This is the first series to demonstrate the efficacy of the Cascade device when used to treat delayed cerebral vasospasm secondary to aSAH. The Cascade device can significantly increase the diameter of a variety of vasospastic segments including the more difficult to treat large vessels such as the ICA. The results are long-lasting with delayed angiography confirming persistent dilatation at 24 h. The bench-side analysis also demonstrates that a significantly greater force can be generated using the Cascade M than either the 4 or 6 mm Solitaire devices which would support our clinical findings that the device can be successfully used to treat cerebral vasospasm.
Bhogal et al. published the initial report on the use of stents retrievers to treat vasospasm several years ago and in this publication a variety of different devices were used all of which appeared to cause vasodilation to varying degrees. Follow-up studies performed in the patients showed a persistent dilatation. This demonstrated that the forces required to treat cerebral vasospasm were within reach of existing devices. It was noted that the success of stentplasty appeared to be higher for smaller vessels. Subsequent mathematical modelling studies corroborated this observation with the concept of a ‘dilatation threshold’ that needs to be reached in order for a sustained treatment effect (Bhogal et al., 2019). Upon reaching this threshold there would be relaxation of the vessel, due to changes in the contractile properties of the smooth muscle cells, but no disruption of the extracellular matrix. Numerous in vivo studies had demonstrated that damage to the extracellular matrix was not required for successful treatment of cerebral angioplasty (Yamamoto et al., 1992; Macdonald et al., 1995; Kobayashi et al., 1993). The concept of a dilatation threshold built upon the earlier work of Fischell who documented ‘arterial paralysis’ occurring post balloon angioplasty in both relaxed and contracted arteries, that these vessels failed to respond to the topical application of vasoconstricting agents, and that the same degree of balloon dilatation in relaxed vessels resulted in significantly less, if any, arterial paralysis compared to contracted vessels. Together these results suggested that contraction predisposed a vessel to mechanical dilatation and that the forces required to achieve this were much lower than previously thought since the extracellular matrix did not need to be disrupted to effect these changes. This idea that pre-contraction predisposes to the successful vasodilatation of vessels suggests that use of chemical vasodilators prior to mechanical vasodilatation may hinder the success of the latter. This was subsequently shown by Kwon et al. (Kwon et al., 2019) who reported higher recurrent vasospasm rates following stentplasty if vasodilators were given prior to stentplasty compared to afterwards (60% vs. 0%).
Su et al. (Su et al., 2020) recently published their results on the use of the Solitaire 6x40mm to treat vasospasm following unsuccessful IA infusion of verapamil/nicardipine. All stentplastied vessels showed calibre improvement with the average increase in vessel diameter being 106.5 ± 64.2% (range 41.8–213.6%). A greater calibre change of vessels in the posterior circulation than in the anterior circulation was noted. In our series the average increase in the diameter was approximately 300%. Our in vitro have shown that the Cascade devices are able to generate markedly greater radial forces than both the 4 and 6 mm Solitaire devices. This is important because previous studies using a variety of different stent-retrievers to treat cerebral vasospasm have shown a varied ability to treat cerebral vasospasm, which has been attributed to the radial force generated by the commercially available stent-retrievers when used in an off-label manner to treat cerebral vasospasm. The Cascade allows the operator to alter the force applied to the vessel by varying both the degree to which the device is unsheathed as well as how much the device is expanded. In larger proximal vessels full expansion of the device may be required however, in small more distal vessels the force required to cause arterial relaxation is likely to be lower and hence maximal expansion is likely not required. This was noted in several of our cases with repeated expansion and partial unsheathing was required to treat focal areas of persistent stenosis.
The most recent study, and to date the only prospective study to assess stentplasty in DCV, was published by Gupta et al. (Gupta et al., 2021). The VITAL study was a prospective, open-label, single-arm study to assess the safety and efficacy of the NeVa VS device – another stent designed specifically to target vasospasm. The primary endpoint was the ability of the NeVa VS to treat vasospasm with less than 50% spasm of the vessel, compared to baseline, following use of the NeVa VS and assessed by an independent core lab. A total of 70 patients were consented for recruitment in to the study but only 30 were treated. The mean age was 52 ± 11 years and the majority were female (86.7%). Prior to treatment the mean NIHSS score was 12.7 ± 12.8 and ASPECT score was 8.5. The MCA was the most commonly treated vessel (43/74, 58.1%). In total 34 procedures were performed with a total of 95 deployments in 74 vessel with a mean number of 1.3 ± 0.6 device deployments per vessel and mean deployment of 5.5 ± 2.2mins. Pre-treatment the degree of stenosis was 65.6 ± 14.7% and post-treatment it was 29.4 ± 19.3% with 86.5% of vessels successfully meeting the primary end-point. Subject-based procedural success was 92.2%. Retreatment of a vessel after the previous treatment with NeVa VS was low and required in in only 5/74 vessel segments (6.8%). In three of the 95 deployments (3.2%) a thrombotic event occurred that and related to the device. There were no vessels ruptures related to the NeVa VS however, in one patient where two deployments of the NeVa VS did not result in significant vasodilation a balloon angioplasty was performed with a consequent rupture of the MCA.
Non-occlusive devices offer a number of advantages relative to the use of balloons when considering cerebral vasospasm. Unlike balloons, they do not impede the anterograde cerebral blood flow which has been shown to rapidly decrease the tissue perfusion distally (Rasmussen et al., 2015). The risk of vessel rupture is likely to be lower compared to balloon angioplasty as the forces generated are significantly lower with stents. The increased familiarity with stents amongst interventional neuroradiologists is also likely to make stentplasty an inherently safer procedure compared to balloon angioplasty. More recently the growing interest and development of techniques to target distal vessel thrombectomy will also likely benefit the treatment of cerebral vasospasm in smaller distal vessels as familiarity of navigation and the use of devices in these vessels will no doubt improve. The treatment of vasospasm should aim to treat as many of the spastic segments as possible. A failure of this could inadvertently result in an arterial steal phenomenon being created such that there is preferential flow in a treated vessel that will now have lower resistance, with a precipitous drop in the flow in any vessels that remain vasospastic. This scenario was shown by Levitt et al. (Levitt et al., 2014) and in one of the cases presented by this group balloon angioplasty of the M1 segment resulted in improved flow within the MCA territory but reduced flow within the ACA territory. The easier navigability and lower profile of stents and stent-like devices compared to balloons may represent another potential advantage. In our own series, navigation of the Cascade into the ACA has proven straight-forward even in cases of severe vasospasm. Furthermore, the Cascade device may have several inherent advantages when used for cerebral vasospasm. In our experience fully unsheathing the device to treat the vasospasm initially is our preference. If after expanding the fully unsheathed device focal areas of vasospasm persist, a partially unsheathed device can be used to target the focal areas of spasm since this generates similar levels of force but over a smaller area. As was shown in our in vitro tests, the force generated by the Cascade starts to decrease if the device is expanded beyond the diameter of the vessel or constraining tube. Put another way once the vessel is dilated to its normal diameter further expansion of the device is unlikely to result in rupture due to the decrease in force applied due to braid deformation. This is the opposite of balloons whose force can be essentially continually increased until the balloon, the vessel, or both ruptures. This suggests that it would be very difficult to rupture a vessel using the Cascade device as long as one uses the device in a reasonable manner.
Given the potential advantages of stents to treat cerebral vasospasm there has been growing interest in this area. The pRELAX (phenox, Bochum, Germany) and Neva VS are the first of a new breed of retrievable stents designed with the specific intention of treating vasospasm. Early results of the pRELAX devices have recently been presented with promising results and publications are awaited. It is worthwhile noting that only the pRELAX device has been given a CE mark for treatment of cerebral vasospasm and use of other devices is currently off-label.
Our study is limited by its retrospective design and low number of cases included in the study.