Evaluating the TubridgeTM Flow Diverter for Large Cavernous Carotid Artery Aneurysms

Background: The Tubridge TM ow diverter (TFD) was recently developed in China; however, its safety and ecacy in treating large cavernous carotid artery aneurysms (LCCAs) are unclear. Objective: To evaluate the safety and ecacy of the TFD in patients receiving TFDs to treat LCCAs (10– 25 mm). Methods: Between June 2013 and May 2014, seven patients with LCCAs were enrolled in our study, and all seven patients underwent TFD implantation combined with coils. Results: Angiographic follow-up images were available for all seven patients at a median of 57.5 ± 16.7 (range, 6–69) months. Seven patients obtained favorable angiographic results dened as O’Kelly– Marotta Scale C and D. Clinical follow-up data were available for all seven patients at a median of 73.32 ± 3.6 (range, 66–78) months. No patients developed new neurological decits. Six patients achieved a modied Rankin scale score of 0, and diplopia improved in the remaining patient. Conclusions: Results were excellent for the aneurysms treated with TFDs in our patients with LCCAs. TFDs are feasible for the treatment of LCCAs, but a multicenter, controlled clinical trial is needed to evaluate the long term safety and ecacy of the TFD to treat LCCAs.


Introduction
Cavernous carotid artery aneurysms (CCAs) account for ≤ 5% of all intracranial aneurysms [1][2][3][4][5] . According to the etiology, CAAs can be divided into traumatic, mycotic, and idiopathic, and idiopathic aneurysms are most common. Because CCAs are located in extradural space, symptomatic and large aneurysms usually manifest as symptoms and signs of a mass effect on the surrounding structures 3,6,7 , and patients present with intractable cranial neuropathy requiring intervention 8 . The treatment of large intracranial aneurysms, compared with small aneurysms, is associated with high complication and recurrence rates 9,10 Several ow diverting devices have been developed with the goal of changing intrasaccular hemodynamics and reconstructing the parent artery, namely, the Pipeline ow diverter (Covidien, Irvine, CA), the Flow-Redirection Endoluminal Device (FRED; MicroVention, Tustin, CA), the Silk ow diverter (Balt Extrusion, Montmorency, France), and the Surpass stent (Stryker Neurovascular, Kalamazoo, MI). The frequency of use of these devices has increased sharply in the treatment of intracranial aneurysms. The Tubridge™ ow diverter (TFD) is a braided, self-expanding device with ared ends. Compared with other ow diverter devices, TFDs are made of a nickel-titanium alloy, which has the advantages of superelasticity and shape-holding memory. In addition, the use of platinum-iridium radiopaque micro laments allows for improved visualization of the length and diameter during the endovascular procedure. TFDs are available in several lengths (12-45 mm) and diameters (2.5-6.5 mm) and can provide a high degree of metal coverage (approximately 30.0-35.0%) at the aneurysmal neck after full opening, with a lower shortening rate 11 .
Previously, a multicenter, prospective, randomized, controlled clinical trial veri ed the safety and e cacy of the TFD in unruptured large and giant intracranial aneurysms 12 . However, as a novel device, outcomes of TFDs to treat large CCAs (LCCAs, 10-25 mm) have not yet been clari ed. The purpose of this study was to evaluate the safety and e cacy of TFDs in the treatment of LCCAs.

Patient population
This was a single-center, retrospective study that was approved by the institutional Ethics Committee.
Written informed consent for study inclusion was obtained from all patients. Between June 2013 and May 2014, 1378 patients were came to our hospital for endovascular treatment of intracranial aneurysm.
132 patients were diagnosed with CCAs. Among the 132 patients, 67 patients were diagnosed with LCCAs, and seven patients received TFDs to treat LCCAs.

Endovascular Procedure
For all enrolled patients, dual antiplatelet therapy (300 mg/day acetylsalicylic acid (ASA) and 75 mg/day clopidogrel) were given for at least 3 days before the endovascular procedure. All TFD placement procedures were performed under general anesthesia and via the transfemoral approach. Using the preoperative road map, a Traxcess-14 (Micro-Vention, Tustin, CA) microguidewire carried the Endopipe (Microport, Shanghai, China) stent catheter to the middle cerebral artery, and then an appropriate microcatheter was carried by the Traxcess-14 microguidewire and navigated into the aneurysmal sac.
Next, we withdrew the microguidewire and performed additional coiling in all the aneurysms through the microcatheter to the aneurysmal sac. Then, we delivered the appropriate TFD through the Endopipe stent catheter and released the TFD after satisfactory positioning. The treatment procedure was welldocumented.

Postoperative Medication
Each patient was prescribed 300 mg of ASA plus 75 mg of clopidogrel for 6 weeks, then the dose of ASA was reduced to 100 mg from 6 weeks to 3 months. Clopidogrel was discontinued after 3 months, and 100 mg of ASA was continued inde nitely.

Imaging and clinical assessment
We used the O'Kelly-Marotta Scale 13 to classify both the immediate postoperative angiographic results and the follow-up angiographic results. This grading scale is used to evaluate aneurysms treated with ow diversion and indicates both the degree of contrast stasis and the amount of aneurysm lling. The scale is widely used to evaluate the e cacy of ow diverter devices such as the Pipeline and Silk devices.
We de ned O'Kelly-Marotta Scale C or D as a favorable outcome. Angiographic results were con rmed by at least two experienced neurointerventionists. We collected each patient's clinical information, including whether the original symptom had improved and whether any new symptoms appeared, postprocedure.

Patient And Aneurysm Characteristics
Between June 2013 and May 2014, seven patients each with a large cavernous CCA were enrolled in our study. Clinical presentation included diplopia in four patients (one accompanied by blepharoptosis), ocular pain in one patient, facial tic in one patient, and right fontal sinus pain in one patient (Table 1). No patients had a history of subarachnoid hemorrhage or other vascular genetic history such as arteriovenous malformation. Table 1 shows the patients' demographics and clinical information.

Immediate Angiographic And Clinical Results
We implanted seven TFDs; each patient was treated with a single TFD plus coils. Six of the seven patients received loose packing of the aneurysmal sac, and only patient 4 received dense packing of the aneurysmal sac. Two patients were graded as O'Kelly-Marotta Scale grade A, and four patients were graded as B; one patient was graded as C (Table 1). No new neurological de cits developed after the endovascular treatment in any of the patients, and no bleeding or ischemic events occurred during or after the endovascular treatment.

Angiographic Follow-up Results
We selected the nal digital subtraction angiographic follow-up image for each patient as the time point to evaluate the e cacy of TFD placement. Angiographic follow-up data were obtained for all seven patients (Table 2), with a median imaging follow-up period of 57.5 ± 16.7 (range, 6-69) months. All seven patients obtained favorable angiographic follow-up results ( ve patients' O'Kelly-Marotta Scale grades were D (Figs. 1 and 2), and two patients were grade C). In one of the seven patients, (Fig. 3), parent artery occlusion was seen in the 6-month digital subtraction angiographic image. The occlusion was located in the TFD, but there was no clinical manifestation associated with cerebral infarction because the left internal carotid artery provided su cient blood for right anterior circulation through the anterior communicating artery. Rankin scale score of 0, and the remaining patient experienced improved diplopia (Table 2).

Discussion
Compared with small aneurysms, treating large aneurysms is technically challenging, with a much higher complication and recanalization rate 8,14 . Long-term angiographic outcomes showed that recurrence rates for large aneurysms treated with coiling alone or stent-assisted coiling were 57.9% and 23.5%, respectively 15 , indicating that satisfactory outcomes cannot be achieved via conventional endovascular treatment. Parent artery occlusion can be used to treat large aneurysms, but this requires a negative balloon occlusion test, and new aneurysms occurred in other areas in 4.5% of patients after parent artery occlusion 16 . In addition, when treating LCCAs, our goals are to reduce the risk of rupture and thromboembolism, and relieve cerebral nerve paralysis caused by the aneurysmal mass effect. Recently, higher numbers of large aneurysms are being treated with ow-diverter devices, and the e cacy and safety of these devices are being proven. Flow diverter devices contrast with the traditional treatment concept of intracranial aneurysmal sac tamping, and reconstruct the parental artery, which is a big step in the treatment of intracranial aneurysms. In the present study, we reported our preliminary ndings related to the use of TFDs in LCCAs.
In our series, angiographic follow-up data were obtained for all seven patients ( patients experienced resolution (61%) 18 . In our clinical follow-up, patients achieved even better results, with six patients experiencing complete resolution (85.7%) of the aneurysmal mass effect symptoms.
The use of ow diverter devices theoretically does not require coiling. However, for large, complex aneurysms, additional coils could play a role in improving occlusion rates and decreasing the risk of catastrophic aneurysm rupture after the use of ow diverter stents 17,19 . In our study, every patient was treated with a TFD and coils because we believe that the additional coils accelerate thrombus formation to decrease the pressure from the aneurysmal sac caused by blood retention within the sac after TFD implantation. In an earlier experience using the Pipeline ow diverter, Siddiqui et al 20 recommended avoiding dense packing of the aneurysmal sac because this can lead to acute thrombotic or compressive occlusion. Our ndings were similar; six patients were treated with low coil-packing densities, and their cranial nerve de cits resolved completely. The only patient (patient 4) treated with dense aneurysmal packing obtained subtotal cranial nerve de cit improvement. We conclude that loose aneurysmal packing does not affect alleviation of the mass effect.
The reported complication rates for ischemia and bleeding following aneurysmal repair are 5.5-9.76% and 2.0-6.1% respectively, with morbidity and mortality rates of 9.8-17.7% and 3.8-4.9%, respectively 21,22 ; the incidence of complications is higher for giant aneurysms 23 . The incidence of complications in the ow diverter device group in our study was lower than that in conventional parent artery occlusion with a single coil and stent-assisted coiling when treating cavernous aneurysms 24 . In our case serious, one patient had occlusion of the parent artery, but showed no signs of ischemia because the left internal carotid artery provided su cient blood ow for right anterior circulation through the anterior communicating artery. But the result need to be taken seriously, not all patients can compensate adequately after unilateral internal carotid artery occlusion, ischemic events may occur once compensation is insu cient. One meta-analyses indicated ischemic rates after ow diverter implantation was 7.5% 25 and a 9%-10% incidence of ischemic events should be anticipated when using ow diverters for large aneurysms 12 . We did not encounter hemorrhagic complications, and the morbidity and mortality rates were both 0%.

Limitations
The present study involved only seven patients, because LCCAs are rare. In addition, not all patients underwent angiographic magnetic resonance imaging, so we were able to evaluate resolution of patients' mass effects only according to resolution of their clinical symptoms; we had no clear imaging evidence. A prospective, multicenter, controlled clinical investigation with a large sample and long-term follow up is essential.

Conclusions
Our patients with LCCAs treated with TFDs obtained excellent results, with a high percentage of patients experiencing remission of their aneurysmal mass effect symptoms. TFDs could be feasible for treating LCCAs; however, a multicenter, randomized, controlled clinical trial with long-term follow-up is still necessary.

Declarations
Ethics approval and consent to participate The ethics committee of Beijing Tiantan Hospital approved this study.

Consent for publication
This was a retrospective study and there was no informed consent Availability of data and materials Please contact author for data requests Competing interests