysms.,,, In the current practice, the aneurysm characteristics that may make the aneurysm eligible for flow diverter treatment are enumerated below; however, the indications are expanding and flow diversion is being used with an increasing frequency by experienced operators for newer and off-label indications. The indications include:
Large or giant ophthalmic segment carotid and vertebral aneurysms
The basic concept of flow diversion is to deflect the blood flow away from the neck or the in-flow zone of the aneurysm. Thus, the technique of flow diversion relies on the concept of 'heal the hole' or an 'endoluminal remodelling' of the parent artery. The resultant stasis of blood flow in the aneurysm leads to an inflammatory response. It is postulated that the flow diverter acts as a scaffolding for neointimal proliferation, resulting in endothelialization and remodelling of the parent vessel. Therefore, the flow diversion approach is, at present, intutively perceived as being a more physiological treatment as compared to clipping and coiling of aneurysms., In order to disrupt the flow from the parent artery to the neck of the aneurysm, while maintaining the patency of sidewall branches, the device must fulfil two requirements: a low porosity (metal-free to metal-covered area); and a high pore density (number of pores per square millimetres for a given porosity).
The various devices which are available for commercial use are as follows:,,,,,,
Pipeline embolization device (PED; Medtronics Inc., Minneapolis, Minnesota, USA): It is a woven tube of 48 wires of platinum and cobalt-chromium alloy (25% platinum and 75% nickel–cobalt chromium alloy) with a porosity of 65–70%.
SILK flow diverter (SFD; Balt Extrusion, Montmorency, France): It is a braided cylinder of 48 filaments of cobalt–chromium alloy and has 12 platinum wires to aid in providing radio-opacity. It has a varying number of metal struts, from 48 to 96. It maintains the pore density at close to 70% across different device diameters.
FRED (Flow Re-Direction Endoluminal Device, Microvention, Tustin, CA, USA) flow diverter: It has a dual layer design that consists of a low porosity inner mesh and a higher porosity outer mesh. The device is composed of 48 braided nitinol inner strands and 16 outer struts with 4 interwoven marker strands as well as proximal and distal markers. The dual layer is restricted to the mid-section and covers approximately 80% of the device length.
p64 (Phenox, Bochum, Germany): It is a braided flow diverter composed of 64 nitinol wires. Two platinum wires wrapped around the shaft assist in providing radio-opacity. The 64 wires are grouped into eight bundles proximally, with each bundle consisting of eight wires. The porosity of the device is 51–60%.
The Surpass FDS (Stryker Neurovascular, Fremont, CA, USA): It is a cobalt–chromium, low porosity, self-expanding, tubular-shaped, braided mesh stent. It has a low porosity of 70% and a uniformly distributed high pore density of 21–32 pore/mm 2 that remains constant, regardless of the stent diameter.
The advantages of the flow diverter are that either minimal or no intraluminal manipulation of the aneurysmal sac by the catheter and wires occurs in most of the cases. This reduces the chances of rupture of the aneurysm, that may be precipitated by the use these devices.,
Shrinkage of an aneurysm is the expected outcome after flow diversion, resulting in resolution of cranial nerve palsies due to the aneurysmal mass effect. This phenomenon is most relevant in ophthalmic segment aneurysms, as these aneurysms may be associated with clinically significant neuro- ophthalmological disorders despite a low risk of rupture. Thus, these devices could bring about an effective management of visual symptoms by relieving the direct mass effect of the aneurysm on the optic nerve; or, the resolution of impairment of eye movements due to the mass effect of the aneurysm on the cranial nerves III, IV, V, and VI.,,,,
Sahlein et al., reported an improvement in visual symptoms in 64% of patients and a worsening of these symptoms in 2.6% of them. New visual symptoms related to the aneurysms were seen in 5% of patients. Zanaty et al., reported the results of treatment of 44 ophthalmic segment aneurysms with the PED. A complete resolution of the symptoms was achieved in 73% patients, and a worsening of symptoms was noted in 1 (4.5%) patient.
Of course no new modality, howsoever elegant, can be without its downsides, particularly when it is being used in the emergency care treatment of a disease like subarachnoid haemorrhage. A delayed haemorrhage has occasionally been an unfavourable outcome of the procedure. In the study by Kallmes et al., and Bhogal et al.,, the overall rupture rate was only 0.6%; however, it increased with the aneurysm size (giant aneurysms 4.5%, large aneurysms 0.6%, small aneurysms 0%). Most of these complications arose after distal manipulation of micro- wires or micro-catheters, difficult deployment of the device, and balloon inflation for remodelling of the device.
Kulcsar et al., proposed four factors that might serve as predisposing factors for an aneurysmal rupture after a patient undergoes a flow diversion procedure. These include a very large/giant size of the aneurysm; in the case of symptomatic aneurysms; the aspect ratio of the aneurysm being >1.6; and an inertia-driven flow within the aneurysm. The other postulated reasons include the hemodynamic alterations of flow after the flow diverter placement and a complex geometry of the aneurysm.,,, The reasons for delayed aneurysmal rupture include an increased intra-aneurysmal pressure because of a flow alteration (i.e., a restriction in the outflow of blood of the aneurysm with a high inflow of blood within it); and, a weakened aneurysmal wall as a result of the protease formation, associated with aneurysm sac thrombosis and accompanying inflammation. The combination of flow diversion therapy and a simultaneous endosaccular coil embolization is being considered for the prevention of a delayed aneurysmal rupture.,
An intra-parenchymal haemorrhage, sometimes remote from the aneurysmal location, is another dreaded complication. The postulated reasons for this complication are the concomitant administration of antiplatelet therapy, the presence of hyperperfusion after parent artery reconstruction, the haemorrhagic transformation of ischemic lesions, and the wire perforation of the luminal wall of the aneurysm or the parent blood vessel during the device deployment. When an intraparenchymal haemorrhage of this nature occurs, the prognosis remains extremely poor.,,,
Rouchaud et al., reviewed 443 articles reporting on flow diverter therapy. Among these articles, 53 reported the occurrence of a delayed intracranial haemorrhage. There were 81 aneurysmal ruptures and 101 intraparenchymal haemorrhages. Although the risk of aneurysmal rupture after the flow diverter therapy is very low (0–1.1%), when it does occur, it results in a very poor outcome. Kallmes et al., performed a pooled analysis of 3 studies, combing the data from 1092 patients treated with the pipeline embolization device; the neurological morbidity and mortality rates were 5.7% and 3.3%, respectively. Following the coil embolization in critical aneurysms like the cavernous segment aneurysms of the internal carotid artery or the posterior circulation giant aneurysms, post-embolization neurological worsening is often noticed due to the mass effect produced, and flow diversion is able to avoid this mass effect on crucial neural structures.
The clinical experience obtained in the few trials with the flow diverters is as follows: One trial, conducted between January and November 2007, was the Pipeline Embolization Device for the Intracranial Treatment of Aneurysms (PITA). It recruited 31 patients in whom the aneurysm was treated with the pipeline embolization device. One of the 4 contributing centres recently reported on 8 additional aneurysms. A few procedure-related neurological complications were reported; a new stroke rate of 6% occurred in the PITA trial.
Based on the results of the Pipeline for Uncoilable or Failed Aneurysms (PUFS) multi-centre trial, and a comprehensive review and metanalysis, the treatment of large and giant ICA aneurysms with the PED has become a standard treatment option. However, in these studies, all aneurysms with a maximal diameter <10 mm were included; only 24 giant (>25 mm) aneurysms were treated, and no distinction was made between the smaller and larger aneurysms in terms of occlusion and complication rates. The PUFS study showed a major ipsilateral stroke or neurologic death rate of 5.6% or 2.6%, respectively.
A meta-analysis of the published literature until 2014, of 59 studies with more than 2493 patients, was done by Zhou et al. The overall complete occlusion rate was 82.5%, and the success rate of the flow diverter implantation was 97.4%. The occlusion rate for anterior circulation aneurysms was 83.3%; with regard to complete occlusion, the odds ratio for the occlusion of anterior circulation aneurysms was significantly higher than that of posterior circulation aneurysms. Currently, the period for ensuring complete occlusion of an aneurysm following the flow diverter treatment remains unknown; nevertheless, the published data suggest that the overall complete aneurysmal occlusion rates at >6 months follow-up are 68%-88% and 68%-94% following the usage of the PED and SILK flow diverters, respectively. Besides, higher occlusion rates can be achieved for aneurysms of the anterior circulation than for those of the posterior circulation. The occlusion and permanent morbidity rates emanating from publications that had at least included 40 cases were 76.1 (13.7%) and 3.4 (2.7%), respectively. For rest of the publications, the two rates were 76.3 (16.5%) [P 1 / 4 0.44] and 7.4 (6.4%) [P < 0.05], respectively. Both the occlusion and morbidity rates showed an improved trend at high volume university centres.,,,, The flow diverter treatment has, so far, also proven to be an effective treatment for the management of tandem intracranial aneurysms and blister aneurysms. The advantages of endoluminal reconstruction of a dysplastic segment lies in the treatment of all the aneurysms present in tandem, with a single stent.,,, There are also concerns raised regarding the usage of the flow diverters in acutely ruptured aneurysms, where the aneurysm has not been adequately secured; and, the enthusiastic use of flow diverters for saccular coilable/clippable aneurysms as well as for aneurysms located at the vessel bifurcations. With the advent of newer technology, the existing assessment scales have become redundant while assessing the inter-observer reliability and follow up. Hence, newer scales have been proposed by Kallmes et al. The other scales that may be used for assessment are the Kamran-Byrne score, the O'Kelley-Krings-Marotta scale and the Bavinzski-Dodier (BD) scale, which claim to be simplified and reproducible.,,
The most controversial part in the usage of flow diversion for intracranial aneurysms is the regulation of post-flow diversion anti-platelet therapy. There are no long-term trials, and consequently, guidelines on the optimal anti-platelet therapy that may be used. The heterogeneity of the response to anti-platelet therapy, especially clopidogrel, where the ineffectiveness of the treatment is reported to be as high as 30%-40%, is of special concern. The hypo-responders to anti-platelet therapy have the risk of developing in-stent thrombosis; and, hyper responders have the risk of haemorrhagic events taking place in them.
As flow diversion was introduced just about 10 years ago, the long-term clinical results are yet not there. Angiographic occlusion rates cannot be measured on the conventional endovascular scales; thus, very limited trials, that are related to angiographic outcomes, are available. Intuitively, promoting endothelization on a metal stent; and, assuming that the ability to ensure that the degree of endothelialisation is under optimal control by drug therapy, are presumptions, and at the moment, slightly far-fetched. A more delayed incidence of in-stent thrombosis can be expected in the future. At the moment, the cost of the device, and the limited availability of platelet aggregation measuring devices as well as neurovascular catheterisation laboratories may be the major limiting factors in the Indian context.
There is no doubt that the flow diverters have changed the way in which we treat difficult aneurysms. Long-term quality data is still awaited. Until the results from the more comprehensive data evaluations emerge, the current indications for placement of flow diverters remain aneurysms that have no better solutions, as judged by skilled and thoughtful practitioners.